It is well known that hepatitis C virus (HCV) infection may progress to cirrhosis and is linked to the development of hepatocellular carcinoma (HCC). Previous studies have
shown that compensated HCV-cirrhosis is related to a certain morbidity and mortality in European patients, but little is known in regard to the clinical outcomes of a similar group of patients in the United States. This study investigated this category of patients in terms of the incidence of decompensation, development of HCC, mortality, and the predictive risk factors for morbidity and mortality. The potential effects of interferon (IFN) therapy on outcomes of the disease also were assessed. A total of 112 patients with compensated HCV-cirrhosis and a documented history of either intravenous drug abuse (IVDA) or transfusion were consecutively enrolled. The mean follow-up interval was 4.5 (2-7.7) years. The cumulative probabilities for decompensation and development of HCC were 22.2% and 10.1% in 5 years, with an estimated yearly incidence of 4.4% and 2.0%, respectively. The cumulative survival probability was 82.8% from entry and 51.1% from decompensation in 5 years, with estimated yearly events of mortality and liver transplantation of 3.4% and 9.8%, respectively. It was found that age at entry and initial exposure, initial levels of albumin, platelet count, and prothrombin time (PT) were predictive risk factors for developing decompensation, whereas age at entry and initial exposure, history of transfusion, lower initial levels of albumin, platelet count, and viral load were predictive risk factors for events of mortality and liver transplantation. The incidence of decompensation was significantly lower in patients treated with IFN, but age may have played a contributory role. In contrast, neither HCC development nor mortality was significantly altered by IFN therapy. In conclusion, our study indicated that patients with compensated HCVcirrhosis in the United States progressed slowly and experienced eventual morbidity and mortality. Once decompensation develops, the disease will be more progressive and result in even higher mortality. Further studies will be required to determine the efficacy of IFN on clinical outcomes in this group of patients. (HEPATOLOGY 1999;29: 1311-1316.)
Chronic hepatitis C is a progressive disease that is related to the development of cirrhosis and hepatocellular carcinoma (HCC). The incidence of progression of chronic hepatitis C to cirrhosis has been reported to vary from 8% to 46%. Recently, a 25-year follow-up study indicated that chronic hepatitis C is associated with a 17-fold increased risk of mortality from liver disease and a sixfold increased risk of developing HCC. Extensive studies had focused on the natural course of disease progression from chronic hepatitis C to cirrhosis, HCC, and to mortality, and on the long-term outcomes of these diseases and their related complications. Recently, two European research groups reported the long-term outcomes of patients with compensated hepatitis C virus (HCV)-cirrhosis that was associated with measured mortality and morbidity. 9,10 However, little is known in the United States in regard to the long-term clinical course of this group of patients. In addition, the predictive risk factors for disease progression and prognosis remain inconclusive. Yet, such information is important for understanding the natural history of disease and for optimizing patient care.
Currently, interferon (IFN) represents the mainstay of treatment for chronic hepatitis C. Studies have shown that IFN therapy may slow disease progression and improve intrahepatic pathological changes in patients with chronic hepatitis C. 12,13 However, there is controversy as to whether patients with compensated HCV-cirrhosis would also benefit from IFN therapy. The present study is aimed at assessing the prevalence and predictive risk factors for decompensation, HCC development, and for mortality in patients with compensated HCVcirrhosis in the United States. The long-term outcomes of these patients and the potential effects of IFN therapy on the outcomes of the disease are also evaluated.
PATIENTS AND METHODS
Patient Population. The present study included patients who were evaluated at the liver center at Huntington Memorial Hospital from January 1990 to August 1995. As previously reported, 9,10 the term ''entry'' into the study was defined as the time of diagnosis of compensated HCV-related cirrhosis. All patients who fulfilled the following inclusion criteria were consecutively enrolled. The inclusion criteria at entry included: 1) either biopsy-proven (n ϭ 106, 94.5%) or clinically diagnosed (n ϭ 6, 5.5%) cirrhotic patients. The pathological diagnosis was based on international criteria, 18 whereas clinical diagnosis was based on the criteria reported by Bonacini et Abbreviations: HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IFN, interferon; IVDA, intravenous drug abuse; AFP, ␣-fetoprotein; PT, prothrombin time; OR, odds ratio.