MAY 19-22, 2002, SAN FRANCISCO

CHRONIC HEPATITIS C
Preliminary results of peginterferon alfa-2b (PEG-IFN) and ribavirin in nonresponders and relapsers. Ira Jacobson and colleagues are conducting a study in which patients with chronic hepatitis C virus (HCV) infection who had either not responded or relapsed after prior interferon (IFN) monotherapy or combination therapy were randomized to receive PEG-IFN 1.0 ug/kg/wk plus ribavirin 1000 -1200 mg/d (Group 1) or PEG-IFN 1.5 ug/kg/wk plus ribavirin 800 mg/d (Group 2). At the time of this report, 231 patients had completed 24 weeks of treatment. Preliminary results demonstrate high viral response rates for patients who had relapsed after combination therapy (88%) or had not responded to prior IFN monotherapy (55%). There is a trend for Group 2 patients to achieve higher viral response rates than Group 1 patients. (Abstract 79). In another study, Eric Lawitz et al. randomized patients who had not responded to prior IFN monotherapy (n=122) or combination therapy (n=501) and patients who had relapsed after combination treatment (n=130) to receive either “induction” therapy (PEG-IFN 1.5 ug/kg/wk plus ribavirin 1000-1200 mg/d for 12 weeks followed by PEG-IFN 1.0 ug/kg/wk plus ribavirin 800 mg/d for 36 weeks) or fixed dose therapy (PEG-IFN 1.0 ug/kg/wk plus ribavirin 800 mg/d for 48 weeks). For those patients who had completed 24 weeks of study therapy at the time of this report, no differences in viral response rates were seen between the induction and fixed dose treatment groups for the monotherapy nonresponders (52% vs. 32%), combination nonresponders (33% vs. 26%), or combination relapsers (76% vs.71%). (Abstract 80)

HCV patients with normal alanine aminotransferase (ALT) levels. Most antiviral studies have excluded HCV patients with normal ALT levels. Ira Jacobson and The New York Normal ALT Study Group report final results from a trial that evaluated 2 doses of IFN combined with ribavirin in patients with chronic HCV infection and normal ALT levels. Patients were randomized to receive 24 weeks of either IFN 3 MU tiw plus ribavirin 1000 -1200 mg/d (Group 1; n=29) or IFN 5 MU tiw plus ribavirin 1000 -1200 mg/d (Group 2; n=27). The sustained response (SR) rate 24 weeks after cessation of therapy for Group 1 vs. Group 2 patients (24% vs. 37%) was not different (p=NS). In the subgroup of patients with genotype 1 HCV, there was a trend towards a higher SR rate in Group 2 vs. Groups 1 patients (37% vs. 10%; p=0.07). No patient developed sustained ALT elevations with study therapy. These results show that SR rates for HCV patients with normal ALT levels are somewhat lower than those historically achieved for HCV patients with elevated ALT levels and that genotype 1 HCV patients may benefit from a higher dose of IFN. (Abstract 82)

IFN and ribavirin therapy following liver transplantation (LT). Recurrence of HCV following LT is universal. Rajender Reddy and coworkers randomized 32 HCV patients to receive either IFN 1.5 MU tiw escalating to 3 MU tiw plus ribavirin 400 mg/d escalating to 1000 mg/d or placebo for 48 weeks. Study treatment was started 14 to 28 days after LT. At 24 weeks of post-treatment follow-up, 3 (16%) of 21 IFN/ribavirin patients vs. no placebo patients were HCV RNA negative (p=NS). No differences in mean Knodell score or HCV RNA levels were found between treatment groups. Better treatments are needed. (Abstract 199)

