End-stage liver disease complications

Curr Opin Gastroenterol. 2013; 29(3):257-63 (ISSN: 1531-7056)

Rahimi RS; Rockey DC
aAnnette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas bDepartment of Internal Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

PURPOSE OF REVIEW: Chronic liver disease causes significant morbidity and mortality because of any number of complications including hepatic encephalopathy, ascites, hepatorenal syndrome (HRS), and esophageal variceal hemorrhage (EVH).

RECENT FINDINGS: Predictors of response to lactulose, probiotics, and L-ornithine-L-aspartate therapy in minimal hepatic encephalopathy (MHE) have been reported. Although rifaximin was slightly more effective than lactulose in the maintenance of remission and decreased re-admission in patients with MHE, it was not as cost-effective as lactulose. Beta-blockade has been associated with paracentesis-induced circulatory dysfunction. Those who respond to nonselective beta-blockers have a predictable overall lower probability of developing ascites and HRS. Noradrenaline was as effective as terlipressin for the treatment of type 1 HRS and was less costly. Hemorrhagic ascites, defined as an ascitic fluid red blood cell (RBC) count of at least 10 000/μl, appeared to be a marker for poor outcome in patients with cirrhosis. In patients with acute EVH, band ligation, pharmacologic vasoconstrictors, and antibiotics are effective; notably, intravenous proton pump inhibitor therapy in lieu of vasoconstrictors achieved similar hemostatic effects with fewer side-effects.

SUMMARY: Refinement in the clinical management strategies for patients with cirrhosis and its complications appear to continue to contribute to improved patient outcomes.

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Proteonomix Announces Agreement with the University of Medicine and Dentistry of New Jersey (UMDNJ) to Conduct a Phase 1 Trial with UMK-121 in End-Stage Liver Disease

PRESS RELEASE

Sept. 14, 2012, 9:00 a.m. EDT

Preeminent Liver Expert Dr. Baburao Koneru to Serve as Principal Investigator

PARAMUS, N.J., Sep 14, 2012 (BUSINESS WIRE) -- Proteonomix, Inc. (otc/bb:PROT), a biotechnology company focused on developing therapeutics based upon the use of human cells and their derivatives, today announced it has entered into an agreement with Piscataway, N.J.-based University of Medicine and Dentistry of New Jersey (UMDNJ) to conducted a Phase 1 clinical trial with its proprietary, patent-pending mobilization technology UMK-121 in patients with end-stage liver disease (ESLD). The Company also announced that Chief Executive Officer Michael Cohen made a presentation at the National Investment Banking Association's (NIBA) 123rd Investment Conference yesterday at the New York Marriott Downtown in New York City.

The single-center Phase 1 clinical trial, Mobilization of Stem Cells with UMK 121 in Patients with Cirrhosis, will enroll 15 patients with ESLD. The trial will study the safety of mobilization of stem cells in this patient population, as well as the effects of mobilization of stems cells from bone marrow to the peripheral circulation on liver function. Baburao Koneru, M.D., Professor and Chief of the Division of Transplant and Hepatobiliary Surgery at New Jersey Medical School, will serve as the trial's principal investigator.

"We are extremely pleased to announce that our trial will be conducted at this highly respected institution under the direction of Dr. Koneru, who is a renowned expert in the field of liver function," said Mr. Cohen. "Our presentation to the investment professionals attending the NIBA conference provided an opportunity to discuss the potential of UMK-121 in ESLD as we make preparations to commence this clinical trial, which we hope to initiate in the coming months."

UMK-121 combines two existing FDA-approved drugs with the intention of mobilizing mesenchymal stem cells from bone marrow to the peripheral circulation. This proprietary drug combination is designed to reduce inflammation and increase angiogenesis to restore liver function, potentially extending the life of ESLD patients awaiting liver transplant.

