Natural history of chronic hepatitis C

Although concomitant alcoholism is widely believed to enhance liver disease progression in persons with hepatitis C virus (HCV) infection, this relationship has not been well quantified. To quantify the relationship of transfusion-associated HCV infection and history of heavy alcohol abuse to development of cirrhosis. Retrospective cohort study. Liver clinics in university and government hospitals. Extended follow-up of 1030 patients in prospective investigations of transfusion-associated viral hepatitis conducted in the United States between 1968 and 1980. Development of cirrhosis and history of heavy alcohol abuse were determined from review of interviews with patients or their proxies, medical records, death certificates, and autopsy and biopsy reports. Logistic regression was used to estimate the risk for cirrhosis associated with transfusion-associated HCV infection and history of heavy alcohol abuse. The absolute risk for cirrhosis was 17% among patients with transfusion-associated HCV; 3.2% among patients with transfusion-associated non-A, non-B, non-C hepatitis; and 2.8% among controls. Patients with transfusion-associated HCV were more likely than controls to develop cirrhosis (odds ratio, 7.8 [95% CI, 4.0 to 15.1]). A history of heavy alcohol abuse was associated with a fourfold increased risk for cirrhosis. Hepatitis C virus infection plus a history of heavy alcohol abuse led to a substantial increase in risk for cirrhosis (odds ratio, 31.1 [CI, 11.4 to 84.5]) compared with controls without such a history. Heavy alcohol abuse greatly exacerbates the risk for cirrhosis among patients with HCV infection. This finding emphasizes the need to counsel such patients about their drinking habits.

The sequelae during the first two decades after acute hepatitis C virus (HCV) infection have been well studied, but the outcome thereafter is unknown. To conduct an extended study of the natural history of HCV infection by using archived serum specimens originally collected between 1948 and 1954. Retrospective cohort study. A university, a Veterans Affairs medical center, and a medical follow-up agency that had access to the serum specimens and accompanying demographic and medical records. 8568 military recruits who were evaluated for group A streptococcal infection and acute rheumatic fever between 1948 and 1954. Blood samples were taken from the recruits and, after testing, were stored frozen for almost 45 years. The presence of antibodies to HCV was determined by enzyme-linked immunoassay, supplementary recombinant immunoblot assay, and polymerase chain reaction for HCV RNA. Morbidity and mortality were also assessed. Of 8568 persons, 17 (0.2%) had positive results on enzyme-linked immunosorbent assay and recombinant immunoblot assay. The rate was 1.8% among the African-American persons and 0.1% among the white persons in the total sample (relative risk, 25.9 [95% CI, 8.4 to 80.0]). During the 45-year follow-up, liver disease occurred in 2 of the 17 HCV-positive persons (11.8%) and 205 of the 8551 HCV-negative persons (2.4%) (ethnicity-adjusted relative risk, 3.56 [CI, 0.94 to 13.52]). Seven of the 17 HCV-positive persons (41 %) and 2226 of the 8551 HCV-negative persons (26%) had died by December 1996 (ethnicity-adjusted relative risk, 1.48 [CI, 0.8 to 2.6]). Of persons who were HCV-positive, 1 (5.9%) died of liver disease 42 years after the original phlebotomy, 5 (29%) died of non-liver-related disease a median of 37 years after the original phlebotomy, and 1 (5.9%) died of unknown causes. One hundred nineteen HCV-negative persons (1.4%) died of liver disease. The rate of HCV infection from 1948 to 1954 among a sample of military recruits parallels that among present-day military recruits and volunteer blood donors. During 45 years of follow-up, HCV-positive persons had low liver-related morbidity and mortality rates. This suggests that healthy HCV-positive persons may be at less risk for progressive liver disease than is currently thought.

This community-based prospective study examined the effects of viral infections and lifestyle habits on hepatocellular carcinoma (HCC) risk in Japan. A baseline survey was conducted for 981 males and 2,078 females in June 1992 and evaluated hepatitis B surface antigen, second-generation hepatitis C virus antibody, and history of cigarette smoking and habitual alcohol consumption. By March 1997, 14 males and 8 females had been newly diagnosed with HCC. After controlling for gender and age by using the Cox model, the authors found that positivity for hepatitis B surface antigen (hazard ratio = 7.28, 95% confidence interval: 1.62, 32.61; p < 0.01) and positivity for high-titer hepatitis C virus antibody (hazard ratio = 40.38, 95% confidence interval: 11.71, 139.21; p < 0.001) were significantly associated with HCC risk, although a history of smoking or alcohol consumption was not significantly related to risk. There was a significant interaction on an additive scale for the risk of HCC development between high-titer hepatitis C virus antibody status and a history of smoking (p < 0.05) in spite of no significant interaction on a multiplicative scale. Although preventing the transmission of hepatitis viruses is most important for reducing the risk of HCC, intervention regarding lifestyle habits such as cigarette smoking should not go unheeded.