Optimal Follow-up Time to Determine the Sustained Virological Response in Patients With Chronic Hepatitis C Receiving Pegylated-interferon and Ribavirin

From Journal of Gastroenterology and Hepatology

Masashi Namikawa; Satoru Kakizaki; Yutaka Yata; Yuichi Yamazaki; Norio Horiguchi; Ken Sato; Hitoshi Takagi; Masatomo Mori

Authors and Disclosures

Posted: 02/07/2012; J Gastroenterol Hepatol. 2012;27(1):69-75. © 2012 Blackwell Publishing

Abstract and Introduction

Abstract

Background and Aim: This study evaluated whether the assessment of hepatitis C virus (HCV)-RNA at 12 weeks (FW+12) post-treatment follow-up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real-time polymerase chain reaction (PCR) HCV assay.
Methods and Results: Two hundred and twenty-two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg-IFN) and ribavirin were administered for 24–72 weeks based on the genotype and viral load. Serum HCV-RNA was measured using real-time PCR at pretreatment, the end of treatment, FW+4, FW+8, FW+12, FW+16, FW+20 and FW+24. Two hundred patients had a virological response at the end of treatment. One hundred and forty-eight of 200 (74.0%) patients with a virological response at the end of treatment had an SVR at the FW+24. The positive predictive value (PPV) to identify patients with SVR at FW+4, FW+8, FW+12 was 87.1, 96.1, 98.0%, respectively. The viral load showed a reversion to the basal level as early as 8 weeks in relapse patients. There were only three patients who relapsed after FW+12 and all three of these patients were females with genotype Ib and a high viral load.
Conclusion: The assessment of serum HCV-RNA FW+12, using the highly sensitive real-time PCR assay, is almost as effective as FW+24 to predict SVR. However, there are false negatives in female patients with a high viral load of genotype Ib when the SVR is predicted by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV-RNA FW+12 may be effective in most patients.

Introduction

The recommended therapy for chronic hepatitis C is a combination of pegylated interferon (Peg-IFN) and ribavirin, and the major purpose of therapy to reach the sustained virological response (SVR).^[1–4] The current standard for the determination of SVR is undetectable serum hepatitis C virus (HCV)-RNA 24 weeks (FW+24) after the end of treatment^[5] and the continued viral response after FW+24.^[1–4] This standard is based on the results of many previous reports that late relapse is rarely observed after FW+24.^[6,7] This criterion is based on investigations using qualitative HCV-RNA assays with the lowest limits of detection of 50–100 IU/mL, to establish undetectable serum HCV-RNA at the end of therapy and after treatment.^[6,7]

A highly sensitive method to detect HCV-RNA was recently developed and applied in clinical settings.^[8,9] The highly sensitive methods include transcription-mediated amplification (TMA) and a real-time polymerase chain reaction (PCR) HCV assay.^[8–12] Martinot-Peignoux et al.^[8] reported the efficacy of a new assay based on TMA to predict SVR at FW+12. The TMA assay has a lowest detection limit of 5–10 IU/mL.^[8] Theoretically, this highly sensitive method could detect residual serum HCV-RNA in a proportion of patients, who had been classified as having a virological response with a less sensitive assay.^[8] Therefore, the assessment of HCV-RNA FW+12, using the TMA assay, is considered to be as effective as FW+24 to predict SVR.^[8]

The real-time PCR assay is also highly sensitive to detect HCV-RNA and a popular method to assess the HCV-RNA.^[9–12] Bortoletto et al.^[9] reported that TMA and the real-time PCR HCV assay have comparable sensitivity and specificity in identifying minimal residual HCV-RNA. The lower limit of quantitative detection of the real-time PCR assay is 15 IU/mL^[10–12] in comparison to the lowest detection limit of 5–10 IU/mL of the TMA assay.^[8] However, even HCV-RNA signals below the quantitative limit are detected by the real-time PCR assay. Therefore, it is difficult to determine whether the TMA or the real-time HCV assays are optimal for the detection of minimal residual viremia at the end of antiviral therapy with Peg-IFN and ribavirin and in predicting relapse after withdrawal of treatment.

This study evaluated whether the assessment of HCV-RNA FW+12 by the real-time PCR HCV assay was as effective as FW+24 to evaluate SVR.

Methods

Patients

Two hundred and twenty-two patients with chronic hepatitis C treated with combination Peg-IFN and ribavirin therapy from April 2008 to March 2010 at Gunma University Hospital and its affiliated hospitals were included in this study. All patients fulfilled the following inclusion criteria: (i) more than 5 log IU/mL of HCV-RNA in the baseline serum, and (ii) an elevated serum ALT level for least 6 months before initiation of treatment. In addition, patients were excluded if they presented any of the following conditions: (i) decompensated liver disease; (ii) other causes of liver disease such as hepatitis B infection; (iii) autoimmune disorders; (iv) hemoglobin value < 11 g/dL; (v) white blood cell count < 3000/μL; (vi) thrombocytopenia < 70 000/μL; (vii) neoplastic disease; (viii) severe cardiac disease; (ix) other severe concurrent disease such as a preexisting psychiatric conditions; or (x) pregnancy or lactation. Informed consent was obtained from all patients enrolled in the study after a thorough explanation of the aims, risks and benefits of this therapy.

Treatment Regimens

Peg-IFN and ribavirin were administered for 24–72 weeks according to the genotype and viral load. One hundred and seventy-five patients received Peg-IFN α2b (PegIntron, Schering Plough, Tokyo, Japan) at a dose of 1.5 μg/kg per week and ribavirin (Rebetol, Schering Plough, Tokyo, Japan) at a dose of 600–1000 mg/kg per day adjusted according to body weight (600 mg for patients weighing under 60 kg, 800 mg for those between 60 kg and 80 kg, 1000 mg for those over 80 kg) for 24–72 weeks. Forty-seven patients received Peg-IFN α2a at a dose of 180 μg/week (Pegasys, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan) and weight-based ribavirin 600–1000 mg/kg per day same dosage as described above (Copegus, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan). Patients infected with genotype I and all previously treated patients were treated for 48 weeks. The genotype I patients who remained positive for HCV-RNA at 12 weeks after the start of treatment, but who become negative for HCV-RNA after 13–36 weeks of treatment received an additional 24 weeks (total 72 weeks) treatment according to the 2008 Japanese guidelines for the treatment of patients with chronic hepatitis C.^[13] Patients infected with genotype II were treated for 24 weeks. The patients were followed-up for another 24 weeks after the treatment. The clinical characteristics including age, gender, body weight, and previous treatment were recorded. The aspartate aminotransferase (AST) to platelets ratio index (APRI) was calculated as the serum liver fibrosis scores according to previously published formulas: APRI = [AST (U/L)/upper limit of normal (U/L)] × 100/platelets count (10⁹/L).^[14] The time of undetectable HCV-RNA was defined as the first time that achieved undetectable HCV-RNA during the treatment period.

Study Design

The patients were included if they completed a full course of therapy. The end of treatment virological response was defined as undetectable serum HCV-RNA levels at the end of therapy. A nonresponse was defined as detectable serum HCV-RNA levels at the end of treatment. Patients with a virological end of treatment response were followed. Serum biochemistry and the HCV RNA titer were measured at pre-treatment (Pre), the end of treatment (FW+0), as well as at 4 (FW+4), 8 (FW+8), 12 (FW+12), 16 (FW+16), 20 (FW+20), and 24 (FW+24) weeks after the end of treatment. An SVR was defined as undetectable HCV-RNA in serum 24 weeks (FW+24) after the end of treatment. A virological relapse (VR) was defined as undetectable serum HCV-RNA levels at the end of treatment and detectable serum HCV-RNA at the FW+24 post treatment follow-up. Among VR patients, late VR was defined as patients with relapse occurring after FW+12. Early VR was defined as patients with relapse occurring before and/or at FW+12. The serum samples were evaluated by the real-time PCR assay (Cobas TaqMan HCV assay, Roche Diagnostics Japan, Tokyo, Japan), in which the lower limit of quantitative detection is 15 IU/mL.^[10–12] HCV-RNA signals below the quantitative limit (15 IU/mL, 1.2 log IU/mL) were also detected and referred to as "low positive." HCV-RNA were measured pre-treatment and every 4 weeks after the treatment (FW+0, FW+4, FW+8, FW+12, FW+16, FW+20, FW+24) in all cases until a VR was proven. HCV-RNA assessment after the VR was optional in the cases with agreement to visit. The first time point in which viral relapse was proven was defined as VR+0, and 4 and 8 weeks after the VR+0 were defined as VR+4 and VR+8, respectively.

Single Nucleotide Polymorphisms of Interleukin-28B

The VR patient relapsed after FW+8 were genotyped for three interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs), which were previously reported to be associated with therapy outcome: rs8099917, rs11881222, and rs8103142. Blood samples were genotyped using the Invader assay, as described previously.^[15,16]

Statistical Analysis

Continuous variables are presented as the mean ± standard deviation (SD). Fisher's exact probability test for frequency tables was used for the statistical analysis. Distributions of continuous variables were analyzed by the Mann–Whitney U-test. The positive predictive value (PPV) was defined as the probability that the patients fulfilling the criteria at each week become SVR. Results are expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The comparison of continuous variables at different time points was performed using the Wilcoxon signed-rank test. A P-value < 0.05 was considered to be significant.

Results

Clinical Characteristics and Response to Therapy

Two hundred of 222 patients demonstrated a virological response at the end of treatment. The characteristics of the 200 patients with a virological response at the end of treatment are shown in Table 1. The male : female ratio was 94:106. The mean patient age was 57.3 ± 11.1 years old (range 20–75). The mean body weight was 59.5 ± 11.5 kg. One hundred and fifty-three patients were naïve to IFN treatment, while 47 patients had received previous treatment. A schematic tree of the follow-up protocol is illustrated in Figure 1. Serum HCV-RNA outcomes during the 24 weeks post-treatment follow-up are shown in Table 2.

Figure 1. Schematic tree of the follow-up protocol.

