Reversion of disease manifestations after HCV eradication

Abstract

Chronic infection with the hepatitis C virus (HCV) may lead to hepatic fibrosis and eventually cirrhosis, at which stage, patients have a substantial risk of liver failure, hepatocellular carcinoma (HCC) and liver-related death. Moreover, HCV infection is associated with several extrahepatic manifestations which impact the quality of life and increase the non-liver-related mortality rate. For patients with compensated liver disease, interferon (IFN)-based antiviral therapy has been a treatment option for over two decades. Long-term follow-up studies indicated that among those with sustained virological response (SVR) the extend of hepatic fibrosis can regress and that their risk of cirrhosis-related complications (including HCC) is reduced, also in case of cirrhosis. Recent population-based studies extended these observations for solid extrahepatic outcomes, such as end-stage renal failure and cardiovascular events. Most importantly, SVR has been associated with prolonged overall survival. These results highlight the importance of the development of new direct-acting antivirals (DAAs), by which almost all patients are able to eradicate HCV in a comfortable manner. Based on the excellent first experiences with the DAAs, physicians gained confidence to use these drugs among patients with decompensated cirrhosis on a more regular basis as well. This was not possible with interferon therapy. Also in this high risk population the DAAs show high SVR rates with improvements in biochemical parameters of liver function shortly after therapy, especially in case of SVR. In fact, some patients could actually be removed from the liver transplantation waiting list due to clinical improvement following DAA therapy. How these short-term results translate into a prolonged (long-term) survival has yet to be determined, as well as which patients with decompensated liver disease are likely or not to benefit from viral eradication. Here we review the current data regarding the beneficial clinical outcome with antiviral therapy as well the remaining uncertainties in this field, both for patients with compensated liver disease and patients with decompensated liver disease.

Clinical outcomes of direct-acting antiviral therapy in patients with compensated hepatitis C virus-related cirrhosis

“…However, it has been demonstrated that the achievement of a sustained virological response after interferon-based therapy is associated with lower rates of hepatocellular carcinoma and with lower rates of hepatic decompensation [9,10] . A regression of fibrosis after viral eradication has also been reported [11] .…”

“…Only 37.8% of patients were naïve, and 11% had liver graft cirrhosis. All patients were Child-Pugh A class at the start of the treatment and the median MELD score was 7 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). At the initiation of therapy, mean bilirubin level was 1.06 ± 0.27 mg/dL, mean platelet count was 117,788 ± 50,546/mm 3 , and mean albumin level was 4,140 ± 424 mg/dL.…”

“…A recent prospective multicenter study did not find any evidence of an increased risk of hepatocellular carcinoma recurrence in patients treated with direct-acting antivirals [16] . One report additionally demonstrated an improvement in liver function tests among patients with decompensated liver disease after treatment with oral antiviral therapy [11] .…”

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“…Preliminary evidence has shown reduced HCC recurrence rates after resection and reduced death from all causes in HCC patients. [39][40][41][42][43][44] As the new therapies become incorporated into many aspects of HCC treatment, it is likely that they will enhance survival rates for HCC ablation, resection, and transplant.…”

Hepatocellular carcinoma in the setting of Interferon-free treatment for chronic HCV hepatitis - experience of a single center

“…Furthermore, the risk of complications persists even after achieving SVR, although there is evidence demonstrating improvement in liver function tests after using DAAs [10,11] . Also, even after achieving SVR, re-infection is a possibility that can occur in 10%-15% of patients, especially in individuals at risk, such as intravenous drug users [12] .…”