January 24, 2011

Check-up liver biopsy

The Irish Times - Tuesday, January 25, 2011

I’m booked in for a liver biopsy and wonder what the procedure will involve?

A liver biopsy is used to help diagnose many liver diseases. The procedure can help assess the stage of liver disease in conditions such as hepatitis C infection. It may also detect cancer, infections and the cause of abnormal levels of liver enzymes found in blood tests.

A liver biopsy takes a sample of tissue from the liver for laboratory examination. It may be performed either as a day-case procedure or during a hospital admission.

A sedative medication or pain medication is usually given by injection before the test. If the biopsy is done through the abdominal wall, you will be lying on your back with your right hand under your head. You will be asked to lie as still as possible throughout the test.

Ultrasound is used to guide the biopsy needle. The skin is cleansed, and local anaesthetic injected to numb the area. A small cut is made in the skin.

The biopsy needle is inserted, usually guided by ultrasound. You will be instructed to hold your breath while the biopsy is taken. This is to reduce the chance of puncturing the lung or tearing the liver.

Once the biopsy needle is removed, pressure will be applied to stop the bleeding and a bandage placed over the insertion site.

My doctor said something about having the test done through a vein in my neck.

Liver biopsy can also be performed by inserting a needle into the jugular vein in the neck. Again, you will lie on your back on a table and the internal jugular vein will be located. The skin will be cleansed and local anaesthetic will be injected to numb the area. A needle is then inserted to pass a catheter through the veins to the liver. X-ray equipment will be used to check the location of the catheter.

A specialised needle is then used through the catheter to take the biopsy sample. In both types of biopsy, you may feel a mild stinging sensation from the anaesthetic needle and when the anaesthetic is injected. The biopsy needle may feel like deep pressure and dull pain. Some people experience pain in the shoulder.

Risks may include a collapsed lung, complications from the sedation, accidental injury to the gallbladder or kidney and internal bleeding.


Outcome of liver transplantation based on donor graft quality and recipient status

Transplant Proc. 2010 Jul-Aug;42(6):2327-30.

Nemes B, Gelley F, Zádori G, Piros L, Perneczky J, Kóbori L, Fehérvári I, Görög D.

Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary. nemes@trans.sote.hu


BACKGROUND: Availability of suitable donor organs has always limited the number of liver transplantations performed. Use of marginal donor organs is an alternative to overcome organ shortage.

OBJECTIVE: To analyze the effect of various combinations of donor organ quality and recipient status on the outcome of liver transplantation.

MATERIALS AND METHODS: Data from 260 whole-liver transplantations performed between January 2003 and September 2009 were analyzed retrospectively. Study groups were established according to donor organ quality (marginal score 0-1 vs 2-5) and recipient status (Model for End-Stage Liver Disease [MELD] score <17 or >17). In patients at low risk, 102 received optimal grafts (good-to-good group [G/G], and 75 received marginal grafts (bad-to-good group [B/G]. In patients at high risk, 46 received optimal grafts (good-to-bad group [G/B], and 37 received marginal grafts (bad-to-bad group [B/B].

RESULTS: No differences were observed in cumulative patient and graft survival rates; however, total survival differed in the early period after transplantation, that is, within 1 year. There was a higher rate of overall postoperative complications including initial poor graft function, bleeding, infection, and kidney failure in group B/B compared with group G/B (25 of 37 patients [67.5%] vs 27 of 46 patients [59.0%]), group B/G (25 of 37 patients [68%] vs 39 of 75 patients [52%], and group G/G (25 of 37 patients [68%] vs 43 of 102 patients [42%]) (P = .04). Patients with a high MELD score (G/B and B/B) demonstrated increased risk of postoperative complications. Use of donor organs with marginal score of 2 or higher in patients with high MELD scores increased early patient mortality.

CONCLUSION: In summary, patients with a high MELD score (G/B and B/B) are at an increased risk of post-OLT complications. In contrast, use of marginal grafts (B/G and B/B) increased the rate of hepatitis C virus recurrence and decreased the response rate to antiviral therapy. The combination of impaired donor grafts and recipients at high risk should be avoided.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID: 20692473 [PubMed - indexed for MEDLINE]


Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C

J Gastroenterol. 2011 Jan 19. [Epub ahead of print]

Chayama K, Hayes CN, Yoshioka K, Moriwaki H, Okanoue T, Sakisaka S, Takehara T, Oketani M, Toyota J, Izumi N, Hiasa Y, Matsumoto A, Nomura H, Seike M, Ueno Y, Yotsuyanagi H, Kumada H.

Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan, chayama@hiroshima-u.ac.jp.


BACKGROUND: Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy.

METHODS: We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment.

RESULTS: When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%.

CONCLUSIONS: Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.

PMID: 21246384 [PubMed - as supplied by publisher]


Utilization of surveillance for hepatocellular carcinoma among hepatitis C virus-infected veterans in the United States

Ann Intern Med. 2011 Jan 18;154(2):85-93.

Davila JA, Henderson L, Kramer JR, Kanwal F, Richardson PA, Duan Z, El-Serag HB.

the Houston Center for Quality of Care and Utilization Studies, The Michael E. DeBakey Veterans Affairs Medical Center, and Baylor College of Medicine, Houston, Texas; University of North Carolina, Chapel Hill, North Carolina; and St. Louis University School of Medicine, St. Louis, Missouri.


Background: Surveillance for hepatocellular carcinoma (HCC) is recommended for patients with hepatitis C virus (HCV) infection and cirrhosis. However, whether surveillance is being done as recommended is unknown. Objective: To examine the prevalence and determinants of HCC surveillance among HCV-infected patients with cirrhosis in Veterans Affairs (VA) health care facilities in the United States. Design: Retrospective cohort study of HCV-infected patients using data obtained from the national VA Hepatitis C Clinical Case Registry. Setting: 128 VA medical centers. Patients: HCV-infected patients with cirrhosis diagnosed between fiscal years 1998 and 2005. Measurements: Abdominal ultrasonography and measurement of α-fetoprotein for HCC surveillance were identified from administrative data by using a previously validated algorithm. Patients were categorized as having routine (tests done during at least 2 consecutive years in the 4 years after cirrhosis diagnosis), inconsistent (at least 1 test, but not routine), or no surveillance in the 4 years after cirrhosis diagnosis. Predictors of surveillance were identified by using hierarchical random-effects regression. Results: 126 670 patients with HCV were identified; 13 002 (10.1%) had cirrhosis. Approximately 42.0% of patients with cirrhosis received 1 or more HCC surveillance tests within the first year after the cirrhosis index date; however, a decline in receipt of surveillance was observed in the following 2 to 4 years. Among patients with cirrhosis and at least 2 years of follow-up, routine surveillance occurred in 12.0%, inconsistent surveillance in 58.5%, and no surveillance in 29.5%. Lower medical and psychological comorbid conditions, presence of varices, and the absence of decompensated liver disease were associated with a higher likelihood of receiving routine surveillance. Limitations: Hepatocellular carcinoma surveillance tests were indirectly identified from registry data. Physician recommendations could not be captured. Conclusion: Few HCV-infected veterans with cirrhosis received routine HCC surveillance. New strategies are needed to improve the implementation of HCC surveillance in clinical practice. Primary Funding Source: Houston Veterans Affairs Health Services Research and Development Center of Excellence and the National Cancer Institute.

PMID: 21242365 [PubMed - in process]


Boomers may be vulnerable to hepatitis

~ Another article inaccurately stating sex as a
transmission risk of Hepatitis C ~
(see below highlighted in RED)

You may contact the author of the article:
Richard Craver
(336) 727-7376
Published: January 24, 2011

Hepatitis C, like heart disease, is considered as a "silent killer" by health-care officials.

With hepatitis C, the potential victim may have been carrying the virus for decades without knowing it until damage to the liver appears.

About 3.2 million Americans have chronic liver problems related to the virus, and an additional 3 million are not aware they are infected.

Considered particularly vulnerable to the disease are baby boomers — those born between 1946 and 1964 — because of lifestyle decisions made in their younger years.

That's why local physicians focused on infectious diseases are encouraged that two powerful drugs targeting hepatitis C — Vertex Pharmaceuticals' telaprevir and Merck & Co.'s boceprevir — could be available by summer if they gain Food and Drug Administration approval.

Some specialists are drawing comparisons to the early 1990s, when potent combination therapies emerged to treat AIDS.

