Hepatitis B virus reactivation is a risk factor for development of post-transplant lymphoproliferative disease after liver transplantation

Abstract:  Post-transplant lymphoproliferative disease (PTLD) is believed to be associated with immunosuppressive regimens, underlying diseases and lymphotropic viral infections after organ transplantation. Hepatitis B virus (HBV) has been identified as a risk factor for non-Hodgkin's lymphoma, but no association between HBV and PTLD has been shown. In this study, we reviewed a series of 203 consecutive patients who underwent liver transplantation (LTx) for benign liver disease in our center. The patients comprised 144 patients with hepatitis B and 59 contemporary patients without hepatitis B. After LTx, 36 of the 144 patients with hepatitis B experienced HBV reactivation, while the remaining 108 patients did not. There was no difference in the incidences of PTLD between patients with and without hepatitis B (p = 0.497). Overall, four patients (11.1%) with HBV reactivation developed PTLD, compared to only one patient (0.9%) without HBV reactivation (p = 0.007). The relative odds for developing PTLD in patients with HBV reactivation were 17.5. No differences were observed for the follow-up periods, immunosuppressive regimens and rejection episodes (p  >  0.05 for all). These data suggest that PTLD may be more prevalent in patients who experience HBV reactivation after liver transplantation. HBV reactivation may be a risk factor for development of PTLD.     

Impact of hepatitis C virus infection on short-term outcomes in renal transplantation

Hepatitis C virus is an RNA virus with 6 known genotypes. Prevalence of hepatitis C virus infection in the world is almost 3%. In patients undergoing hemodialysis, prevalence of hepatitis C virus positivity is reported to be from 1%-54% depending on the methods used for detection. Liver disease in kidney transplant recipients has been attributed to hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, ethanol, hemosiderosis, and drugs such as azathioprine and cyclosporine A. Hepatitis C virus infection is currently the main cause of chronic liver disease in this group, and it may affect allograft outcome. Whether hepatitis C virus infection after renal transplantation adversely affects graft and patient survival remains controversial. Several series have reported no impact on short- and long-term patient and graft survival. In fact, comparative studies using different immunosuppressive protocols are not available. The differences in the results of these studies may be explained by confounding factors, for example, differences in immunosuppressive protocols, study design, methodology of diagnosing hepatitis C virus infection, and differences in hepatitis C virus genotypes. Treatment protocols for hepatitis-C-virus--associated liver disease should be considered before renal transplantation. Nevertheless, transplantation is the best option for patients with hepatitis C virus with end-stage renal disease, and less hepatotoxic immunosuppressive agents may decrease the incidence of posttransplant liver disease in patients with hepatitis C virus. This review will discuss the studies with specific emphasis on the impact of hepatitis C virus infection on short-term outcome in renal transplantation.     

Liver transplantation in HCV/HIV positive patients

Since the introduction of highly active antiretroviral therapy (HAART) in 1996 for human immunodeficiency virus (HIV)-infected patients, the incidence of liver diseases secondary to co-infection with hepatitis C has increased. Although data on the outcome of liver transplantation in HIV-infected recipients is limited, the overall results to date seem to be comparable to that in non-HIV-infected recipients. Liver transplant centers are now accepting HIV-infected individuals as organ recipients. Post-transplantation HIV replication is controlled by HAART. Hepatitis C re-infection of the liver graft, however, remains an important problem because cirrhotic changes of the liver graft may be more rapid in HIV-infected recipients. Interactions between the HAART components and immunosuppressive drugs influence drug metabolism and therefore meticulous monitoring of drug blood level concentrations is required. The risk of opportunistic infection in HIV-positive transplant patients seems to be similar to that in HIV-negative transplant recipients.     

拉米呋定与乙肝疫苗预防HBcAb阳性供肝儿童肝移植术后新发乙肝病毒感染效果的对照研究

目的 比较拉米呋定与乙肝疫苗方案预防乙型肝炎核心抗体(hepatitis B core antibody,HBcAb)阳性供肝儿童肝移植术后新发乙型肝炎病毒(hepatitis B virus,HBV)感染效果.方法 对天津市第一中心医院自2013年5月—2019年6月251例接受HBcAb阳性供肝儿童肝移植的资料进行...     

