Liver transplantation for viral hepatitis in 2015

Liver transplantation(LT) is a life-saving treatment forpatients 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.     

Management of Chronic Hepatitis B in Special Populations: Immunosuppressed Patients and Chronic Kidney Disease

Hepatitis B virus (HBV) infection remains an important cause of liver disease in the population with chronic kidney disease, including patients on long-term dialysis and renal transplant (RT) recipients. Diminished survival due to hepatitis B has been observed after RT. A thorough evaluation, including liver biopsy as well as assessment of serum markers of HBV replication (ie, hepatitis B e antigen and/or HBV DNA) is required before transplantation. Tolerance to interferon is poor both in dialysis patients and after renal transplant. Oral antiviral therapy now permits safe and potent antiviral treatment of HBV-related liver disease in chronic kidney disease patients with prevention of progressive liver disease. Preliminary evidence shows an improved survival of HBsAg positive renal allograft recipients on antiviral therapy. However, numerous issues concerning the treatment of hepatitis B in the population with chronic kidney disease remain unclear and further clinical trials are needed.     

Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation

New nucleos(t)ide analogues(NAs) with high genetic barrier to hepatitis B virus(HBV) resistance(such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation(LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physi-cians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decom-pensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus(HCV) recurrence after LT, which is the combination of sub-cutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infec-tion has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.     

Hepatitis virus infections in heart transplant recipients: epidemiology, natural history, characteristics, and impact on survival

BACKGROUND & AIMS: We have observed a high prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in heart transplant recipients (HTRs). The aim of this study was to assess the epidemiology, natural history, and clinical and biological characteristics of viral hepatitis in HTRs. METHODS: From 1983 to 1992, 874 patients underwent heart transplantation at the Pitié-Salpêtrière Hospital, Paris, France, 459 of whom qualified for analysis. A total of 140 patients had posttransplantation hepatitis B, C, or non-A-E. Sixty-nine patients developed HBV infection, 49 HCV infection, 11 HBV-HCV coinfection, and 11 non-A-E hepatitis. RESULTS: HBV was transmitted nosocomially from patient to patient, most likely during endomyocardial biopsies. HCV was mainly transmitted through blood transfusions or the transplanted organ. Clinical and biological findings after 2 years of follow-up showed that 3 patients with an HBV genotype A precore mutant had severe or subfulminant hepatitis and that patients with HBV and HCV infection always progressed to chronicity. In general, patients had mild alanine aminotransferase level increases, a high level of viral replication, and few severe histologic lesions, except for patients infected by precore HBV mutants. Patients coinfected by HBV and HCV tended to have more severe liver lesions. The survival rate 5 years after transplantation in patients with viral hepatitis (HBV, 81%; HCV, 89%; HBV and HCV coinfection, 100%; non-A-E hepatitis, 73%) was similar to that in patients without liver test abnormalities (76%). The actuarial survival curve was also similar in patients with or without liver test abnormalities. CONCLUSIONS: In our experience, histologic liver lesions do not progress rapidly in patients with post-heart transplant infection caused by HBV or HCV. HBV or HCV infection seems to have little impact on the 5-year survival rate of HTRs.     

Treatment of recurrent hepatitis C after liver transplantation

Chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States and Europe, and more than 20,000 patients worldwide have undergone transplantation for complications of chronic hepatitis C. In North America, HCV accounts for 15% to 50% of the liver transplants performed in United States transplant programs. To maximize the long-term survival of liver transplant recipients who have HCV infection, eradication of infection is the ultimate goal. Pretransplant antiviral therapy with the goal of achieving viral eradication before transplantation is a consideration in some patients, especially those who have mildly decompensated liver disease. This article focuses on the management of liver transplant recipients who have HCV infection at the time of transplantation. Prophylactic and preemptive therapies, as well as treatment of established recurrent disease, are the strategies reviewed.     

