Liver-related effects of chronic hepatitis C antiviral treatment

Abstract

More than five years ago, the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral (DAA) drugs. They proved highly efficient in curing patients with chronic hepatitis C (CHC), including patients with cirrhosis. The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis, but the exact cause of the expected benefit was unclear. Further, little was known about how the underlying liver disease would be affected during and after viral clearance. In this review, we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects, such as macrophage activation, and the time-dependent effects of therapy, with specific emphasis on inflammation, structural liver changes, and liver function, as these factors are all related to morbidity and mortality in CHC patients. It seems clear that antiviral therapy, especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis. There seems to be a time-dependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions. These improvements lead to favorable effects on liver function, followed by an improvement in cognitive dysfunction and portal hypertension. Overall, the data provide knowledge on the several beneficial effects of DAA therapy on liver-related parameters in CHC patients suggesting short- and long-term improvements in the underlying disease with the promise of an improved long-term prognosis.

Keywords: Antiviral treatment; Chronic hepatitis C; Galactose elimination capacity; Hepatic encephalopathy; Inflammation; Liver cirrhosis; Liver fibrosis; Metabolic liver function; Portal hypertension; Urea synthesis capacity.

Figure 1

Release of viral particles, viral proteins, and RNA from hepatocytes in hepatitis C infection, and subsequent shedding of soluble CD163 and soluble mannose receptor from the surface of macrophages in response to exogenous and endogenous stimuli. PAMP: Pathogen-associated molecular pattern; DAMP: Damage-associated molecular pattern; MR: Mannose receptor; sMR: Soluble mannose receptor; sCD163: Soluble CD163.

Figure 2

Proposed time-line for liver-related effects of direct-acting antiviral therapy. DAA: Direct-acting antiviral; EOT: End of treatment; SVR12: Sustained virologic response at 12 wk post-treatment; SVR52: Sustained virologic response 1 year after treatment.