HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians
JULY 1998
SERUM ALT
Rate of fibrosis in HCV patients. Dr. Philippe Mathurin and colleagues studied hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection and persistently normal serum alanine aminotransferase (ALT) levels. These patients were compared with chronic HCV patients with elevated serum ALT levels matched for independent factors associated with fibrosis. Liver biopsy was performed in 67 normal ALT patients and 101 patients with elevated ALT. Normal ALT patients had a lower stage of fibrosis (P < 0.001) and a slower median rate of progression of fibrosis (P < 0.001). The authors conclude that the natural history of chronic HCV infection in patients with persistently normal serum ALT levels is associated with a lower risk of developing severe liver disease. (Mathurin P, et al. Hepatology 1998; 27: 868-872)
Serum alanine aminotransferase activity. Dr. Annie Piton and colleagues examined factors associated with serum alanine aminotransferase (ALT) activity in 1,033 healthy blood donors. Multivariate regression analyses showed that body mass index (BMI) and male sex were independently associated with the serum ALT concentration (P< 0.0001). Depending on the definition of upper limits of normal, the prevalence of subjects with a normal ALT serum level varied by 14% for blood donors, 11% for hepatitis C patients prior to interferon therapy, and 17% for hepatitis C patients after interferon therapy. The authors conclude that the normal serum ALT range should be adjusted for sex and BMI so that a common population can be more precisely defined for blood donor selection and hepatitis C clinical studies. (Piton A, et al. Hepatology 1998; 27: 1213-1219).
CHRONIC VIRAL HEPATITIS AND HEPATOCELLULAR CARCINOMA
Risk factors for hepatocellular carcinoma. Dr. Akinori Kasahara and his coworkers in The Osaka Liver Disease Study Group identified risk factors for hepatocellular carcinoma (HCC) in 1,022 patients with chronic hepatitis C virus (HCV) infection followed for a median of 36 months (range, 13-97 months) after interferon therapy. The analysis was derived from six trials that investigated various interferons (alfa-2a, alfa-2b, natural alfa, and beta) administered by different treatment schedules. The following risk factors were associated with an increased incidence of HCC: 1) a persistent elevation of serum alanine aminotransferase level (no response) despite interferon therapy (P=0.008), 2) age ³ 55 years (P=0.006), and 3) the male sex (P=0.02). HCV subtype was not found to be a risk factor and the degree of hepatic fibrosis was of borderline significance as a risk factor (P=0.052). (Kasahara A, et al. Hepatology 1998; 27: 1394-1402)
Progression to hepatocellular carcinoma. A retrospective analysis assessing the effect of interferon-µ therapy on the risk of progression to hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis and cirrhosis was recently reported by the International Interferon-a Hepatocellular Carcinoma Study Group. Patients enrolled in this multicenter study were positive for HBsAg or anti-HCV antibodies, had histological evidence of chronic hepatitis and cirrhosis, and had been screened for HCC yearly for at least 3 years from the diagnosis of cirrhosis. Patients in the interferon arm had received ³ 3MU of interferon-a 3 x weekly for ³ 3 months. HCC developed in 66 of 356 (19%) of untreated patients and in 29 of 281 (10%) of interferon treated patients (relative risk 1.99: 95% CI 1.09-3.64 [P=0.027]). The risk reduction for the interferon treated patients was observed to be greater for chronic hepatitis C patients than for those with chronic hepatitis B. The authors concluded that interferon therapy lowers the rate of progression to HCC in patients with chronic viral hepatitis. (Lancet 1998; 351: 1535-1539)
AUTOANTIBODIES AND PRIMARY BILIARY CIRRHOSIS
Retroviral antibodies in primary biliary cirrhosis. Dr. Andrew Mason and colleagues performed analyses for HIV-1 and the human intracisternal A-type particle (HIAP) on serum samples from patients with primary biliary cirrhosis (PBC; n=77), other chronic liver diseases (CLD; n=126), systemic lupus erythematosus (SLE; n=48), and healthy volunteers (n=25) to investigate the role of retroviruses in the development of PBC. Seroreactivity to HIV-1 and HIAP proteins was found in few healthy volunteers (4% and 4%, respectively) and in few patients with alcohol-related CLD (4% and 0%, respectively). In contrast, the sera of 35% and 51% of PBC patients reacted to HIV-1 (P=0.003) and HIAP proteins (P<0.0001). Similar seroreactivity results to that of the PBC patients were observed for patients with SLE, a known autoimmune disorder. The authors conclude that the retroviral antibody reactivity found in PBC patients is due to either an autoimmune or to an immune response to viral proteins that share antigenic determinants with the retroviruses. (Mason AL, et al. Lancet 1998; 351: 1620-1624)
Antinuclear autoantibodies in primary biliary cirrhosis. Dr. Birgit Luettig and coworkers studied the sera of 42 primary biliary cirrhosis (PBC) patients for the presence of antinuclear autoantibodies (ANA) prior to and after liver transplantation. Forty-three percent of these patients were found to be ANA positive prior to liver transplantation. Although the ANA titers fell, none of the ANA positive patients became ANA negative following liver transplantation. In contrast, sera from patients with autoimmune hepatitis, inflammatory bowel disease, connective tissue diseases, hepatitis C virus inflection, and primary sclerosing cholangitis were ANA negative. The authors conclude that the ANAs are disease-specific for PBC and persist despite the absence of the original target organ. (Luettig B, et al. Journal of Hepatology 1998; 28: 824-828).
INTERFERON THERAPY
Treatment of HCV RNA carriers. Dr. Angelo Sangiovanni and co-workers recently performed a study in which 31 previously untreated patients with detectable serum HCV RNA, persistently normal serum ALT levels, and histological evidence of chronic hepatitis were randomized to receive interferon-a-2a at a dose of 3 MU three times a week for 6 months (n=16) or no therapy (n=15). Patients were followed for a mean of 66 months (range 22-240 months). Serum HCV RNA continued to be detectable by reverse-transcription PCR in 15 of the interferon treated patients and in 14 controls at the end of the treatment period. In addition, serum ALT levels became transiently elevated (ALT flare-ups) in two-thirds of the interferon patients (10) and in only one of the control patients. The authors concluded that these HCV RNA carriers do not respond to low dose interferon-a therapy. (Sangiovanni A, et al. Hepatology 1998; 27: 853-856)
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