Evolution of hepatitis B management in kidney transplantation

Chronic hepatitis B virus(HBV)infection adversely influences the clinical outcomes of renal transplant recipients owing to increased hepatic complications.Management of HBV infection in kidney transplant recipients presents a challenge to clinicians,especially in endemic regions.Interferon precipitates renal allograft dysfunction.Treatment with lamivudine,the first oral nucleoside analogue available,resulted in effective viral suppression,reduced liver-related complications,and improved patient survival so that medium-term data showed comparable patient survival rates between hepatitis B surface antigen-positive and HBsAg-negative kidney transplant recipients in the era of effective antiviral therapies.Entecavir has replaced lamivudine as first-line therapy for treatment-na?ve subjects in view of the propensity for drug resistance with the latter.Management of HBV infection in kidney transplant patients needs to take into consideration the nephrotoxicity of nucleoside/tide analogues such as adefovir and tenofovir.Prevention of HBV-related complications in kidney transplant recipients starts much earlier prior to transplantation,with vaccination of patients with chronic kidney disease and donor-recipient matching with regard to HBV status.In addition to anti-viral treatment,patients with chronic HBV infection must have regular surveillance for liver cancer and assessment for the development of cirrhosis.     

Human hepatitis viruses-associated cutaneous and systemic vasculitis

Human hepatitis viruses (HHVs) include hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus, and hepatitis E virus and can cause liver inflammation in their common human host. Usually, HHV is rapidly cleared by the immune system, following acute HHV invasion. The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion, in the acute stage. Nevertheless, the viral infectious process can persist for a long period of time, especially in HBV and HCV infection, leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer. HHV infection brings about complications in other organs, and both acute and chronic hepatitis have been associated with clinical presentations outside the liver. Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation; moreover, there is growing evidence for a possible causal relationship between viral pathogens and vasculitis. Except for hepatitis delta virus, other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis via different mechanisms, including direct viral invasion of vascular endothelial cells, immune complex-mediated vessel wall damage, and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells. Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection. Although therapeutic guidelines for HHV-associated vasculitis have not yet been established, antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids. Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.     

Aktueller Stand der Lebertransplantation

End-stage liver disease due to viral hepatitis is a frequent indication for liver transplantation as the ultimate treatment option in Germany and worldwide. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) lead to liver cirrhosis and progressive organ failure requiring patients to be short-listed for liver transplantation. Treatment options for viral hepatitis before and after liver transplantation have improved considerably in recent years. The effective antiviral treatment of chronic HBV infections with up to date nucleos(t)ide analogues featuring high antiviral potency and low rates of resistance has been followed by a considerable decrease in hepatitis B associated liver transplantations. The effective but expensive combination prophylaxis of human hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues after transplantation has reduced the number of HBV reinfections to almost negligible numbers. Hepatitis C virus reinfection occurs regularly after liver transplantation. Factors such as donor age and excessive immunosuppression negatively influence the course of HCV reinfection. The practicability and value of modern triple therapy regimens including interferon, ribavirin and protease inhibitors as well as substances still in clinical development before and after liver transplantation still need to be evaluated.     

Hepatitis C virus and kidney disease

Hepatitis C virus (HCV) infection remains frequent in patients on renal replacement therapy and has an adverse impact on survival in infected patients on chronic hemodialysis as well as renal transplant (RT) recipients. Nosocomial spread of HCV within dialysis units continues to occur. HCV is also implicated in the pathogenesis of renal dysfunction often mediated by cryoglobulins leading to chronic kidney disease as well as impairing renal allograft function. The role of antiviral therapy for hepatitis C in patients with renal failure remains unclear. Monotherapy with conventional interferon (IFN) for chronic hepatitis C is probably more effective in dialysis than in non-uraemic patients but tolerance is lower. Limited data only are available about monotherapy with pegylated interferon and combination therapy (pegylated IFN plus ribavirin) for chronic HCV in the dialysis population. Clinical experience with antiviral therapy for acute HCV in dialysis population is encouraging. Interferon remains contraindicated post-RT because of concerns about precipitating graft dysfunction. Sustained viral responses obtained by antiviral therapy in renal transplant candidates are durable after renal transplantation and may reduce HCV-related complications after RT (post-transplant diabetes mellitus, HCV-related glomerulonephritis, and chronic allograft nephropathy).     

