The changes in quantitative HCV RNA titers during interferon alpha 2B therapy in patients with chronic hepatitis C infection.

OBJECTIVE: Our aim was to analyze the outcomes and the patterns of response to interferon treatment in patients with chronic hepatitis C using serum HCV RNA as the primary endpoint of therapy. METHODS: Seventy anti-HCV-positive patients were treated with 3 million U of interferon-alpha-2b thrice weekly for 24 wk and followed for an additional 24 wk after cessation of therapy (wk 48). Serum HCV RNA was measured by a reverse transcriptase-polymerase chain reaction method that has a sensitivity of < 100 viral copies per ml. RESULTS: The mean pretreatment HCV RNA was 2.8 +/- 2.2 x 10(6) viral copies per ml. Genotype 1 patients had significantly higher mean baseline viral titers than those with genotype 2 (p = 0.03). At wk 48, 12 (17%) patients were HCV RNA negative and considered virological complete responders (CR) to treatment. The remaining patients were HCV RNA positive at wk 48 and were considered nonresponders to therapy. There were two types of virological nonresponder patients, responder relapse (RR) and no response (NR). The mean baseline HCV RNA level was significantly lower in the virological CR patients (p = 0.0004). At wk 12 and 24 of interferon treatment, both the virological CR and RR patients had lower serum HCV RNA concentrations than the patients in the NR category (p = 0.0001), while at wk 48, only. the virological CR patients had undetectable HCV RNA when compared to the RR and NR patients (p = 0.04). Transient decreases in the HCV RNA titers of > or = 1 log in magnitude were observed in 49% of the NR patients, which rose to pretreatment levels either during or after interferon therapy. CONCLUSIONS: Our findings indicate that measurement of serum HCV RNA precisely defined the responses to interferon therapy. Because the goal is to eliminate virus in patients with chronic hepatitis C infection, then HCV RNA should be used as the primary endpoint of treatment.

Clinical sequelae of hepatitis C acquired from injection drug use.

We determined the course of hepatitis C infection in 125 patients with a history of injection drug use. The mean age at presentation was 43.5 years, and the mean age of initiating injection drug use was 23.1 years. Fatigue and hepatomegaly were present in as many as 60% of patients. All had antibodies to the hepatitis C recombinant protein C25, and 99% were positive for hepatitis C virus RNA. After the initial workup, 33 (26%) patients had chronic hepatitis, 46 (37%) had chronic active hepatitis, 45 (36%) had cirrhosis, and 1 (0.8%) presented hepatocellular carcinoma. During follow-up, hepatocellular carcinoma developed in 2 other patients. In 74 patients with a 1-year history of injection drug use, the mean number of years to the development of chronic hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma were 15.6, 17.6, 19.4, and 26.3 years, respectively. In this subgroup of patients, heavy alcohol abuse did not appear to influence the progression of liver disease. The 2-year case-fatality rate was 2%. Our findings indicate that hepatitis C is a progressive disease, but only a few died during the average 20.4 years after the initiation of injection drug use. Antiviral treatment to eradicate the virus and halt the progression of disease is indicated in this group of patients.

Clinical outcomes after transfusion-associated hepatitis C.

BACKGROUND: The extent of serious complications in people who have acquired chronic hepatitis C infection after a blood transfusion is unclear. METHODS: We studied 131 patients with chronic post-transfusion hepatitis C who were referred to our center between February 1980 and June 1994. Eighty-two other patients were excluded because they had multiple transfusions, hemophilia, intravenous drug use, human immunodeficiency virus infection, hepatitis B infection, hemochromatosis, or alcoholic liver disease. Liver biopsies were performed in 101 patients; biopsies were not performed in the other 30 patients, all with signs of cirrhosis, because the results of coagulation tests were abnormal. RESULTS: The mean age of the patients was 57 years (range, 21 to 81) at the time of our initial evaluation. The mean age at the time of the blood transfusion was 35 years (range, 1 to 76). The mean duration of follow-up after presentation to us was 3.9 years (range, 1 to 15). Eighty-eight of the patients (67.2 percent) initially had fatigue, and 89 (67.9 percent) had hepatomegaly. Twenty-seven patients (20.6 percent) initially had chronic hepatitis, 30 (22.9 percent) had chronic active hepatitis, 67 (51.1 percent) had cirrhosis, and 7 (5.3 percent) had hepatocellular carcinoma. Hepatocellular carcinoma developed in an additional seven patients an average of 36 months (range, 7 to 121) after the initial visit. During follow-up, 20 patients (15.3 percent) died: 8 from complications of cirrhosis (1 after a liver transplantation); 11 from hepatocellular carcinoma; and 1, with chronic active hepatitis, from pneumonia. CONCLUSIONS: In a group of patients seen at a referral center, chronic post-transfusion hepatitis C was a progressive disease and, in some patients, led to death from either liver failure or hepatocellular carcinoma.

Clinical manifestations of hepatitis A: recent experience in a community teaching hospital.

A study of the clinical profile of 59 patients who presented with hepatitis A virus infection showed that dark urine, fatigue, gastrointestinal complaints, and fever were the most common presenting symptoms. The most frequent physical findings were hepatomegaly and jaundice. The mean presenting laboratory tests included total bilirubin of 5 mg/dL, alkaline phosphatase of 269 units/L, and serum aspartate aminotransferase and alanine aminotransferase levels of 1442 mIU/mL and 1952 mIU/mL, respectively. Atypical manifestations included relapse, cholestasis, rash, and arthralgia. Two patients presented with hepatitis A and concomitant type I autoimmune chronic hepatitis, and both required immunosuppressive therapy. Five patients who presented with hepatitis A were pregnant, and during follow-up, none of their infants developed elevated serum transaminase values or had detectable IgM anti-HAV antibody. All 59 patients experienced complete clinical and biochemical recovery within 6 months after onset of illness.