FW+4 to FW+12 Post Treatment Follow Up

The serum HCV-RNA levels were undetectable at FW+4 in 170 (85.0%) patients of the 200 patients with a virological response at the end of treatment, and 148 of these demonstrated an SVR (PPV 87.1%, 95% CI 82.0–92.1; Table 2A). The serum HCVRNA levels were undetectable at FW+8 in 154 of 200 (77.0%) patients, and the PPV for SVR was 96.1% (95% CI 93.0–99.2). The serum HCV-RNA levels were undetectable at FW+12 in 151 of 200 (75.5%) patients; the PPV for SVR was 98.0% (95% CI 95.8–100). Therefore, 49 of 52 patients with virological relapse (VR) showed a relapse within FW+12. In the patients with genotype I, the PPV of SVR was 73.1% at FW+4, 89.1% at FW+8, 94.2 % at FW+12, respectively (Table 2B). In the patients with genotypes IIa and IIb, the PPV of SVR was 96.0% at FW+4, 100.0% at FW+8, 100.0 % at FW+12, respectively (Table 2C). In the patients with genotypes IIa and IIb, the PPV of SVR was 100.0% at and after FW+8.

FW+16 to FW+20 Post Treatment Follow Up

The serum HCV-RNA levels were undetectable at FW+16 in 150 of 200 (75.0%) patients, and the PPV for SVR was 98.7% (95% CI 96.8–100 Table 2A). The serum HCV-RNA levels were undetectable at FW+20, in 149 of 200 (74.5%) patients, and the PPV for SVR was 99.3% (95% CI 98.0–100). There was only one patient with VR at each time point. In the patients with genotype I, PPV of SVR was 96.1% at FW+16, 98.0% at FW+20, respectively (Table 2B). In the patients with genotypes IIa and IIb, PPV of SVR was 100.0% at both FW+16 and FW+20 (Table 2C).

Sustained Virological Response and Virological Relapse

One hundred and forty-eight (74%) patients were SVR at the end of the post-treatment follow-up (FW+24), and 52 (26%) patients had a VR (Table 2A). The characteristics of the patients with SVR and VR are shown in Table 1. The mean age and the ratio of female patients were significantly higher in VR patients in comparison to SVR patients. The pretreatment viral load was significantly higher in VR patients in comparison to SVR patients (P < 0.05). The ratios of genotype I and retreatment patients were significantly higher in VR patients in comparison to SVR patients (P < 0.01). The adherence of ribavirin and the time of undetectable HCV-RNA were found to be significantly worse in the VR patients in comparison to SVR patients (P < 0.01). There were no differences in the serum alanine aminotransferase, hemoglobin, platelet levels, APRI, and adherence of Peg-IFN between the SVR and VR patients.

There were six patients that showed a viral relapse after FW+8 (Table 2A). Furthermore, there were only three patients who relapsed after FW+12 (late VR). Therefore, the PPV for SVR was 98.0% at FW+12. In the patients with genotypes IIa and IIb, the PPV for SVR was 100% at FW+12. The characteristics of six patients that showed a viral relapse after FW+8 are shown in Table 3. All six of these patients were female with genotype Ib and with a high viral load. The genotypes of the IL28B SNPs were major homo type in all six of these patients. As a result, the genotypes were T/T in rs8099917, A/A in rs11881222, and T/T in rs8103142, respectively. The patient demonstrating a relapse at FW+24 (Case 6) was a 67-year-old genotype Ib patient treated for 72 weeks with the combination therapy Peg-IFN α-2a plus ribavirin. The pretreatment serum HCV-RNA load was 6.5 log IU/mL, and the liver histology showed moderate liver disease (A2/F2; Metavir scoring system). The serum HCV-RNA levels were undetectable 8 weeks after the initiation of treatment. The adherence to Peg-IFN and ribavirin therapy was 91.4% and 72.7%, respectively. A comparison of the three late VR patients (after FW+12 VR) and the other 49 early VR patients (before and/or at FW+12) is shown in Table 4. No statistical differences were found in the characteristics, including the HCV genotype, viral load, age, sex, body weight, APRI, type of Peg-IFN, adherence of Peg-IFN, adherence of ribavirin, time of undetectable HCV-RNA and previous treatment between the late VR patients and early VR patients.

Serum HCV-RNA Outcome in Relapse Patients

Fifty-two of 200 patients with an end of treatment virological response showed virological relapse during the follow-up periods. After VR was proven in these cases, some patients then had their HCV-RNA levels regularly measured every 4 weeks, but other patients did not do so. In the end, only 28 patients had their HCV-RNA levels measured every 4 weeks after VR. The first time point at which viral relapse is proven is defined as VR+0. Serum HCV-RNA levels in relapse patients at baseline, the VR+0, and 4 (VR+4), 8 (VR+8) week after the VR+0 are shown in Figure 2. Serum HCV-RNA levels were: 6.4 ± 0.7 log IU/mL at baseline, 4.3 ± 1.7 log IU/mL at VR+0, 5.5 ± 1.2 log IU/mL at VR+4, and, 5.8 ± 0.9 log IU/mL at VR+8. The viral titers of VR+0 (P < 0.01), and VR+4 (P < 0.05) were significantly smaller than those at baseline. However, there were no differences in the viral titers between baseline and VR+8. The viral load showed a reversion to the basal level at 8 weeks after VR. Forty-nine of 52 patients with VR relapsed within FW+12 and the serum HCV-RNA levels in VR patients reverted to the basal level at 8 weeks after VR. These results show that the viral load increases rapidly in patients who have relapsed; namely, reaching close to baseline levels as early as 24 weeks post-treatment.

Figure 2. Serum hepatitis C virus (HCV)-RNA outcome in 28 virological relapse (VR) patients. Baseline, pre-treatment; VR0, the first time point in which viral relapse was proved; VR+4, 4 weeks after VR+0; VR+8, 8 weeks after VR+0. **P < 0.01, *P < 0.01 in comparison to baseline.

Discussion

The findings of this study demonstrated that the assessment of serum HCV-RNA 12 weeks after the end of treatment, using the highly sensitive real-time PCR assay (PPV 98.0%), is closely similar to that after 24 weeks for predicting SVR. There were only three patients who relapsed after FW+12 (late VR) and all three of these patients were female patients with a high viral load of genotype Ib. As a result, in the patients with genotypes IIa and IIb, the PPV of SVR was 100.0% at FW+12. Therefore, the assessment of serum HCV-RNA FW+12 is as applicable as FW+24 to predict SVR except in female patients with a high viral load of genotype Ib.

Martinot-Peignoux et al.^[8] reported the usefulness of a new assay based on TMA to predict SVR at the FW+12. They reported that the assessment of HCV-RNA FW+12 is as effective as that after 24 weeks to predict SVR with 99.7% PPV. The real-time PCR method, used in the current study, is also highly sensitive to detect HCV-RNA and it is commonly used in Japan. Bortoletto et al.^[9] reported that TMA and the real-time PCR HCV assay have comparable sensitivity and specificity in identifying the minimal residual serum level of HCV. This study demonstrated that the assessment of HCV-RNA by real-time PCR at FW+12 was almost as effective as that at FW+24 to evaluate SVR in 200 Japanese patients. PPV (98.0%) of FW+12 in our study was almost as relevant as those of TMA assay (99.7%).^[8] However, there were some false negative results with real-time PCR, especially in female patients demonstrating a high viral load of genotype Ib. Bortoletto et al.^[9] reported that minimal residual viremia was detectable with the real-time PCR assay in patients with genotype II and with genotype IV, but not with TMA. They noted increased sensitivity of the real-time PCR assay across all major HCV genotypes in comparison to TMA.^[9,17,18] Although the current standard at FW+24 is reasonable for Japanese patients by real-time PCR, the assessment of serum HCV-RNA FW+12 may therefore be appropriate for almost all patients, except for genotype Ib female patients.

Zeuzem et al.^[19] reported similar results in patients treated with standard interferon α2a or Peg-IFN α2a by PCR (Amplicor HCV Monitor vs 2.0). Only six of 348 patients (2%) became HCV-RNA positive between FW+12 and FW+24.^[17] These results suggest that the addition of ribavirin to Peg-IFN enhances the SVR rates but does not affect the timing of relapse.^[9,19] Our study also showed that the adherence of ribavirin enhances the SVR rate but it does not affect the timing of relapse. Martinot-Peignoux et al. found no differences in VR patients treated with Peg-IFN α2a and ribavirin and in patients treated with Peg-IFN α2b and ribavirin.^[8] The present study also found no differences between Peg-IFN α2a and Peg-IFN α2b. Therefore, the type of Peg-IFN does not affect the VR.

Early determination of post-treatment response status in patients can help patients make decisions and might allow relapse patients to begin alternative therapy earlier.^[9] Viral load showed a reversion to the basal level within 8 weeks after the relapse in this study. The viral load increases rapidly after relapse, nearly reaching basal levels, confirming the importance of identifying relapse patients early. Patients might benefit from early retreatment with different regimens when the viral load is still low. Indeed, some patients received additional treatment just after the appearance of VR in this study.

The baseline characteristics associated with virological relapse were age, sex, HCV genotype, viral load and past history of IFN. Patients with these characteristics showed a poor response to combination Peg-IFN and ribavirin therapy.^[20–22] Therefore, genotype I female old patients with previous treatment had risk factors for VR. Three of 52 VR patients showed late VR patients (5.8%). There were no significant differences in characteristics between late VR and early VR patients. Although female patients with genotype I, and a history of receiving previous treatment tended to be included in the late VR group, it did not reach the statistical significance. This may be due to the small number of late VR patients. The adherence to Peg-IFN and ribavirin by late VR patients was 95.1 + 7.6%, and 67.8 + 9.4%, respectively. The adherence to Peg-IFN and ribavirin in early VR patients was 81.5 + 21.6%, and 60.5 + 24.8%, respectively. There were no significant differences in adherence to Peg-IFN and ribavirin between the late VR and early VR patients. A genetic polymorphism near the IL28B gene, encoding interferon-lambda-3 (IFN-lambda-3), has been reported to be strongly associated with response to treatment.^[23,24] In this study, the genotypes of the IL28B SNPs were major homo type in all three late VR patients. Because IL28B SNPs predict null virological response, it seems to have no value for predicting the late VR in this study. Further study is needed to clarify the differences between late VR and early VR patients because of the small number of late VR patients.