Long-term follow-up of patients with HCV-related cirrhosis. Angelo Sangiovanni and colleagues followed a cohort of 154 patients with compensated Child’s class A HCV-related cirrhosis at baseline for a median of 113 mo (range, 1-170 mo). Hepatocellular carcinoma (HCC) developed in 48 patients (31%) and 21 patients died of tumor progression. Other causes of death were gastroesophageal bleeding (n=5), liver impairment (n=6), extrahepatic neoplasia (n=6), post-liver transplantation (n=1), liver unrelated causes (n=2), and unknown causes (n=3). Although cirrhosis remained Child’s class A in 115 (75%) patients, ascites developed in 39 (25%) patients, jaundice in 21 (14%) patients, and gastrointestinal bleeding in 15 (10%) patients. Patients with compensated HCV-related cirrhosis have poor clinical outcomes and HCC is the most common cause of death. (Abstract 214)

CHRONIC HEPATITIS B

Natural history of chronic asymptomatic HBV infection. Mauro Manno and associates report a 30-yr follow-up of 296 blood donors found to be HBsAg (+), compared with 157 HBsAg (-) controls. After 30 years, the mortality rate was 10% for the HBsAg (+) donors and 9% for the HBsAg (-) donors. In the study group, 67% of the donors remained HBsAg (+), 42% tested HBV DNA (+) by PCR, and 22% developed anti-HBs. Survival of asymptomatic HBV carriers is similar to that of the general population. (Abstract 85)

HBV genotypes. HBV genotype may have clinical implications, but there are little data concerning the prevalence of HBV genotypes in the US. Chi-Jen Chu and colleagues reviewed data from 468 consecutive patients with chronic HBV infection seen in 17 US liver centers (patients receiving antiviral therapy and patients with recurrent HBV post-liver transplantation were excluded). The median age of this patient population was 43 years and 56% of the patients were Asian (A), 27% were White (W), 10% were African American (AA), and 17% were other. HBV DNA was detected in 99% of HBeAg (+) patients and in 70% of HBeAg (-) patients. The percentages of HBV genotypes were as follows: A (33%), B (21%), C (34%), D (9%), E (1%), F (1%), and G (1%). Genotypes A and C were associated with a higher prevalence of HBeAg compared to genotypes B and D (p<0.001). Genotype D patients were most likely to have decompensated cirrhosis. The precore (PC) variant was most common in genotype D patients, while the core promoter (CP) variant was most commonly found genotypes C and D. These data demonstrate a strong correlation between HBV genotype and severity of liver disease, prevalence of HBeAg, and prevalence of PC and CP variants. (Abstract 86)

PRIMARY BILIARY CIRRHOSIS (PBC)

Ursodeoxycholic acid (UDCA) decreases recurrence of colorectal adenomas. Lawrence Serfaty et al. conducted a study in which 114 PBC patients were enrolled in a colonoscopic surveillance program. The first colonoscopic examination occurred prior to UDCA therapy in 62 patients (untreated group) and after therapy in 52 patients (treated group). The prevalence of adenomas at the first colonoscopy was 13% vs. 24% in the treated vs. untreated group (p=0.16). Adenomas > 5 mm were seen less frequently in the treated group (14% vs. 67%; p=0.02). The adenoma recurrence rate after 3 years of follow-up was 7% in the treated vs. 28% in the untreated group (p=0.04). UDCA-treated PBC patients had smaller adenomas and a lower adenoma recurrence rate. (Abstract 610)

NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)

Clinical survey results. Harpreet Gujral and colleagues report a survey of practicing hepatologists in the US about the role of liver biopsy in NAFLD. Thirty-nine responded: 82% considered NAFLD to be a potentially progressive disease, and 94% and 97%, respectively, indicated that biopsy is important for establishing the diagnosis and prognosis. However, only 7% of respondents thought a liver biopsy should be performed in patients with radiologic evidence of fatty liver and normal serum aminotransferase levels. Fifty-six percent of physicians recommended biopsy for NAFLD patients with persistently elevated aminotransferase levels, and 46% would perform a liver biopsy in patients with NAFLD not responding biochemically to weight loss. (Abstract 212)