About the University of Medicine and Dentistry of New Jersey

The University of Medicine and Dentistry of New Jersey (UMDNJ) is New Jersey's only health sciences university with more than 6,000 students on five campuses attending three medical schools, the State's only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and New Jersey's only school of public health. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, which provides a continuum of healthcare services with multiple locations throughout the State.

About National Investment Banking Association (NIBA)

NIBA is the only national not-for-profit trade association of regional and independent brokerages, investment banking firms, institutional investors and related capital market service providers. Since its inception, NIBA member firms have successfully completed more than 1,000 equity offerings totaling approximately $10 billion in new capital. The member firms of NIBA represent more than 8,000 registered representatives with an estimated $78 billion in assets under management, and are responsible for 90% of all Initial Public Offerings under $20 million. For more information, please visit www.nibanet.org .

About Proteonomix, Inc.

Proteonomix is a biotechnology company focused on developing therapeutics based upon the use of human cells and their derivatives. The Proteonomix family of companies includes Proteoderm, StromaCel, PRTMI and THOR Biopharma. Proteoderm is a wholly owned subsidiary that has developed an anti-aging line of skin care products. StromaCel develops therapeutic modalities for the treatment of cardiovascular disease and plans to file an IND application for treatment of patients who have suffered post-myocardial infarction. Proteonomix Regenerative Translational Medicine Institute, Inc. (PRTMI) intends to focus on the translation of promising research in stem cell biology and cellular therapy to clinical applications of regenerative medicine. Additional information is available at www.proteonomix.com and www.proteoderm.com .

Certain statements contained herein are "forward-looking statements" (as defined in the Private Securities Litigation Reform Act of 1995). Proteonomix, Inc. cautions that statements made in this press release constitute forward-looking statements and makes no guarantee of future performance. Actual results or developments may differ materially from projections. Forward-looking statements are based on estimates and opinions of management at the time statements are made.

SOURCE: Proteonomix, Inc.

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LIVER DISEASE IN KASHMIR CHALLENGES & HOPE

Non-alcoholic fatty liver disease (NAFLD) has taken us by storm globally

HEALTH BY PROF M S KHUROO

Liver disease is now established as the fifth most common cause of death after heart disease, stroke, chest infections and cancer. Disturbing is the data that unlike other major causes of mortality, liver disease is increasing over the years rather than declining. For medical fraternity worldwide, there have never been more challenges thrown by liver disease and yet there shall never be more tools/hope available with us to overcome these. Thus liver disease globally is passing through both-despair and hope; an excellent opportunity for many of us to exploit for the better.

Today we have a large pool of chronic carriers of hepatitis viruses across the globe. Estimated numbers of Hepatitis BVirus (HBV)& Hepatitis CVirus (HCV) infected worldwide are staggering -350 million and 500 million respectively. Of the 40 million HIV carriers, 3 million are infected with HBV and 4.5 million with HCV. It is estimated that HBV results in one million deaths worldwide yearly and HCV causes whooping 5 million deaths. End Stage Liver Disease (ESLD) and liver cancer constitute major causes of deaths related to HBV &HCV infections. Universal hepatitis B vaccination at birth in endemic areas has been shown to be highly effective in reducing carrier rates in children as well as the incidence of ESLD and liver cancer. Today 182 countries have now included hepatitis B vaccination in national immunization program and we must follow this in our EPI program aggressively to change the epidemiology of HBV in our country.

Hepatitis E virus (HEV) has turned out to be the most enigmatic human agent since we discovered the agent in 1980. HEV causes large-scale waterborne epidemics in developing countries involving hundreds and thousands of adult population. Around half to two-thirds of endemic hepatitis in such countries are caused by HEV. HEV has increased incidence and severity in pregnant women and is the commonest cause of acute liver failure in our society. In recent years, hepatitis E is recognized as a clinical problem in industrialized countries. HEV agent has entered in to food borne chain and is spread by consuming raw or undercooked pig livers available in super-markets in such countries. Recently we calculated HEV infections load globally. In 2005 an estimated 20 million incident HEV infections had occurred resulting in 3.3 million symptomatic cases, 70,000 deaths and 3000 stillbirths. In India alone, over 2.2 million cases of hepatitis E are thought to occur annually. Because of the impact of this infection globally it is imperative that measures be taken to control this python. Clean drinking water and safe sewage disposal are the corner stones of control, however, it may take more than hundred years before we get to drink a glass of clean portable water in India. Two HEV candidate vaccines have successfully completed phase 3 trials and ready for the prime time. As of today, HEV are not commercially available.

