Natural history of chronic HBV carriers in northern Italy: morbidity and mortality after 30 years

Background &amp; aims: Increased morbidity and mortality from liver disease have been reported in chronic hepatitis B surface antigen (HBsAg) carriers, but data on survival are equivocal. To assess the impact of hepatitis B virus (HBV) infection on survival and liver-related complications, we re-evaluated, after a mean follow-up of 30 years, a cohort of 296 blood donors excluded from donation 30 years ago when HBsAg screening became mandatory. Methods: Clinical and ultrasound examination and biochemical and virologic tests were performed. The cause of death was recorded and survival was compared with a control population of 157 HBV-negative blood donors selected at baseline. Results: Thirty-two (10.8%) cases and 14 controls (8.9%) (P = 0.625) had died; 3 of 32 (9.3%) and 1 of 14 (7.1%) deaths were liver-related. Hepatocellular carcinoma (HCC) caused death in 2 of 296 and 1 of 157 subjects (0.6% in each group). Alcohol-induced cirrhosis occured in the remaining subject. By Cox regression analysis, survival was independently predicted by older age, abnormal γ-glutamyl transpeptidase (GGT) levels, and presence of medical comorbidities at baseline. Unequivocal liver disease was found in 4 carriers only. No disease decompensation occurred during follow-up. Fifty-nine (32.2%) carriers cleared HBsAg (yearly incidence, 1.0%). Full-length serum HBV DNA was present in 32.2% of persistently HBsAg-positive individuals (average titer always <10 5 copies/mL). Conclusions: Over a 30-year period, chronic HBV carrier blood donors from Northern Italy did not develop clinically significant liver disease, hepatocellular cancer, or other liver-related morbidity or mortality at a higher rate than uninfected controls. The presence of medical comorbidities, older age at diagnosis, and abnormal GGT levels were independent predictors of death among chronic HBV carriers.