A virological perspective on the need for vaccination

Superinfecton of chronic carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV) with hepatitis A virus (HAV) is often associated with more severe liver disease than infection with HAV alone. Superinfection commonly causes markers of HBV and HCV replication to fall to significantly lower levels. The pathogenesis of acute liver damage characteristic of viral hepatitis is thought to be mediated by host cytotoxic T-lymphocytes (CTLs) directed against virus-infected hepatocytes. It has been proposed that the more aggressive liver disease observed in individuals infected with HAV in addition to chronic HBV/HCV is a result of the induction of interferon (IFN)-alpha during acute HAV infection. This accounts for the antiviral effect on the active markers of HBV/HCV replication, and the enhanced CTL response against HBV/HCV-infected hepatocytes. Alternatively, HAV may indirectly stimulate the T helper 1 (Th1)-type cytokine responses, such as interleukin (IL)-2, IFN-gamma and tumour necrosis factor (TNF)-alpha, which directly promote the antiviral CTL response. Clearance of HBV infection, and possible HAV and HCV, is associated with a specific CTL response, while viral persistence in chronic HBV and HCV infection has been attributed to an imbalance in the Th1-Th2 arms of the immune response. Vaccination against hepatitis A should be considered for patients with chronic HBV/HCV infection, to minimize the risk of exacerbating underlying liver disease.     

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.     

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus(HIV)positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers.Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients coinfected with hepatitis B virus(HBV).However,liver transplantation in HIV positive patients with hepatitis C virus(HCV)has poorer outcomes overall,requiring careful selection of candidates.This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management.In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.     

Does antiviral therapy for hepatitis B and C prevent hepatocellular carcinoma?

Approximately 75% to 80% of hepatocellular carcinomas (HCC) worldwide are attributed to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Thus, effective prevention of HBV and HCV infection and progression from acute HBV and HCV infection to chronic hepatitis, cirrhosis and HCC might prevent as many as 450,000 deaths from HCC each year. The most effective approach to preventing HCC is to prevent HBV and HCV infection through vaccination. Indeed HBV vaccine is the first vaccine demonstrated to prevent cancers. However, a vaccine for HCV is not available and for persons who are chronically infected with HBV or HCV, antiviral therapy is the only option for preventing HCC. Direct evidence supporting a benefit of antiviral therapy on the prevention of HCC has been shown in a few randomized controlled trials. There is abundant evidence that antiviral therapy, in patients with long-term virological response, can improve liver histology, providing indirect support that antiviral therapy may prevent HCC by slowing progression of liver disease and possibly even reversing liver damage. Nevertheless, the risk of HCC remains in patients with chronic HBV or chronic HCV infection if treatment is initiated after cirrhosis is established. These data indicate that treatment might be of greater benefit if instituted earlier in the course of chronic hepatitis B or C. Safer, more effective, and more affordable antiviral therapies are needed for both hepatitis B and hepatitis C so more patients can benefit from treatment and more HCCs can be prevented.     

