Review article: the treatment of hepatitis C virus recurrence after liver transplantation

BACKGROUND: Recurrent hepatitis C represents a major challenge for the liver transplant community. Given the potentially significant impact that hepatitis C recurrence has on graft and patient survival, several treatment strategies have been utilized to prevent/slow the progression to hepatitis C-related graft failure. AIM: To review the efficacy and applicability of treatment strategies for managing recurrent hepatitis C. METHODS: Search of MEDLINE (1990 to December 2006) and national meeting abstracts. Search terms included hepatitis C, liver transplantation, treatment, sustained virological response (SVR), and end of treatment virological response. An emphasis was placed on randomized trials. RESULTS: The largest study of treatment prior to liver transplantation (n = 124) achieved SVR in 24%. Eight randomized trials (n = 383) examined the efficacy of preemptive therapy with SVR ranging from 0-33%. Eligibility for treatment was low and dose reduction common. Four randomized trials (n = 245; all abstracts) have reported SVR from 33-42% for treating those with histological evidence of recurrent disease. CONCLUSIONS: Therapies for treating hepatitis C recurrence have limited applicability and tolerability, and they have a low SVR. Based on available results, preemptive therapy is not recommended. Pegylated interferon and ribavirin is currently the preferred choice for treating established recurrence. There is an urgent need for safer and more effective anti-viral therapy in this situation.     

Review article: liver transplantation for hepatocellular carcinoma

Despite recent advances in techniques of in situ tumour ablation, surgical therapy remains at present the mainstay treatment for primary hepatic malignancies. After an initial endeavour in the establishment of liver transplantation as a treatment option, in particular for unresectable liver tumours, only a few indications, for example early hepatocellular carcinoma in cirrhosis, are currently agreed upon. Other indications, such as peripheral cholangiocarcinoma and hepatocellular carcinoma in noncirrhotics have largely been abandoned or are still under debate, as is the case with fibrolamellar carcinoma. The selection of patients suffering from hepatocellular carcinoma in cirrhosis for liver transplantation is still based on tumour size and node number, because the current state of diagnostic imaging fails to reliably predict the most important prognostic parameter: vascular infiltration. Other selection criteria are under investigation. Studies on multimodal therapy are also underway but have not yet demonstrated a clear benefit.     

Review article: current management of chronic hepatitis B

Chronic hepatitis B can be diagnosed in patients with increased aminotransferases, hepatitis B virus viraemia and necroinflammation with fibrosis on liver biopsy. Although, ideally, all patients with chronic hepatitis B should be treated, therapeutic intervention is currently recommended for cases with a relatively satisfactory likelihood of response and/or advanced disease. A realistic therapeutic approach aims to sustain hepatitis B e antigen (HBeAg) loss and hepatitis B e antibody (anti-HBe) seroconversion in HBeAg-positive chronic hepatitis B and to sustain biochemical and virological remission in HBeAg-negative chronic hepatitis B. Currently, three drugs are licensed for chronic hepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. In patients with HBeAg-positive chronic hepatitis B, all of these drugs achieve HBeAg loss (24-33%) and anti-HBe seroconversion (12-30%) rates significantly superior to those observed in untreated placebo controls. In patients with HBeAg-negative chronic hepatitis B, the sustained off-therapy response rate is 20-25% after a > or =12-month course of interferon-alpha and minimal (<10%), if any, after a 12-month course of lamivudine or adefovir. Long-term lamivudine induces an initial response in 70-90% of patients, but only 30-40% of patients remain in remission after the third year due to progressively increasing viral resistance. Long-term adefovir achieves a response in approximately 70% of patients at 12 months, which is maintained at 24 months with rare (<2%) drug resistance. Adefovir is also effective against lamivudine-resistant strains. Many other anti-viral agents, immunomodulatory approaches and combination therapies are currently being evaluated in chronic hepatitis B.     