In conclusion, testing for HCV-RNA, using the highly sensitive real-time PCR assay, at FW+12, is therefore considered to be as effective as testing at FW+24 to assess a sustained virological response in patients receiving combination Peg-IFN and ribavirin therapy. As a result, the post-treatment follow-up to identify patients with SVR or VR could be shortened to 12 weeks post-treatment. However, there was a low incidence of false negatives in female patients with a high viral load of genotype Ib for predicting the SVR by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV-RNA FW+12 may be also be relevant and useful for evaluating similar patients other than Ib female patients.

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Source

Bread a culprit in Americans eating too much salt

Bread basket is photographed in a shop in Warsaw February 7, 2012. Credit: Reuters/Peter Andrews

By David Beasley

Tue Feb 7, 2012 6:00pm EST

(Reuters) - Nine out of 10 American adults consume too much salt and the leading culprit is not potato chips or popcorn but slices of bread and dinner rolls, the Centers for Disease Control and Prevention said on Tuesday.

Forty-four percent of salt consumed can be linked to 10 types of foods, CDC said. Bread and rolls lead the list followed by cold cuts and cured meat, pizza, poultry, soups, sandwiches, cheese, pasta dishes, meat dishes and snacks such as pretzels and potato chips.

Bread may not have much salt in a single serving, but when eaten several times a day can raise daily salt intake. A single slice of white bread could contain as many as 230 milligrams of salt, according to the CDC.

High salt intake can raise blood pressure, which can lead to heart disease and stroke, the CDC said.

The average American consumes 3,266 milligrams of salt daily, not counting salt added at the table, which is far above the recommended 2,300 milligrams, the CDC said.

For six out of 10 Americans, including those who are over age 51 or have high blood pressure or diabetes, 1,500 milligrams is the recommended daily salt limit.

Even foods that seem healthy such as cottage cheese may be high in salt, the agency reported. Even raw chicken and pork is often injected with salt.

The CDC recommended eating more fruits and vegetables and carefully reading the labels on food products to find those with the lowest salt content.

"Heart disease and stroke are leading causes of death in the United States and are largely dependent on the high rate of high blood pressure," CDC Director Dr. Thomas R. Frieden told reporters in a telephone news conference Tuesday.

One in three American adults has high blood pressure, he added.

"One of the things that is driving blood pressure up is that most adults in this country eat or drink about twice the amount of sodium as is recommended," Frieden said. "Most of that extra sodium comes from common grocery store and restaurant items and a very small proportion from the salt shaker at the table."

Nearly two-thirds of the salt consumed by Americans is found in store products, 24.8 percent from restaurants and the remainder from other sources such as vending machines and the home salt shaker, the study found.

Salt per calorie of food consumed was much higher at restaurants than from store-bought food, the CDC said.

Frieden recommended that food producers and restaurants voluntarily reduce the amount of salt in their food. A 25-percent drop in the salt content of the top 10 sodium sources would save 28,000 lives a year, he added. It would also give consumers more choice, he said.

"People can choose how much food to add at the table," he said. "They can't take it out once it's there."

The Grocery Manufacturer's Association said that the food industry has been trying to reduce the salt content of thousands of products while keeping it tasty for consumers.

"While progress is being made, reducing sodium in products without affecting the taste or consumer acceptance of products is no easy task," the industry group said in a statement emailed to Reuters.

The group said that challenges of reducing salt include finding substitutes for it that maintain the taste, and making sure that food safety standards are met because salt is a major preservative in many foods.

(Editing by Greg McCune)

Source

A Newly Published Study Associates Alcoholic-Induced Liver Damage to The Abnormal Metabolism of an Essential Nutrient

A newly published study on Alcoholic Liver Disease (Steatohepatitis) suggests that alteration in the metabolism of an essential nutrient (methionine) leads to the reduced levels of molecules (glutathione) needed to counter alcohol-induced liver injury and reviews the dietary supplementation of methionine, as a treatment. Nutri-Med Logic Corp agrees that consumption of alcohol causes such alteration but states that another culprit in alcohol-induced liver injury is the hyperactivity of a gene, which could be moderated through supplementation of another nutrient: Poly-Enyl-Phosphatidyl-Choline

Miami, Florida (PRWEB) February 08, 2012

A newly published study investigates the dietary supplementation of an essential nutrient (methionine) as a potential treatment for the alcohol-induced liver damage. Concurring, in most part, with the investigation of this study, Nutri-Med Logic Corp states that countering alcohol-induced liver injury depends on the proper activities of a pro-oxidant gene (CYP2E1), as well as the availability of nutrients such folate and choline (methyl group), which increase the levels of methionine and ultimately the production of a potent anti-oxidant (glutathione). However, Nutri-Med Logic Corp adds that any nutrient capable of contemporaneously providing the methyl group as well as directly moderating the activities of the pro-oxidant gene takes precedence.

One such important nutrient is Poly-Enyl-Phosphatidyl-Choline, an extract of soy that has been the target of studies for more than two decades, for its therapeutic potentials in Alcohol-induced Fatty Liver, Hepatitis, Fibrosis and Cirrhosis.

Elimination of alcohol takes place in two parts: converting alcohol to acetaldehydes and then to acetate. While acetate is harmless, known and used by the body, but acetaldehydes are one of the most damaging molecules implicated in pathology of alcohol-induced liver diseases, vitamin inactivation, hangover and even suggested to alter neurotransmitter, thus causing addiction.

The xenobiotics, elimination of foreign substances such as alcohol, is mainly done through a process called phase II enzymes. Glutathione, an endogenous anti-oxidant, represents the most powerful component of the phase II enzymes.

According to this published study, alcohol alteration of methionine reduces the availability of glutathione, which together with the hyperactivity of the pro-oxidant gene CYP4502E1 exert injuries to the liver.

Production of glutathione through methionine is dependent on the methyl group of folate or choline; the difference being that folate contains one methyl group but choline (betaine) contains three methyl groups. Studies going back to 1954 have established that alcohol consumption increases the requirement of choline intake. J Exp Med. 1954 Dec 1;100(6):615-27In conclusion.

Availability of methyl, through choline, increases the production of glutathione, needed to counter acetaldehydes. Poly-Enyl-Phosphatidyl-Choline is a pure and potent dietary source of choline.

On the other hand, alcohol-induced hyperactivity of the gene CYP2E1 not only results in accumulation of fat in the liver, producing alcoholic fatty liver, alcoholic hepatitis but also results in conversion of liver’s stellate cells to myofibroblasts and the subsequent production of collagens, which ultimately results in fibrosis and cirrhosis.

Poly-Enyl-Phosphatidyl-Choline, contains a component called DLPC (dilinoleoy-Phosphatidylcholine), which a plethora of studies have conclusively demonstrated its ability to moderate the alcohol-induced hyperactivities of the pro-oxidant gene CPY2E1.

In conclusion, Nutri-Med logic Corp agrees with this recently published study and the role of methionine in Steatohepatitis as well as the inconclusive results from supplementation of methionine but adds that more than two decade of studies have produced credible and favorable results from supplementation of another nutrient: Poly-Enyl-Phoshaptidyl-Choline.

Nutri-Med Logic Corp is the producer of PolyEnylPhosphatidylCholine (PPC 425mg), an extract of soy and the recommended dietary supplement for those with Fatty Liver and Alcoholic Liver Disease, in Europe for decades.

Nutri-Med Logic Corp is also the producer of the Natural, Balanced, Deodorized and Concentrated Omega-3, which is also a Pharmaceutical Grade Omega-3;
Producer of a Pharmaceutical Grade R-Alpha Lipoic Acid, the dietary supplement of choice for the Diabetics, in Germany for more than 40 years;

Nutri-Med Logic Corp invites you to visit its News Archives and Review other News Releases on the potential benefits of PolyEnylPhosphatidylcholine, Omega-3 and R-Alpha Lipoic Acid.

Nutri-Med Logic's products are Formulated Based on Nutritional Logic, made from the highest quality raw materials that are manufactured in pharmaceutical facilities, encapsulated in pharmaceutical facilities and packaged in pharmaceutical facilities.

It must be noted that the studies, sources or statements above have not been evaluated by The FDA and, thus, one should not relate the cause of any diseases, stated herein, to lack of the dietary supplements, stated herein, nor equate their supplementation to prevention, treatment or cure.

Source

Combining HCV Med Boceprevir with Boosted HIV Protease Inhibitors Can Lower Drug Levels

Provided by HIVandHepatitis.com

Published on Tuesday, 07 February 2012 00:00

Written by Liz Highleyman

HIV/HCV coinfected people who take the HCV protease inhibitor boceprevir (Victrelis) for hepatitis C treatment along with a ritonavir-boosted HIV protease inhibitor may experience drug-drug interactions that reduce concentrations of both drugs to ineffective levels, Merck warned this week.

The approval this past May of the HCV protease inhibitors boceprevir and telaprevir (Incivek) have ushered in a new era of chronic hepatitis C treatment. Both drugs are approved only for HIV negative people, but studies in progress indicate that boceprevir and telaprevir -- when added to pegylated interferon plus ribavirin -- improve the likelihood of virological response for HIV/HCV coinfected people as well.

Despite the absence of completed trials, some clinicians are already prescribing the new HCV drugs off-label for coinfected patients due to their need for better treatment and the lack of other options. The new findings underscore advocates' insistence that interactions between HCV direct-acting antiviral agents and antiretroviral drugs and other medications commonly used by people with hepatitis C should be thoroughly evaluated early in the development process.

In the ongoing Phase 2b boceprevir coinfection trial, previously untreated HIV/HCV coinfected patients with HCV genotype 1 were randomly assigned to receive pegylated interferon/ribavirin with or without boceprevir. Participants were on optimized antiretroviral therapy with stable undetectable HIV viral load and CD4 counts of at least 200 cells/mm³. Based on prior drug-drug interaction data, they were limited to regimens containing a ritonavir-boosted protease inhibitor plus 2 selected nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).

