A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum α-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP.

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.

Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy.

We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre-donation (baseline); 8 were retested at a mean ± SD of 11±3 days after donation (T1), 10 were retested at a mean of 91±9 days after donation (T2), and 10 were retested at a mean of 185±17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single-photon emission computed tomography (SPECT).

Very low viral load (VLVL) relapse following treatment of naïve patients with chronic hepatitis C.

Background: Sustained virologic response (SVR) to treatment of naïve patients with chronic hepatitis C (HCV) with pegylated interferon and ribavirin is 50-60%. Patients who relapse have a poor response to re-treatment. We report a group of relapse patients with SVR to low-dose re-treatment after 6 months.

Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial.

Unlabelled: Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred and twenty-seven participants in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.

Frequency of elevated hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C.

Objectives: Prospective studies of serum hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C are lacking. The aim of this study was to determine the frequencies and performance of elevated α-fetoprotein (AFP), AFP-L3, and des-γ-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C.

Methods: Patients in the HALT-C Trial were tested every 3 months for 42 months.

Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT-C Trial.

Background & Aims: The gradual accumulation of hepatic fibrosis in chronic liver disease results in clinical complications. The rate of hepatic fibrosis score progression (RFSP) in predicting clinical outcomes was assessed by extending the 4-year Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial to include preenrollment liver biopsies.

Methods: The RFSP was calculated from the linear regression slope of Ishak fibrosis score vs time in 457 patients with liver biopsies (≥10-mm length) prior to the HALT-C Trial (575 biopsies) plus 1101 on-study biopsies (total 1676 biopsies).

Prognostic value of Ishak fibrosis stage: findings from the hepatitis C antiviral long-term treatment against cirrhosis trial.

Unlabelled: Studies of the prognostic value of Ishak fibrosis stage are lacking. We used multi-year follow-up of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C. Baseline liver biopsy specimens from 1050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists.

Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma.

Background & Aims: The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. The aim of this study was to compare the accuracy of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the early diagnosis of HCC.

Methods: Among 1031 patients randomized in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial, a nested case-control study of 39 HCC cases (24 early stage) and 77 matched controls was conducted to compare the performance of AFP and DCP.

Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial.

Background & Aims: The Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis, and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine whether suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes.

Methods: Seven hundred sixty-four patients treated during the lead-in phase of HALT-C trial were randomized to either peginterferon alfa-2a (90 microg/week) maintenance therapy or no treatment (control) for 3.

Coffee intake is associated with lower rates of liver disease progression in chronic hepatitis C.

Unlabelled: Higher coffee consumption has been associated inversely with the incidence of chronic liver disease in population studies. We examined the relationship of coffee consumption with liver disease progression in individuals with advanced hepatitis C-related liver disease. Baseline coffee and tea intake were assessed in 766 participants of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C-related bridging fibrosis or cirrhosis on liver biopsy and failed to achieve a sustained virological response to peginterferon plus ribavirin treatment.

Evolution of hepatic steatosis in patients with advanced hepatitis C: results from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial.

Unlabelled: Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin.

Noninvasive evaluation of liver disease severity.

In assessing the severity of chronic liver disease, one measures either the fibrotic structure of the liver or liver function. This article reviews the methods for evaluating the severity of liver disease noninvasively by estimating function or structure.

Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial.

In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based therapy. In this study, we assessed virologic response to retreatment with peginterferon alfa-2a and ribavirin (RBV), as a function of the baseline fibrosis score (Ishak staging) and platelet count, in 1,046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All patients had failed prior treatment with IFN or peginterferon +/- RBV and had Ishak fibrosis scores > or = 3.

Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C.

Background & Aims: Iron overload may cause or contribute to hepatic injury and fibrosis. Mutations in the HFE gene may influence development or progression of chronic liver disease by increasing iron stores or modulating immune responses. The aim of this work was to assess the influence of HFE mutations and serum and hepatic measures of iron status on baseline features and response to lead-in therapy in subjects with advanced chronic hepatitis C enrolled in the Hepatitis C Anti-viral Long-term Treatment to prevent Cirrhosis (HALT-C) Trial.

Factors affecting the quantitative liver-spleen scan in normal individuals.

The quantitative liver-spleen scan (QLSS) can estimate the functional hepatic mass and the organ volumes by precise measurement of sulfur colloid (SC) distribution. The normal range determined in prior studies was estimated from patients with absence of chronic liver disease in which intense fasting appeared to produce slightly abnormal values. This study was to determine the effect of fasting or fed status and colloid particle size on quantitative measurements from the QLSS in a small cohort of normal individuals.

Precore mutant hepatitis B reactivation after treatment with CHOP-rituximab.

A patient with stage IV non-Hodgkin's lymphoma and chronic hepatitis who was treated with chemotherapy and rituximab developed fatal reactivation of hepatitis B. High viral load titers of hepatitis B DNA were demonstrated. DNA sequencing analysis revealed the presence of the precore mutant strain.