Review article: hepatocellular carcinoma: indications for liver transplantation

The role of liver transplantation for hepatocellular carcinoma has evolved over the years and currently is one of the curative therapies for small tumours. The survival rates are similar with those for nonmalignant liver disease after transplantation. The treatment of small tumours eligible for both resection and transplantation depends on the experience of the transplant centre and the waiting time for a liver graft. With waiting times for liver transplant becoming gradually longer, prioritization of the tumour patients has been suggested. Adjuvant therapies may delay the tumour progression while patients wait for a transplant. The living donor and the domino liver transplantation are useful alternatives given the shortage of organs but the experience is still limited in the Western world and the selection for the domino livers is fairly restricted.     

Review article: improved preservation of the liver for transplantation

This paper reviews the development of the techniques used for liver preservation and describes their clinical use. Recent advances with the introduction of lactobionate based solutions for simple cold storage are described and illustrated by their effect on the Cambridge/King's College Hospital transplant programmes. Better preservation of the liver has simplified the logistics of the transplant procedure, improving organ usage and allowing increased sharing of livers for urgent or paediatric cases.     

Review article: hepatitis C virus and calcineurin inhibition after renal transplantation

The impact of hepatitis C virus on patient and graft survival after renal transplantation remains controversial. However, recent studies have given emphasis on the detrimental role of hepatitis C on long-term patient and graft survival after renal transplantation. Various mechanisms can promote the lower survival in hepatitis C virus-positive recipients, i.e. post-transplant diabetes mellitus, liver disease and infections. Novel evidence has been accumulated showing the inhibitory activity of ciclosporin on the hepatitis C virus replication rate in human hepatocytes; ciclosporin has been shown in vitro to suppress hepatitis C virus replication as effectively as interferon alpha. This effect has not been seen with tacrolimus and is separate from its immunosuppressive activity. Data from patients with normal kidney function or after bone marrow transplantation show that ciclosporin inhibits hepatitis C virus replication. It appears that the progression of liver fibrosis is slower in hepatitis C virus-positive liver transplant recipients treated with ciclosporin than tacrolimus. In contrast, the clinical outcome of hepatitis C in hepatitis C virus-positive patients after liver transplantation treated with ciclosporin vs. tacrolimus has given mixed results. No information after renal transplantation is available. Various parameters can promote the worsening of hepatitis C after renal transplantation but choice of calcineurin inhibition is one of the few risk factors that can potentially be modified by the physician. Prospective, comparative trials of ciclosporin and tacrolimus with large size and adequate follow-up after renal transplantation are in progress.     

Review article: current antiviral therapy of chronic hepatitis B

Background The long‐term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma. Aim To review the current treatment of chronic hepatitis B, with a focus on diagnosis and management of resistance and active management of suboptimal responses. Methods A systematic review of the literature, with a focus on recent guidelines, was undertaken. Results Among the six drugs licensed for the treatment of chronic hepatitis B in the US, the preferred agents in 2008 will include entecavir, peginterferon alfa‐2a, possibly telbivudine, and tenofovir following licensure. When using an oral agent, a major focus of management is on the selection of a drug with high potency and low rate of resistance, and active on‐treatment management to optimize therapy. Preventing the sequelae of antiviral drug resistance and appropriate management when resistance is initially detected are also the major focus of current management. The addition of an antiviral agent that is not cross‐resistant is critical to restore suppression of viral replication. Conclusions Newer agents and modified treatment strategies, especially using combination therapy, hold promise to optimize the management of patients with chronic hepatitis B by achieving the high potency and the lowest rate of resistance.     

Review article: current antiviral therapy of chronic hepatitis B

Aliment Pharmacol Ther 2011; 34: 1145–1158

Summary

Background The indications and endpoints for treatment of chronic hepatitis B continue to evolve. The aim of the therapy for chronic hepatitis B is to achieve a long‐term continued suppression of the hepatitis B virus (HBV) DNA to prevent disease progression leading to the development of cirrhosis and hepatocellular carcinoma. Aim To summarise current literature on therapy of chronic hepatitis B, with a focus on indications for therapy, preferred treatment options, and management of resistance and partial responders. Methods A systematic review of the literature, with a focus on international guidelines, was performed. Results Seven drugs are licensed for the treatment of chronic hepatitis B in many countries. The selection of a drug with high potency and low rate of resistance is essential to achieve rapid and long‐term viral suppression. The prevention of the sequelae of antiviral drug resistance and appropriate management of viral breakthrough are major goals of current management. The addition or change to an antiviral agent that is not cross‐resistant is critical to restore suppression of viral replication for patients with breakthrough resistance. Patient adherence to medication is essential to achieve adequate HBV DNA suppression. Conclusions The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa‐2a. Future studies are required to determine if combination therapy using two oral agents or peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy.     