Non-alcoholic fatty liver disease (NAFLD) has taken us by storm globally. Kashmir is in the middle of an epidemic of metabolic syndrome and NAFLD. NAFLD is a potentially progressive liver disease and shall pose serious health problem to our community in near future. What could be the possible reasons for introduction of metabolic syndrome and NAFLD in our community of late? For sure the focus has to be our changing sedentary life style and changing food habits. You might be shocked to know that a plate of wazwan shared by 4 persons served 40,000 kilo-calories and indulgence in this delicacy shall throw any body’s metabolic system in to disarray and load liver with fat, similar to what binge drinking can do in the West. So if we need to fight this metabolic syndrome and liver disease caused by NAFLD, we need to be on roads and gyms rather than driving luxurious cars, go back to our delicious Haak (Cabbage) and rice rather than delicacy of Wazwan and maintain a body mass index at least under 25.

In this despair and hope for challenges posed by liver disease, where does liver transplantation stand? Should we talk about this esoteric advanced costly procedure once our community is infested with parasites, infections, poor portable water, bad sewage disposal and poor life style practices. My answer is yes and I shall dilate upon this to support this. It is worth mentioning that patients with ESLD and acute liver failure do not have the luxury of liver dialysis as those with renal failure patients have and liver transplant is the only hope for millions of such patients as of today. In spite of the shortage of organs and long waiting list of patients on cadaveric program Liver transplant has substantially changed management of such patients. Living Donor Liver Transplant has removed many bottlenecks and strengthened such programs in the West.

Today function has been organized to focus on awareness of liver transplant in our community. For this we have invited senior medical faculty and important members of civil society to compliment the visiting team. We have supported young physicians from various disciplines to attend this function and interact with the visiting team. It is our wish that these young minds develop interest in various aspects of liver transplant may be transplant hepatology, surgery, pathology, radiology and so on.

This interest and training shall help patients with liver diseases in Kashmir to get correct advice on transplant patients and also help those transplanted and on follow up in J&K. In future this may strengthen the ties with other transplant centers to develop a satellite liver transplant program in the State in coming years.

(Author is Ex-Director SKIMS Srinagar; Ex-Head Gastro & Liver Transplantation Program KFSH Riyadh; Director Digestive Disease Center Dr Khuroo’s Medical Clinic Srinagar Kashmir India)

Lastupdate on : Sat, 7 Apr 2012 21:30:00 Mecca time
Lastupdate on : Sat, 7 Apr 2012 18:30:00 GMT
Lastupdate on : Sun, 8 Apr 2012 00:00:00 IST

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Tocotrienols Reach Organs, Impart Clinical Benefits

EDISON, NJ— A recently published human study reported orally supplemented tocotrienols (as Tocomin SupraBio®, from Carotech) are distributed to various tissues and vital organs and produce significant clinical benefits. Half of end-stage liver disease patients given the supplement for 12 weeks had a reduced Model for End Stage Liver Disease (MELD) score, while only 20 percent of patients taking tocopherols (the regular vitamin E) had similar score reductions.

The trial was conducted by Chandan K. Sen, Ph.D., and his team from the Ohio State University Medical Center and registered at NIH's ClinicalTirals.gov website. The study was designed to determine the levels of vitamin E isomers in human tissues and vital organs following oral supplementation with Tocomin SupraBio, a patented and bioenhanced natural full spectrum palm tocotrienol softgel.

