SAN FRANCISCO – The risk of hepatocellular carcinoma remains sufficiently high in some subgroups who have achieved sustained virologic response to treatment to justify continued cancer surveillance, according to findings from a large cohort study presented at the annual meeting of the American Association for the Study of Liver Diseases.
The risk of hepatocellular carcinoma (HCC) after sustained virologic response (SVR) was relatively elevated in those who were infected with genotype 3 of the hepatitis C virus (HCV), those with diabetes, and those older than 65 years. But those who had cirrhosis at the time of SVR appear to have the highest risk and need for continued surveillance, reported Dr. Hashem B. El-Serag, chief of the gastroenterology and hepatology section at Baylor College of Medicine, Houston.
Dr. Hashem B. El-Serag
In this study, data from the national Veterans Affairs (VA) health system were available for 10,730 patients who achieved SVR. When compared to 11,290 patients who did not achieve SVR, the risk of HCC was reduced by two thirds (hazard ratio, 0.358), but Dr. El-Serag labeled this finding “old news.” Instead, his focus was on the 100 cases of HCC identified after SVR over the course of 30,000 patient-years of follow-up.
While the annualized overall incidence of HCC after SVR was 0.32%, incidence rates ranged greatly by subgroup. For those with genotype 3 HCV at the time of SVR, the incidence was 0.558 cancers/year (versus 0.334 for genotype 1). A similar increase in HCC was observed in patients with diabetes (0.558/year). The rate climbed to 0.953/year for those who were age 65 years or older at the time of SVR.
The incidence of HCC was 1.54%/year in those with cirrhosis at the time of SVR, which was the highest rate among subgroups evaluated. This figure is notable because guidelines suggest that surveillance for HCC is justified for patients with an estimated annual risk of 1.5% per year, according to Dr. El-Serag.
“The presence of cirrhosis at SVR carried a 4.45 increase in the adjusted hazard ratio for HCC when compared to the absence of cirrhosis [P less than .0001],” he reported. Being 65 and older was associated with a nearly fivefold increase in hazard ratio of HCC compared with younger patients (HR 4.69; P = .0003), while the presence of diabetes was associated with a nearly twofold risk (HR 2.07; P = .0001).
It is notable that no concentration of cases of HCC was observed over the course of follow-up. Rather, there was a relatively equal distribution over time.
In addition to the known limitations of cohort studies, Dr. El-Serag cautioned that almost all SVRs in this database were achieved with interferon-based therapies. This is important, because the risk for HCC may differ when SVR is achieved with the newer direct-acting antivirals (DAAs). Another limitation is that most patients in the VA database are male.
However, the data strongly suggest that HCC risk after SVR differs markedly among subpopulations of HCV patients. While these findings have implications for considering continued surveillance of HCC, they also may be meaningful for timing of HCV therapy.
“It is obvious that if you treat and cure [patients early in the course of their disease and while they are young], your risk of HCC is much lower than if you treat late and old,” said Dr. El-Serag.
This is the first study to evaluate risk of HCC after SVR in a large and diverse population, according to Dr. El-Serag. The moderator of the oral session in which the report was presented, Dr. Joseph K. Lim, director of the viral hepatitis program at Yale University, New Haven, Conn., characterized the findings as “incredibly important.” Despite the frequency with which SVR is now being achieved with DAAs, these data confirm that some groups of patients may remain at substantial risk of HCV complications even after successful therapy.
Dr. El-Serag reeported that he has a financial relationship with Gilead.