November 3, 2010

Viread Fails to Control Chronic Hep B in Some HIV-Positive People

November 3, 2010

About 12 percent of HIV-positive people with chronic hepatitis B virus (HBV) infection failed to control their HBV after one year with Viread (tenofovir), combined with either Epivir (lamivudine) or Emtriva (emtricitabine). These data were presented at the American Association for the Study of Liver Diseases, which was being held October 29 to November 2 in Boston.

Viread, with or without Epivir or Emtriva, is considered a first-line treatment for chronic HBV infection. Because those drugs also control HIV, guidelines recommend that coinfected people start treatment right away—if therapy for chronic HBV is needed—and include those drugs in their regimens. Long-term data indicate these drugs are effectivedo at controlling HBV in coinfected individuals, but questions remain about how and when they are most useful.

To better explore the efficacy of Viread, researchers at King’s College Hospital in London, examined the medical records of 113 coinfected people receiving care at their clinic. The researchers found that 14 (12.4 percent) of the study participants had detectable HBV levels in their blood despite being on a Viread-containing regimen for at least 48 weeks and despite having undetectable HIV levels.

Before starting a full HIV regimen containing Viread, nine of the 14 people had taken Epivir by itself and three three had taken Viread by itself to treat their HBV. At the time they started taking a full HIV regimen, 36 percent had HBV that was resistant to both Epivir. None had detectable HBV resistance to Viread. Of the 14 who had detectable HBV levels one year after starting a Viread-containing HIV regimen, nine saw their HBV levels become undetectable after two years of treatment.

“Despite optimal adherence to [Viread] treatment, as evidenced by control of HIV, 14 [patients] failed to achieve an undetectable HBV DNA after 48 weeks of treatment,” the authors state. “In [five of] 14 patients, HBV DNA remained detectable at a low level nearly 4 years into [Viread] treatment, but no patient developed [Viread] HBV resistance.”

Though the authors hypothesize that the failure to control HBV might be due to HIV, or cumulative HBV resistance at very low levels, and that further research is warranted, they conclude: “The long-term clinical significance of low low-level HBV viremia in this population is unclear.”

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By Cheryl Lathrop

BOSTON -- November 3, 2010 -- Chronic liver disease is a risk factor for an adverse pregnancy outcome, but alcoholic liver disease increases these risks and should be considered a severe risk factor for obstetric complications, researchers said here at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

Knut Stokkeland, MD, Department of Medicine, Visby Hospital, Visby, Sweden, and colleagues reported findings from their study at a poster session here on November 1.

The researchers used the Swedish Hospital Discharge Register in Sweden (from 1969-2006) to identify women with liver disease. A total of 27,321 singleton children born of mothers hospitalised with liver disease were identified.

The Swedish Medical Birth Register (in operation since 1973) was used to identify the children. All children were then paired with 10 controls. The data registered at birth was: birth weight, preterm status, small for gestational age, stillbirth, and the Apgar score.

From these, it was determined that 720 children were born of mothers who had been hospitalised with alcoholic liver disease (ALD), and 8,595 children were born of mothers with non-alcoholic liver disease (NALD). ALD increased the risks to the pregnancy and was a severe risk factor in obstetric complications.

For ALD (n = 720), there were 5 (0.69%) stillbirths [controls 0.38%], 100 (13.9%) moderately preterm births [controls 6.2%], 10 (1.4%) very preterm births [controls 0.84%], 8 (1.1%) with an Apgar score <7 at 5 minutes after birth [controls 1.2%], and 62 (8.61%) that were small for their gestational age [controls 3.1%].

For NALD (n = 8,595), there were 35 (0.41%) stillbirths [controls 0.34%], 782 (9.1%) moderately preterm births [controls 5.3%], 123 (1.4%) very preterm births [controls 1.0%], 128 (1.52%) with an Apgar score <7 at 5 minutes after birth [controls 1.2%], and 348 (4.1%) that were small for their gestational age [controls 3.3%].

