Adefovir treatment in posttransplant hepatitis B virus infection resistant to lamivudine plus hepatitis B virus immunoglobulin

Failure of prophylaxis for hepatitis B virus (HBV) recurrence in liver transplant patients with HBV immunoglobulin (HBIG) or lamivudine or both can be associated with rapid development of liver failure. Some of these patients develop a devastating clinicopathological state characterized by jaundice and rapidly progressive liver failure or fibrosing cholestatic hepatitis. We present two liver transplant recipients who experienced HBV recurrence while they were under lamivudine and HBIG prophylaxis. One of them had finding of severe HBV infection; the other, fibrosing cholestatic hepatitis. After commencing adefovir dipivoxil both patients showed improvements in clinical status and laboratory data. At month 4 of treatment, HBV DNA values became negative and liver function tests almost normalized. In addition, in one case showed HBs ag/anti-HBs seroconversion. When failure of prophylaxis with lamivudine and HBIG occurs, adefovir dipivoxil should be considered to be a safe and effective choice for recurrent HBV infections in liver transplant patients.     

Hepatitis B treatment: Lessons for the nephrologist

Hepatitis B affects approximately 350 million people worldwide, and an estimated 1.25 million people in the United States. Although most people infected with the virus do not develop significant hepatic disease from hepatitis B, 15-40% will develop serious complications. These complications include cirrhosis, the development of hepatocellular carcinoma , and hepatic decompensation. Patients with renal failure have increased risk of acquiring the virus through blood transfusions and contact with bodily fluids at hemodialysis centers, and of developing complications from hepatitis B virus infection. Renal transplant patients are at increased risk for exacerbations of hepatitis B with immunosuppression. Thus, it is crucial for the nephrologist to have a clear understanding of the natural history and treatment of hepatitis B, both pre- and post-renal transplant.     

Adefovir dipivoxil as the rescue therapy for lamivudine-resistant hepatitis B post liver transplant

INTRODUCTION: Complications of hepatitis B virus (HBV) infection are among the most common indications for liver transplant in many parts of Asia. However, none of the current posttransplant hepatitis B prophylaxis strategies, namely, lamivudine, hepatitis B immunoglobulin monotherapy, or combination therapy, is ideal. Our aim was to evaluate the use of adefovir dipivoxil (ADV) as a rescue therapy for posttransplant HBV patients who developed lamivudine resistance. METHODS: Twenty-two consecutive patients with HBV-related liver disease, who underwent first liver transplants from 1995 to 2002, received HBV prophylaxis with indefinite lamivudine with substitution of ADV for patients who developed drug resistance and clinical deterioration, defined as persistent elevation of transaminases or histologic deterioration. RESULTS: Sixteen patients (73%) were alive at their last follow-up and six (38%) had developed hepatitis B recurrence at a median of 46 (range 9 to 74) months posttransplant. Two with persistently normal transaminases and normal liver histology at 3 and 42 months postrecurrence have been continued on lamivudine. Four showed clinical deterioration and received ADV for a median of 24 months; all displayed normalization of transaminases and a 2 to 5 log drop in HBV DNA titers. Three had paired biopsies before and after substitution of ADV with two showing improvement and one stable appearance. The median serum creatinine value increased slightly from 126 to 138 micromol/L (P = 0.72). CONCLUSION: ADV is an effective rescue therapy for patients with lamivudine-resistant hepatitis B post-liver transplant. Further studies are needed to ascertain the optimal posttransplant hepatitis B prophylaxis.     

Management of chronic hepatitis B in the liver transplant setting

Chronic viral hepatitis is the leading indication for orthotopic liver transplantation worldwide. Hepatitis B immunoglobulin and lamivudine (LAM) have been widely adopted as an effective treatment strategy against recurrent hepatitis B virus (HBV) infection in posttransplant patients. However, immunosuppression and the anti-hepatitis B surface (anti-HBs)–mediated immune pressure on HBV may culminate in the emergence and/or selection of immune escape HBV mutants. The emergence of mutations in the tyrosine methionine, aspartate, aspartate motif of the DNA polymerase represents a significant problem of long-term LAM therapy. Newer nucleoside analogs, such as adefovir dipivoxil (ADV) and entecavir, may provide a rescue therapy for LAM-resistant strains to avoid potential aggressive courses of HBV graft reinfection in liver transplant recipients. Previously, the selection of novel ADV-resistant mutations has been described in approximately 2% of patients over a 2-year treatment period. Five-year resistance surveillance programs are currently ongoing to monitor the emergence of ADV-resistant mutants in the long-term. Because of significant advances in detection, monitoring, and treatment options of hepatitis B, patient and graft survival have become excellent over the last years.     

