Direct-acting antiviral therapy reduces variceal rebleeding and improves liver function in hepatitis C virus-related cirrhosis: A multicenter retrospective cohort study

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.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

Background: In patients with unresectable hepatocellular carcinoma (HCC), the advances in direct-acting antiviral (DAA) therapy for chronic hepatitis C remain unclear. We aimed to investigate the characteristics of DAA therapy, when compared to interferon (IFN) therapy. Methods: In this hospital-based study, all HCC patients in Barcelona Clinic Liver Cancer (BCLC) stage B or C, who received pegylated IFN or DAA, were retrospectively screened from 2009 to 2020. Patients without viremia, without HCC, or with HCC in BCLC stage 0, A, or D prior to antiviral therapy were excluded. Rates of and odds ratio (OR) for sustained virological response (SVR) achievement were analyzed. Results: Nineteen and 78 patients were recruited into the IFN and DAA groups, respectively. The median age was significantly older in the DAA group (DAA vs. IFN: 69.5 [25–75% IQR: 62.8–77.3] vs. 64.0 [25–75% IQR: 61.0–68.0]; p < 0.05). The SVR rates were higher in the DAA group as per protocol (DAA vs. IFN: 94.5% vs. 76.5%; p < 0.05) and in BCLC stage B (DAA vs. IFN: 95.2% vs. 76.5%; p < 0.05). All patients in BCLC stage C received DAA therapy, with the SVR rate being 90.9%. In multivariable regression analysis, the 4-week virological response (OR 5.6, 95% CI: 1.3–25.4) and HCC within the up-to-7 criteria (OR 3.7, 95% CI: 1.1–12.9) were independent factors associated with SVR (all p < 0.05). Conclusions: Compared to IFN therapy, more elderly patients with unresectable HCCs were able to receive DAA therapy, while achieving a significantly higher SVR rate.

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Improvements in the hepatocellular carcinoma (HCC) recurrence rate and survival have been frequently reported following virus eradication after hepatitis C virus (HCV)-related HCC cure. However, the efficacy of direct-acting antiviral (DAA) therapy in patients who included those with advanced HCC and decreased hepatic functional reserve is unknown. A comparative examination was retrospectively conducted of 141 patients with hepatitis C who started DAA therapy within 1 year after undergoing curative HCC treatment and showed a sustained viral response (SVR) and 327 patients who underwent curative treatment for HCV-related HCC and did not subsequently receive antiviral therapy. Whether DAA therapy was given was identified as an independent factor related to both HCC recurrence and survival. Both the recurrence and survival rates improved significantly with DAA therapy in Child-Pugh (CP)-A, whereas no difference in the recurrence rate was seen with DAA therapy in CP-B. However, the survival rate was significantly higher in the DAA group in this class. Similarly, dividing the patients by the Milan criteria showed significant improvements in the recurrence rate and survival with DAA therapy in patients within the Milan criteria. Patients with HCC beyond the Milan criteria showed no difference in recurrence rates, but the DAA group tended to have higher survival rates. Thus, DAA after curative therapy for HCC can be expected to improve survival in patients with advanced HCC or decreased hepatic functional reserve. HCV should be aggressively eradicated in all patients eligible for curative treatment of HCC.

Direct acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Background and aims In Egypt, ∼14.7% of the population has hepatitis C infection and genotype 4 infection accounts for more than 90% of the hepatitis C virus infections. Available data with newer all-oral regimens in the treatment of genotype 4 infection suggest that sustained virological response (SVR) 12 rates in treatment-naïve cirrhotic and noncirrhotic patients are greater than 95%. The study aimed to evaluate the virological response 12 weeks after treatment (SVR12), change in the model for end-stage liver disease score, and adverse clinical events during the study period. Patients and methods This prospective study included 451 patients with chronic hepatitis C and liver cirrhosis over a 3-month period started at January 2017. And the study was ethically approved by the Medical Research Ethics Committee, Faculty of Medicine, Al-Azhar University. The enrolled patients were classified into three groups: group I included 162 patients with chronic hepatitis C and liver cirrhosis subjected to direct-acting antivirals (DAAs) therapy (100/162 compensated cirrhosis and 62/162 decompensated cirrhosis), group II included 234 patients known to have chronic hepatitis C without liver cirrhosis subjected to DAAs therapy, and group III included 55 patients with chronic hepatitis C and liver cirrhosis not subjected to DAAs therapy according to the national protocol of therapy (as a control group). Treatment was administered for 12 weeks that included variable regimens of DAAs according to the Egyptian Ministry of Health protocol. Results We included 451 patients with chronic hepatitis C infection and liver cirrhosis; 47.8% of the patients were male, 84.4% were treatment naive, and 54.9% had cirrhosis. Of the study participants, 150 patients in group I and 53 patients in group II received sofosbuvir+daclatasvir+ribavirin, 183 patients received daclatasvir+sofosbuvir (group II), seven patients in group II received sofosbuvir+ledipasvir, five patients received sofosbuvir+ledipasvir+ribavirin (in group I), and seven patients in group I and nine patients in group II received ombitasvir/paritaprevir/ritonavir+ribavirin. Twelve weeks after end of treatment (SVR12) were 91.3% and 96.5% observed in group I and group II, respectively irrespective of the regimen of therapy. Treated patients in group I had a mean negative change in model for end-stage liver disease (−0.722; SD, 2.603) representing an improvement in liver function, whereas untreated patients in group III showed a minimal mean positive change (0.00; SD, 2.92) representing a deterioration in liver function (P&lt;0.001). Improvements were observed in the Child-score (Child–Pugh–Turcotte) in group I versus untreated patients in group III. Hepatic encephalopathy was evident in 6.1% of patients in group I after treatment versus 38.1% in untreated patients (group III), and ascites developed in 30.2% of patients after treatment (group I) versus 65.4% in untreated patients (group III). Conclusion Oral regimens of DAAs are effective in the treatment of hepatitis C virus infection even in patients with liver cirrhosis, leading to improvements in liver functions.