For ALD, 79.3% of the mothers smoked [controls 20.2%], 72.29% of the parents lived together [controls 95.0%], and 26.3% had a body mass index (BMI) >30 [controls 24.3%]. For NALD, 34.4% of the mothers smoked [controls 18.0%], 86.3% of the parents lived together [controls 94.6%], and 12.0% had a BMI >30 [controls 8.7%].

"Children born of women who were hospitalised with liver disease after birth were studied," Dr. Stokkeland added. "The risks were similar even for these children."

[Presentation title: Increased Risks for Obstetric Complications in Mothers With Alcoholic Liver Disease. Abstract 1204]

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Journal of Clinical Gastroenterology:
November/December 2010 - Volume 44 - Issue 10 - pp 713-719
doi: 10.1097/MCG.0b013e3181d47f71
LIVER, PANCREAS AND BILIARY TRACT: Original Articles

Papadopoulos, Nikolaos MD

Abstract

Goals: Comparison of nitric oxide (NO) levels in cirrhotic patients with and without hepatic encephalopathy (HE), evaluation of possible correlation between HE and other clinical or laboratory characteristics, and estimation of utilization of NO levels in clinical practice.

Background: HE is a neuropsychiatric complication of cirrhosis. The exact pathogenetic mechanisms underlying the presence of HE are not known. However, dysfunction of the NO pathway and ammonia detoxification are thought to play a major role.

Study: Sixty-seven cirrhotic patients, 36 (53.7%) without HE, and 31 (46.3%) with HE were included in the study. Eighteen healthy individuals were used as control group. Clinical and laboratory data, including ammonia and stable end products of NO using Griess reaction, were collected.

Results: NOx levels were statistically significantly higher in cirrhotic patients (225.5 μmol/L) than in control group [(67.94 μmol/L) (P=0.000)]. NOx levels were, also, statistically significantly higher in patients with HE compared with patients without HE (324.67 μmol/L vs. 141.96 μmol/L, P=0.000). Significant correlation between the presence of HE and NOx, ammonia, C-reactive protein, albumin, Model for End-Stage Liver Disease score, and Child-Pugh classification revealed. NOx levels also correlated with severity of HE. NOx and ammonia are independent factors predicting HE according to regression analysis. Diagnostic accuracy for the diagnosis of HE using a combination of NOx and ammonia was superior compared with standalone NOx or ammonia utilization.

Conclusions: NOx levels are correlated with the presence and severity of HE. NOx levels determination, in addition to ammonia levels, could contribute in diagnosis of HE.

Source
Gut doi:10.1136/gut.2010.214916

Paper

Yilei Mao 1, Huayu Yang 1, Haifeng Xu 1, Xin Lu 1, Xinting Sang 1, Shunda Du 1, Haitao Zhao 1, Wang Chen 1 Yiyao Xu 1, Tianyi Chi 1, Zhiying Yang 1, Jianqiang Cai 2, Hui Li 3, Jianguo Chen 4, Shouxian Zhong 1, Smruti R Mohanti 5, Reynold Lopez-Soler 5, J Michael Millis 5, Jiefu Huang 1, Hongbing Zhang 3

+ Author Affiliations

1 Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC, Chinese Academy of Medical Sciences, Beijing, China
2 Cancer Institute and Hospital, PUMC, Chinese Academy of Medical Sciences, Beijing, China
3 State Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences and School of Basic Medicine, PUMC, Chinese Academy of Medical Sciences, Beijing, China
4 Qidong Liver Cancer Institute, Jiangsu Province, China
5 Liver Transplantation and Hepatobiliary Surgery, University of Chicago, Illinois, USA

Correspondence to
Yilei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, 1# Shuaifuyuan, Dongcheng District, Beijing, 100730 China; maoy@public3.bta.net.cn, dolphinyahy@hotmail.com

Contributors YM, HY and HX contributed equally to this work.

Revised 7 June 2010
Accepted 21 June 2010
Published Online First 28 September 2010

Abstract

Background and aims Golgi protein 73 (GP73) as a potential serum marker for hepatocellular carcinoma (HCC) has not been validated in large cohort studies. Furthermore, its significance in the assessment of tumour recurrence after HCC resection remains unknown. The aim of this study was to determine the value of serum GP73 in the diagnosis of HCC.