Among the 80 total study subjects, one group of healthy participants had blood and skin tests and were then given 400 mg/d Tocomin for 12 weeks, while another group of surgical patients provided tissue samples of cardiac muscle, liver, abdominal adipose tissues, and brain tissues, and were randomized to either 400 mg/d tocotrienols (Tocomin) or tocopherols for a mean supplement duration of 20 weeks (range: one to 96 weeks).

The researchers found the healthy subjects had negligible levels of tocotrienols in both blood and skin prior to tocotrienols supplementation; after 12 weeks of supplementation, blood and skin levels of tocotrienols increased. In addition, the observed alpha-tocotrienol concentration in blood was 20-fold higher than the amount required to provide neuroprotection. Further, the adipose tissue in tocotrienol supplemented patients contained approximately 10-times the tocotrienol levels, compared to controls. Tocotrienol supplementation also significantly increased alpha, gamma, and delta-tocotrienol levels in the human brain. According to the researchers, alpha-tocotrienol was transported to human brain at a concentration reported to be neuroprotective in earlier studies. In both heart muscle and liver, alpha, gamma, and delta-tocotrienol levels were significantly higher in tocotrienol supplemented patients as compared to subjects receiving tocopherol alone.

As far as health benefits, the researchers utilized the MELD scoring system, which is clinically used to assess the severity of chronic liver disease—the higher the MELD score, the more severe the condition and increased urgency for liver transplantation. They noted MELD score is a reliable marker for mortality in end-stage liver disease. Over the period of the study the researchers noticed that tocotrienols supplemented end stage liver disease patients experienced a reduction in their MELD scores. Among subjects supplemented with tocopherol alone, only 20 percent (one out of five) experienced reduced MELD score, while 50 percent (seven out of 14) of the tocotrienol supplemented subjects showed MELD score improvement.

In fact, MELD score reduction associated with tocotrienol supplementation was most evident in patients with viral hepatic cirrhosis: four out of six patients (67 percent) with hepatitis C and one single hepatitis B patient had reduced MELD score. Researchers noted standard of care therapy is available for viral hepatitis, but it is poorly tolerated due to its toxicity and side effects.

“It is very exciting to learn from this human study that oral supplementation of bioenhanced palm tocotrienol complex that Tocomin SupraBio, improves accumulation of tocotrienols in the blood, skin, adipose, brain, heart and liver," said WH Leong, VP of Carotech. "The study also shows that Tocomin SupraBio® significantly lowered the MELD score in end stage liver disease patients. and may therefore be an exciting oral supplement with potential to benefit these patients. Tocopherol again did not show the same level of efficacy." He further stated this human study also proved tocotrienols are absorbed and accumulated in vital human organs even in the presence of tocopherol, thereby unequivocally dispelling claims that tocopherol prevents the absorption of tocotrienols.

Editor's Note: For more information on tocotrienols, check out INSIDER's On-Demand webinar entitled, "Partner Series—Natural Vitamin E Tocotrienol in Neuroprotection and Stroke Prevention," as well as the INSIDER Tocotrienols Solution Center , which includes slideshows and video from the recent SupplySide workshop on tocotrienols.

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Proteonomix, Inc. (PROT) Announces Completion of Payment for Its Clinical Trial of UMK-121 in Patients With End Stage Liver Disease

Dec. 27, 2011, 2:35 p.m. EST

MOUNTAINSIDE, NJ, Dec 27, 2011 (MARKETWIRE via COMTEX) -- PROTEONOMIX, INC. a biotechnology company focused on developing therapeutics based upon the use of human cells and their derivatives, announced today that it has completed all payments required from Proteonomix to commence a Clinical Study entitled "UMK-121 in Patients with Liver Disease."

As previously announced, the Company entered into an Agreement to conduct the clinical trial with the University of Miami. That Agreement required the University to pay expenses associated with the clinical study and The Company was required to assist financially with the clinical study.

