Caring for liver transplant patients suffering from chronic hepatitis C virus (HCV) infection is a challenging task for transplant surgeons and primary physicians alike. HCV is the leading cause of liver transplantation in the USA and comes with a myriad of complications that increase morbidity and mortality. This review focuses on patient follow-up, spanning from before the liver transplant occurs to the patient's long-term health. Pretransplant, both donor and recipient variables, must be carefully chosen to ensure optimal surgical success. Risk factors must be identified and HCV viral load must be reduced to a minimum. In addition to standard transplant complications, HCV patients suffer from additional problems, such as fibrosing cholestatic hepatitis and widespread viremia. Physicians must focus on the balance of immunosuppressive and antiviral medications, while considering possible side effects from these potent drugs. Over the years following surgery, physicians must identify any signs of failing liver health, as HCV-positive patients have an increased risk for cirrhosis and certain life-threatening malignancies.

The first generation direct antiviral agents (DAAs) highlighted substantial prognosis improvement among liver transplant (LT) candidates and recipients with recurrent hepatitis C virus (HCV) infection. During 2014, second generation DAAs are associated with high sustained virological response rates (> 95%), shortened duration courses and relatively few toxicities. In keeping with the currently available data, patients with decompensated cirrhosis awaiting LT is preferable to be treated with interferon-free, new generation DAAs, with or without ribavirin combinations. Although data about the safety of new DAAs combinations in this patient population are limited, sofosbuvir and daclatasvir pharmacokinetics do not appear to change significantly in moderate or severe liver impairment, while other new DAAs (simeprevir, asunaprevir) seem to be contraindicated in patients with severe liver impairment (Child-Pugh class C). On the other hand, sofosbuvir should not be given in patients with glomerular filtration rate ≤ 30 mL/min, but ongoing trials will clarify better this issue. With the objective that newer antiviral combinations will yield safer and more efficient manipulation of HCV recurrence post-transplant, the European Association for the Study of the Liver has recently updated its recommendations towards this direction. Nevertheless the new antivirals' high cost may be the biggest challenge to their implementation worldwide.

Chronic hepatitis C (CHC) is the most common indication for liver transplantation (LT). Aggressive treatment of hepatitis C virus (HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon (IFN)-based regimens can be used in dual-agent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals (e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free anti-HCV therapy for pre- and post-LT remains high.

Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting.

To assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines.

All Phase 2 and 3 studies, as well as abstract presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment-naïve and experienced individuals, as well as cirrhotic and co-infected individuals were included.

Sofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication.

Therapies for chronic HCV have evolved dramatically in recent years. Interferon-free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.

Approximately 70 000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. Early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases (liver cirrhosis and liver cancer) and its complications. In addition, it may increase work productivity and life expectancy of infected individual, and can prevent further viral transmission. Early recognition can substantially reduce the long term financial burden of related morbidity from socioeconomic point of view. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can kill the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of two direct acting first generation protease inhibitor drugs (boceprevir and telaprevir) to the dual therapy increased the chance of sustained clearance of virus to 63-75% and 59-66%, respectively. These two protease inhibitor drugs are available and financed for a segment of Hungarian patients since May 2013. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. For initiation of treatment as well as for on-treatment decisions accurate and timely molecular biology tests are mandatory. Staging of liver damage (fibrosis) non-invasive methods (transient elastography and biochemical methods) are acceptable to avoid concerns of patients related to liver biopsy. Professional decision for treatment is balanced against budget limitations in Hungary, and priority is given to those with urgent need using a national Priority Index system reflecting stage of liver disease as well as additional factors (activity and progression of liver disease, predictive factors and other special circumstances). All naïve patients are given a first chance with dual therapy. Those with genotype 1 infection and with on-treatment or historic failure to dual therapy are eligible to receive protease inhibitor based triple therapy provided, they reach financial cutoff eligibility based on Priority Index. Duration of therapy is usually 48 weeks in genotype 1 with a response-guided potential to reduce duration for non-cirrhotic patients. Patients with non-1 genotypes are treated with dual therapy (without protease inhibitors) for a genotype and response driven duration of 16, 24, 48, or 72 week. Careful monitoring for early recognition and management of side-effects as well as viral response and potential breakthrough during protease-inhibitor therapy are recommended.

Hepatitis C virus (HCV) infection is the most common indication for liver transplantation worldwide; however, recurrence post transplant is almost universal and follows an accelerated course. Around 30% of patients develop aggressive HCV recurrence, leading to rapid fibrosis progression (RFP) and culminating in liver failure and either death or retransplantation. Despite many advances in our knowledge of clinical risks for HCV RFP, we are still unable to accurately predict those most at risk of adverse outcomes, and no clear consensus exists on the best approach to management. This review presents a critical overview of clinical factors shown to influence the course of HCV recurrence post transplant, with particular focus on recent data identifying the important role of metabolic factors, such as insulin resistance, in HCV recurrence. Emerging data for genetic markers of HCV recurrence and their usefulness for predicting adverse outcomes will also be explored.

Drug-drug interactions (DDIs) in the treatment of chronic hepatitis C infection became a potential challenge with the introduction of direct-acting anti-virals (DAAs). Both currently approved DAAs, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), are substrates and inhibitors of P-glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDIs.

To analyse the risk for DDIs in patients with chronic HCV genotype 1 infection considered for PI treatment at a tertiary referral centre.

The first 115 consecutive patients selected for a PI therapy at Hannover Medical School were included. All changes to co-medication before and during PI treatment were documented. Drugs were checked for DDIs with TVR and BOC using DDI websites and the respective prescribing information.

Out-patient medication contained 116 different drugs. Median number of drugs/patient was 2 (range 0-11). The risk for DDIs was substantial for 38% of the drugs affecting 49% of patients. Only 4% of the drugs were strictly contraindicated. DDIs between a PI and drugs newly prescribed during anti-viral therapy were considerable in 42% of the patients. Suspected DDIs were managed by dose adjustments and discontinuation of co-medication in 7% and 21% of the patients respectively.

Many patients with chronic HCV genotype 1 infection are affected by potential DDIs if treated with a protease inhibitor, but only in a minority of cases co-medication is strictly incompatible. Overall, the challenge of DDIs is time-consuming, but well manageable by a careful review of the patient's drug chart and monitoring during treatment.

Antiviral treatment is recommended for chronic hepatitis C patients with advanced fibrosis to reduce and prevent cirrhosis-related complications.

To evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy for patients with advanced fibrosis in a clinical practice setting.

This prospective, multicentre study consisted of 102 patients with advanced fibrosis (METAVIR score F3-4) who were infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin (RBV).

The sustained virological response (SVR) rate was 69.6% (71 of 102). Notably, for treatment-naïve and prior relapse patients the SVR rate was over 80%. Previous treatment response, interleukin 28B polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at week 4) were independently associated with SVR. To achieve SVR, an adequate dosage of PEG-IFNα2b (≥1.2 μg/kg/week) and RBV (≥7.5 mg/kg/day) is preferable; however, the mean weight-adjusted TVR dosage had little impact on treatment outcome. Although severe blood cytopaenia and a dermatological disorder were frequently found, the rate of discontinuation due to adverse effects was 12.7%. The inosine triphosphatase CC allele (rs1127354) was independently associated with the development of severe anaemia, and lower serum albumin level (<35 g/L) was associated with the occurrence of infection.

The great gain in the SVR rate by telaprevir-based triple therapy offsets the problems with adverse effects; thus, it should be considered as a potent treatment protocol for patients with advanced fibrosis, especially for those with treatment-naïve and prior relapse.