Treatment with adefovir dipivoxil in a renal transplant patient with renal insufficiency and lamivudine-resistant hepatitis B infection

Lamivudine is a safe, effective treatment for hepatitis B virus (HBV) reactivation after renal transplantation. However, prolonged lamivudine therapy can produce resistance to the drug. Adefovir dipivoxil (ADV) has demonstrated efficacy in patients with lamivudine resistance, but there is limited clinical experience in patients with either renal transplants or severe renal insufficiency. A 47-year-old man with asymptomatic HBV infection underwent renal transplantation in November 1995. In September 2000 lamivudine therapy was initiated to treat HBV reactivation. The outcome was good, with negative HBV DNA levels. Two years later, significant viral replication developed again. At that time the patient already had advanced renal insufficiency due to chronic graft nephropathy. The transaminase levels were increased, and the HBV DNA reached greater than 200,000 copies/mL by polymerase chain reaction, with development of ascites and cirrhosis. The patient was started on ADV 10 mg every 72 hours (dose adjusted to renal function). There was rapid normalization of hepatic enzymes and progressive decline of the viral load. HBV DNA became negative after 6 months of ADV treatment. The renal function has since remained stable. This case suggests that ADV can be safe and effective in the treatment of renal transplant patients with lamivudine-resistant hepatitis B, even in the presence of advanced renal insufficiency.     

Loss of serum HBsAg after interferon-A therapy in liver transplant patients with recurrent hepatitis-B infection

Reinfection with hepatitis B virus after orthotopic liver transplantation is nearly universal in patients who have not received posttransplant immunoprophylaxis. Recurrence almost invariably leads to chronic liver disease. Interferon has been used both prophylactically and therapeutically but has not been effective. We treated 2 liver transplant patients with recurrent hepatitis B virus (HBV) infection (serum hepatitis B surface antigen [HBsAg] and HBV DNA positive on polymerase chain reaction, and positive liver biopsy result) with interferon, 3 to 6 MU three times weekly for 6 to 22 months. A full response to therapy was manifested in both patients by normalized serum alanine aminotransferase levels and the loss of serum HBsAg and HBV DNA. The effectiveness of interferon in our patients may have been related to coinfection with hepatitis D virus in the first case and the high interferon dose (6 MU, three times weekly) and long treatment period (22 months) in the second. No episodes of rejection were noted during therapy. We conclude that interferon can induce a complete response in liver transplant patients with recurrent HBV infection. Future studies should investigate the use of interferon therapy at higher doses and/or for longer periods. (Liver Transpl Surg 1997 Jul;3(4):394-7)     

Hepatocellular carcinoma following renal transplantation: experience in northern Taiwan

BACKGROUND: Transitional cell carcinomas (TCC) have been reported to be the most common post-renal transplantation malignancy in Taiwan; they are considered to be related to the use of herbal drugs. However, in 2004, hepatocellular carcinoma (HCC) was the most prevalent malignancy at our institute. We therefore extended our observations through 2006 to include a larger renal transplant cohort. MATERIALS AND METHODS: Patients were given an immunosuppressive regimen consisting of either cyclosporine or FK 506, mycophenolate mofetil, and copticosteroid. Critical diagnostic follow-up procedures were performed trimonthly. Aggressive surgical procedures were performed when operable cancers were found. Immunosuppressants were reduced thereafter to prevent recurrence. RESULTS: Among 663 patients, 55 developed 58 malignancies which were diagnosed after a mean of 70 months posttransplantation. Among these 55 patients, 25 died. HCC accounted for 22 malignancies, followed by 15 cases of TCC, and 8 cases of posttransplantation lymphoproliferative disorder (PTLD). Fifteen known hepatitis B carriers received lamivudine therapy; none had recurrences and only 2 acquired HCC. These 2 patients are still living, whereas the remaining 20 subjects with HCC are deceased. Of the 37 patients who received anti-CD25 induction therapy, none displayed PTLD. CONCLUSIONS: HCC remains the most common post-renal transplantation malignancy in northern Taiwan. The high rates of hepatitis B and C endemic to Taiwan and the prevalence of hepatitis C virus (HCV) genotype 1b infections in northern Taiwan may explain this finding. Frequent alpha-fetoprotein measurements and liver ultrasonograms are recommended for early detection of HCC among Taiwanese renal transplant recipients. Anti-CD25 induction therapy appears to be helpful to prevent the development of PTLD among Taiwanese renal transplant recipients.     