"These drugs represent a major step forward for treating both new hepatitis C patients and those who have failed therapy," said Dr. Stan Link, an infectious-disease specialist at Forsyth Medical Center.

The new drugs are aimed at blocking an enzyme named protease that's key for the virus to reproduce. But they must be taken together with standard medications that are thought to boost the immune system.

According to the U.S. Centers for Disease Control and Prevention, nearly 70 percent of people with the hepatitis C virus will develop chronic liver disease.

Complications from hepatitis C cause between 4,600 and 12,000 deaths each year in the U.S. Deaths related to the disease are expected to increase to nearly 40,000 a year by 2040.

Transmission risks include injecting illegal drugs — the most common form — getting a tattoo with an unclean needle, having sex with an infected person and receiving donated blood, blood products and organs before 1992.

Hepatitis C "cuts across every segment of society," said Dr. Arun Sanyal of Virginia Commonwealth University in Richmond, the past president of the American Association for the Study of Liver Diseases. "I can tell you our hepatitis C treatment clinic is a great social equalizer."

The current two-drug treatment, which takes 48 weeks, cures about 40 percent of patients with the most common variety of the virus. A cure is defined as no sign of the virus six months after their last dose.

"Those 48 weeks of treatment can be very rough, contributing to depression, hair and weight loss, and severe fatigue," Link said.

Adding one of the new drugs to the regimen is projected to raise the cure rate to 75 percent, while cutting the treatment schedule in half, or to 24 weeks. Telaprevir's main risk is a rash that is sometimes severe, and boceprevir's is anemia.

Link said that while the treatment won't be inexpensive — potentially costing $25,000 to $30,000 a person — he expects most insurance companies will cover it as a less costly alternative to a liver transplant.

The CDC has begun a study at four hospitals to determine whether a one-time hepatitis C test for baby boomers makes sense.

Link and Dr. Marina Nunez, an assistant professor of infectious disease at Wake Forest University Baptist Medical Center, said the potential new drugs could encourage doctors and baby boomers to get tested for hepatitis C.

"We're constantly getting more referrals for hepatitis C treatment, perhaps as more doctors are more conscientious of asking their baby-boomer patients about whether they had any of the risk factors for the virus," Nunez said.

Link said he is recommending that recently diagnosed patients postpone starting therapy until the new drugs are available.

"The potential is there that the odds of their cure rate will be higher," Link said. "Being able to cut the treatment cycle in half will hopefully make it more tolerable for more people."


Also See: New Hope For Hepatitis C, An Often Hidden Disease

Treatment of chronic hepatitis B: Evolution over two decades

J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:138-43. doi: 10.1111/j.1440-1746.2010.06545.x.

Yuen MF, Lai CL.

Department of Medicine, the University of Hong Kong, Queen Mary Hospital, China. mfyuen@hkucc.hku.hk


There has been a recent paradigm shift in the indications and endpoints of treatment for chronic hepatitis B (CHB). Hepatitis B e antigen (HBeAg)-negative disease is being increasingly recognized. Antiviral treatment for both HBeAg-positive and HBeAg-negative patients should aim at long-term suppression of HBV DNA, with the ultimate ideal endpoint of hepatitis B surface antigen (HBsAg) seroconversion. Conventional interferon alpha (IFN-α), the only agent licensed in 1991, has been superseded by pegylated IFN-α. HBeAg seroconversion using pegylated IFN-α is 33%, with only 25% of HBeAg-positive patients achieving undetectable HBV DNA by polymerase chain reaction (PCR) assay. Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine, an L-nucleoside, is limited by the development of resistance in 76% of patients after 5 years of therapy. Telbivudine, another L-nucleoside, is more potent than lamivudine but resistance still develops in 25% of HBeAg-positive and 11% HBeAg-negative patients after 2 years. Adefovir, an acyclic phosphonate, is relatively weak, but is effective against lamivudine- and telbivudine- resistant mutations, for which it should be used in combination (add-on therapy) rather than substituted. Resistance to adefovir develops slowly, rising to 29% for HBeAg-negative patients by year 5, but more rapidly when used alone for lamivudine-resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir and tenofovir. Entecavir, a cyclopentane (D-nucleoside), is very potent, with 94% of patients having undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of treatment-naïve patients. Tenofovir, another acyclic nucleotide, is more potent with less renal toxicity compared to adefovir. It is effective against lamivudine-resistant mutations when used alone. No resistance to tenofovir has been described after its use for 3 years or longer, often for patients with human immunodeficiency virus/HBV co-infection. With these current, potent antiviral agents associated with very low rates of resistance, long-term HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved in a proportion of patients. In addition, long-term treatment with these antiviral agents is associated with a reduced risk of development of hepatocellular carcinoma.