Michael Cohen, President of the Company, stated: "The financing that was required to complete the Company's obligation with respect to the Trial was provided Friday, December 23, 2011. We previously thanked the University for its generous assistance in the agreement to conduct a clinical trial of UMK-121. The Company has previously described the terms of the agreement to license and develop and the patent application of the UMK-121 technology. The Company will work together with the University and the principal investigators to initiate the clinical study."

Mr. Cohen continued, "Our UMK-121 pharmaceutical therapy is advancing toward its first human clinical trial in ESLD ('End Stage Liver Disease') patients. We hope to provide patients who are suffering from this debilitating and mortal condition with alternatives. We believe that the commercialization of this technology can provide Proteonomix with significant revenue potential. According to United Network for Organ Sharing ('UNOS') there are over 100,000 patients on the transplant waiting list at any given time. According to the ('NIH') there are over 500,000 patients in end stage Kidney disease. According to Organ Donation and Transplantation ('NWHIC') over 60,000 Americans suffer from End Stage Liver Disease ('ESLD'). The Company will continue to provide information about the clinical study in the upcoming weeks and months consistent with our understanding with the University and ethical considerations."

About Proteonomix, Inc.:

Proteonomix is a biotechnology company focused on developing therapeutics based upon the use of human cells and their derivatives. The Proteonomix Family of companies includes Proteoderm, StromaCel, PRTMI and THOR Biopharma. Proteoderm, Inc. is a wholly owned subsidiary that has developed an anti-aging line of skin care products. StromaCel, Inc. develops therapeutic modalities for the treatment of Cardiovascular Disease (CVD). Proteonomix Regenerative Translational Medicine Institute, Inc. ("PRTMI") intends to focus on the translation of promising research in stem cell biology and cellular therapy to clinical applications of regenerative medicine. Proteonomix intends to create and dedicate a subsidiary to each of its technologies. Please also visit http://www.proteonomix.com/ , http://www.proteoderm.com/ , http://www.otcqb.com/ and http://www.sec.gov/ .

Forward-looking statements:

Certain statements contained herein are "forward-looking statements" (as defined in the Private Securities Litigation Reform Act of 1995). Proteonomix, Inc. cautions that statements made in this press release constitute forward-looking statements and makes no guarantee of future performance. Actual results or developments may differ materially from projections. Forward-looking statements are based on estimates and opinions of management at the time statements are made

Source

A Revised Model for End-Stage Liver Disease Optimizes Prediction of Mortality Among Patients Awaiting Liver Transplantation

Gastroenterology
Volume 140, Issue 7 , Pages 1952-1960, June 2011.

D. Leise, W. Ray Kim, Walter K. Kremers, Joseph J. Larson, Joanne T. Benson, Terry M. Therneau

Received 30 June 2010; accepted 14 February 2011. published online 21 February 2011.

Abstract

Background & Aims
The Model for End Stage Liver Disease (MELD) was originally developed based on data from patients who underwent the transjugular intrahepatic portosystemic shunt procedure. An updated MELD based on data from patients awaiting liver transplantation should improve mortality prediction and allocation efficiency.

Methods
Wait-list data from adult primary liver transplantation candidates from the Organ Procurement and Transplantation Network were divided into a model derivation set (2005–2006; n = 14,214) and validation set (2007–2008; n = 13,945). Cox regression analysis was used to derive and validate an optimized model that updated coefficients and upper and lower bounds for MELD components and included serum levels of sodium. Main outcomes measure was ability to predict 90-day mortality of patients on the liver transplantation wait list.

Results
Optimized MELD score updated coefficients and implemented new upper and lower bounds for creatinine (0.8 and 3.0 mg/dL, respectively) and international normalized ratio (1 and 3, respectively). Serum sodium concentrations significantly predicted mortality, even after adjusting for the updated MELD model. The final model, based on updated fit of the 4 variables (ie, bilirubin, creatinine, international normalized ratio, and sodium) had a modest yet statistically significant gain in discrimination (concordance: 0.878 vs 0.865; P < .01) in the validation dataset. Utilization of the new score could affect up to 12% of patients (based on changed score for 459 of 3981 transplants in the validation set).