Use of adefovir in the treatment of the chronic hepatitis B virus infection with resistance to lamivudine

Current therapies for the treatment of chronic hepatitis B virus (HBV) infection do not eliminate viral replication once therapy is stopped, resulting in a rapid rebound of viremia in a majority of patients. Prolonged therapy results in emergence of resistant virus, which is a major clinical concern. The appearance of resistant HBV is associated with decreased seroconversion rates as well as worse liver histology. Adefovir dipivoxil, a nucleotide analogue with potent antiviral activity against HBV and human immunodeficiency virus (HIV), has shown in vivo and in vitro to have activity against lamivudine-resistant HBV. We present a series of 6 patients with chronic HBV infection and lamivudine-resistant HBV treated with adefovir dipivoxil. The viremia decreased in all patients; in 4 of them, serum HBV DNA was negative by chain reaction (PCR) in a mean period of 10 months from beginning of treatment. Resistance to adefovir after 12 months of treatment has not been detected. Alanine aminotransferase (ALT) levels decreased in all patients and, at this moment, 5 of 6 patients present normal levels. There were no toxic side effects due to adefovir treatment. The data confirm that adefovir treatment has efficacy against HBV lamivudine-resistant forms.     

肝移植术后HBV再感染的治疗

目的分析肝移植术后乙型肝炎病毒（HBV）再感染患者的抗病毒治疗与乙肝病毒基因变异情况。方法317例HBV相关终末期肝病患者肝移植术后15例单独使用LAM，302例使用小剂量乙肝免疫球蛋白（hepatitis B immune globulin，HBIG）和拉米夫定（lamivudine，LAM）（或adefovir dipivoxil，ADV）联合预防HBV再感染，同时检测HBV血清标志物、血清HBV DNA、YMDD区变异、及肝活检组织乙型肝炎标记物。结果术后LAM组有4例术前HBV DNA阳性患者术后HBV再感染，LAM＋HBIG联合用药组16例HBV再感染，两组术后HBV再感染差异有统计学意义（26．7％VS．5．30％，P〈0．01）。317例患者术后12例发生YMDD变异，发生率为3．79％，再感染病例60％（12／20）。经加用ADV治疗后5例HBV DNA转阴性，4名患者HBV DNA滴度下降，肝功能显著改善，3例发生纤维淤胆性肝炎，2例死亡，1例经再次肝移植治愈。结论小剂量HBIG＋LAM可以有效地预防肝移植术后HBV再感染；在小剂量HBIG＋LAM用药基础上HBV再感染可能产生YMDD（tyrosine，methionine，aspartate，aspartate）变异；ADV可作为LAM耐药后用药，对于发生突破性感染的患者应采取以ADV为主的综合治疗。     

Efficacy of combined lamivudine and adefovir dipivoxil treatment for severe HBV graft reinfection after living donor liver transplantation