Methods Serum GP73 and alpha-fetoprotein (AFP) were compared in a total of 4217 human subjects in this multicentre study, including 1690 healthy adults, 337 hepatitis B virus (HBV) carriers, 512 patients with cirrhosis, 789 patients with HCC, 61 patients with other malignant liver lesions, 206 patients with benign liver lesions and 622 patients with 14 different kinds of non-liver cancers. The main outcome measures were the specificity and sensitivity of GP73 in patients at risk for the development of HCC.

Results Using 8.5 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 74.6% (95% CI 71.5% to 77.6%) and 97.4% (95% CI 96.8 to 98.3%), compared with 58.2% (95% CI 55.2% to 62.1%) and 85.3% (95% CI 83.4% to 88.1%) for AFP (p<0.001) using 35 ng/ml as a cut-off value. The GP73 level was significantly increased in patients with HCC compared with healthy controls (14.7 vs 1.2, p<0.001). Although GP73 levels in HBV carriers (2.9) and patients with cirrhosis (4.7) were somewhat elevated, they were much lower than that in patients with HCC (p<0.001). GP73 decreased following surgical resection of HCC lesions and increased with tumour recurrence. Fourteen types of non-liver cancers were analysed; all the benign and other malignant liver lesions had moderate elevations of GP73, albeit at a much lower level than in HCC.

Conclusions GP73 is an accurate serum marker for the detection of HCC and its recurrence after surgery, with higher sensitivity and specificity than AFP. Clinical implementation of serum GP73 measurement as a standard test for HCC is recommended.

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Published on: 2010-11-03

Despite ongoing findings on the relationship between elevated levels of alanine and aspartate aminotransferases (ALT and AST) and metabolic syndrome (MetS), this association in diabetic patients without a known cause for liver enzymes elevation other than diabetes, per se, remains unclear. In this study, we aimed to assess the relationship between circulating liver enzymes and MetS in a relatively large sample of patients with diabetes.

Methods: A total of 670 diabetic patients, without known causes of hepatocellular injury, were enrolled.

Patients with ultrasonographic signs of fatty liver disease were not included. Fasting blood samples were obtained and biochemical characteristics were measured.

MetS was defined according to the international diabetes federation criteria.

Results: Serum ALT and AST were significantly higher in patients with MetS (p<0.001). High waist circumference and low HDL-cholesterol were significantly associated with elevated ALT (OR=2.56 and 2.0, respectively) and AST (OR=2.23 and 2.21, respectively).

ALT and AST were significantly associated with MetS (OR=2.17 and 2.31, respectively). These associations remained significant after multiple adjustments for age, sex, BMI, diabetes duration, HbA1c and medications.

There was a significant (p<0.01) positive association between the number of the MetS features and the level of ALT or AST.

Conclusion: In diabetic patients without ultrasonographic evidence of fatty liver, elevated aminotransferases are independently associated with MetS. Despite negative ultrasound results in diabetic patients with MetS, the serum level of liver aminotransferases may be elevated and should be more thoroughly monitored.

Author: Alireza EsteghamatiArsia JamaliOmid KhalilzadehSina NoshadMohammad KhaliliAli ZandiehAfsaneh MortezaManouchehr Nakhjavani

Credits/Source: Diabetology &Metabolic Syndrome 2010, 2:65

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By Cheryl Lathrop

BOSTON -- November 3, 2010 -- Low arterial partial pressure of oxygen (PaO2) is an independent risk factor of mortality in patients with liver cirrhosis, researchers said here on November 1 at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

Initiation of long-term oxygen therapy (LTOT) improves PaO2, and possibly survival, according to Valentin Fuhrmann, MD, Department of Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria, and colleagues.

Respiratory insufficiency and pulmonary complications are a frequent finding in patients with liver cirrhosis and impaired arterial oxygenation is a common consequence. Although the European Respiratory Society task force on pulmonary hepatic vascular disorders recommends initiation of LTOT in patients with PaO2 <=60 mm Hg, there is a lack of clinical data supporting this recommendation.