Association with hepatocellular carcinoma (HCC). Jorge Marrero and coworkers analyzed information obtained from a prospective database of all HCC patients seen at a single-center liver clinic. At the time of this report, 104 HCC patients had been enrolled into the database. Their underlying liver diseases were as follows: HCV (51%); cryptogenic liver disease (CLD) (25%); alcoholic liver disease (10%); HBV (6%); PBC/AIH/hemochromatosis (4%), other (4%). Of the 25 patients with CLD, 15 patients had features suggestive of NAFLD. NAFLD may be the underlying liver disease in approximately 15% of patients with HCC; thus patients with cirrhosis due to NAFLD should be considered for tumor surveillance programs. (Abstract 218)

Hemochromatosis

Interim report of the Hemochromatosis and Iron Overload Screening Study (HEIRS). Paul Adams and colleagues report results from the dataset created from the first 20,130 participants enrolled into HEIRS. The female to male ratio is 1.77:1, and 50% of the subjects are Caucasian, 24% African American, 12% Asian, 11% Hispanic, and 2% other or unidentified. Fifty-nine of 62 C282Y homozygotes were in the Caucasian subgroup, resulting in a C282Y +/+ prevalence of 1 in 169 in Caucasians (1 in 322 overall). The screening transferrin saturation and ferritin level were elevated in 50% of C282Y +/+ subjects, 10.5% of C282Y/H63D subjects, 4.8% of H63D +/+ subjects, 2.6% of C282Y +/- subjects, and 1.9% of H63D +/- subjects. (Abstract 215)

Characteristics of patients with iron overload. Mark Mallory et al. analyzed the clinical characteristics of 186 consecutive patients referred to a single-center iron overload clinic. Eighty patients (43%) met the criteria for hemochromatosis (56 C282Y +/+, 18 C282Y/H63D, 6 other). The remaining 106 patients had secondary iron overload. The most common causes of secondary iron overload were NASH (19%), HCV (16%), and alcohol abuse (11%). Hemochromatosis patients, compared to those with secondary iron overload, more often had diabetes mellitus, hypogonadism, skin bronzing, arthritis, and decreased libido. (Abstract W1116)

HEPATOCELLULAR CARCINOMA

Treatment of HCC in patients with HCV. Sasan Roayaie and associates performed a retrospective review of clinical information concerning 229 consecutive patients with HCV and HCC who underwent hepatic resection or LT at a single institution. Hepatic resection patients had Child’s A cirrhosis, a platelet count >100,000/ul, and a technically resectable tumor. Unresectable patients were considered for LT. Sixty-three patients were treated with a hepatic resection (5 patients subsequently had LT) and 166 patients underwent LT. Although the 5-year disease-free survival rate was greater for the transplant patients compared to the resection patients (51% vs. 27%; p=0.0001), there was no difference in the 5-year survival rates (55% vs. 53%). Multivariate analysis revealed only primary tumor size to be an independent prognostic factor for disease-free survival. Hepatic resection in patients with adequate liver function yields survival results similar to those with LT. (Abstract 221)

Screening of patients with HCV-related cirrhosis for HCC. Derek Patel and coworkers utilized a Markov model that reflected the natural history of HCV-related cirrhosis to construct a decision analysis schema for screening for HCC. Screening procedures (ultrasound and AFP) followed by cadaveric LT, living donor LT, or hepatic resections were compared to no intervention. HCC screening was cost-effective and was most effective when followed by living donor LT. (Abstract 222)

Cirrhosis

Colchicine treatment of alcoholic cirrhosis. Timothy Morgan and the Department of Veterans Affairs Cooperative Studies Program conducted a study in which 549 patients with alcoholic cirrhosis (Child’s score >6) were randomized to receive colchicine 0.6 mg bid for 24 to 72 months or placebo. No differences in mortality rates from all causes or from liver disease were observed between the two treatment groups. This study demonstrated that colchicine therapy did not improve survival in patients with alcoholic cirrhosis. (Abstract 342)

Hepatology Watch is produced through educational grants from and

Hepatology Watch is a registered trademark of Market Development Group

Back to Issues Archive