Liver Cancer Risk 60% Lower After SVR in Nationwide Danish Study

Study author Sofie Hallager presenting the results
Warren Tong

Cirrhotic hepatitis C (HCV) patients in Denmark had a 63% lower risk of hepatocellular carcinoma (HCC) and a 76% lower risk of decompensated cirrhosis if they achieved sustained virologic response (SVR) with therapy. But even among patients who achieved SVR, multiyear incidence of HCC and decompensated cirrhosis stood at about 5%.

Two decades after infection with HCV, 5% to 25% of patients have cirrhosis and, without successful treatment, many go on to HCC or end-stage liver disease and death. Denmark has 16,000 to 18,000 people with chronic HCV infection. This study aimed to estimate all-cause mortality and liver-related morbidity in HCV-infected cirrhotics who did or did not achieve SVR 24 weeks after HCV therapy ended (SVR24).

The researchers explored data in the Danish Database for Hepatitis B and C linked to several national health registries. The analysis included people at least 18 years old with chronic HCV monoinfection and cirrhosis in a study period from January 2002 through December 2013. All cohort members had at least six months of follow-up. The researchers identified cirrhosis by liver biopsy, transient elastography ≥17 kPa or clinical diagnosis.

The analysis included 232 HCV-positive cirrhotics with SVR24 and 275 without SVR24. About two-thirds of both groups were men. The group with SVR24 was significantly younger (median 51.3 versus 53.9 years) and a significantly lower proportion had HCV genotype 1 (33.2% versus 52.0%), while significantly higher proportions had genotype 2 (8.2% versus 3.3%) or genotype 3 (46.1% versus 36.0%) (P < .05 for all differences). The groups with and without SVR24 did not differ significantly by proportions with decompensation (7.8% and 11.6%), diabetes mellitus (12.5% versus 14.6%) or HCC (2.2% versus 5.1%).

Among all cohort members, cumulative five-year incidence of decompensated cirrhosis measured 14.3%, while cumulative five-year incidence of HCC measured 9.2%. All-cause mortality stood at 7.33 per 100 person-years and HCC incidence at 2.51 per 100 person-years. Analyses adjusted for age, sex and other potential confounders identified three independent predictors of HCC: alcohol overuse (adjusted incidence rate ratio [aIRR] 2.20, 95% confidence interval [CI] 1.57 to 3.07), HCV genotype 3 versus 1 (aIRR 1.65, 95% CI 1.19 to 2.29) and genotype 3 versus 2 (aIRR 2.66, 95% CI 1.19 to 5.92). Incidence of decompensated cirrhosis measured 3.44 per 100 person-years. Alcohol overuse was independently associated with decompensation (aIRR 2.03, 95% CI 1.35 to 3.05).

Through 12.5 years of follow-up, cumulative incidence of decompensated cirrhosis measured 4.8% in people with SVR24 versus 17.1% in those without SVR24. Cumulative incidence of HCC stood at 5.4% with SVR24 versus 13.3% without SVR24.

All-cause mortality was lower with than without SVR24 (2.2 versus 6.7 per 100 person-years, adjusted mortality rate ratio not significant at 0.66, 95% CI 0.42 to 1.06). HCC incidence was lower with than without SVR24 (0.9 versus 3.6 per 100 person-years, adjusted incidence rate ratio significant at 0.37, 95% CI 0.22 to 0.62). And decompensated cirrhosis incidence was lower with than without SVR24 (0.8 versus 4.0 per 100 person-years, adjusted incidence rate ratio significant at 0.24, 95% CI 0.10 to 0.54).

The researchers concluded that liver-related morbidity and mortality are high in people with chronic HCV and cirrhosis in Denmark, but SVR24 is linked to reduced morbidity and mortality. These findings, the investigators added, underline an "urgent need to cure patients with [chronic hepatitis C]."

Mark Mascolini writes about HIV and hepatitis virus infection.