Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real‐world experience study

Abstract

We followed for 2 years patients treated with direct-acting agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator-initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2-year follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post-treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2-year follow-up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2-year monitoring for possible disease progression.

Direct-acting Antiviral in the Treatment of Chronic Hepatitis C: Bonuses and Challenges

“…In the study, they observed the evidently dropped aminotransferases (P < 0.0001), a progressive increase in serum albumin (P = 0.010), and a decrease in serum bilirubin (P = 0.011) as well as in gamma globulin (P = 0.0003) between baseline level and that after treatment [14]. A similar change was observed in other studies related to DAA and liver function repair [15,16], which confirms this tendency.…”

“…Interestingly, with respect to patients who were diagnosed as liver fibrosis and cirrhosis, R. Flisiak et al found that their liver function improvement after DAA treatment was often better than that of non-cirrhotic patients [15]. The success of DAA treatment can reduce the liver stiffness value, which means the regression of fibrosis, the down-regulation of inflammatory activity and the improvement of blood circulation and the regression of hepatic steatosis [20].…”

Impact of liver‐stiffness measurement on hepatocellular carcinoma development in chronic hepatitis C patients treated with direct‐acting antivirals: A systematic review and time‐to‐event meta‐analysis

“…Recently, DAAs were developed for CHC treatment that showed good efficacy, high SVR rates, and improved patient outcomes 35–37 . However, there is controversy regarding HCC development, as several studies reported a persistent risk of HCC after DAA treatment in CHC patients 38–40 . Regarding cumulative incidence of HCC, 1‐year cumulative incidence was estimated to be 3.7% in this meta‐analysis, similar or even slightly higher than pretreatment 1‐year cumulative incidence (2.4%) from Masuzaki et al 34 .…”

Changes of patient profile, treatment effectiveness and safety during 4 years access to interferon-free therapy for hepatitis C virus infection

“…As demonstrated previously, treatment of patients with advanced liver disease is sometimes introduced too late to reverse development of hepatocellular carcinoma. 32 In 2015-2016, the majority of patients were treatment-experienced, whereas in 2018, previous therapy was reported only in 15%. In all 3 time intervals, a large majority (71%-81%) of retreated patients failed dual therapy with pegylated interferon plus ribavirin.…”