Our objective was to address two shortfalls in the hepatitis C virus (HCV) literature: (1) Few data exist comparing post-treatment liver-related mortality/morbidity in HCV-sustained virologic response (SVR) patients to non-SVR patients and (2) no data exist examining liver-related morbidity among treatment response subgroups, particularly among noncirrhotic SVR patients, a group who in the main are discharged from care without further follow-up. A retrospective cohort of 1,215 previously naı ¨ve HCV interferon patients (treated 1996-2007) was derived using HCV clinical databases from nine Scottish clinics. Patients were followed up post-treatment for a mean of 5.3 years. (1) By Cox-regression, liver-related hospital episodes (adjusted hazard ratio [AHR]: 0.22; 95% confidence interval [CI]: 0.15-0.34) and liver-related mortality (AHR: 0.22; 95% CI: 0.09-0.58) were significantly lower in SVR patients, compared to non-SVR patients. (2) Rates of liver-related hospitalization were elevated among all treatment subgroups, compared to the general population: Among noncirrhotic SVR patients, adjusted standardized morbidity ratio (SMBR) up to 5.9 (95% CI: 4.5-8.0); among all SVR patients, SMBR up to 10.5 (95% CI 8.7-12.9); and among non-SVR patients, SMBR up to 53.2 (95% CI: 49.4-57.2). Considerable elevation was also noted among patients who have spontaneously resolved their HCV infection (a control group used to gauge the extent to which lifestyle factors, and not chronic HCV, can contribute to liver-related morbidity), with SMBR up to 26.8 (95% CI: 25.3-28.3). Conclusions: (1) Patients achieving an SVR were more than four times less likely to be hospitalized, or die for a liver-related reason, than non-SVR patients and (2) although discharged, noncirrhotic SVR patients harbor a disproportionate burden of liver-related morbidity (i.e., up to six times that of the general population). Furthermore, alarming levels of liver-related morbidity in spontaneous resolvers is an important finding warranting further study. (HEPATOLOGY 2011;54:1547-1558) W ith an estimated worldwide prevalence of 2.35% 1 (equating to 160 million persons chronically infected), the hepatitis C virus (HCV) presents a global public health challenge. In cohorts of HCV patients, up to 24% develop liver cir-rhosis within 20 years of infection, 2 and thereafter, the annual incidence of hepatocellular carcinoma, and decompensated cirrhosis, is 3.5% and 6.5%, respectively. 3 In Scotland, McDonald et al. found liver-related mortality (LRM) to be 25 times higher 4 and liver-related morbidity