Achieving SVR May Not Reduce Risk of HCC in Patients with HCV

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Findings from a recent study are underscoring the importance of continued surveillance for hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV), even after successful treatment with direct-acting antiviral (DAA) therapy.¹

Results of the study, which was conducted in a cohort of more than 200 patients at 2 hospitals in Hong Kong, showed cirrhosis, evidence of portal hypertension, elevated bilirubin, lower platelet count, lower albumin, and advanced age were risk factors for HCC development after achieving sustained virological response (SVR) with DAA therapy.¹

The World Health Organization recommends therapy with pan-genotypic DAAs for all adults, adolescents, and children > 3 years of age with chronic HCV, estimated to be able to cure more than 95% of the 58 million global cases.² A leading cause of liver-related death worldwide, HCC is often caused by chronic HCV. DAA therapy aims to reduce HCV-related complications from cirrhosis, including HCC – however, studies have produced conflicting results about the incidence of de-novo HCC occurrence and HCC recurrence.³

“It has been shown that DAA therapy can lower portal hypertension, improve liver dysfunction and induce fibrosis regression after achieving SVR,” wrote Victor Yung Sin Chow, of Our Lady of Maryknoll Hospital in China, and colleagues.¹ “Therefore, it was reasonable to expect that DAA-induced SVR would reduce the risk of HCC by preventing cirrhosis, or by eliminating the carcinogenic effect of HCV.”

To assess the risk of early HCC development in patients with chronic HCV, investigators retrospectively enrolled consecutive patients treated with DAAs at Princess Margaret Hospital and Our Lady of Maryknoll Hospital between August 1, 2015, and July 31, 2021. A total of 279 patients were included in the analyses. Among the cohort, the mean age was 59 (Standard deviation [SD], 12.8) years, 65.6% of patients were male, and 73.5% were HCV treatment-naïve.¹

The main study outcomes were de-novo HCC occurrence after the initiation of DAA therapy, defined by investigators as new HCC in patients without a previous history of HCC, and HCC recurrence in patients with a history of HCC who achieved complete radiologic response following HCC curative treatment. Additional secondary outcomes were the development of other liver-related complication(s) in previously compensated cirrhosis and/or all-cause mortality after the initiation of DAA therapy.¹

Among the cohort, the overall SVR rate was 98.9%. During a median follow-up of 23.4 months after DAA initiation, 15 (5.4%) patients developed HCC.¹

The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8% and 30.9%, respectively (P <.001). Investigators noted patients with cirrhosis had a greater 1-year cumulative incidence of HCC compared to those without cirrhosis (5.1% vs 0.7%; P = .036).¹

Univariate analysis showed significant factors associated with HCC after DAA were: history of treated HCC (P <.001), cirrhosis (P = .0499), evidence of portal hypertension (P = .006), higher AFP at the start or end of DAA therapy (both P <.001), higher bilirubin (P <.001), lower platelets (P = .035), lower albumin (P = .007), and older age (P = .007).¹

Receiver operating characteristic curve analysis showed the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. The 1-year cumulative incidence of HCC was 0.5% (95% CI, 0–1.6%) and 12.6% (95% CI, 3.1–22.1%) for the groups with AFP level < 10.5 ng/mL and ≥ 10.5 ng/mL at the start of DAA therapy, respectively. For the groups with AFP level < 5.6 ng/mL and ≥ 5.6 ng/mL at the end of DAA therapy, the 1-year cumulative incidence of HCC was 0.6% (95% CI, 0–1.7%) and 11.8% (95% CI, 2.8–20.8%), respectively.¹

Investigators pointed out potential limitations associated with the study’s small sample size, lack of an untreated controlled arm, and unadjusted confounding factors associated with the progression of liver disease and HCC development. Of note, most of these limitations were associated with the retrospective study design.¹

“The risk of early HCC recurrence, despite achieving complete radiologic response following previous curative HCC treatment and achieving SVR following DAA therapy, is high. This highlights the importance of regular and frequent HCC surveillance, especially within the initial 2 years after treatment,” investigators concluded.¹

References:

1. ^{Chow VYS, Cheung WI. Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong. BMC Gastroenterol. https://doi.org/10.1186/s12876-023-03099-2}
2. ^{World Health Organization. Hepatitis C. Newsroom. July 18, 2023. Accessed February 5, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}
3. ^{Axley P, Ahmed Z, Ravi S, Singal AK. Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review. J Clin Transl Hepatol. doi:10.14218/JCTH.2017.00067}