Resistance to lamivudine and hyperimmune globulin (HBIG) may cause severe graft reinfection with progression to fulminant hepatic failure in liver transplant recipients. In this report, we describe the clinical course of a patient with perinatally acquired chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma who developed severe fibrosing cholestatic hepatitis after living donor liver transplantation because of the emergence of lamivudine and HBIG-resistant chronic hepatitis B. Immunohistochemistry demonstrated that more than 30% of hepatocytes stained positively for hepatitis B core antigen. Hepatitis B virus sequence analysis revealed several mutations in the polymerase gene (L528M, M552I, M552V) as well as in the surface gene region encoding the immunogenic major hydrophilic loop of the small surface protein (G130N, M133T, D144G). The amino acid exchange at codon 144 has already been described to escape neutralization by HBIG. Combined treatment with lamivudine and adefovir dipivoxil (ADV) was associated with a dramatic biochemical, virological and clinical response with resolution of jaundice, ascites, peripheral edema and pleural effusions. Serum bilirubin normalized, HBV DNA levels significantly decreased and liver biopsy was remarkable for the absence of viral protein. These results indicate that ADV may provide a sustained rescue treatment for aggressive courses of HBV graft reinfection in liver transplant recipients.     

Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD mutant using add-on adefovir dipivoxil plus lamivudine.

Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We report the results of liver transplantation in 16 patients with pretransplantation YMDD mutants after receiving lamivudine treatment for a median of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at (n = 5) liver transplantation, and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3) to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1 patient remained positive for HBV DNA (by quantitative polymerase chain reaction [qPCR]) at the time of liver transplantation, and the titer was greater than10(5) copies/mL in 8 patients. The median follow-up after liver transplantation was 21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2 months after transplantation, and 15 patients (94%) were alive with the original graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the latest follow-up. Fourteen patients had cleared hepatitis B surface antigen (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA, however, was negative, and there was no biochemical or histological evidence of recurrence. Adefovir dipivoxil was well tolerated with no significant renal toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus lamivudine therapy provides effective prophylaxis in patients with pretransplantation YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.     

Management of chronic viral hepatitis before and after renal transplantation

Hepatitis C virus (HCV) infection is present in 2-50% of renal transplant recipients and patients receiving hemodialysis. Renal transplantation confers an overall survival benefit in HCV positive (HCV+) hemodialysis patients, with similar 5-year patient and graft survival to those without HCV infection. However, longer-term studies have reported increased liver-related mortality in HCV-infected recipients. Unfortunately, attempts to eradicate HCV infection before transplant have been disappointing. Interferon is poorly tolerated in-patients with end-stage renal disease and ribavirin is contraindicated because reduced renal clearance results in severe hemolysis. Antiviral therapy following renal transplantation is also poorly tolerated, because of interferon-induced rejection and graft loss. Although the prevalence of hepatitis B virus (HBV) infection has declined in hemodialysis patients and renal transplant recipients since the introduction of routine vaccination and other infection control measures, it remains high within countries with endemic HBV infection (especially Asia-Pacific and Africa). Renal transplantation is associated with reduced survival in HBsAg+ hemodialysis patients. Unlike interferon, lamivudine is a safe and effective antiviral HBV treatment both before and after renal transplantation. Lamivudine therapy commenced at transplantation should prevent early posttransplant reactivation and subsequent progression to cirrhosis and late liver failure. This preemptive therapy should also eradicate early liver failure from fibrosing cholestatic hepatitis. Because cessation of treatment may lead to severe lamivudine-withdrawal hepatitis, most patients require long-term therapy. The development of lamivudine-resistance will be accelerated by immunosuppression and may result in severe hepatitis flares with decompensation. Regular monitoring with liver function tests and HBV DNA measurements should enable early detection and rescue with adefovir. Chronic HCV and HBV infections are important causes of morbidity and mortality in renal transplant recipients. The best predictor for liver mortality is advanced liver disease at the time of transplant, and liver biopsy should be considered in all potential HBsAg+ or HCV+ renal transplant candidates without clinical or radiologic evidence of cirrhosis. Established cirrhosis with active viral infection should be considered a relative contraindication to isolated renal transplantation.     

Predominance of pre-S1 mutated hepatitis B virus in a patient following treatment with adefovir dipivoxil

A liver transplant recipient reinfected with a lamivudine-resistant mixed wild-type/pre-S1–deleted hepatitis B virus (HBV) strain and rescued with adefovir dipivoxil was still HBV DNA positive after more than 1 year of therapy. Analysis of serum HBV DNA, amplified by polymerase chain reaction and directly sequenced by dideoxy nucleotide chain-termination method, showed that adefovir inhibited the wild type, but not the pre-S1–deleted HBV. Predominance of the pre-S1–deleted strain over wild type after adefovir treatment suggests that either adefovir inhibited the wild type more effectively or the pre-S1 mutant replicates more efficiently. The normality of liver condition confirms that to exert its pathogenic effect, the pre-S1–deleted strain requires the presence of wild-type virus. (Liver Transpl 2003;9:188-190.)     