Conclusions
Modification of MELD score to update coefficients, change upper and lower bounds, and incorporate serum sodium levels improved wait-list mortality prediction and should increase efficiency of allocation of donated livers.

Keywords: Liver Disease, Surgery, Prognosis, Survival

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Adult Stem Cells Treat End-Stage Liver Disease

by David Prentice
January 26, 2011

A team of researchers in California and in Egypt report therapeutic benefit treating end-stage liver disease patients with adult stem cells A total of 48 patients were treated with their own adult stem cells–36 patients with chronic, end-stage hepatitis C-induced liver disease, and 12 patients with end-stage autoimmune liver disease. Researchers used the factor G-CSF, commonly used to mobilize bone marrow adult stem cells into the circulation, to obtain the cells from each patient. The CD34+ stem cells were then isolated, amplified to increase numbers of cells, partially differentiated in culture, then re-injected into each patient via their hepatic artery or portal vein. The results were published in Cell Transplantation

According to co-author Dr. Mark A. Zern of University of California-Davis Medical Center:

“This enabled us to transplant as many as one billion of these cells per patient. For all patients there was a statistically significant decrease in peritoneal cavity fluid, or ‘ascites’. There was also clinical and biochemical improvement in a large percentage of patients who received the transplantation. The finding of improvement in ascites in a significant number of patients is impressive and somewhat surprising, suggesting that cell transplantation might be clinically significant beyond the improvement in laboratory parameters.”

The mechanism by which the infusion of CD34+ adult stem cells improves liver function is still unclear. As to whether any partial differentiation into liver cells was needed for the therapeutic results, Dr. Stephen Strom at the University of Pittsburgh and section editor for Cell Transplantation, noted:

“Other research groups are now showing similar results with cells without any hepatic characteristics, including fractionated and unfractionated bone marrow and mesenchymal stem cells. Taken together, these data suggest that the positive effects these researchers find may be the result of paracrine effects from factors secreted by the donor cells.

Published data in 1999 suggested that some bone marrow adult stem cells could form liver hepatocytes. Others reported similar results in 2000 using mice, by observing liver cells of human bone marrow adult stem cell transplant patients, and in experiments showing regeneration of liver in mice. However, some published evidence also indicates that the regenerative capacity of bone marrow adult stem cells is due to paracrine effects, i.e., secreted factors.

No matter what the mechanism, various clinical trials are investigating use of adult stem cells for liver diseases. Published results from earlier trials show therapeutic benefit of adult stem cells for liver repair and regeneration.

In a published 2010 report, a Korean group found some improvement in liver cirrhosis patients using their own adult stem cells.

In 2006 a U.K. group reported improvement in patients with liver insufficiency treated with their own adult stem cells, and the same group reported in 2008 the long-term improvement of chronic liver disease patients, using the patients’ own adult stem cells in a trial similar to the current Egyptian trial.

Also in 2006, a German group reported increased liver regeneration in liver cancer patients using adult stem cells, and a Japanese team found improved liver function in cirrhosis patients after using the patients’ own bone marrow adult stem cells.

Adult stem cells continue to provide ethical and successful results for patients.

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Cell Transplantation reports a success in treating end-stage liver disease

Public release date: 11-Jan-2011

Contact: David Eve
celltransplantation@gmail.com
Cell Transplantation Center of Excellence for Aging and Brain Repair

Tampa, Fla. (Jan. 10, 2011) – Transplanting their own (autologous) bone marrow-derived stem cells into 48 patients with end-stage liver disease resulted in therapeutic benefit to a high number of the patients, report researchers publishing in the current issue of Cell Transplantation (19:11). Yet, the mechanism by which the infusion of CD34+ stem cells improves liver function remains elusive, they say.