Impact of hepatitis serology on development of leukopenia after solid organ transplantation

BACKGROUND: Homologous organ transplantation is an accepted therapeutic modality for end-stage disease of the kidney and liver. In posttransplantation periods leukopenia is a common problem with a wide range of differential diagnoses. Not only can it lead to an increased incidence of infections, but preclude the use of adequate immunosuppressive therapy and antimicrobial regimens because of their potential leukopenic side effects. One reason for leukopenia is viral hepatitis, which is frequently seen in transplant recipients. Herein this report, we searched for the relationship of leukopenic bouts among kidney and liver transplantation recipients to hepatitis serology. METHODS: We retrospectively evaluated the records of 569 patients who received solid transplants between January 1996 and October 2006. Because 27 patients did not come for follow-up examinations, their data were excluded, and 14 patients had 2 transplantations, yielding 556 primary transplantation cases for leukopenic attacks. RESULTS: Leukopenic attacks showed a strong relationship with hepatitis B virus (HBV) infection, but were independent of HBV DNA status (P = .002). No relationship with hepatitis C virus (HCV) infection status was found. CONCLUSIONS: Leukopenia is a common, important complication that can be seen during the posttransplantation period of recipients affecting both mortality and morbidity. HBV infection is a risk factor for development of leukopenia after transplantation. Adequate treatment of HBV infection in transplant recipients is important to obtain leukocyte counts in the normal range, allowing easier and safe antibacterial and immunosuppressive therapy in the posttransplantation period.     

HCV infection and hemodialysis

Hepatitis C virus (HCV) infections are frequent in hemodialyzed patients and are mainly related to transfusions and nosocomial contamination. HCV-related infection may result in cirrhosis in 10% of dialysis patients and is worsened by transplantation because of the immunosuppressive therapy for prevention of graft rejection. Because there is a risk for significant liver disease and because cirrhosis contraindicates a renal transplantation, a liver biopsy should be performed early in HCV-RNA positive hemodialysis patients to evaluate histologic impact of the liver disease. A combined liver-kidney transplantation should be discussed in dialysis patients with cirrhosis. Standard alpha-interferon is the only treatment for HCV in dialysis patients because ribavirin is contraindicated by a high risk for hemolytic anemia. It leads to an overall 30% rate of sustained viral eradication. It is indicated in dialysis patients with acute hepatitis C, significant liver disease (fibrosis score > or =2), or symptomatic cryoglobulinemia, and to candidates for renal transplantation, whatever the severity of the liver disease. Indeed, alpha-interferon is contraindicated in kidney recipients given the risk for rejection. Preventive treatment for HCV is only respect for universal hygiene rules in the dialysis setting because there is no available vaccine.     

Late onset cytomegalovirus disease in liver transplant recipients: de novo reactivation in recurrent hepatitis C virus hepatitis

Late onset cytomegalovirus (CMV) disease (occurring more than 1 year post-transplant] was documented in two liver transplant recipients with recurrent hepatitis C virus hepatitis in the absence of factors known to precipitate CMV disease, i. e., primary acquisition of CMV, allograft rejection, augmented immunosuppression, concomitant infections, or blood transfusions. Both patients had CMV enteritis (with CMV adrenalitis in one case]; however, other symptoms and signs of overt CMV infection, i. e., fever, leukopenia, or atypical lymphocytes, were lacking. Hepatitis C virus is an immunomodulatory virus; impaired CMV-specific T-cell responses may have accounted for the predisposition of our patients to unprovoked, late onset CMV disease. Given the high incidence of hepatitis C virus recurrence after liver transplantation, awareness of the occurrence and recognition of the unusual presentation of CMV disease in this setting is both clinically relevant and significant, particularly since CMV is treatable if recognized promptly. Received: 25 September 1997 Received after revision: 27 January 1998 Accepted: 2 March 1998     

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.     