The data released this week, however, show that boceprevir may reduce the mean trough (lowest) concentrations of ritonavir-boosted atazanavir (Reyataz), darunavir (Prezista), and lopinavir/ritonavir (Kaletra) by 40% to 60%. Darunavir/ritonavir and lopinavir/ritonavir also lowered boceprevir levels by 30% to 40%. These reductions are considered clinically significant, meaning they could lead to viral breakthrough and development of drug resistance.

Below is an edited excerpt from a "Dear Healthcare Provider" letter by Merck Vice President S. Sethu K. Reddy, MD, describing the drug-drug interactions and steps clinicians should take. Reddy emphasized that "Merck does not recommend the coadministration of Victrelis and ritonavir-boosted HIV protease inhibitors."

IMPORTANT DRUG WARNING

SUBJECT: Results of Pharmacokinetic Study in Healthy Volunteers Given Victrelis (boceprevir) and Ritonavir-Boosted HIV Protease Inhibitors May Indicate Clinically Significant Drug Interactions for Patients Coinfected with Chronic Hepatitis C and HIV

February 6, 2012

Dear Health Care Professional,

The purpose of this communication is to inform you of recent pharmacokinetic study results evaluating drug interactions between Victrelis, an oral chronic hepatitis C virus (HCV) NS3/4A protease inhibitor, and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors in healthy volunteers (n=39).

Victrelis is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection, in combination with peginterferon alfa and ribavirin (PR), in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are treatment-naive or who have failed previous interferon and ribavirin therapy. In the pharmacokinetic study, concomitant administration of Victrelis with Norvir (ritonavir) in combination with Reyataz (atazanavir) or Prezista (darunavir), or with Kaletra (lopinavir/ritonavir) resulted in reduced exposures of the HIV medicines and Victrelis.

Specifically, Victrelis reduced mean trough concentrations of ritonavir-boosted atazanavir, lopinavir, and darunavir by 49%, 43%, and 59%, respectively. Mean reductions of 34% to 44% and 25% to 36% were observed in AUC and Cmax of atazanavir, lopinavir, and darunavir. Coadministration of ritonavir-boosted atazanavir with Victrelis did not alter the exposure of Victrelis, but coadministration of Victrelis with lopinavir/ritonavir or ritonavir-boosted darunavir decreased the exposure of Victrelis by 45% and 32%, respectively.

These drug interactions may be clinically significant for patients infected with both chronic HCV and HIV by potentially reducing the effectiveness of these medicines when coadministered. Victrelis is not indicated for use in patients who are infected with both HIV-1 and chronic HCV. The safety and efficacy of Victrelis (boceprevir) has not been established in this coinfected population. Merck does not recommend the coadministration of Victrelis and ritonavir-boosted HIV protease inhibitors.

Health care providers who might have initiated Victrelis in combination with PR in HIV-HCV coinfected patients on fully suppressive antiretroviral therapy containing a ritonavir-boosted protease inhibitor should discuss these findings with those patients, and closely monitor those patients for HCV treatment response and for potential HCV and HIV virologic rebound.

Patients should be advised to contact their health care provider before stopping any of their medications.

Merck is sharing these pharmacokinetic data with regulatory authorities in the countries where Victrelis is approved. Merck will be submitting requests to regulators to update the product labeling with these data.

These data have been submitted for scientific presentation at an upcoming medical forum.

For more information, please consult the enclosed Prescribing Information for Victrelis.

The Prescribing Information can also be found at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.

Should you have any questions, require further information on product safety, or wish to report an adverse event with Victrelis, please contact Merck at 1-877-888-4231. Alternatively, an adverse event can be reported directly to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Sincerely,
S. Sethu K. Reddy, MD

2/7/12

Source

SSK Reddy, Merck. Results of Pharmacokinetic Study in Healthy Volunteers Given Victrelis (boceprevir) and Ritonavir-Boosted HIV Protease Inhibitors May Indicate Clinically Significant Drug Interactions for Patients Coinfected with Chronic Hepatitis C and HIV. Dear Health Care Professional letter. February 6, 2012.

What is the role of a physician assistant in the fields of gastroenterology and hepatology?

GIPA Scope of Practice

GIPA offers the following guidelines for the role of Physician Assistants (PAs) practicing in Gastroenterology and Hepatology. These guidelines are meant to serve as a guide in practice, but are not to take the place of state/federal legislation or other regulatory boards. State laws and regulations define the PA profession in each state and establish registration and competency requirements, as well as the responsibilities of the supervising physician.

In most states the Board of Medical Examiners is responsible for licensing and regulating PAs. Gastrointestinal Physician Assistants (GI PAs) may provide care for patients in various settings including outpatient clinics/offices, HMOs, inpatient hospital settings, and government institutions. Most GI PAs have hospital privileges and membership on the medical staff. GI PAs may also be involved in education, teaching, and administrative functions pertaining to the fields of Gastroenterology and Hepatology. Some GI PAs are involved with research and publication.

GI PAs always practice with the supervision of a physician, but exercise autonomy in diagnosing and treating illnesses within their scope of practice and that of their supervising physician. Individual PA duties are dependent on the scope of his or her supervising physician's practice and the desire of the physician to delegate certain tasks or responsibilities. The range of duties and responsibilities of a GI PA are as varied as the number of different GI practices. Besides performing routine duties such as histories & physical exams, daily patient rounds, patient education, and discharge summaries, GI PA's may perform diagnostic/therapeutic procedures. Whether a GI PA performs these procedures is subject to state regulation, PA training/experience, the scope of the supervising physician, and the needs of the practice. Such procedures may include, but are not limited to:

• Flexible Sigmoidoscopy
• Paracentesis
• Liver Biops

GI PAs report that the most frequent work-ups they are presented with include, but are not limited to, the following chief complaints:

• Work-up of abdominal pain
• Work-up of dyspepsia
• Work-up of nausea/vomiting
• Work-up of dysphagia
• Work-up of constipation
• Work-up of diarrhea
• Work-up of gastrointestinal bleeding
• Work-up of elevated liver enzymes

GI PAs obtain medical histories and perform physical exams, order and interpret laboratory data, order and read radiological studies, formulate a differential diagnosis and establish a working diagnosis, formulate a treatment plan, prescribe medication, perform procedures, round in the hospital, and dictate H & Ps and daily progress notes for patients with Gastrointestinal and Liver Disease including, but not limited to the following diagnoses:

• GERD
• Esophageal Dysmotility
• Esophageal Cancer
• Gastroduodenal Ulcer Disease
• Zollinger-Ellison Syndrome
• Gastric Carcinomas
• Carcinoid
• Celiac Sprue
• Whipple’s Disease
• Ileus/Obstruction/Pseudo-obstruction
• Gastrointestinal Lymphoma
• Hepatitis C
• Hepatitis B
• Autoimmune Hepatitis
• Fatty Liver and NASH
• Alcoholic Hepatitis +/- Cirrhosis
• Spontaneous Bacterial Peritonitis
• Primary Biliary Cirrhosis
• Hemachromatosis
• Wilson’s Disease
• Budd-Chiari Syndrome
• Neoplasms of the Liver
• Acute and Chronic Cholecystitis
• Biliary Dyskinesia
• Choledocholithiasis and Cholangitis
• Primary Sclerosing Cholangitis
• Carcinoma of the Biliary Tract
• Acute and Chronic Pancreatitis
• Pancreatic Insufficiency
• Pancreatic Carcinomas
• Irritable Bowel Syndrome
• Diverticular Disease
• Anorectal Disease
• Crohn’s Disease
• Ulcerative Colitis
• Infectious Colitis
• Microscopic Colitis
• Ischemic Colitis
• Colon Cancer Screening

Frequently Asked Questions (FAQs)

Issue Brief

Gastroenterology Physician Assistants
PO Box 82511
Tampa, FL 33682
Phone: (813)988-7795
Fax: (813)988-7796
email: GIPA@Focus-ED.net

Source

Amateur tattoos carry hepatitis C risk: CDC

By Amy Norton

NEW YORK | Tue Feb 7, 2012 3:27pm EST

NEW YORK (Reuters Health) - If you're planning on getting a tattoo, make sure it's from a professional and not your friend, says a new report from the Centers for Disease Control and Prevention (CDC).

In an analysis of several dozen past studies, CDC researchers found that tattoos from non-professionals appear to carry a risk of the blood-borne liver infection hepatitis C. That included tattoos done by friends or family, or ones done in prison.

On the other hand, there was no evidence that tattoos done by professionals carried a hepatitis C risk.

Hepatitis C is passed through contact with infected blood. In the U.S., there are roughly 18,000 new infections each year, most of which occur when people who inject heroin and similar drugs share tainted needles or syringes.

But in almost 20 percent of acute hepatitis C infections, the person has no known risk factor, said Dr. Rania A. Tohme, a medical epidemiologist at the CDC who led the new study.

Given that -- and the popularity of tattoos -- there have been concerns that the body art could be a risk factor for hepatitis C.

Based on these findings, it's the tattoos from non-pros that consumers should beware, according to Tohme.

"Tattoos and piercings can transmit hepatitis C and other infections if performed under non-sterile conditions," Tohme told Reuters Health in an email. "People should not have tattoos or piercings done by friends or by people who are not trained professionals."

The findings, published in the journal Clinical Infectious Diseases, are based on a collection of studies published since 1994.

In general, people who had tattoos done by non-professionals faced a hepatitis C risk that was two to four times higher than average.

Prison tattoos are a particular concern, Tohme's team writes, because tattooing is so common, and many prisoners may have other risk factors for hepatitis C. And outbreaks of the infection have been linked to tattooing among prisoners.

But no U.S. outbreaks have been tied to professional tattoo parlors.

"To this date, there has been no evidence that tattoos and piercings performed in professional parlors in the United States have been implicated in transmission of hepatitis C virus," Tohme said.

Still, you can take some precautions if you're thinking of inking up.