The study, carried out by a team of researchers in California and in Egypt, is now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/

According to the study's corresponding author, Dr. Mark A. Zern of the University of California Davis Medical Center, Sacramento, CA, patients with end-stage liver failure in Egypt have few treatment options but for transplantation. A shortage of donors and cost factors make that strategy unrealistic. Accordingly, this study sought to evaluate the safety and efficacy of transplanting autologous bone marrow-derived CD34+ stem cells in 48 patients, 36 of whom had chronic, end-stage hepatitis C-induced liver disease, and 12 with end-stage autoimmune liver disease.

"For all patients there was a statistically significant decrease in peritoneal cavity fluid, or 'ascites,'" said Dr. Zern. "There was also clinical and biochemical improvement in a large percentage of patients who received the transplantation."

The researchers reported that they obtained "reasonable numbers of CD34+ cells" that were then "amplified and partially differentiated into hepatocyte precursor cells."

"This enabled us to transplant as many as one billion of these cells per patient," explained Dr. Zern. "The finding of improvement in ascites in a significant number of patients is impressive and somewhat surprising, suggesting that cell transplantation might be clinically significant beyond the improvement in laboratory parameters."

They also report using granulocyte-colony stimulating factor (G-CSF) to "mobilize…CD34+ stem cells into peripheral circulation." The researchers anticipated that G-CSF would likely enhance a variety of circulating bone marrow-derived cells, producing growth factors which could "positively affect liver regeneration and perhaps have a positive effect on portal hypertension."

The team also reported that prior to transplantation, the cells were already beginning to develop a hepatocyte phenotype while in culture, suggesting that the cells may have acted as hepatocyte-like cells following engraftment. The researchers plan to compare routes of infusion to determine if peripheral infusion of transplanted cells will be adequate.

"The use of peripheral infusion would dramatically reduce both costs and risks for this cell transplantation, thus making the treatment an even more viable option in Egypt and throughout the world," concluded Dr. Zern.

"It would be very interesting to determine if the differentiation to hepatic precursors was a necessary step for this treatment," said Dr. Stephen Strom, a professor of pathology in the Department of Pathology at the University of Pittsburgh and section editor for Cell Transplantation. "Other research groups are now showing similar results with cells without any hepatic characteristics, including fractionated and unfractionated bone marrow and mesenchymal stem cells. Taken together, these data suggest that the positive effects these researchers find may be the result of paracrine effects from factors secreted by the donor cells. I look forward to reading about the outcome of future studies to determine the optimal route of administration and dose of these cells, as well as more long term follow up."

###

Contact: Dr. Mark A. Zern, UC Davis Medical Center, 4635 Second Ave. Ste. 1001, Sacramento, CA
Tel: (916) 734-8063; Fax: (916) 734-8097
Email: mazern@ucdavis.edu

Citation: Salama, H.; Zekri, A-R..; Zern, M.; Bahnassy, A.; Loutfy, S.; Shalaby, S.; Vigen, C.; Burke, W.; Mostafa, M.; Medhat, E.; Alfi, O.; Huttinger, E. Autologous Hematopoietic Stem Cell Transplantation in 48 Patients With End-Stage Chronic Liver Diseases. Cell Transplant. 19(11):1475-1486; 2010.

The editorial offices for CELL TRANSPLANTATION are at the Center of Excellence for Aging and Brain Repair, College of Medicine, the University of South Florida and the Diabetes Research Institute, University of Miami Miller School of Medicine. Contact, David Eve, PhD. at celltransplantation@gmail.com or Camillo Ricordi, MD at ricordi@miami.edu

News Release by Randolph Fillmore, Florida Science Communications, http://www.sciencescribe.net/

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CRP Level Predicts Short-Term Mortality Better Than MELD Score in End-Stage Liver Disease: Presented at AASLD

By Cheryl Lathrop

BOSTON -- November 3, 2010 -- In patients with end-stage liver disease (ESLD), the C-reactive protein (CRP) level predicts short-term mortality better than, and independently of, the Model for End-Stage Liver Disease (MELD) score, researchers said here at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

This is important because the determination of patients with the highest risk of mortality is crucial to optimise the allocation of liver grafts, according to Jean-Paul Cervoni, MD, Service d'Hépatologie, CHU Jean Minjoz, Besançon, France, and colleagues.