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

PMID: 21199525 [PubMed - in process]


Hepatic steatosis and hepatitis C: Still unhappy bedfellows?

J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:96-101. doi: 10.1111/j.1440-1746.2010.06542.x.

Hwang SJ, Lee SD.

Department of Family Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.


Hepatic steatosis is commonly seen in patients with chronic hepatitis C virus (HCV) infection, and the prevalence is much higher prevalence than in the general population or in patients with chronic hepatitis B. Hepatic steatosis in patients with chronic hepatitis C can be due to alcohol consumption and host metabolic factors such as high body mass index (BMI), obesity, hyperlipidemia, metabolic syndrome and diabetes mellitus in which insulin resistance plays an important role. However, in genotype 3 HCV infection, hepatic steatosis can result from direct viral cytopathic effect. Demographic and clinical characteristics associated with hepatic steatosis in patients with chronic hepatitis C including older age, higher BMI, more genotype 3 infection, and higher mean serum levels of triglyceride, alanine aminotransferase and γ-glutamyl transpeptidase. The clinical relevance of hepatic steatosis in patients with chronic hepatitis C includes a close correlation with hepatic fibrosis, and a poor response to combination peginterferon and ribavirin treatment. In addition, hepatic steatosis has been reported to associate with increased frequency of hepatocellular carcinoma in patients with chronic HCV infection. Whether life style modification such as weight reduction or adding an insulin resistance reducing agent such as metformin or thiazolidinediones combined with current standard peginterferon plus ribavirin treatment will benefit to the chronic hepatitis C patients with hepatic steatosis deserves further evaluation.

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

PMID: 21199519 [PubMed - in process]


Fatty liver disease associated with cardiovascular risk in patients with HIV

Michael Carter
Published: 24 January 2011

Hardening of the arteries is common in HIV-positive patients, and is associated with fatty liver disease, US investigators report in the online edition of HIV Medicine.

“HIV-infected persons with fatty liver disease may warrant early cardiovascular assessment and institution of risk reduction methods,” comment the researchers.

Cardiovascular disease is an increasingly important cause of illness and death in patients with HIV. Studies conducted in HIV-negative individuals have shown that the presence of a fatty liver is associated with hardening of the coronary artery (atherosclerosis), an important risk factor for heart disease.

A team of investigators lead by Dr Nancy Crum-Cianflone wished to see if this was also the case for HIV-infected individuals.

They write: “Given that liver test abnormalities and fatty liver disease are common in among HIV infected persons, determining their relationship with coronary artery atherosclerosis may be helpful in the development of screening guidelines and risk stratification for underlying cardiovascular risk in this population.”

Between 2008 and 2010 they undertook a cross sectional study involving 223 HIV-positive adults. All the patients had a CT scan which checked for hardening, or calcification, of the coronary artery and fatty liver disease.

Atherosclerosis in the coronary artery was diagnosed if any calcification was detected (a score above 0), and a score above 100 was considered clinicially significant. Fatty liver was defined as a liver-to-spleen ratio < 0.1.

Information was also gathered on the patients’ demographics, CD4 cell count and viral load, use of antiretroviral drugs, lipid levels, and medical histories. A series of statistical analyses were then performed to see which factors were associated with hardening of the coronary artery.

With a median age of 43 years (range 36-50), the patients were relatively young. Risk factors for cardiovascular disease were common, and 39% had hypertension and 6% diabetes. Fatty liver can be a complication of viral hepatitis, but only 3% of the study population were co-infected with hepatitis C.

Most patients (83%) were taking antiretroviral therapy, 70% had an undetectable viral load and median CD4 cell count was 586 cells/mm3.

CT scanning showed that 34% of individuals had some hardening of the coronary artery, and that this was clinically significant for 8% of patients. Fatty liver was diagnosed in 13% of individuals.

Prevalence of fatty liver for patients with no evidence of hardening of the coronary artery was 8%. But this increased to 18% for individuals with a calcification score between 1-100, and was 41% for patients with clinically significant arterial hardening.