Tohme said to make sure the tattoo artist is using sterile equipment, including single-use needles and ink that has not been used on anyone else.

"Disposable piercing needles, tattoo needles and razors are used on one person and then thrown away. Reusing needles or razors is not safe," Tohme said.

In the U.S., new cases of hepatitis C infection have fallen sharply since the 1980s, according to the CDC.

But chronic hepatitis C infection remains a major public health problem, the agency says.

Between 75 percent and 85 percent of people infected with hepatitis C develop chronic infection, which can eventually cause serious liver diseases like cirrhosis (scarring of the liver) and liver cancer.

An estimated 3.2 million Americans have chronic hepatitis C, about half of whom are unaware of it. (The initial infection most often causes no symptoms.)

There are medications for treating chronic hepatitis C, though they are not effective for everyone and have side effects like fatigue, nausea, headache and sleep problems.

SOURCE: bit.ly/w6rw3u Clinical Infectious Diseases, online January 30, 2012.

Source

A protein could reduce need for transplants in patients with acute liver failure

2012/2/6

Cardiotrophine-1 increases survival in animals with acute liver failure, according to research undertaken by scientists at the Applied Medical Research Centre (CIMA in its Spanish initials) of the University of Navarra and the Biomedicine Institute (IBIOMED) of the University of León. The research results were published in the Journal of Virology.
The research showed that a protein, cardiotrophine-1 (CT-1), increases the survival rate of animal models with acute liver failure due to the RHD virus. The work, part of the Biomedical Centre for Research into Hepaticand DigestiveDiseases (CIBERehd), was published in the Journal of Virology, the journal of the North American Microbiology Society.

Acute liver failure is not a common disease (about two thousand cases annually in the United States), and is characterised by the massive destruction of liver tissue due to viral infections, ingestion of toxic products orautoimmune reactions. The only resolutive treatment is a liver transplant, but 30% of patients die without having received a transplant.

Natural defence

CT-1 is a protein that fulfils functions of natural defence against the cell death of the liver. IBIOMED researchers at the University of Leon and the CIMA of the University of Navarra studied itstherapeutic effect on models that developed acute liver failure after inoculation with RHD virus. “we confirmed that, while all the infected animals died within 3 days, 70% of the those models treated with CT-1 survived in the long term. These surprising therapeutic effects are due to the fact that CT-1 attenuates the inflammation and increases the production of molecules with hepatoprotectorand pro-regenerativeactivity”, explained doctors Ms Maria JesúsTuñón and Mr Jesús Prieto, research coordinators.

Research results suggest that this protein could be useful as a treatment in situations of damage due to acute liver failure. Based on these findings, the Food and Drug Administration (FDA) of the United States of America has designated CT-1 as an “orphan medication” for acute liver failure. “If we confirm its effectiveness in clinical trials, we will have a drug that could enhance the prognosis of this class of patients and reduce the need for transplants in these cases”, pointed out Dr.Prieto. Digna Biotech, the biotech company focused on the development of products investigated at the CIMA, has programmed the start of the clinical trials (phase I) for the coming months.

Source

BioLineRx In-Licenses Second Oral Hepatitis C Treatment

PRESS RELEASE

Feb. 6, 2012, 7:00 a.m. EST

Worldwide, exclusive deal signed with Genoscience and RFS Pharma for development and commercialization of BL-8030

JERUSALEM, Feb 06, 2012 (BUSINESS WIRE) -- --Advantages of BL-8030 include high specificity, improved resistance profile, reduced toxicity and potentially reduced drug-drug interactions

BioLineRx (tase:BLRX), a biopharmaceutical development company, announced today it has signed a worldwide, exclusive license agreement with Genoscience and RFS Pharma to develop and commercialize BL-8030, an orally available treatment for Hepatitis C. The agreement includes upfront license fees, milestones and royalties payable to both companies, which terms are consistent with BioLineRx's standard in-license agreements.

BL-8030 is a potent and selective second generation NS3 protease inhibitor. The NS3 protease is essential for the replication of the Hepatitis C virus (HCV) and is an important target for HCV therapies. BL-8030 has been shown to have excellent antiviral activity against various HCV genotypes. Pre-clinical studies have demonstrated an improved resistance profile against common protease inhibitor mutants, resulting in a lower probability that the virus will develop resistance to treatment. In addition, BL-8030 has demonstrated a good toxicity profile in pre-clinical studies, exhibiting specificity only to the viral protease and lack of activity against a relevant panel of human proteases as well as a clean profile versus human liver enzymes, which is expected to lead to less drug-drug interactions.

BL-8030 was invented by Professor Philippe Halfon and his team at Genoscience and co-developed with assistance from scientists at RFS Pharma, LLC. Prof. Halfon, Co-Founder and President of Genoscience, is a specialist in molecular virology and infectious diseases, especially HIV, HPV (Human Papilloma Virus) and Hepatitis. In addition he is the founder of several biotechnology companies focusing on antiviral drug discovery and development including ACTgene, Alphabio and Genoscience. RFS Pharma was founded by Professor Raymond F. Schinazi; he currently serves as the Frances Winship Walters Professor of Pediatrics at Emory University. He is also a founder of Pharmasset, Idenix, Triangle and ActivBiotics Pharma.

Prof. Philippe Halfon said, "We were impressed by the drug development expertise of the BioLineRx team and are very pleased to collaborate with them on a second HCV project. There is clearly a huge unmet medical need in finding a safe and effective treatment for HCV, and based on pre-clinical results, we believe that our product, especially when combined with other available Hepatitis C drugs, has the potential to become an important addition to HCV combination therapies and bring remedy to millions suffering from this devastating disease."

"We worked closely with the group at Genoscience to determine the optimum characteristic that led to the discovery of BL-8030 and related protease inhibitors," said Dr. Steven J. Coats, Senior Director of Chemistry at RFS Pharma.

"We are privileged and fortunate to partner with two world class groups in the development of viral therapeutics," said Dr. Kinneret Savitsky, CEO of BioLineRx. "Two years ago, we took a strategic decision to enter the dynamic and rapidly growing field of Hepatitis C. Since that time, we have evaluated numerous projects in the field. A year ago, we identified and decided to focus on the in-licensing of the two most promising candidates: BL-8020, which we've recently licensed, and now BL-8030. We will do our utmost to develop these promising drugs as swiftly as possible for the benefit of Hepatitis C infected individuals around the world."

About Hepatitis C

Hepatitis C is a blood borne infection of the liver caused by the Hepatitis C virus (HCV) which becomes chronic in about 85% of cases. According to the World Health Organization (WHO), up to 170 million people worldwide are chronically infected with HCV. In addition, HCV infection is the leading cause of liver transplantation and is a risk factor for liver cancer. The Hepatitis C market is growing rapidly and is forecasted to reach $16 billion in 2015 in the seven major markets (US, France, Germany, Italy, Spain, UK and Japan).

About BioLineRx

BioLineRx Ltd. is a publicly-traded biopharmaceutical development company. It is dedicated to building a portfolio of products for unmet medical needs or with advantages over currently available therapies. BioLineRx's current portfolio consists of five clinical stage candidates: BL-1020 for schizophrenia has commenced a Phase II/III study; BL-1040, for prevention of pathological cardiac remodeling following a myocardial infarction, is currently undergoing a pivotal CE-Mark registration trial and has been out-licensed to Ikaria Inc. for a total deal value of $282.5 million, in addition to sales royalties; BL-5010 for non-surgical removal of skin lesions has completed a Phase I/II study; BL-1021 for neuropathic pain is in Phase I development and BL-7040 for treating Inflammatory Bowel Disease (IBD) has completed Phase I. In addition, BioLineRx has 13 products in various pre-clinical development stages for a variety of indications, including central nervous system diseases, oncology, infectious diseases, cardiovascular and autoimmune diseases.

BioLineRx's business model is based on acquiring molecules mainly from biotechnological incubators and academic institutions. The Company performs feasibility assessment studies and development through pre-clinical and clinical stages, with partial funding from the Israeli Government's Office of the Chief Scientist (OCS). The final stage includes partnering with medium and large pharmaceutical companies for advanced clinical development (Phase III) and commercialization.

For more information on BioLineRx, please visit www.biolinerx.com .

About Genoscience

Genoscience, a biopharmaceutical company located in Marseille, France, is focused on the development of new drugs for the treatment of viral diseases as HCV. Genoscience's innovative technology platform, which combines internal expertise in resistance with unique molecular modeling through its proprietary software (GenMol(TM)), allows for the development of highly targeted molecules, taking into account the phenomenon of resistance. For further information about Genoscience, please refer to http://www.genosciencepharma.com .

About RFS Pharma, LLC

RFS Pharma, LLC was founded in September 2004 and is located in a 26,500 sq. ft. state-of-the-art research facility in Tucker, Georgia. RFS Pharma is a privately owned biotech company committed to the discovery and development of antiviral agents and other human therapeutics. The company capitalizes on its expertise in nucleoside chemistry to develop drugs to combat infections caused by drug-resistant HIV and hepatitis viruses. RFS Pharma's lead product candidate is amdoxovir, which is in advanced Phase 2 clinical studies for the treatment of HIV-1 infections. In addition, the company has identified promising, early stage compounds for hepatitis infections, analogs that are effective against noroviruses, and has a proprietary novel nucleoside prodrug technology. For further information about RFS Pharma, please refer to our website, www.rfspharma.com .

Various statements in this release concerning BioLineRx's future expectations, plans and prospects, including, without limitation, statements relating to the ability to develop and commercialize the BL-8030 project, constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "may," "expects," "anticipates," "believes," and "intends," and describe opinions about future events. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Some of these risks are: changes in relationships with collaborators; the impact of competitive products and technological changes; risks relating to the development of new products; and the ability to implement technological improvements. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's Form 20-F filed with the Securities and Exchange Commission on July 15, 2011. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.

SOURCE: BioLineRx Ltd.

