The limited treatment varieties for patients with decompensated cirrhosis due to the hepatitis C virus (HCV) remain a challenge. With the introduction of oral direct-acting antiviral (DAA) therapy in the management of chronic active HCV, sustained response rates occurred in >90% of patients with compensated liver disease, with improvement in their survival and the risk of decompensation.
In decompensated cirrhosis, weight-based doses of ribavirin will eventually lead to anaemia that is difficult to treat. Full-dose DAAs may also worsen hepatic decompensation, however longer exposure to low-dose DAAs in decompensated cirrhosis enhances further sustained viral response (SVR) rates. The impact of DAA therapy on the mortality of patients with decompensated cirrhosis has not been investigated. Surprisingly, SVR rates with DAAs in decompensated cirrhosis may approach those achieved in compensated cirrhosis and may extend the life expectancy of this category of patients.
The aim of the current study is to evaluate the efficacy and safety of low-dose DAAs in managing chronic active HCV in patients with decompensated cirrhosis, investigate if SVR improves Child–Turcotte–Pugh (CTP), model for end-stage liver disease (MELD) scores, and the quality of life of these patients. This was a prospective, observational case control study which was conducted between August 2015 and June 2016 in the Hepatology Clinic, Internal Medicine Department, Zagazig University Hospital, Zagazig, Egypt, which is a tertiary referral centre.
Forty patients with decompensated cirrhosis and frequent episodes of hepatic encephalopathy (HE) or difficult to treat ascites were included if they had chronic active HCV proved by the positivity of HCV RNA and elevated transaminases. The patients’ CTP scores were >7 and their MELD scores <29. Patients were excluded if they had been exposed to previous antiviral therapy, had hepatocellular carcinoma, other or mixed causes of liver diseases, or previous liver transplantation.
The control group comprised 40 patients with the same inclusion criteria; all had poorly controlled ascites. They were given supportive treatment comprising silymarin 420 mg, ursodeoxycholic acid 900 mg, and symptomatic treatment for complications of liver disease. The treated patients were given sofosbuvir 200 mg, ribavirin 200 mg, and daclatasvir 60 mg for 6 months and evaluated for the development of SVR, the occurrence of complications, and the effects of SVR on the rate of development of HE, improvement in ascites control, and short-term survival. The primary outcome was SVR 12 weeks post-treatment. The secondary outcome included improved liver synthetic function, change in MELD score, or the occurrence of side effects during the period of study, including death.
At the end of the follow-up, extending to 1 year, the control group showed a highly significant worsening in their MELD score and an increase in their CTP score when compared to the treated group. HE episodes occurred in 34 patients (85%) compared with 8 patients in the treated groups (p=0.000). Ascites was poorly controlled in 32 patients (80%), partially controlled in 7 (17.5%), and completely controlled in 1 (2.5%) which was significantly lower compared with the treated group (p=0.000).
A Kaplan–Meier survival curve was performed to detect the impact of adding antiviral therapy on short-term survival and the occurrence of major events as death. Short-term survival was higher in the treated group compared with the control group (12.8±0.9 versus 9.02±2.02 months, p=0.000); 9 patients (22.5%) in the control group died due to spontaneous bacterial peritonitis leading to hepatorenal syndrome (n=2), HE (n=3), or gastrointestinal bleeding (n=4).
In summary, this is a real-life study that enrolled an adequate number of patients with HCV genotype 4-related decompensated cirrhosis. The treatment of decompensated cirrhotic patients with CTP score >7 and MELD score <29 by a 6-month regimen of low-dose DAAs led to SVR in 90% of patients, with an improvement in CTP and MELD scores and a significant reduction in HE episodes with better control of ascites and improved short-term survival.