Fibrosing cholestatic hepatitis secondary to precore/core promoter hepatitis B variant with lamivudine resistance: successful retransplantation with combination adefovir dipivoxil and hepatitis B immunoglobulin.

Fibrosing cholestatic hepatitis (FCH) is a peculiar variant of hepatitis B virus (HBV) infection in immunocompromised patients characterized by rapid viral replication. Posttransplant patients receiving lamivudine for prophylaxis or treatment of HBV infection may develop drug resistance due to viral mutants, but FCH is rare because escape mutants are usually replication deficient. We report the development of FCH due to lamivudine-resistant HBV mutants in 2 patients at 12 and 13 months after liver transplantation. Rapidly progressive graft failure, accompanied by an escalating HBV DNA level, developed within weeks of onset. Analysis of gene sequence variation by polymerase chain reaction (PCR) and direct sequencing showed that both had a core promoter variant A1762T/G1764A and 1 had a concomitant precore stop codon G1896A variant in prelamivudine and postrecurrence serum samples. Comparison of the HBV polymerase gene in the 2 serum samples revealed a single mutation with methionine-to-isoleucine substitution at codon 552 (M552I) in both patients. "Add-in" treatment with adefovir dipivoxil resulted in a more than 2 to 3log10 reduction in HBV DNA level within 2 weeks and retransplantation was performed with adefovir dipivoxil and hepatitis B immunoglobulin (HBIG) prophylaxis. Both patients were alive at 15 months and 48 months after retransplantation, with normal graft function and serum negative for HBsAg and HBV DNA by quantitative PCR (< 200 copies/mL). The current report demonstrates that recurrent graft infection by precore/core promoter variant with lamivudine-resistant escape mutation may result in FCH. With combination of adefovir and high-dose HBIG, however, long-term survival can be achieved after retransplantation.     

血清肝炎病毒标志物阳性肾移植患者临床用药特点

目的 探讨血清肝炎病毒标志物阳性。肾移植患者术后临床用药特点。方法 40例同种异体。肾移植患者，男22例，女18例。年龄30～56岁。其中乙型肝炎感染29例、丙型肝炎感染9例、乙型肝炎合并丙型肝炎感染2例。患者肝功能正常，随机分为普乐可复组（n=20），环孢素A组（n=20）。观察患者术后肝、肾功能情况及人／。肾存活率。结果 40例患者术后随访2年，普乐可复组肝功能异常发生率、急性排斥反应发生率明显低于环孢素A组（分别为15％vs30％，5％vs20％），2组2年人／肾存活率均为100％。结论 血清肝炎病毒标志物阳性患者接受肾移植术后首选普乐可复作为基础免疫制剂方案，可减少排斥反应发生率，对肝脏的损害程度轻。     

Adefovir treatment for chronic hepatitis B in heart transplant recipients

Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine, very little data are available on safety and efficacy of other drugs. We describe our experience with adefovir dipivoxil (ADV) in eight heart transplant recipients. Studies included a baseline liver biopsy, thrice‐monthly clinical, biochemical, and virological evaluations, including genotyping and viral load, polymerase gene sequencing for resistance mutations, liver and kidney function tests, and liver ultrasound. Of eight patients, six had fibrosis score ≤2 and negative HBeAg and seven had hepatitis B virus (HBV) genotype D. Upon ADV start, median HBV‐DNA was 5.8 logs IU/mL and alanine aminotransferase (ALT) levels were mostly normal. All patients had prior mild‐to‐moderate renal functional impairment. Seven of eight patients started ADV after a previous course of lamivudine. Five of these seven patients became HBV‐DNA undetectable within eight months. One patient with low baseline viremia started ADV de novo and suppressed HBV‐DNA. Median treatment duration was 66 months. ADV daily dose was halved in one patient due to renal function worsening. No ALT flares, hypophosphatemia, liver decompensation, liver cancer, or emergence of resistance was observed. Our data suggest that ADV may be a safe and effective rescue treatment for heart transplant recipients with lamivudine‐resistant chronic hepatitis B.     