Source

Hepatitis C … Veterans … Vietnam …

Culture: Impact of war on language (155)

By Sami El-Shahed - The Egyptian Gazette
Monday, February 6, 2012 08:48:05 PM

Vietnam War & Health. and Medicine (VII). Hepatitis C. Hepatitis C is a major problem in US military veterans. In several studies of Veteran’s Affairs (VA) Medical Centre patients, we find that 8-9% are positive for hepatitis C antibodies. Some VA Medical Centres had 10-20% of patients with hepatitis C antibodies.

---

According to Dr Bradford Waters, Professor of Medicine, University of Tennessee, Memphis, the highest rate of hepatitis C is found in the Vietnam era veterans.

Several studies have been initiated to better understand the high frequency of hepatitis C in veterans of the Vietnam conflict. Areas of research include the demographic characteristics, risk factors for infection and the potential role of military service in the acquisition of hepatitis C.
Underlying this research is the question of what is unique about Vietnam or Vietnam-era veterans to help explain a high prevalence of hepatitis C which was not observed in World War II or Korean era veterans, said Professor Waters who is also Staff Hepatologist, Memphis Veteran Affairs (VA) Medical Centre Associate.

The demographics of hepatitis C in US civilians and VA patients are important. Several epidemiological studies have found hepatitis C to be higher in US males, African-Americans, lower socioeconomic groups and in those Americans in the 40 to 60 year old age groups. In addition to serving primarily males, the VA has historically served large populations of disadvantaged, uninsured and minority veterans.

The VA has had well established programmes for the treatment of ethanol and other substance abuse. These substance abuse programmes have often attracted younger veterans with prior intranasal cocaine and intravenous drug use associated with hepatitis C infection.

As a result of the VA programmes’ providing care for the disadvantaged, uninsured and substance abusing veterans, the VA has acquired significant patient populations with high risk for hepatitis C. Many of the highest risk groups for hepatitis C in the US – identified by the Centres for Disease Control: male, poor socioeconomic group, and between the ages of 30-50 (in a 1988-94 study) – have the same demographic criteria met by many Vietnam era veterans seeking care in the VA. Improved screening of VA patients with risk factors for hepatitis C has helped identify increasing numbers of patients with chronic hepatitis C, Dr Waters explained.

A large multi-centre VA study involving twenty six Medical Centres and approximately 5,800 patients was initiated by the San Francisco VA Medical Centre to study demographic factors and treatment response in VA patients.

The role of tattoos in transmission of hepatitis C has been controversial. In this group of Memphis veterans, 30.2% of patients had tattoos. 92.8% of patients reported multiple risk factors for hepatitis C. In analysis of patients with a single risk factor for hepatitis C, intranasal cocaine use, non-combat occupational exposure, surgery, transfusion, intravenous drug abuse (IVDA) and sex with a prostitute were identified, Dr Waters elaborated.

Medical advances during the Vietnam War included rapid evacuation, improved transfusion and high rates of US casualty survival in an era prior to hepatitis C screening of the blood supply. Many Vietnam combat casualties who survived with multiple transfusions would have died on the battlefield in previous conflicts.

Hepatitis C in Vietnam era veterans is an ongoing national problem. Complex challenges remain in the epidemiology and treatment of hepatitis C. Many Vietnam era veterans are now on the front lines of the hepatitis C epidemic. Improved understanding and treatment of these patients will ultimately benefit all Americans with hepatitis C, Dr Waters concluded.

EASL publishes first European Clinical Practice Guidelines for Wilson's disease

Public release date: 7-Feb-2012

Contact: Travis Taylor
easlpressoffice@cohnwolfe.com
44-207-331-5472
European Association for the Study of the Liver

Geneva, Switzerland: The first European Clinical Practice Guidelines (CPGs) for the diagnosis and management of Wilson's disease are published today by the European Association for the Study of the Liver (EASL) on the EASL website -- www.easl.eu.(1) Developed to assist physicians and healthcare providers in the clinical decision making process, the guidelines describe best practice for the diagnosis and treatment of patients with Wilson's disease -- a rare genetic(2) disorder that, if left untreated, is fatal.

Approximately one in 30,000 people worldwide are affected by Wilson's disease -- a condition in which copper is not excreted by the body effectively, leading to excess copper build up, liver failure and damage to the brain. While Wilson's disease may manifest at any age, the majority of patients present between the ages of 5 and 35.

Lead author Professor Peter Ferenci said: "The clinical presentation of Wilson's disease can vary widely, but it must be considered in any patient who presents with a combination of unexplained liver disease and neurological or neuropsychiatric disorders. In the absence of Kayser-Fleischer rings(3) -- which are typical, but not always present -- the guidelines recommend measurement of urinary copper excretion and hepatic parenchymal copper as diagnostic methods of choice. Notably, age alone should not be the basis for eliminating a diagnosis of Wilson's disease."

The CPGs, based on a systematic review of existing literature, provide best practice diagnosis and treatment protocols with an emphasis on:

• Clinical presentation and prognosis
• Diagnostic strategies (e.g. serum ceruloplasmin, basal 24-hour urinary copper excretion, genetic analysis)
• Importance of family screening
• Treatment options (e.g. chelating agents, zinc, liver transplantation)

With treatment, prolonged survival has become the norm for Wilson's disease patients. The guidelines recommend chelating agents -- drugs that bind to copper and remove it from the body (D-penicillamine or trientine) -- as the initial treatment for symptomatic patients and that, unless liver transplantation is performed, treatment is maintained for life.

Professor Roderick Houwen added: "Unfortunately, as there are no optimally designed randomized controlled trials conducted in Wilson's disease, there is a lack of high-quality evidence to estimate the relative treatment effects of the available drugs. Our evaluation is mostly based on large case series that have been reported in recent decades, which highlights a clear need to conduct more robust randomized controlled trials to better understand treatment for this rare condition."

Professor Mark Thurz, EASL Secretary General, added: "EASL is dedicated to promoting hepatology research and education to improve the worldwide treatment of liver disease. Its series of Clinical Practice Guidelines aims to promote best practice to drive better clinical outcomes and inform both the scientific community and the wider public of the latest developments in the field. We hope these new Wilson's disease guidelines provide clinicians with the most up-to-date, evidence based methods for the management of affected patients."

The Wilson's disease CPGs will be published in the March issue (Volume 56, No. 3) of the Journal of Hepatology -- EASL's official journal.

###

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

• The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
• Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
• Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
• Journal of Hepatology published monthly
• Participation in a number of policy initiatives at European level

1. Ferenci P, et al (2011) Wilson's disease: EASL Clinical Practice Guidelines. European Association for the Study of the Liver. Available at http://www.easl.eu/_clinical-practice-guideline

2. Due to mutations of the ATP7B gene on chromosome 13.

3. Kayser-Fleischer rings are a golden-brown discolouring of the eye's corneal rim. The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber.

Source

Hepatocellular carcinoma

Jonathan Manning, Consultant Gastroenterologist, Scottish Borders. Reviewed by Luke Koupparis, general practitioner, Bristol.

Tuesday, 7 February 2012

Key learning points

• Hepatocellular carcinoma is a well recognised complication of chronic liver disease.
• Viral hepatitis remains the most common cause with alcohol also a significant contributor.
• Screening and surveillance is often performed to detect early lesions where possible.
• Surgery can be considered in fit patients with early stage disease.
• Palliative therapies are now available with lower toxicities and improved patient survival .
• Although key, endoscopy is not the only element in managing such patients.

---

Epidemiology

Hepatocellular carcinoma (HCC) refers to a liver tumour originating from within the liver tissue. Liver metastases are approximately 30 times more common than primary tumours and making this differentiation is imperative to further investigations and management. It ranks as the 5^th most prevalent cancer in the world (7% male cancers and 3% female cancers – approximately ½ million cases per year).

Symptoms

Patients may in fact be asymptomatic and have their tumour picked up on routine scanning for other reasons. Others may present with one or a combination of fatigue, abdominal pain, ascites, weight loss, jaundice or abnormal liver blood tests. Any of these should lead to further investigations by the primary care physician, referral to a Gastroenterologist and/or other Specialist.

Aetiology

Cirrhosis is known to be the greatest risk factor for the development of HCC. Significant geographical differences are apparent in relation to this risk factor. HCC rates of 30% are reported in South Africa but lower rates of 20% in Great Britain and North America. This is likely to be related to the larger cohort of chronic Hepatitis B virus (HBV) infection seen in those countries compared to the developed world.

Figure 1: Severe liver cirrhosis with gross ascites.

In cirrhotic alcoholics there is a four-fold increase in HCC compared to the general non-cirrhotic population. Chronic viral carriage of HBV can increase the HCC risk even in the absence of cirrhosis. The same applies to chronic hepatitis C virus (HCV) infection as well, with a four-fold increase in HCC in HCV patients compared to HBV when cirrhosis is present.

The mechanism of HCC is thought to reflect disorganised DNA during cellular repair or nodule regeneration in the presence of cirrhosis or chronic inflammation. Addressing some of the other chronic liver conditions, iron overload, as seen in genetic haemochromatosis, is also high risk for HCC when cirrhosis is present.

Other high risk cirrhotic patients include alpha₁-antitrypsin deficiency, type 1 glycogen storage disease and porphyria cutanea tarda. Primary biliary cirrhosis and chronic active auto-immune hepatitis with cirrhosis are both considered lower risk scenarios than those stated above. However, cirrhotic hepatitis B or C patients co-infected with HIV are possibly at the greatest risk.

Figure 2: Histology showing chronic hepatitis with ground glass hepatocytes.

Diagnosis

Small lesions can be hard to see in a nodular cirrhotic liver and may simply represent a regenerative nodule. Once a liver lesion has been identified, often by ultrasound, several factors, including it’s likely aetiology, need to be considered. Multi-phase CT scanning, or MRI, may be required to define a lesion further and follow-up interval scanning performed as appropriate, if deemed low risk.
The current evidence suggests that the standard initial imaging interval should be 6-monthly. Higher risk patients do not warrant more intensive screening. In addition to appropriate imaging the serum α-fetoprotein level is often monitored as it can be elevated in HCC. However, it may not increase in 20-40% or so. It may also be elevated in the absence of HCC but in the presence of other cancers, such as cholangiocarcinoma. It is also raised in pregnancy.

