Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection

Abstract

Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to (pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response (SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.

Efficacy and safety outcomes of sofosbuvir-based treatment regimens for hepatitis C virus-infected patients with or without cirrhosis from phase III clinical trials

“…With the advent of DAAs, IFN-free therapeutic regimens for the treatment of chronic HCV infection are now allowed. These regimens lead to remarkable improvements in sustained virologic response (SVR12), defined as undetectable HCV RNA levels 12 weeks after the end of the treatment, thereby providing therapeutic options to patients with contraindications or low prior SVR to IFN-based regimens 4–6. In particular, regimens using sofosbuvir (SOF), a pan-genotypic HCV nucleotide polymerase inhibitor, provide more convenient dosing schedules by shortening the duration of treatment to 12–24 weeks and lead to cure rates close to 90% 7–11…”

Potential Liver Transplant Recipients with Hepatitis C: Should They Be Treated Before or After Transplantation?

“…The tolerability of DAA based regimens is definitely better with exception of those who have impaired renal function. 55 Most of the studies shown in Table 1 have shown good results. What is not shown in the table is that there is also an improvement in liver function and reversal of decompensation to some extent as more and more patients become aviremic.…”

Liver enzymes: No trivial elevations, even if asymptomatic

“…Direct-acting antiviral drugs have revolutionized HCV treatment and have led to a sustained viral response and presumed cure at 12 weeks in more than 95% of cases across all HCV genotypes. 20 Given the recent development of effective and well-tolerated treatments, primary care physicians have assumed a pivotal role in screening for HCV.…”