Natural History of Patients with Recurrent Chronic Hepatitis C Virus and Occult Hepatitis B Co-Infection after Liver Transplantation

It is uncertain whether occult hepatitis B virus co-infection will hasten progressive liver disease in chronic hepatitis C patients after liver transplantation. This study evaluated fibrosis progression and severe fibrosis in 118 consecutive hepatitis B surface antigen-negative patients with virological and histological evidence of recurrent chronic hepatitis C infection co-infected with occult hepatitis B virus after liver transplantation. HBV DNA was detected from serum at the time of recurrent chronic hepatitis C infection by polymerase chain reaction. Each subject underwent a repeat liver biopsy 5 years post-liver transplantation. Occult hepatitis B virus co-infection was present in 41 of the 118 (34.7%) patients. At 5 years post-liver transplantation, 13 of the 41 occult hepatitis B virus co-infected patients compared with 16 of the 77 patients without occult hepatitis B virus co-infection developed fibrosis progression (31.7% vs. 20.8%, respectively, p = 0.39). Eight of 41 the occult hepatitis B virus co-infected patients compared with 13 of the 77 patients without occult hepatitis B virus co-infection had severe fibrosis (19.5% vs. 16.9%, respectively, p = 0.97). In conclusion, occult hepatitis B virus co-infection in patients with recurrent chronic hepatitis C infection was not associated with accelerated fibrosis progression or severe fibrosis after liver transplantation.     

De novo lung cancer diagnosed 32 months after liver transplantation: report of a case

Patients who undergo organ transplantation are now known to be at increased risk of the development of de novo malignant tumors. This is primarily a consequence of immunosuppression, which may promote tumor development and progression by a variety of mechanisms. It was also reported recently that the relative ratio of lung tumors developing in orthotopic liver transplantation patients was 3.7 times greater than in the general population. We report a case of de novo lung cancer diagnosed in a 65-year-old man 32 months after he underwent liver transplantation for hepatocellular carcinoma secondary to hepatitis C virus cirrhosis. He had received tacrolimus as immunosuppressive therapy after the liver transplantation. The tumor was resected, and he remains well almost 3 years later. Previous reports provide evidence that immunosuppressive therapy is a risk factor for de novo lung cancer; thus, it is important to reduce immunosuppression for orthotropic liver transplantation patients, and to screen them carefully to detect the tumor at an early stage.     

肝移植术后预防乙型肝炎病毒再感染281例的分析

目的分析乙型肝炎病毒(HBV)相关性肝病肝移植术后HBV再感染的原因及防治经验。方法回顾性分析281例HBV相关性肝病,移植前后给予抗病毒药物拉米夫定 人乙肝免疫球蛋白(HBIg)预防HBV再感染,其中9例为拉米夫定 阿德夫韦 HBIg,观察临床表现、血清HBV标志物、HBV DNA及肝活检免疫组织化学检测等指标。结果用拉米夫定 HBIg预防的272例中,有7例再感染,血清HBsAg、HBeAb和HBcAb阳性,肝活检免疫组织化学检测有HBsAg表达,其中2例血清HBV DNA阳性,4例经治疗后HBsAg又转阴。用拉米夫定 阿德夫韦 HBIg预防的9例中,血清学和肝活检免疫组织化学检测无HBsAg表达。结论拉米夫定 HBIg或拉米夫定 阿德夫韦 HBIg联合应用,可以有效预防HBV相关性肝病肝移植后HBV的再感染。     

Posttransplantation Hepatitis B Prophylaxis with Combination Oral Nucleoside and Nucleotide Analog Therapy