Liver biopsy is avoided if at all possible due to the high incidence of tumour seeding, particularly if a potentially curative outcome is predicted.

Treatments

This depends on the location, size and number of the tumours and also on the fitness of the patient. Small tumours (<2-3cm) will have a 1-year survival close to 85% but only a 50% 2-year survival. Surgical resection or liver transplantation both offer the only real chance of cure. Tumours that are invading the portal vein or breaching the liver capsule would be considered unresectable and perhaps only amenable to palliative therapies. A size of 5cm is the usual cut off for suitability of a single lesion resection.

Resection offers a greater than 50% 5-year survival with a 70% likelihood of recurrence. Patients with advanced cirrhosis are poor candidates for resection with an increased mortality and risk of liver failure post-operatively. Therefore, a liver transplant offers the best alternative. A shortage of donor organs has lead to live-donor right lobe transplants, with improving results.

Radiofrequency ablation (RFA) is a palliative therapy which can induce tumour necrosis. An electrode is passed via the peripheral vasculature into the liver. Heat can be delivered directly into the lesion and therapy repeated. It can be offered in patients with lesions >2cm, with a procedure-related mortality of 0.3%. Studies have shown upto a 70% 5-year survival with this treatment.

Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) are two other alternatives for palliation. Gelofoam or small metal coils can be inserted into the feeding vessels by interventional radiologists. TACE is the same as TAE but with prior injection of a chemotherapeutic agent into the lesion with improved results but higher associated toxicity.

TACE is considered the first line therapy for non-surgical patients with HCC that has no vascular invasion. However, it is much higher risk in those with Child-Pugh B or C due to the possibility of post-treatment liver failure.

Sorafenib, is a multikinase inhibitor, which has shown a survival benefit in palliative patients. Median survival is increased from 7.9 to 10.7 months. It is offered to those patients with preserved liver function who are not suitable for other treatment modalities.

References

1. Hashem B. El-Serag. N Engl J Med 2011; 365:1118-1127. Hepatocellular Carcinoma.
2. Nishant Merchant, Calvin S. David, and Steven C. Cunningham. Intl J Hepatol 2011; 2011:142085. Review Article: Early Hepatocellular Carcinoma: Transplantation versus Resection: The Case for Liver Resection.
3. Bruix J, Sherman M. Hepatol 2011 Mar;53(3):1020-2. AASLD - Management of hepatocellular carcinoma: an update.
4. Riccardo Lencioni. Oncology Haematology. In Press Jan 2012. Management of hepatocellular carcinoma with transarterial chemoembolization in the era of systemic targeted therapy.

Author and reviewers competing interests: none.

Images: Wellcome.

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Aethlon Medical to Present Hepatitis C (HCV) Treatment Technology at the 32nd Annual Dialysis Conference

PRESS RELEASE

Feb. 7, 2012, 8:15 a.m. EST

SAN DIEGO, Feb. 7, 2012 /PRNewswire via COMTEX/ -- Aethlon Medical, Inc. , the pioneer in developing selective therapeutic filtration devices to address infectious disease, cancer and other life-threatening conditions, announced today that a presentation of the Aethlon Hemopurifier® to treat Hepatitis C virus (HCV) and other infectious disease conditions will occur at the upcoming 32nd Annual Dialysis Conference to be held on February 26-28 at the Henry B. Gonzalez Convention Center in San Antonio, Texas. The presentation, which will be given by Aethlon President Rod Kenley, is scheduled to begin at 9:20 am CST on February 28th.

The Hemopurifier® is a first-in-class medical device that provides rapid real-time clearance of circulating HCV as well as immunosuppressive proteins shed by the virus. The goal of therapy is to improve benefit, dose, duration and tolerability of current and future drug therapies without introducing drug toxicity and interaction risks. Included among the Hemopurifier® treatment opportunities in HCV are the estimated 300,000 infected dialysis patients that currently live with the virus. As a result of their health-compromised end-stage renal condition, dialysis patients are often unable to tolerate HCV drug therapy dosing and duration, resulting in suboptimal treatment outcomes. To optimize outcomes, Hemopurifier® therapy would be combined with reduced dose drug therapy and conveniently administered during regular dialysis, which is scheduled three times per week with each treatment lasting four hours. In regards to the size of the overall HCV treatment opportunity, it is estimated that approximately 4 million Americans and 170 million people worldwide are infected with HCV, which leads to chronic liver disease or cirrhosis, and is the leading cause of liver transplant in the U.S.

On February 1, 2012, Aethlon reported that intermittent administration of Hemopurifier® therapy in just the first three days of standard of care peginterferon+ribavirin (PR) drug therapy resulted in immediate and rapid virologic responses in genotype-1 infected HCV patients not on dialysis. An immediate virologic response (IVR) represents a 2-log or 100 fold reduction of HCV RNA at day-7 of therapy and rapid virologic response (RVR) is defined as undetectable HCV RNA at day-30 of the 48-week PR regimen. Average HCV RNA reduction during the three day Hemopurifier® + PR treatment window was 98.79%. In previous studies of HCV-infected dialysis patients, average per treatment reductions of HCV RNA exceeded 50% when Hemopurifier® therapy was included in series with four-hour dialysis sessions in patients not receiving HCV drug therapy.

Aethlon also anticipates that Hemopurifier® therapy could benefit emerging all-antiviral drug cocktails, which face the challenge of overcoming the rate at which viruses attain drug resistance through rapid mutation. The development of drug-resistant strains can occur quickly owing to the extraordinarily high rate of HCV replication. The clearance of circulating hepatitis C virions, including mutant strains, would inhibit the continued replication of drug-resistant viruses and decrease the likelihood of early onset resistance to emerging all-antiviral strategies.

The Extract-1 Study Protocol

The results reported by Aethlon on February 1st, represent interim data from the first three patients treated with Hemopurifier® therapy under the Extract-1 study protocol, which was initiated in the fall of 2011. Under the Extract-1 study protocol, hard-to-treat genotype 1 HCV patients are enrolled to receive three 6-hour applications of Hemopurifier® therapy during the first three days of standard of care PR therapy. On day one of the Extract-1 protocol, PR therapy is initiated within one hour of first Hemopurifer® therapy completion. Hemopurifier® therapy is then administered again once daily for the next two days in combination with PR therapy. During the Hemopurifier® treatment periods, patients are free to watch movies, read books, and perform other tasks in the comfort of a clinic setting.

Clinical Endpoint Assessments

The aim of the Extract-1 study protocol is to assess the safety and clinical impact of intermittent Hemopurifier® therapy when combined with the first three days of peginterferon+ribavirin (PR) standard-of-care. To date, Hemopurifier® therapy in Extract-1 treated patients has been well tolerated and without device-related adverse events during the Hemopurifier® + PR treatment period. At present, the reported data of the Extract-1 study is not statistically significant and should be considered preliminary. Changes in HCV RNA levels are measured with the Roche Cobas TaqMan assay, which has a quantification limit of 15 IU per milliliter (iu/ml). In addition to measuring changes in HCV RNA, the Extract-1 study protocol will quantify the amount of HCV captured within Hemopurifier® treatment cartridges. The goal of PR treatment is to establish a sustained virologic response (SVR), defined as undetectable HCV RNA 24 weeks after completion of therapy. Primary clinical endpoints of the Extract-1 study measure the impact of Hemopurifier® therapy during the initial phase of PR therapy. Each clinical endpoint is based on changes in HCV RNA from baseline viral load measurements taken prior to Hemopurifier® + PR therapy initiation. These endpoints include:

Day Three (3): the change in HCV RNA from baseline to the end of the Hemopurifier® + PR treatment phase;

Day Seven (7): the change in HCV RNA 7 days from initial baseline. A drop of HCV RNA greater than 2 logs at day 7 is known as an Immediate Virologic Response (IVR). Based on the landmark IDEAL Study of 3,070 HCV genotype-1 patients receiving PR therapy, IVR achievement correlates with 90+% SVR rates, yet is observed in less than 5% of patients;

Day 30: the change in HCV RNA 30 days from initial baseline. Undetectable HCV RNA at day 30 is known as a Rapid Virologic Response (RVR). Based on the IDEAL Study, RVR achievement correlates with an SVR likelihood of 86.2%, which is observed in only 10.35% of patients.

Day 3 Results

Patient E-1.03: Baseline HCV RNA dropped from 5,800,000 IU/ml to 1,840 IU/ml when measured on day 3, representing a 3.49 log reduction. HCV RNA reduction during the 3-day Hemopurifier® + PR treatment phase accounted for 99.96% of the overall HCV RNA reduction reported at day-30.

Patient E-1.02: Baseline HCV RNA dropped from 199,500 IU/ml to 31,550 IU/ml when measured on day 3, representing a 0.80 log reduction. HCV RNA reduction during the 3-day Hemopurifier® + PR treatment phase accounted for 84.21% of the overall HCV RNA reduction reported at day-30.

Patient E-1.01: Baseline HCV RNA dropped from 1,340,000 IU/ml to 54,900 IU/ml when measured on day 3, representing a 1.38 log reduction. HCV RNA reduction during the 3-day Hemopurifier® + PR treatment phase accounted for 95.90% of the overall HCV RNA reduction reported at day-30.

Day 7 Results

On average, the treated patients achieved 2.24 log HCV RNA reduction from baseline at day-7, which is beyond the 2 log reduction that defines the IVR criteria achieved in less than 5% of PR treated patients.

Patient E-1.03: Baseline HCV RNA dropped from 5,800,000 IU/ml to 234 IU/ml when measured on day 7, representing a 4.39 log reduction.

Patient E-1.02: Baseline HCV RNA dropped from 199,500 IU/ml to 17,300 IU/ml when measured on day 7, representing a 1.06 log reduction.

Patient E-1.01: Baseline HCV RNA dropped from 1,340,000 IU/ml to 24,400 IU/ml when measured on day 7, representing a 1.74 log reduction.