Viral hepatitis in solid organ transplantation other than liver

Transplantation is the best treatment for end-stage organ failure. Hepatitis virus infections, mainly hepatitis B virus (HBV) and hepatitis C virus (HCV) infections still constitute a major problem because they are common in allograft recipients and are a significant cause of morbidity and mortality after transplantation. Recently, hepatitis E virus infection has been added as an emergent cause of chronic hepatitis in organ transplantation. The prevalence of HBV and HCV infections has markedly decreased in patients who are candidates for transplantation since the introduction of screening, hygiene and prevention measures, including systematic screening of blood and organ donations, use of erythropoietin, compliance with universal hygiene rules, segregation of HBV-infected patients from non-infected patients and systematic vaccination against HBV. A liver biopsy is preferable to non-invasive biochemical and/or morphological tests of fibrosis to evaluate liver fibrosis before and even after transplantation. Treatment with entecavir or tenofovir is indicated in HBV-infected dialyzed patients who have moderate or severe disease (≥A2 or F2 on the Metavir scale) in preparation for renal transplantation. Due to the risks of severe reactivation, fibrosing cholestatic hepatitis or histological deterioration after transplantation, systematic use of nucleoside or nucleotide analogues shortly before or at the time of transplantation is recommended (tenofovir or entecavir are preferable to lamivudine) in all patients, whatever the baseline histological evaluation. In HCV-infected dialyzed patients who are not candidates for renal transplantation, the indication for antiviral therapy is limited to significant fibrosis (fibrosis ≥2 on the Metavir scale). Treatment must be proposed to all candidates for renal transplantation, whatever their baseline histopathology, and interferon-α should be used as monotherapy. After transplantation, interferon-α is contraindicated but may be used in patients for whom the benefits of antiviral treatment clearly outweigh the risks, especially that of allograft rejection. All cirrhotic patients, notably after solid organ transplantation, should be screened for hepatocellular carcinoma. Sustained suppression of necro-inflammation may result in regression of cirrhosis, which in turn may lead to decreased disease-related morbidity and improved survival. Finally, due to the high mortality after renal transplantation, active (namely without sustained viral suppression) cirrhosis should be considered a contraindication to kidney transplantation, but an indication to combined liver-kidney transplantation; on the contrary, inactive (namely with sustained viral suppression) compensated cirrhosis may permit renal transplantation alone. Organ transplantations other than kidney (cardiac or pulmonary transplantations) involve the same diagnosis and therapeutic issues.     

Posttransplantation: future therapies

Recent advances in prophylaxis and treatment of hepatitis B virus (HBV) infection after liver transplantation have improved the outcome of liver transplantation for hepatitis B. Currently, the long-term use of hepatitis B immune globulin (HBIG) and/or nucleoside analogues are the only effective therapies to prevent or ameliorate HBV recurrence in liver transplant patients. However, they are very expensive, and breakthrough infections due to resistant HBV mutants are not infrequent. New strategies are being sought to decrease the risks of breakthrough infection and to increase the cost-effectiveness of liver transplantation for hepatitis B. Vaccination to prevent de novo infection is strongly recommended before transplantation, despite a decreased response in this immunosuppressed population. Adoptive transfer of immunity with such therapies as bone marrow or cytotoxic T lymphocyte transplants or xenotransplantation of an organ from a donor, which is not susceptible to infection by HBV may be effective in preventing or treating recurrent HBV posttransplantation. In addition, gene therapies and use of nucleoside and nucleotide analogues to disrupt various stages of the HBV life cycle may prevent or slow viral replication or assembly of the virus. Ultimately, the most effective therapy for the prevention of recurrent hepatitis B after liver transplantation will involve a combination of HBIG with one or more of the new antiviral agents.     