The occurrence of systemic inflammatory response syndrome (SIRS) was reported to affect the survival of patients with ESLD, but it is not considered by the MELD score. The aim of this study was to improve the prediction of short-term mortality in patients with ESLD by evaluating CRP as a possible surrogate marker of SIRS.

This was a prospective study of 155 consecutive cirrhotic patients with a Child-Pugh score >8, admitted between January 2007 and June 2010. The median age of the patients was 58 years; 86% were male; 83% had alcoholic cirrhosis; 42% had a comorbidity; 29% had SIRS; 15.5% had hepatocellular carcinoma; the median MELD score was 22.5; the median CRP was 26.5 mg/L; and the median procalcitonin was 0.28 ng/mL.

The researchers recorded 170 demographic, clinical, biochemical, and histological variables at admission, and during follow-up on day 15, month 3, and month 6. The primary endpoint was survival at month 3.

The following key events occurred during follow-up (median 2.9 months): 41% got a bacterial infection, 7% had hepatorenal syndrome, 8% had a liver transplant, 26% died at month 3, and 30% died at month 6.

The 3-month survival according to CRP level was as follows: >100 mg/L, 0%; 70 to 100 mg/L, 59%; 40 to 70 mg/L, 64%; 10 to 40 mg/L, 75% and <10 mg/L, 87%.

Variables associated with month 3 mortality were hepatocellular carcinoma, extrahepatic carcinoma, a high MELD score, a high CRP level (>26 mg/L), elevated blood lactate, and renal failure. Variables associated with month 3 mortality were a high CRP level (>26 mg/L), the MELD score, extrahepatic comorbidities, and hepatocellular carcinoma.

Multivariate analysis identified 3 predictors of mortality: extrahepatic comorbidities (P =.021), a high CRP level (P =.013), and MELD score (P =.023). The performance of the 3 variables taken together for predicting death was 0.74 (Area Under the Receiver Operating Characteristic [AUROC]). The performance of the MELD score was 0.61 (AUROC), and the performance of the CRP level alone for the same prediction was 0.66 (AUROC) -- better than the performance of the MELD score.

"This finding suggests that we should build a new MELD-CRP prognosis score," said Dr. Cervoni on November 1.

[Presentation title: CRP Predicts Short-Term Mortality in Patients With End-Stage Liver Disease (ESLD) Independently of MELD Score: A Prospective Study. Abstract 1209]

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Caregiver Relationship Predicts Post-Transplant Anxiety

Depression, anxiety reduced after liver transplant, but improvement is attenuated by emotional distance

Publish date: Aug 12, 2010

THURSDAY, Aug. 12 (HealthDay News) -- Many patients with end-stage liver disease (ESLD) have less depression and anxiety after receiving a liver transplant, but this improvement is attenuated in individuals with emotionally distant caregiving relationships, according to research presented at the International Congress of Behavioral Medicine, held from Aug. 4 to 7 in Washington, D.C.

Anne Eshelman, Ph.D., of the Henry Ford Hospital in Detroit, and colleagues surveyed 74 patients with ESLD before liver transplant and six months' post-op, and asked their primary caregivers what degree of closeness they felt in their relationship.

The researchers found that caregivers reporting maximum closeness were in the majority (44 versus 30). Depression and anxiety decreased after transplant, but more so in the patients whose caregivers reported emotionally close relationships. Gender was a confounding variable, and further analysis suggested emotional closeness was more important for improvement in men than in women.

"For patients with ESLD, depression and anxiety decline sharply after liver transplant, but declines are attenuated for individuals with emotionally distant caregiving relationships. These findings suggest caregiving relationships as a target for psychotherapeutic intervention among patients with ESLD," the authors write.

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