In light of this, the researchers decided to investigate the prevalence and prognostic impact of arterial oxygenation on 1-year transplant-free survival in patients with cirrhosis without hepatocellular carcinoma (HCC).

A total of 540 patients with liver cirrhosis (without HCC) listed for liver transplantation at the Medical University Vienna were included in the study. All patients had arterial blood gas analysis. One-year transplant-free survival was stratified according to PaO2.

The median age of patients was 53 years and 65% were male. The causes of their cirrhosis were as follows: 51% alcohol, 22% viral hepatitis, and 23% other causes. The 1-year transplant-free survival was 74%. And the mean PaO2 was 81 +- 12 mm Hg.

The researchers observed a nonlinear association between PaO2 and mortality. Patients with PaO2 <=60 mm Hg had significantly increased mortality rates compared with patients with PaO2 >60 mm Hg.

The crude mortality ratio in patients with PaO2 <=60 mm Hg was 4.24. After adjustment for Model for End-Stage Liver Disease, age, sex, and sodium, the rate ratio for mortality in patients with PaO2 <=60 mm Hg was 2.74 (P <.01).

Since PaO2 <=60 mm Hg is an independent risk factor of mortality in patients with liver cirrhosis, initiation of LTOT seems to improve PaO2 and possibly survival. "Initiation of long-term oxygen therapy seems to be rational in these patients," said Dr. Fuhrmann.

[Presentation title: Prognostic Impact of Arterial Oxygenation in Liver Cirrhosis. Abstract 1163]

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Growth Factor Drugs Bolster Compliance in Hepatitis C Therapy

By: DENISE NAPOLI, Internal Medicine News Digital Network

11/03/10
 
Having cirrhosis, diabetes, or substance use disorder increased the odds of treatment discontinuation in type 1 hepatitis C virus infection, whereas use of growth factor drugs correlated with treatment persistence, reported Dr. Lauren A. Beste and colleagues in the November issue of Clinical Gastroenterology and Hepatology.
 
The investigators looked at 11,019 patients in the VA health care system with hepatitis C genotype 1 who received at least two prescriptions for pegylated interferon and ribavirin between Jan. 1, 2002 and Dec. 31, 2007.

Patients who completed at least 80% (38.4 weeks) of the standard 48-week treatment regimen were considered to have completed treatment; overall, 5,795 patients (52.6%) reached this goal (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.07.012]).

Although "no indications currently exist for discontinuing treatment [before 12 weeks] due to lack of response," a total of 1,184 patients (roughly 10% of the total cohort) did just that, the authors said. Patients who stopped therapy before 12 weeks were significantly more likely to have cirrhosis, compared with patients who persisted with therapy (adjusted odds ratio [AOR] 1.42; P less than .01), and also were more likely to have diabetes (AOR, 1.25; P = .02) and pretreatment substance use disorder, or SUD (AOR, 1.24; P = .01).

They were also half as likely to use growth factor as were their counterparts who continued with therapy (AOR, 0.56; P less than .01). The growth factors included erythropoietin, darbepoetin, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor.

The authors also assessed patients who discontinued treatment between 12 and 24 weeks of therapy (including 317 patients with known early virologic response who discontinued despite their response). These patients were more likely to have pretreatment depression (AOR, 1.59; P less than .01), were slightly less likely to have other mental illnesses (AOR, 0.65; P = .02), and – once again – were nearly half as likely to use growth factor as were patients who persisted with the therapy (AOR, 0.64; P less than .01).

Finally, the authors looked at patients who discontinued therapy before 38.4 weeks. "No variables significantly predicted discontinuation in this time period in bivariate or multivariate analyses," wrote Dr. Beste, of the VA Puget Sound Healthcare System in Seattle, and her coauthors.

Regarding SUD as a predictor of discontinuation, the authors wrote that "patients with history of substance abuse may benefit from early support and intervention during treatment in order to continue antiviral therapy."

Of the pretreatment depression that emerged as a predictor in the 12-24 week discontinuation group, they wrote: "Prior studies report that the depressive side effects of interferon peak by week 25, which may explain the observed association between depression and discontinuation midtreatment."