Review article: current status of liver transplantation in HIV-infected patients

The increases in survival of patients infected with human immunodeficiency virus is attributed to the introduction of combination human immunodeficiency virus antiviral therapy, better known as highly active anti-retroviral therapy. In fact, survival statistics have improved such that individuals often succumb to other disease entities, notably liver failure and not from acquired immunodeficiency syndrome complications. Liver transplantation has been introduction in this patient population in several centres around the world. This review will discuss the current clinical status of liver transplantation in individuals suffering from human immunodeficiency virus infection.     

Review article: hepatitis vaccination in patients with chronic liver disease

Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.     

Review article: adult-to-adult right hepatic lobe living donor liver transplantation

Spurred on by the critical shortage of cadaveric livers, adult-to-adult right hepatic lobe living donor liver transplantation has grown rapidly as a therapeutic option for selected patients. In the USA alone, the number of living donor liver transplantations has increased six-fold in the last 4 years. The therapy can be complex, bringing together a variety of disciplines, including transplantation medicine and surgery, hepatology, psychiatry and medical ethics. Moreover, living donor liver transplantation is still defining itself in the adult-to-adult application. Uniform standards, guidelines and long-term outcomes are yet to be determined. Nevertheless, initial success has been remarkable, and a basic understanding of this field is essential to any physician contemplating options for their liver failure patients. This review covers a range of topics, including recipient and donor selection and outcomes, donor risk, controversies and future issues.     

Review article: nonalcoholic fatty liver disease and hepatitis C virus--partners in crime

Background Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) are frequent causes of chronic liver disease. In recent years, there have been significant revelations as regards the relationship between NAFLD and CHC. Aim To conduct a systematic, evidence‐based review of the epidemiology, pathophysiology and potential treatments of coexistent NAFLD and CHC. Methods The terms such as hepatitis C, fatty liver, NAFLD, nonalcoholic steatohepatitis and steatosis were searched on PubMed up to January 2008. References from selected articles and pertinent abstracts were also included. Results Hepatic steatosis affects up to 80% of patients with CHC and is dependent on both viral and host factors. While insulin resistance (IR) is associated with hepatic steatosis and hepatitis C virus, genotype‐specific pathogenic mechanisms have been identified and are currently the focus of intense investigation in the literature. Clinical implications of concurrent NAFLD, CHC and IR include increased disease progression, elevated risk of hepatocellular carcinoma, and decreased response to antiviral therapy. Conclusions NAFLD and IR are common in patients with CHC virus infection. IR is a driving force in the development of hepatic steatosis. Because of the clinical implications of hepatic steatosis and IR in the setting of CHC, further studies evaluating treatments, which may increase response to antiviral therapy, are needed.     

Review article: Nucleoside analogues for the treatment of chronic hepatitis B

Current accepted treatment for chronic hepatitis B uses either the immunomodulator interferon alpha or nucleoside analogues lamivudine or adefovir. Interferon has side effects which mean it is often poorly tolerated. Long-term use of lamivudine is associated with increasing viral resistance for each year it is taken and the rebound viraemia that can occur when the drug is stopped is also of concern to many. Adefovir appears to have less of the resistance issues of lamivudine but is still a relatively new drug and at present its use is principally limited to patients with lamivudine-resistant disease. A number of other nucleoside analogues are currently being developed with some now at the stage of early clinical trials. A proportion share the significant resistance problems of lamivudine but many appear to have more potent anti-viral effect than the drugs currently available. If some of these newer anti-viral agents are approved for use in chronic hepatitis B, the potential for prolonged suppression of hepatitis B virus replication with resultant stabilization or improvement in liver disease may be achieved.     

Review article: liver transplantation for HCC. Treatment options on the waiting list

The most widely adopted criteria to admit and maintain patients with HCC and cirrhosis in the waiting list for liver transplantation are the Milano criteria, consisting in the presence of a single tumour 相似文献