A 12-YEAR NATURAL-HISTORY OF HEPATITIS-C VIRUS-INFECTION IN HEMODIALYZED PATIENTS

A twelve year natural history of hepatitis C virus infection in hemodialyzed patients. A prospective non-A, non-B follow-up program, implemented in a hepatitis B surface antigen-free dialysis unit, enabled us to report on the natural history of hepatitis C virus (HCV) infection in hemodialyzed patients between 1980 and 1992. For this program, every patient was prospectively monitored every two weeks for alanine amino transferase (ALT) activity, and every month for gammaglutamyl transpeptidase (GGT) activity and systematic collection of frozen sera. Sequences of stored sera from 217 patients were repeatedly tested for anti-HCV antibodies using second generation assays. Eighty-six of the 217 patients (39.6%), including 61 of the 67 patients with non-A, non-B hepatitis (91%), had HCV infection repeatedly evidenced by positive ELISA in all, and confirmed by RIBA in 84 of 86 (97.5%). In addition, 19 out of 23 patients (82.6%) were positive for HCV RNA by the polymerase chain reaction (PCR). Of the 86 anti-HCV positive patients, 41 had previously acquired HCV infection, and 45 seroconverted during chronic dialysis. Of these, all but one patient developed hepatitis with raised ALT activity which lasted for at least six months in all. Only 29 of 45 patients (64.5%) had a history of blood transfusion. Seventy-eight of the 86 patients (91%) who were followed up for one to 11.5 years (median 5) retained anti-HCV for several years. Nineteen liver biopsies performed in 16 patients showed chronic active hepatitis in 8 (50%) and hepatocellular carcinoma without cirrhosis in one patient. In most cases, the outcome of HCV infection was chronic, since 54 patients (69.2%) exhibited persistently elevated GGT and anti-HCV positivity combined with either abnormal or fluctuating ALT (30.8%) or normal ALT (38.4%), and 16 patients (20.5%) had persistently elevated anti-HCV titers. Resolutive hepatitis C was uncommon since only eight patients (10.3%) gradually lost their HCV markers. The incidence and cumulative risk of seroconversion only decreased after 1988 to 1990, when routine testing of the blood supply for surrogate markers and anti-HCV antibody was started in France. The incidence of post-transfusion hepatitis became nil in 1990 before that of nosocomial infection (1991). HCV prevalence also decreased, from 43.6 to 29.2%. In conclusion, HCV was responsible for 91% of non-A, non-B hepatitis cases. Hepatitis was identified as the primary HCV infection in all but one Case. GGT activity emerged as a reliable marker of long-term HCV infection. The severity of the disease seems to correlate with the persistence of ALT and/or GGT changes, combined with that of anti-HCV and HCV RNA positivity. Transmission of HCV was both transfusional and nosocomial. HCV prophylaxis should now focus on the eradication of nosocomial infection.