And regarding the links between cirrhosis and diabetes and discontinuation, they pointed to other studies showing that these patients "may be more susceptible to treatment side-effects." However, they also speculated that blood glucose derangements in diabetic patients receiving treatment may lead to discontinuation.

Finally, Dr. Beste and her colleagues commented on the use of growth factor, which correlated with reduced risk of discontinuation both before 12 weeks and from weeks 12 to 24. They speculated that growth factor use "leads to improvement in low blood counts, allowing providers to continue treatment when otherwise it would be stopped."

Therefore, "appropriate use of growth factors should be prospectively evaluated as a modifiable means to prevent treatment discontinuation," they recommended.

Dr. Beste and her colleagues had no relevant financial disclosures. The study was supported by the Department of Veterans Affairs and the Northwest Hepatitis C Resource Center.

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Hepatologist Arrested for Insider Trading

By Kristina Fiore , Staff Writer, MedPage Today

Published: November 03, 2010

BOSTON -- French physician Yves Benhamou has been arrested and charged with securities fraud after allegedly providing a hedge fund with information about adverse events in a drug trial for which he was an adviser.

The information about the investigational hepatitis C drug Albuferon allowed FrontPoint Partners to avoid losses of $30 million, according to the U.S. Attorney's office in Manhattan.

Benhamou, of Groupe Hospitalier Pitie Salpetriere in Paris, was attending the American Association for the Study of Liver Diseases meeting here when he was arrested on Monday by FBI agents. The agency would not comment about the exact location of the arrest.

The conference took place at the Hynes Convention Center.

A spokesperson for the U.S. Attorney for the Southern District of New York told MedPage Today that Benhamou appeared before a judge in Boston federal court on Tuesday afternoon, where he consented to detention with the right to contest.

He is being transported to New York for arraignment.

In the complaint, Benhamou is charged with one count of conspiracy to commit securities fraud and one count of securities fraud. The conspiracy charge carries a maximum sentence of five years in prison and the fraud charge carries a maximum of 20 years.

Benhamou allegedly conspired with a portfolio manager for FrontPoint Partners -- formerly a Morgan Stanley company -- whom several reports have identified as Chip Skowron, MD, PhD, a board member of AmeriCares, the nonprofit humanitarian aid organization.

In exchange for a "stream of payments," Benhamou allegedly supplied information about a fatality and a case of lung disease that occurred in Albuferon trials being conducted by drugmaker Human Genome Sciences of Rockville, Md.

FrontPoint Partners then allegedly sold more than six million shares of Human Genome Sciences before the disclosure about the adverse events was made public.

The complaint charges that Benhamou also consulted with other hedge funds and investors who purchased and sold securities in the healthcare sector, and the U.S. Attorney's office told MedPage Today that the investigation is ongoing.

At the AASLD meeting, Benhamou presented research on several drugs being developed by a number of companies, including Boehringer Ingelheim and Tibotec.

Several of the co-authors on those presentations did not return requests for comment, nor did the pharmaceutical companies.

A spokesperson for Human Genome Sciences told MedPage Today that the company is fully cooperating with the investigation, and that Benhamou is no longer a consultant for the company.

In a statement, Manhattan U.S. Attorney Preet Bharara said Benhamou allegedly "abused his position as a medical doctor."

"By profiting from his sensitive position and providing the hedge fund an unfair advantage," he added, "Benhamou undermined the integrity of the securities market and sold out his employer."

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By Cheryl Lathrop

BOSTON -- November 3, 2010 -- The prognostic value of previously proposed stages for cirrhosis of the liver should be carefully updated, researchers said here at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

The results of a study show that the survival of patients with stage 4 cirrhosis appears to be largely underestimated.

Savino Bruno, MD, Ospedale Fatebenefratelli, Milan, Italy, and colleagues reported findings from the Italian Association for the Study of the Liver (Associazione Italiana per lo Studio del Fegato [AISF])-EPASCO study during a poster session here on November 1.