Hepatitis B and hepatitis C virus and chronic kidney disease

The most common cause of liver disease in patients with chronic kidney disease (CKD) remains infection by hepatitis B virus (HBV) and/or hepatitis C virus (HCV). The adverse effects of HBV and/or HCV infections upon survival in patients with CKD have been repeatedly confirmed. An excess risk of death in HBsAg positive or anti-HCV antibody-positive patients may be at least partially attributed to chronic liver disease with its attendant complications. A negative impact of HCV infection on survival after renal transplantation has been linked to extrahepatic complications, including chronic glomerulonephritis, sepsis, chronic allograft nephropathy, post-transplantation diabetes mellitus, and abnormal metabolism of calcineurin-inhibitors. Transmission of HCV infection by grafts from HCV-infected donors has been unequivocally demonstrated. Registry analyses suggest that recipients of kidneys from anti-HCV antibody positive donors are at increased risk of mortality. Renal grafts from HCV-infected donors should be restricted to viremic anti-HCV positive recipients. Several drugs have been recently licensed for therapy of HBV infection but availabledata in patients with CKD is mostly limited to experience with lamivudine. The standard of care for hepatitis C infection in patients on regular dialysis is monotherapy with conventional interferon, according to recent guidelines. Only dire circumstances justify interferon use after renal transplantation.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.     

Management of Hepatitis B Virus Coinfection: HIV, Hepatitis C Virus, Hepatitis D Virus

Coinfection of hepatitis B virus (HBV) with HIV, hepatitis C virus (HCV) and hepatitis D virus (HDV) is common because of shared modes of transmission. Increasing prevalence of high risk sexual behavior and intra venous drug use (IVDU) contributes to a majority of the cases with coinfection. Occult HBV or prior HBV infection is frequently encountered in patients coinfected with HIV or HCV. Although HBV is a preventable disease, failure to screen and inadequate vaccination in the high risk individuals account for vast under-recognition of the cases with HBV infection. Chronic liver disease from viral hepatitis B and C has emerged as the major cause of morbidity and mortality worldwide as well as in the United States. This is especially true in cases coinfected with HIV. The potential long term risks of untreated hepatitis include cirrhosis and hepatocellular carcinoma. There have been several advancements in the understanding of natural history and management options of chronic viral hepatitis. This article discusses and reviews the natural history, epidemiology, and management of HBV patients coinfected with HIV, HCV, or HDV. It includes an updated summary of the outcomes with liver transplantation and post transplant recurrence in the coinfected population with HBV. It also discusses the role of occult HBV in HIV and HCV coinfection respectively.     

Management of hepatic complications in HIV-infected persons

In the era of effective antiretroviral therapy (ART), liver disease is the second most common cause of death among persons with human immunodeficiency virus (HIV) infection. Liver disease-related deaths mostly result from chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). In addition, recent reports suggest that HCV infection may be transmitted sexually between HIV-infected men who have sex with men. Management of these conditions in HIV-infected persons requires careful consideration, balancing the potential benefits of therapy with the potential for significant treatment-related adverse effects (HCV infection) and viral resistance and/or hepatitis flares (HBV infection). Furthermore, several antiretroviral agents are active against HBV infection, including lamivudine, emtricitabine, tenofovir, and, more recently, entecavir. Despite the complexity and potential for antiretroviral-associated hepatotoxicity, ART usually is safe for patients with viral hepatitis coinfection, and, in some cases, treatment for HIV infection may be beneficial for the liver.     

Surgical approach for hepatitis C virus-related hepatocellular carcinoma

Hepatitis C is a strong prognostic factor for patients with hepatocellular carcinoma(HCC). Although liver resection and liver transplantation offer the chance of a cure for HCC,adequate management of co-existing infection with hepatitis C virus(HCV) is important to enable better long-term outcomes after surgery for HCV-related HCC. For patients undergoing liver resection,perioperative anti-viral treatment is recommended,since a decreased HCV viral load itself is reportedly associated with a lower tumor recurrence rate and a longer overall survival. For patients undergoing transplanatations for HCC complicated by end-stage liver disease,the post-transplant management of HCV infection is also necessary to prevent progressive graft injury caused by active hepatitis under the immunosuppressive condition that is needed after liver transplantation. Although only a few lines of solid evidence are available for postoperative antiviral treatment because of the limited indication and frequent adverse events caused by conventional high-dose combination interferon therapy,new direct acting anti-viral agents would enable interferon-free anti-viral treatment with a higher virologic response and minimal side effects.