Accelerated hepatocellular carcinoma recurrence rate after postoperative direct-acting antivirals treatment – preliminary report

Abstract

Aim of the studyNew interferon-free direct-acting antiviral (DAA) therapy has led to major progress in hepatitis C virus (HCV) treatment. Current outcomes are promising, especially in compensated cirrhosis. However, there are reports of accelerated hepatocellular carcinoma (HCC) recurrence after surgery in patients treated with DAAs. The influence of DAA therapy on the timing and frequency of recurrence after surgical treatment needs further observation.Material and methodsFifty-one HCV infected patients with advanced liver cirrhosis and history of surgical treatment for HCC in 2012-2016 were analyzed in a case-control study. Nineteen patients received DAA therapy (DAA group) after tumor remission achieved by surgery and 32 patients were not treated with DAA (NDAA group). Follow-up included multiphase computed tomography scan or magnetic resonance imaging of the liver and alpha-fetoprotein level in 3-6-month intervals.ResultsAn sustained virological response was achieved in 18 (95%) DAA treated patients. Hepatocellular carcinoma recurrence was observed in 8 (42.1%) patients from the DAA group and in 21 (65.6%) from the NDAA group (p = 0.058). Relapse occurred within 265 days after surgery in the DAA group vs. 532 days in the NDAA group (p = 0.033). The one-year recurrence-free survival (RFS) rate was 47.3% vs. 75% in the DAA and NDAA group respectively (p = 0.45).ConclusionsUse of DAA therapy in patients with a history of HCC may result in significantly accelerated relapse of the disease. The number of analyzed patients in this study is too small to state unquestionable conclusions. Further observation with a longer follow-up and larger patient group is needed. The study confirms that contemporary HCV treatment is highly effective.

Systematic review with meta‐analysis: effectiveness of direct‐acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

“…Study characteristics were summarised in Tables and . Fifty‐six studies were included, with a total of 5522 patients with HCC, while 27 studies enrolled non‐HCC patients as control groups. Fifty‐three (95%) studies were observational cohorts (45 retrospective and eight prospective) and three studies were clinical trials.…”

“…There are several issues relevant to DAA therapy among patients with HCC. First, initial data suggested a potential increased risk of HCC recurrence, [8][9][10][11][12][13][14] although subsequent studies did not support these findings. [15][16][17][18][19][20][21][22] Second, in response to the controversy around HCC recurrence risk, the timing of DAA therapy in relation to HCC management became a point of debate.…”

Epidemiology and Elimination of HCV-Related Liver Disease

“…Since these early studies, many cohort studies have been conducted to analyze this issue ( Table 1 ). Of the 14 published studies available as of 1 June 2018, four concluded that there was an increased risk of HCC recurrence after DAA treatment [ 60 , 77 , 80 , 81 ] while the other 10 did not conclude in an increased risk, the recurrence rate being compared or not to a control group according to the study design [ 79 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Influence of Interferon-free Direct-acting Antiviral Therapy on Primary Hepatocellular Carcinoma Recurrence: A Landmark Time Analysis and Time-dependent Extended Cox Proportional Hazards Model Analysis

“…Several systematic reviews and metaanalyses have shown that IFN-free DAA therapy does not affect HCC recurrence (10)(11)(12)(13). In contrast, single-center studies have shown that IFN-free DAA therapy may have either promotive or suppressive effects on HCC recurrence (14)(15)(16)(17)(18). Thus, the studies reported to date present conflicting data.…”