Liver transplant recipients are at risk of developing recurrent hepatitis B after liver transplantation for hepatitis B virus (HBV)‐related liver disease. We evaluated the efficacy of a new hepatitis B prophylaxis regimen involving conversion from at least 12 months of HBIg with lamivudine to combination therapy with an oral nucleoside and nucleotide analog. Between June 2008 and May 2010, a total of 61 liver transplant recipients were converted to a combination of a nucleoside and nucleotide analog. The mean (±standard deviation) follow‐up time after conversion was 15.0 (±6.1) months. Recurrent HBV occurred in two (3.3%) patients at 3.1 and 16.6 months after HBIg cessation. The overall person time incidence rate for HBV recurrence after HBIg cessation was 2.7 cases per 100 person‐years. The estimate of HBV recurrence was 1.7% at 1 year after HBIg cessation. HBIg cessation a minimum of 12 months after liver transplantation with subsequent combination therapy with a nucleoside and nucleotide analog provides effective prophylaxis against recurrent HBV infection. The clinical implications of HBsAg detection without clinical, biochemical or molecular manifestations of recurrent hepatitis B require further study.     

Liver transplantation and hepatitis C

End-stage liver disease caused by chronic hepatitis C viral infection is one of the major indications for liver transplantation. However, evidence for ongoing viral replication can already be found days after surgery and may lead sequentially to lobular hepatitis, chronic active hepatitis, fibrosis and liver cirrhosis. In some patients, this evolution is remarkably fast, most probably enhanced by the immunosuppressive therapy. A minority of patients develop a clinical picture of progressive cholestatic liver disease with histological signs of chronic rejection, which may necessitate retransplantation. While the 1- and 5-year survival rates for all patients transplanted because of hepatitis C virus (HCV)-induced liver cirrhosis are satisfactory, severe complications of disease recurrence are nonetheless expected during the first and second decade after liver transplantation. Larger and preferably randomized studies are needed to investigate whether combination therapy with interferon and ribavirin, preferably initiated as soon as possible after liver transplantation, prevents the fast evolution to cirrhosis without the appearance of chronic rejection and the expected complications of recurrent end-stage HCV-induced liver disease. The final goal should be the inhibition of viral replication even before liver transplantation, but other antiviral strategies should probably be used to attain this goal in patients with decompensated cirrhosis. Although the recurrence of a hepatitis C infection and concomitant disease in the liver graft may cause substantial morbidity, end-stage liver disease and liver failure caused by a chronic hepatitis C infection remain good indications for liver transplantation.     

Does hepatitis C virus affect the reactivation of hepatitis B virus following renal transplantation?

BACKGROUND: Hepatitis B virus (HBV) is endemic in Taiwan. Transplantation followed by long-term immunosuppressive medications may precipitate HBV reactivation. Interference of hepatitis C virus (HCV) with HBV gene expression and replication has been confirmed in many studies involving non-transplant populations. This study investigates the incidence of HBV reactivation following renal transplantation and compares the clinical outcome, especially the liver outcome, of patients with or without HCV co-infection. METHODS: Fifty-one of 512 renal transplant recipients were positive for hepatitis B surface antigen before surgery, and were followed for 81.6+/-7.5 (4-120) months. Seventeen of 51 patients acquired HCV before transplantation and six patients acquired HCV after renal transplantation. RESULTS: At the end of this assessment, we had 28 patients who suffered HBV reactivation and another 23 patients who suffered no HBV reactivation. Initially, we found a significant difference of HCV carriage (P<0.05) between patients with (seven out of 28 or 25%) or without (21 out of 23 or 91.3%) HBV reactivation. Further inspection showed that 21 of the 28 patients without HCV co-infection and seven of the 23 patients with HCV co-infection suffered HBV reactivation. After comparison, we found a lower incidence of HBV reactivation in patients with HCV co-infection than in patients without HCV co-infection (P<0.05). In contrast to the latter, we found that patients with HCV co-infection suffering HBV reactivation tended to have a late onset of HBV reactivation (P<0.05). Otherwise, there was no difference in hepatitis severity, in terms of peak alanine aminotransferase, total bilirubin levels and hepatitis reactivation-related death, between these two groups of patients. Finally, a multivariable analysis also revealed that HCV carriage was indeed an independent variable leading to the reduced incidence of HBV reactivation in patients with HCV co-infection. CONCLUSION: HCV might affect the reactivation of HBV by decreasing the incidence or delaying the onset of HBV reactivation in renal transplant recipients carrying both HBV and HCV.     