Treatment of hepatitis B reinfection after liver transplantation

Patients with chronic replicative hepatitis B virus (HBV) infection who undergo orthotopic liver transplantation (OLT) in the absence of prophylactic antiviral therapy have a high risk of graft reinfection. Serial monitoring of serum HBV DNA and HBV sequence analysis, especially of the polymerase and the "a" epitope of the surface antigen, may be a requisite diagnostic tool in order to provide optimal therapeutic management for inhibition of viral replication before and after OLT. Combination therapy with hepatitis B immunoglobulin (HBIG) and lamivudine has been widely adopted as an effective prophylactic treatment regimen against recurrent HBV disease. The major issue of concern has been the development of lamivudine resistance due to the emergence of mutations in the YMDD motif of the HBV DNA polymerase gene. Among newer antivirals, adefovir dipivoxil and entecavir have been demonstrated to be effective against both wild-type and lamivudine resistant mutants. Due to the availability of antiviral drugs, outcome of patient and graft survival has dramatically improved and has become similar or even better as compared to patients with non-HBV-related liver diseases.     

Severe clinical course of de novo hepatitis B infection after liver transplantation.

The aim of this study is to determine the origin, clinical outcome, allograft histological characteristics, and virological outcome of de novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). We studied 136 hepatitis B surface antigen (HBsAg)-negative liver transplant recipients. HBV DNA was detected by dot-blot hybridization and polymerase chain reaction (PCR). The S gene was sequenced. Hepatitis C virus (HCV) RNA was assessed by PCR. The long-term clinical and histological outcome was determined. Six of 136 HBsAg-negative patients (4.4%) became HBsAg positive after transplantation. The source of HBV infection was reactivation of latent HBV infection in 2 patients and was not identified in 4 patients. Two donors had isolated core antibody. Two of these 6 patients developed acute liver failure related to hepatitis B. The 4 other patients had severe chronic hepatitis related to hepatitis B. All patients had high-level HBV replication. No significant mutations in the S gene were found. These data suggest that de novo hepatitis B infection is not a mild disease and might represent a significant cause of graft dysfunction. This is the first report of fulminant hepatitis caused by de novo hepatitis B infection after OLT.     

Management of hepatitis B virus infection in liver transplant recipients: prospects and challenges

Although survival of liver transplantation for patients with hepatitis B infection is comparable to uninfected transplant recipients, prevention of hepatitis B virus (HBV) reinfection remains an important goal. In this article, several aspects of the hepatitis B reinfection and its management will be examined. Approximately 50% of the treatment failures that occur with hepatitis B immune globulin (HBIg) prophylaxis are due to mutations in the 'a' determinant of the HBV. In patients without mutations, failure of HBIg therapy may relate to the frequency and dose of HBIg, the type and amount of immunosuppression, and the pre-transplant replication status. Antiviral therapy with lamivudine and famciclovir has been used successfully to treat patients who have failed HBIg treatment and as monotherapies for liver transplant recipients. Combining antiviral and immunomodulatory therapies appears efficacious, at least in the short term. New developments related to immunotherapy predict three potential trends in future use: 1) i.v. formulated HBIg, 2) monoclonal antibodies, or 3) hepatitis B immune plasma. In conclusion, there are an increasing number of therapeutic options for the management of patients undergoing liver transplantation for hepatitis B infection. Continued improvement in patient outcomes requires further understanding of each therapeutic agent and the specific patient characteristics that may influence efficacy.     

Management and treatment of the HCV‐infected kidney transplant patient

The prevalence of hepatitis C virus infection is increased in patients with end stage kidney disease compared to the general population and is an adverse outcome determinant. Direct‐acting antiviral therapy for hepatitis C virus is changing the management paradigm of infected kidney transplant candidates and recipients, with potential to reduce patient morbidity and mortality. This review describes the hepatic and nonhepatic manifestations of hepatitis C virus in kidney transplant patients as well as management and treatment strategies to optimize transplant outcomes, highlighting the importance of direct‐acting antivirals in this population.