Overall, 59% of patients with fatty liver also had coronary atherosclerosis, and the correlation between the two conditions was significant (p = 0.02).

Statistical analysis that controlled for potentially confounding factors showed that three factors were significantly associated with calcification of the coronary artery: older age (each ten year increase, p < 0.01); fatty liver disease (p < 0.01), and hypertension (p < 0.01).

The relationship between hardening of the coronary artery and fatty liver disease was extremely robust, and was unaltered when the investigators excluded the small number of patients with hepatitis C, or those with metabolic syndrome. It was also present when patients with alcohol use were excluded from analysis.

“In our study, HIV-infected persons, despite their relatively young age, had a high prevalence of subclinical heart disease,” write the authors. They believe rheir results “emphasize the importance of cardiovascular disease among HIV-infected patients and suggest that addressing underlying heart disease may be an important component of further normalizing the life expectancy of this group.”

Inflammation could, the authors believe, be causing both the hardening of the arteries and the fatty liver disease observed in their patients.

Dr Crum-Cianflone and her colleagues conclude: “Fatty liver disease is associated with underlying cardiovascular disease and should be considered as a novel marker for risk stratification among HIV-infected persons.”


Crum-Cianflone N et al. Fatty liver disease is associated with underlying cardiovascular disease in HIV-infected persons. HIV Med, online edition (DOI: 10.1111/j.1468-1293.2010.00904.x), 2011 (click here for the free abstract).


Merck Says Hepatitis B Vaccine Safe; Unrelated to TG Swab Recall

By Nazvi Careem
Published Jan 24, 2011

Healthcare company Merck said its hepatitis B and hepatitis C medicines are safe to use despite the recent recall of Triad Group alcohol prep pads by FDA.

New Jersey: The hepatitis B vaccine and hepatitis C powder produced by healthcare company Merck are safe and are not affected by the recall of potentially contaminated Triad Group alcohol swab products, according to the manufacturer.

In a press release issued on January 23, Merck moved to reassure consumers its medicines, which may be co-packaged with Triad Group products, were not affected by the recent recall initiated by the FDA and the Triad Group.

It said consumers should continue to use its Intron A and Pegintron medicines but discard the alcohol prep pads that are included in the packages.

“It is important to note that the Merck medicines are not contaminated, and should continue to be used in accordance with the package insert, and as directed by a healthcare provider, except the alcohol prep pad should be discarded,” said the press release (http://www.merck.com/newsroom/news-release-archive/prescription-medicine-news/2011_0123.html).

On January 3, the FDA and Triad Group, a manufacturer of over-the-counter products, announced the recall of alcohol prep pads, swabs and swabsticks over concerns about possible contamination with Bacillus cereus.


The recall affected products marked as “STERILE” in addition to non-sterile items with the FDA warning that their use may lead to life-threatening infections, particularly among high-risk groups such as immune-suppressed and surgical patients.

The pads and swabs are usually used as a disinfectant by wiping an area of the body before an injection.

The FDA stressed that the recall is confined to Triad Group products and not the items from other manufacturers that it might be packaged with (http://www.fda.gov/Safety/MedWatch/default.htm, last checked January 24, 2011).

The Merck products accompanying the potentially contaminated Triad Group swabs are sold in Latin America, excluding Brazil, Canada, Europe and Asia Pacific, excluding Japan.

The company said its medicines distributed in the United States are not affected by the recall of Triad Group products.

Hepatitis B vaccine

Intron A contains the man-made protein Interferon and is used in the treatment of chronic hepatitis B, in addition to hairy cell leukaemia, malignant melanoma, follicular lymphoma, AIDS-related Kaposi’s sarcoma, chronic hepatitis C and condylomata acuminata.

Pegintron is a powder that is used to make a solution used in the treatment of chronic hepatitis C in patients three years and older.

Merck said, after talks with health experts at regional government level, it would start to package orders for countries minus the alcohol prep pads until another source of the material can be identified.

It will also urge consumers in affected markets to discontinue using the pads, swabs and swabsticks because of the risk of contamination.

In addition, Merck plans education programmes in the various countries so patients can be fully informed on the products and its risks.

The information will be made available to regulatory agencies in respective countries and those conducting clinical trials using the products.