Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals

Abstract

Background & Aims The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this study was to assess the efficacy of all-oral-DAA regimens in HCV+ cirrhotic patients who have or had HCC compared to those without HCC. Methods A retrospective cohort study was conducted on all cirrhotic patients who were treated for HCV with DAAs at our institution between January 2014 and November 2015. Results A total of 421 HCV+ patients with cirrhosis were identified, of whom 33% had active or a history of HCC. Failure to achieve sustained virologic response (SVR) occurred in 21% of patients with HCC compared to 12% of patients without HCC (p = 0.009). Of the 29 patients with HCC who did not achieve SVR, 27 (93%) occurred when an active tumor was present. DAA therapy in the presence of an inactive tumor or after removal of tumor (resection/transplant) resulted in excellent SVR rates, similar to those without HCC (p <0.0001). In multivariable analysis, the primary predictor of DAA treatment failure was the presence of active HCC at the time of HCV treatment initiation (adjusted odds ratio = 8.5, 95% confidence interval = 3.90–18.49). Conclusions The presence of active HCC tumor at the initiation of HCV therapy is significantly associated with all-oral DAA treatment failure. HCV treatment after curative therapies for HCC resulted in excellent SVR. Lay summary The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 8 times more likely to fail hepatitis C treatment than patients without liver cancer.

On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C

“…Therefore, higher pre-treatment levels of NKG2D (as shown in Table 1 and Fig 2) could result from such imbalance of inflammatory cytokines from both immune cells or other hepatic non-parenchymal cells such as hepatic stellate cells, especially in highly fibrotic livers, like the cases in IFN − /DAA group of this current study, even if no HCC was clinically evident at the time point of start of IFN-free DAA administration. Recently, Prenner et al showed in a retrospective study that the existence of active HCC might reduce the rate to achieve SVR by IFN-free DAAs[37]. As we also showed in Table 1 that non-SVR correlated to early emergence of clinically evident HCC, pre-treatment existence of clinically undetectable HCC may be suggested as a causative factor for treatment failure.…”

Hepatocellular Carcinoma Occurrence and Recurrence after Antiviral Treatment in HCV-Related Cirrhosis. Are Outcomes Different after Direct Antiviral Agents? A Review

“…NKG2D is a well known immunoreceptor with implications in activating the immune responses against both infected and transformed cells. The [48]. Similar results were confirmed by Prenner et al [47,49], who showed that the presence of active HCC had a negative impact on achieving SVR.…”

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Eradicating hepatitis C infection results in numerous health benefits, including reduced rates of all‐cause mortality, cirrhosis, hepatic decompensation, and HCC . Successful treatment also confers improvement in extrahepatic manifestations of HCV disease, including cryoglobulinemic vasculitis and HCV‐related non‐Hodgkin lymphoma and other lymphoproliferative disorders, as well as improved productivity and quality of life .…”