Clinical worsening after achieving a sustained virological response (SVR) needs to be clarified and explained. Persistence of hepatitis C virus (HCV) core antigen interacts with the host proteins to interfere with signaling pathways and increases the susceptibility to hepatic carcinogenesis.

This study aimed to investigate the risk factors that increase the progression of liver disease and hepatocellular carcinoma in a subgroup of HCV patients who achieved a SVR.

Eighty-nine HCV patients with hepatic decompensation were selected 8.2 ± 1.8 months after achieving SVR24. HCV core antigen and HCV RNA were detected in peripheral blood mononuclear cells. Matched control (n = 100) and training (n = 200) groups were recruited.

Eighty-five patients showed a progression of Child-Turcotte-Pugh and model for end-stage liver disease scores, with positive RNA in peripheral blood mononuclear cell (357.4 ± 42.1 IU/million cell) and positive hepatitis C virus core antigen (n = 73); four patients were excluded. Susceptibility to decompensation and hepatocellular carcinoma after direct-acting antiviral drugs increased with age [odds ratio (OD) = 1.87], and was associated with male sex (OD = 1.65), diabetes (OD = 3.68), thrombocytopenia (OD = 2.44), pretreatment Alfa-fetoprotein (OD = 3.41), and occult HCV (OD = 4.1).

Clinical deterioration after SVR could be explained by occult HCV mainly in older male patients with diabetes and thrombocytopenia.

Hepatitis C infection represents a global health problem affecting ∼200 million chronically infected patients worldwide. Owing to the development of a fibrogenic and inflammatory micromilieu in the liver, hepatitis C virus (HCV)-infected patients are at a high risk of developing fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral agents (DAAs), however, has spurred a revolution in the treatment of HCV patients with sustained viral response (SVR) rates exceeding 90% in real-life settings. Recent clinical trials suggest that these novel treatments will not only alter the epidemiology of HCV infection but also the incidence of HCV-induced complications including hepatic decompensation, liver transplantation and hepatocarcinogenesis. Here, we summarize data from clinical trials carried out in HCV patients with compensated and decompensated cirrhosis and analyze the impact of viral clearance on HCC development and treatment. Finally, we review and discuss current and future treatment options of HCV patients with HCC in pre- and post-transplantation settings.

Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.

Liver transplant candidates and recipients with hepatitis C virus (HCV)-related liver disease greatly benefit from an effective antiviral therapy. The achievement of a sustained virological response before transplantation can prevent the recurrence of post-transplant HCV disease that occurs universally and correlates with enhanced progression to graft cirrhosis. Previous standard-of-care regimens (e.g., pegylated-interferon plus ribavirin with or without first generation protease inhibitors, boceprevir and telaprevir) displayed suboptimal results and poor tolerance in liver transplant recipients. A new class of potent direct-acting antiviral agents (DAA) characterized by all-oral regimens with minimal side effects has been approved and included in the recent guidelines for the treatment of liver transplant recipients with recurrent HCV disease. Association of sofosbuvir with ribavirin and/or ledipasvir is recommended in liver transplant recipients and patients with decompensated cirrhosis. Other regimens include simeprevir, daclatasvir, and combination of other DAA. Possible interactions should be monitored, especially in coinfected human immunodeficiency virus/HCV patients receiving antiretrovirals.

Hepatitis C virus (HCV) infection remains the leading indication for liver transplant, and viral eradication prior to liver transplant to prevent disease recurrence has traditionally been challenging because of the poor tolerability and efficacy of available therapies. However, with the recent introduction of potent interferon (IFN)-free direct acting antiviral regimens, viral eradication prior to liver transplant is now possible.

Although data are limited, several proof of concept studies have now shown high rates of safety and efficacy in patients with compensated as well as mild-to-moderately decompensated cirrhosis. Although, treatment on the liver transplant waiting list can safely prevent postliver transplant recurrence in selected patients, the ideal regimen and treatment duration have yet to be determined.

Although IFN-free therapies represent a tremendous advance in our ability to cure this previously difficult to treat population, additional data on the safety of these regimens, particularly in patients with severely decompensated cirrhosis, the consequences of virologic failure and the impact of viral eradication on short- and long-term liver function are urgently needed.

Telaprevir is one of the first direct-acting antiviral drugs approved for the treatment of the hepatitis C virus (HCV) genotype 1. Following its approval in 2011, new data regarding the pharmacokinetics and pharmacodynamics were reported, leading to important clinical applications.

This article reviews the pharmacokinetic and pharmacodynamic properties of telaprevir for the treatment of the HCV. The areas covered include data regarding the drug's absorption, distribution, metabolism and excretion, in addition to the antiviral activity strategy such as the clinical dose selection and treatment duration.

Telaprevir presents several pharmacological properties that could limit its administration such a high-fat, high-calorie meal; the need to be administrated with pegylated IFN plus ribavirin; and the drug-drug interaction profile. As a consequence and considering the new therapeutic arsenal against the HCV, the use of telaprevir as part of HCV therapy will be limited.

Interferon-free regimes are now the treatment of choice for patients with chronic hepatitis C; previously patients who were 'difficult-to-treat' using interferon-containing treatments can now safely be treated with such therapies. More than 90% of patients infected with HCV genotype 1 or 4, compensated cirrhosis, or who have had liver transplantation, can be cured with the use of sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the combination of paritaprevir with ritonavir, ombitasvir and with or without dasabuvir. Addition of ribavirin seems to shorten treatment duration. However, the safety of these drugs is not fully explored in patients with decompensated cirrhosis (that is, those with Child-Pugh class C disease), and protease inhibitors should not be used in this group. The optimal use of interferon-free regimes in patients with renal failure or after kidney transplantation is currently being studied. However, new and improved drugs are needed to treat patients infected with HCV genotype 3. Unfortunately, the broad application of new HCV treatments is limited by their high costs. In this Review, I discuss the treatment of patients with hepatitis C with compensated and decompensated cirrhosis, before and after orthotopic liver transplantation and in patients with impaired kidney function.

Viral hepatitis is both a leading indication for liver transplant (LT) and an important cause of posttransplant graft loss and mortality. Treatment and prevention of hepatitis B virus in LT recipients, with the observed corresponding improvement in post-LT outcomes, is among the great success stories in transplantation. By comparison, treatment of hepatitis C virus with safe and effective regimens is only just becoming a reality. Chronic hepatitis E virus infection in LT recipients represents a newly described phenomenon that can also lead to graft loss; early diagnosis and treatment may be key in the management of these patients.