Based on a previous systematic review, a staging classification of the prognosis for patients with cirrhosis of the liver has been proposed. In particular, stage 3 (ascites +- oesophageal varices) and stage 4 (portal hypertensive gastrointestinal bleeding +- ascites) were reported being associated with a cumulative 1-year mortality rate of 20% and 57%, respectively.

The AISF-EPASCO is a prospective 3-year follow-up study that assessed both the mortality rate (at 1 and 3 years) and predictors associated with poor outcome of patients with cirrhosis since the first episode of decompensation.

Between March 2006 and October 2007, consecutive cirrhotic patients admitted for the first episode of clinical decompensation (ascites, spontaneous bacterial peritonitis, hepato-renal syndrome, jaundice, gastrointestinal bleeding, porto-systemic encephalopathy) in 29 Italian referral centres were registered in a pre-established, electronic case report form database. Patients with previous or concurrent diagnosis of hepatocellular carcinoma were excluded. All patients were treated according to current international guidelines.

A total of 417 patients were analysed. There were 346 stage 3 patients and 71 stage 4 patients.

The researchers confirmed the rate of 1-year mortality in stage 3 cirrhosis, but survival of patients in stage 4 formerly reported appeared to be largely underestimated. One-year liver-related mortality was 18.0% for stage 3 (previously found to be 20%) and 5.9% (previously found to be 57%) for stage 4. In patients with stage 4 cirrhosis, the presence of ascites did not affect survival.

"The prognostic value of previously proposed stages should be carefully updated," said Dr. Bruno.

[Presentation title: Low Rate of Mortality in Patients With Stage 4 Cirrhosis: The Need of a Reassessment of an Old Classification. The A.I.S.F.-EPASCO Prospective Multicentre Study. Abstract 1160]

Source
Nancy A. Melville

November 3, 2010 (San Antonio, Texas) — Researchers say they have identified a genetic polymorphism in the promoter region of interferon alpha/beta receptor 1 (IFNAR1), which increases the risk for major depression in patients with hepatitis C virus (HCV) being treated with pegylated interferon and ribavirin.

The study involved 170 treatment-naive patients with HCV infection who were genotyped for polymorphism –408 in the promoter regions of IFNAR1 (C/C C/T T/T) and treated with pegylated interferon and ribavirin. The results indicate that those carrying the C/C allele had a greater risk of developing major depression, but also had an increased likelihood of HCV viral clearance.

Previous research has shown that as much as 20% to 30% of hepatitis C patients receiving antiviral treatment experience major depression, which can result in dose reductions and a shorter duration of treatment. The need to identify patients at risk is therefore exceptionally pressing, according to the study's lead author, Muhamad Aly Rifai, MD, from the Lehigh Valley Health Network in Bethlehem, Pennsylvania.

"The identification of patients with this polymorphism may be useful in helping us determine who is at a greater risk of depression and tailor preventive treatment strategies to prevent discontinuation or adverse effects during their treatment," Dr. Rifai told attendees here at the American College of Gastroenterology 2010 Annual Scientific Meeting and Postgraduate Course.

In addition to genotyping, patients were assessed using the Center for Epidemiological Studies Depression Scale. Patients completed visual analog self-report questionnaires before HCV antiviral treatment, and at weeks 0, 2, 4, 6, 8, 12, 16, 20, and 24 of treatment. Kaplan–Meier analyses were used to compare the incidence of major depression between different genetic profiles.

As is consistent with previous research, the results indicated that 28% of patients receiving the antiviral treatment developed major depression (47 of 170).

According to the Mantel–Cox rank test, the C/C allele was associated with an increased rate of developing major depression (P < .05) and an increased rate of HCV viral clearance (P = .0081).

Dr. Rifai noted that previous research has also suggested an improved HCV clearance rate with the C/C allele. "There have been multiple reports from Japanese researchers that this allele is associated with an improved likelihood of HCV viral clearance; however, the numbers were low."

The C/T and T/T alleles, meanwhile, appeared protective regarding the risk of developing major depression (P = .012).

The differences in the genetic groups were significant in a Cox regression analysis that was adjusted for age, sex, response to interferon alpha treatment, viral genotype, and previous psychiatric history (χ2, 8.02; df, 1; P = .005).