Day 30 Results

Two of the three patients achieved a RVR at day 30, which is normally achieved in only 10.35% of patients receiving PR therapy, yet correlates with a 86.2% SVR versus a 30.4% SVR in patients who fail to achieve a RVR. Based on the IDEAL study, it would normally require the enrollment of approximately 20 PR treated patients to accomplish 2 RVR outcomes. It should also be noted that patient E-1.02 missed RVR achievement by 25 iu/ml.

Patient E-1.03: Baseline HCV RNA dropped from 5,800,000 IU/ml to undetectable (<15 IU/ml) when measured on day 30, representing a 5.58 log reduction.

Patient E-1.02: Baseline HCV RNA dropped from 199,500 IU/ml to 40 IU/ml when measured on day 30, representing a 3.69 log reduction.

Patient E-1.01: Baseline HCV RNA dropped from 1,340,000 IU/ml to undetectable (<15 IU/ml) when measured on day 30, representing a 4.95 log reduction.

Beyond high SVR rates, RVR achievement also provides HCV infected individuals the opportunity to reduce PR duration from 48 to 24 weeks (6-month reduction) in RVR patients that maintain undetectable HCV RNA through week 12 of PR therapy. RVR patients are also unlikely to discontinue PR therapy as a result of a non-virological response, which represents the primary reason why 46% of PR therapy patients don't complete their treatment regimen.

RVR achievement also plays a pivotal role in curbing treatment relapse, defined as undetectable HCV RNA at PR completion that again becomes detectable in the 24-week window after therapy completion. As reflected in the IDEAL study, the time to first undetectable HCV RNA correlates with the incidence of treatment relapse. Approximately 50% of patients who achieve complete HCV suppression for the first time by week 24 of therapy suffer from treatment relapse, while less than 10% of RVR patients relapse from therapy.

The Extract-1 study is being conducted at Medanta, The Medicity Institute (Medicity), a $360 million multi-specialty medical institute recently established to be a premier center for medical tourism in India. The principal investigator of the study is Vijay Kher, M.D., Chairman of the Department of Nephrology at the Medanta Kidney & Urology Institute. Dr. Kher previously served as the principal investigator of Hemopurifier® therapy studies conducted at the Apollo and Fortis hospitals in Delhi, India.

Based on the initial Extract-1 study outcomes, Aethlon will seek permission to open up the treatment study to HCV infected individuals who reside outside of India. The company also plans to expand its GMP manufacturing capabilities and upon quantification of HCV capture within Hemopurifier® treatment cartridges, will resubmit an Investigational Device Exemption (IDE) that will request FDA permission to initiate treatment studies in the U.S. The Company is also interested in collaborative clinical opportunities aimed at determining the synergistic effects of Hemopurifier® therapy combined with non-interferon based drug regimens.

About Aethlon Medical

The Aethlon Medical mission is to create innovative medical devices that address unmet medical needs in cancer, infectious disease, and other life-threatening conditions. Our Aethlon ADAPT(TM) System is a revenue-stage technology platform that provides the basis for a new class of therapeutics that target the selective removal of disease enabling particles from the entire circulatory system. The Aethlon ADAPT(TM) product pipeline includes the Aethlon Hemopurifier® to address infectious disease and cancer; HER2osome(TM) to target HER2+ breast cancer, and a medical device being developed under a contract with the Defense Advanced Research Projects Agency (DARPA) that would reduce the incidence of sepsis in combat-injured soldiers and civilians. For more information, please visit www.aethlonmedical.com .

Certain of the statements herein may be forward-looking and involve risks and uncertainties. Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aethlon Medical, Inc. to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such potential risks and uncertainties include, without limitation, the ability to recruit genotype-1 hepatitis C infected patients, including dialysis patients, positive results at the conclusion of the Extract-1 study, the ability to attain permission and to attract patients outside of India, the company's ability to expand its GMP manufacturing capabilities, the Company's ability to attain clinical collaborations to determine the Hemopurifier's® effect with non-interferon based drug regimens, there is no assurance that FDA will approve the initiation of the Company's clinical programs or provide market clearance of the company's products, future human studies of the Aethlon Hemopurifier® as an adjunct therapy to improve patient responsiveness to established cancer therapies, the company's ability to raise capital when needed, the Company's ability to complete the development of its planned products, the Company's ability to manufacture its products either internally or through outside companies and provide its services, the impact of government regulations, patent protection on the Company's proprietary technology, product liability exposure, uncertainty of market acceptance, competition, technological change, and other risk factors. In such instances, actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company's Securities and Exchange Commission filings.

Contacts:

James A. JoyceChairman and CEO858.459.7800 x301jj@aethlonmedical.com 

Jim FrakesChief Financial Officer858.459.7800 x300jfrakes@aethlonmedical.com 

John P. SalvadorDirector, Communications858.459.7800 x307jps@aethlonmedical.com 

SOURCE Aethlon Medical, Inc.

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Is acupuncture a risk factor for hepatitis C in Asian patients?

4.08PM 07 February 2012

Several years ago, I was refused from donating blood because I had recently received acupuncture as a participant of a trial. Even today, the NHS is very clear on this point: the current leaflet handed out to all blood donors states, 'you must not give blood if you have had acupuncture, unless this was done in the NHS or by statutory registered health care professional'.

But is this wise?

A Californian team investigated 494 patients with hepatitis C in order to determine the risk factors for this infection.¹ Specifically they wanted to find out whether the risk factors differ between various ethnic groups. 55% of all patients were Caucasian, 20% Hispanic and 25% Asian.

The laboratory profiles of these sub-groups were similar. 94% and 86% of Caucasians and Hispanics had commonly known risk factors for hepatitis C such as blood transfusion, drug injection or tattooing. For Asian patients, the picture was significantly different: in this population, acupuncture was a prominent risk factor. Some 50% of this subgroup had had acupuncture prior to the infection (Caucasians = 31%, Hispanics = 20%).

Many British GPs regularly see Asian patients; these findings from the US therefore beg the question whether UK Asians might be at similar risks. Patients can, of course, only be infected, if the acupuncture needle is not sterile. Thus the chances of acquiring an infection via adequately handled disposable needles should be zero. All regulated acupuncturists are told to use proper and safe techniques. It follows that, in the UK, the risk of hepatitis C infection through acupuncture should be zero.

But what about the unregulated acupuncturists who Asian patients might consult? What about the TCM-outlets in our high streets? What about amateur Asian acupuncturists who are on no register at all? To the best of my knowledge, there is no research to answer these questions.

To be on the safe side, therefore, acupuncture should be considered as a potential source of hepatitis C, particularly in Asian patients. To prevent such infections, GPs should urge their Asian patients not to frequent unregistered acupuncturists. And to prevent infections via blood donors, the categorical statement by the NHS mentioned above seems correct.

References

1. Ho EY, Ha NB, Ahmed A, Ayoub W, Daugherty T, Barcia G et al. Prospective study of risk factors for hepatitis C acquisition by Caucasian, Hispanic, and Asian American patients. J Viral Hepatitis 2012; 19:e105-e111.

Source

Cirrhosis patients losing muscle mass have a higher death rate

Public release date: 7-Feb-2012

Contact: Raquel Maurier
raquel.maurier@ualberta.ca
780-492-5986
University of Alberta Faculty of Medicine & Dentistry

These patients should be bumped up on liver transplant lists

Medical researchers at the University of Alberta reviewed the medical records of more than 100 patients who had a liver scarring condition and discovered those who were losing muscle were more apt to die while waiting for a liver transplant. These cirrhosis patients were placed at a lower spot on the transplant list because they had a higher functioning liver and were seemingly less sick than others with the same condition, based on scoring systems physicians commonly use today.

Michael Sawyer, the principal investigator in the recently published review, says the results demonstrate physicians need to consider muscle mass when assessing where a patient with cirrhosis needs to be placed on the transplant list. Muscle mass, which can be seen through CT images commonly ordered for cirrhosis patients, needs to be considered in conjunction with other factors doctors currently look at, says Sawyer, who is a researcher in the Department of Oncology with the Faculty of Medicine & Dentistry and a practising oncologist at the Cross Cancer Institute.

The review conducted by Sawyer and his colleagues was just published in the peer-reviewed journal, Clinical Gastroenterology and Hepatology, in the United States. An editorial about this research was also published in the February issue of the journal.

Sawyer and his team studied 112 patients with cirrhosis who were awaiting liver transplants at the University of Alberta Hospital and discovered 40 per cent of them had muscle wasting or low muscle mass. Cirrhosis is the final phase of chronic liver diseases, characterized by scarring of the liver and poor liver function. Those with low muscle mass lived for about 19 months if they couldn't get a transplant, while those with normal muscle mass lived for about 34 months without a liver transplant.

"Patients with cirrhosis who have low muscle mass are actually more sick than what current scoring systems are telling us and many of them die while waiting on the liver transplant lists," says Sawyer.

"Patients with low muscle mass will get put on the list thinking they can wait for around three years, but really they can only wait for about one-and-a-half years.

"Those in the medical field have been looking for better methods to assess patients with cirrhosis and this may be that missing piece to the puzzle. If we can combine this measure of muscle mass with the current scoring system, it will provide a better way of predicting survival rates of patients awaiting liver transplants."

The team's research was funded by the Alberta Cancer Foundation, who said the findings will improve care for patients. The study originally looked at the incidence of low muscle mass in both cirrhosis patients and patients with liver cancer. The liver cancer findings are yet to be published.

"Dr. Sawyer's research is an example of how new knowledge and the understanding of disease is vital to advancing clinical care," says Myka Osinchuk, CEO of the Alberta Cancer Foundation. "It is gratifying to know that Dr. Sawyer and his team have taken this research to another, unexpected level and are challenging the medical field to a new way of thinking."

Sawyer and one of his teammates, Aldo J. Montano-Loza, who works in the Division of Gastroenterology in the Faculty of Medicine & Dentistry, have already received further funding from the American College of Gastroenterology to continue their work.

Sawyer is hopeful this additional way of assessing cirrhosis patients awaiting transplants will be incorporated into medical practice within the next three to four years.

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The team recently presented their findings at research conferences in both Canada and Europe.

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