Hepatitis‐Viral

Safe use of livers from deceased donors older than 70 years in recipients with HCV cirrhosis treated with direct-action antivirals. Retrospective cohort study

Can We Move on From the Discussion of Direct Antiviral Agents and Risk of Hepatocellular Carcinoma Recurrence?

With the introduction of direct-acting antiviral (DAA) agents, hepatitis C virus (HCV) treatment has dramatically improved. However, there are insufficient data on the benefits of DAA therapy in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the outcome of patients who received DAA therapy after HCC treatment. We retrospectively reviewed patients with HCV-related HCC in a single medical center, and the outcome of patients with or without DAA therapy was analyzed. In total, 107 HCC patients were enrolled, of whom 60 had received DAA therapy after treatment for HCC. There were no significant intergroup differences in age, sex, laboratory results, or tumor burden. A more advanced stage was noted in the no DAA group (P = 0.003). In the treatment modality, sorafenib was commonly prescribed in the no DAA group (P = 0.007). The DAA group had a longer overall survival (OS) time than the no DAA group (P<0.001). When stratified by Barcelona Clinic Liver Cancer staging, the DAA group had better OS in the HCC stages 0-A and B-C (P = 0.034 and P = 0.006). There were 35 patients who received DAA therapy after curative HCC therapy. At a median follow-up of 20 months, 37.1% patients had HCC recurrence after DAA therapy. There was no statistical difference in recurrence-free survival between patients receiving and those not receiving DAA (P = 0.278). DAA therapy improved the survival outcome of HCC patients and did not increase recurrent HCC after curative therapy.

With the introduction of direct-acting antiviral (DAA) agents, hepatitis C virus (HCV) treatment has dramatically improved. However, there are insufficient data on the benefits of DAA therapy in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the outcome of patients who received DAA therapy after HCC treatment. We retrospectively reviewed patients with HCV-related HCC in a single medical center, and the outcome of patients with or without DAA therapy was analyzed. In total, 107 HCC patients were enrolled, of whom 60 had received DAA therapy after treatment for HCC. There were no significant intergroup differences in age, sex, laboratory results, or tumor burden. A more advanced stage was noted in the no DAA group (P = 0.003). In the treatment modality, sorafenib was commonly prescribed in the no DAA group (P = 0.007). The DAA group had a longer overall survival (OS) time than the no DAA group (P<0.001). When stratified by Barcelona Clinic Liver Cancer staging, the DAA group had better OS in the HCC stages 0-A and B-C (P = 0.034 and P = 0.006). There were 35 patients who received DAA therapy after curative HCC therapy. At a median follow-up of 20 months, 37.1% patients had HCC recurrence after DAA therapy. There was no statistical difference in recurrence-free survival between patients receiving and those not receiving DAA (P = 0.278). DAA therapy improved the survival outcome of HCC patients and did not increase recurrent HCC after curative therapy. .

From the Editor's Desk…

Introduction Directly-acting antiviral (DAA) therapy achieves sustained virological response (SVR) in over 90% of those with chronic hepatitis C (CHC), but even in those with SVR, the risk for liver related morbidity and mortality persists albeit at a lower level. It is hypothesised that the residual risk of liver related outcome in those with SVR is related to the progression or non-regression of structural and haemodynamic changes of advanced liver disease at the time of HCV therapy. Here, we investigate the effect of DAAs on the hepatic architecture and splanchnic haemodynamics in patients with decompensated cirrhosis, using quantitative MRI techniques. Method We prospectively recruited patients receiving DAAs for CHC related decompensated cirrhosis from the East Midlands hub of the Early Access Programme commissioned by NHS England. MRI was performed before and at the end of a 12-week treatment with Daclatasvir, Sofosbuvir and Ribavarin. A respiratory-triggered inversion recovery scheme was used to measure the longitudinal (T1) relaxation time of the liver employing a fat suppressed Echo Planar Imaging-acquisition. Phase-contrast (PC)-MRI was used to assess the velocity, area and bulk flow in the splanchnic circulation without any intravenous contrast agents. Results 9 patients have undergone baseline and post-treatment MR scans and end-of-treatment response (EOTR) was achieved in all 9 patients, but one patient has had virologic relapse. There was a significant reduction in the T1 relaxation time in patients with SVR (baseline T1: 765 ± 112 ms; post-treatment 737 ± 118 ms; p = 0.043) (Figure 1). There were no significant changes in the hepatic artery, portal vein, superior mesenteric artery and splenic artery flow. The changes in the Model for End-Stage Liver Disease (MELD) and United Kingdom Model for End-Stage Liver Disease (UKELD) score are shown in Table 1. Conclusion Treatment of decompensated CHC related cirrhosis with DAA is associated with early improvement in the MR markers of liver architecture. These early changes are likely to reflect the reduction in the inflammation associated with EOTR and is evident before any improvement in conventional liver function tests. This novel quantitative MR methodology will allow us to non-invasively monitor HCV related liver disease. Disclosure of interest None Declared.