"The findings suggest that incorporating genomic predictors in a treatment strategy may help guide the process of determining whether or not to initiate antiviral treatment in patients with hepatitis C," Dr. Rifai said.

The risk of depression among hepatitis C patients using antiviral medications represents a substantial concern for physicians, and the findings could represent valuable information to help address that concern, said session moderator Paul Pockros, MD, head of the Division of Gastroenterology/Hepatology and director of the Scripps Clinic Liver Research Consortium at The Scripps Clinic in La Jolla, California.

"The presentation was provocative because treatment-related depression is extremely common and is probably the single biggest reason patients fear [pegylated interferon and ribavirin] therapy and are poorly adherent to treatment," said Dr. Pockros.

"If this test were validated, it would offer another genomic pretreatment test that would be useful, just as [interleukin] 28B testing, and likely ITPA deficiency testing, will be."

The study received no funding. Dr. Rifai has disclosed no relevant financial relationships. Dr. Pockros reports being a consultant, speaker, and/or on the advisory board for Genentech, Vertex, Merck, Gilead, BMS, Abbott, Phenomix, Tibotec, Pharmasset, Pfizer, Conatus, 3RT, Novartis, J&J, Achillion, and Regulus; and receiving grants or contracts from Genentech, Vertex, Gilead, BMS, Abbott, Quest, Conatus, Tibotec, Pfizer, Globeimmune, Debio, Novartis, and Mochida.

American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Abstract 32. Presented October 19, 2010.

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IMC - Immuron Presents Clinical Data at Liver Conference

Highlights:

· Data accepted by peer review
· Successful clinical data from Phase 1/II trial published
· Focus on a potential treatment for unmet medical need

3 November 2010, Melbourne and Sydney Australia: Immuron (ASX: IMC) has presented posters detailing its recent results on the treatment of the liver disease non-alcoholic steatohepatitis (NASH) and aspects of metabolic syndrome at the American Association for the Study of Liver Disease (AASLD) 2010 annual conference currently being convened in Boston.

The AASLD annual conference is the most important conference relating to liver disease and is attended by the world’s key opinion leaders, clinicians, scientists and pharmaceutical companies involved in liver diseases. Immuron is delighted to be able to present its clinical trial results at the meeting.

The posters report on Immuron’s recent successful results in a Phase I/II clinical trial of its hyperimmune bovine colostrum product IMM 124E for the treatment of NASH and aspects of metabolic syndrome (announced 24 August 2010) and earlier animal studies.

This clinical trial completed recently at the Hadassah Hebrew University Medical Center has successfully shown that oral administration of IMM 124E is safe and effective, and exerts an immunomodulatory effect in patients with insulin resistance/type 2 diabetes, hyperlipidemia and NASH. All primary and secondary endpoints were successfully achieved with improvements observed across all clinical parameters. The product was well tolerated and no drug related adverse events were recorded during the clinical trial. Details of the results are set out in the table below.

The primary endpoint of an improvement in liver enzyme levels (AST, ALT, AP and GGT) was attained.

The secondary endpoints of improvement in levels of insulin resistance and lipid levels were measured using the HBA1C test, and Oral Glucose Tolerance Test (OGTT), and lipid tests. The majority of patients improved in measures of insulin resistance.

Further physiological markers of the metabolic syndrome were tested (GLP-1 and Adiponectin levels). There was improvement in these markers as well.

In addition to these results, seventy percent of patients showed a significant increase in regulatory T cell measurements.

Currently, there is no approved or effective treatment for the chronic liver disease NASH. The treatment of NASH is a significant unmet medical need. With incidence rising, treatment of NASH represents a large and growing market currently estimated to be worth multiple billions of dollars.

Immuron’s Chief Executive Officer, Dr Grant Rawlin, said “Our recent clinical trial demonstrated that we have a serious product candidate for the treatment of NASH, one of the most common liver diseases in the western world. We are delighted to have the opportunity to share our findings at one of the most prestigious liver disease conferences in the world.”

Abstracts of the posters have been published in the journal Hepatology and can be accessed from Immuron’s website.

Mizrahi M, Lalazar G, Shabat Y, Adar T, Ben Ya'acov A, Ilan Y. Alleviation of insulin resistance and liver damage by oral administration of ETEC colostrums is mediated by increased GLP-1, adiponectin serum levels and Tregs: Results of a phase I/II clinical trial in NASH. Hepatology, 52:163A, 2010.

Adar T, Lichtenstein Y, Lalazar G, Mizrahi M, Zolotarov L, Ben Ya'acov A, Ilan Y. Induction of CD4+CD25+FOXP3+ regulatory T cells by oral administration of IgG enhanced colostrums suppressed the chronic inflammatory state in OB/OB mice alleviating the insulin resistance and liver injury. Hepatology, 52:262A, 2010.

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AASLD: Long-Term Outcomes Better With SVR

By Kristina Fiore , Staff Writer, MedPage Today
Published: November 03, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine
 
BOSTON -- Achieving sustained virologic response after treatment for hepatitis C is a boon to patients even 20 years down the road, researchers said here.
 
In a cohort of patients who started treatment at the National Institutes of Health in 1984, none who achieved sustained response developed hepatocellular carcinoma, and all had improved measures of liver function in the long run, Chester Koh, MD, of the National Institute for Diabetes and Digestive and Kidney Diseases, and colleagues.

"Relapse was uncommon, there were no deaths due to liver disease, and no occurrences of hepatocellular carcinoma," Koh reported during an oral presentation at the American Association for the Study of Liver Diseases (AASLD) meeting here.
 
The short-term benefits of a sustained virologic response after therapy are established, but the long-term benefits are less defined. The goals, however, are clear -- prevent liver-related disability or early death.
 
To assess long-term changes in markers of disease activity and fibrosis, the researchers assessed a total of the first 103 patients to achieve sustained virologic response after being treated at the NIH using interferon alfa-2b or peginterferon, both with or without ribavirin.

They compared serum markers of hepatic inflammation, function, and fibrosis before treatment and at the patient's last visit.

Also, any patient seen since 2007 also had a transient elastography to assess liver composition.

Only three of the patients relapsed -- at 0.7, 6.4, and 6.5 years after therapy -- making for a 10-year relapse rate of 5.7%. The remaining 97% of patients maintained a virological response.

Of those 100 patients, 56 were men. There were 88 whites, four African-Americans, and eight Asians.

About 45% had genotype 1 virus; 53% had type 2 and 3 disease.

The researchers found that no patients died of liver-related causes during the 22-year study period, nor were there any cases of hepatic decompensation or hepatocellular carcinoma.

Koh said that the literature shows that these patients may still be susceptible to hepatocellular carcinoma, "but the rates are still low."

Noninvasive markers of liver disease all improved over time, Koh said, including changes in mean alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphotase (ALP), globulin, IgG, alpha fetoprotein, GGT, rheumatoid factor, platelet count, and AST-platelet ratio index (P<0.001 for all).

Among the 75 patients who had elastography, 60% had normal interpretations, 31% had moderately elevated histology, and 9% had tissue in the cirrhotic range, Koh reported.

He said elastography readings, but not serum markers at the time of last follow-up, correlated with pre-treatment liver fibrosis (P<0.001).

Among the seven patients who had cirrhosis before starting therapy, six had an abnormal elastography at follow up.

Koh said that despite long-term sustained virologic response, those with pre-existing cirrhosis still have evidence of hepatic fibrosis.

Arun Sanyal, MD, of Virginia Commonwealth University and president of AASLD, said the findings imply that once patients achieve a sustained response, it "is durable and extends survival."

"We now have data that strongly indicate hepatitis C is a curable disease," he said, referring also to new drugs in development.

Still, in this particular study, he noted that a similar analysis will need to be continued to determine the effects of those newer drugs and newer regimens.

Koh reported no conflicts of interest.

Primary source: American Association for the Study of Liver Diseases

Source reference:
Koh C, et al "Clinical, virological, biochemical outcomes after 20 years of sustained virological response (SVR) in chronic hepatitis C: The NIH experience" AASLD 2010; Abstract 228.

Source