Herpes simplex virus sepsis and acute liver failure

Abstract:  Acute liver failure is a life threatening disease mostly triggered by drug-induced or toxic liver damage or viral hepatitis. Herpes Simplex virus (HSV) hepatitis is rare and accounts for only 1% of all acute liver failures. The importance of HSV-induced acute liver failure is based on its extremely severe clinical course with lethality rates of almost 75%. HSV hepatitis is just one of several clinical manifestations of HSV sepsis leading more frequently to encephalitis, pneumonia and esophagitis. Local herpes infection or recurrence of dermal lesions (herpes labialis, herpes genitalis), however, is common and account for the high prevalence of HSV-1 or HSV-2 infection in adults. Another rare entity is visual dissemination, which mostly affects immunocompromised patients. Compromised cellular immunity is a major risk factor for HSV sepsis because of either primary infection or reactivation of occult chronic HSV infection. Delayed diagnosis without antiviral therapy significantly contributes to the unfavorable outcome. Typically, anicteric hepatitis is seen in patients with HSV hepatitis. Because of its low incidence, however, and the lack of dermal manifestations, HSV hepatitis is rarely considered in the context of acute liver failure. In addition, diagnostic tests might not always be available. Therefore, it is a generally accepted consensus to begin antiviral therapy pre-emptively with acyclovir in cases of acute liver failure of unknown origin, in which high urgency (HU) liver transplantation remains the only therapeutical option. Even in the case of early specific therapy, sepsis may prevail and the indication for HU transplantation must be evaluated carefully. The outcome after liver transplantation for HSV-induced liver failure with reported survival rates of more than 40% is good. Because of the risk of recurrence, lifelong prophylaxis with acyclovir is recommended.     

Effect of poverty and other socioeconomic variables on renal allograft survival

BACKGROUND: Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of patients. Standard dose interferon therapy has been largely unsuccessful for hepatitis C in transplant recipients. METHODS: Twelve patients, at least 7 months posttransplant, with detectable hepatitis C virus RNA in serum and features of hepatitis C on liver biopsy were randomized to interferon-alpha2a, 3 mU daily for 12 months (n=8) or no treatment (n=4). The tolerability of daily interferon dosing in liver transplant recipients was evaluated and effects on hepatitis C virus RNA level, quasispecies evolution, and liver histology were studied. RESULTS: Treated patients had an improvement in histological activity index at the end of therapy relative to controls (median reduction of 2 versus median increase of 1.5) (P=0.04). Four treated patients had a virological response (all bDNA negative, one qualitative polymerase chain reaction negative) compared with none of the untreated patients. Only two of six treated patients tested had evidence of quasispecies diversification on therapy. Seven of eight patients in the treatment group required dose reduction for fatigue and/or depression. They tolerated 1.5 mU of interferon-alpha2a daily. Two treated patients developed graft dysfunction, one of who had histological evidence of rejection and subsequent graft loss. CONCLUSIONS: Low daily doses of interferon were tolerated by liver transplant recipients and provided histological benefit without associated quasispecies diversification in most cases. These findings provide a rationale to study low dose daily or pegylated interferon maintenance therapy for the management of hepatitis C posttransplant.     

The Impact of IL28B Genetic Variants on Recurrent Hepatitis C in Liver Transplantation: Significant Lessons from a Dual Graft Case

IL28B genetic polymorphism is related to interferon‐sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51‐year‐old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated‐interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients.     

Spontaneous Clearance of Hepatitis C Virus Infection Post–Liver Transplantation Is Associated With Rapidly Changing Quasispecies: A Single Case Report

Hepatitis C virus (HCV) clearance post–liver transplantation is uncommon. This is a case report of a patient who, after liver transplantation, developed cholestatic hepatitis characterized by severe graft dysfunction, in conjunction with high viral load. This was, however, followed by viral clearance and normalization of allograft function. The clinical features of this case and the quasispecies patterns during the illness and the clearance periods are described. In addition, management implications in terms of immunosuppressive therapy are discussed. (Liver Transpl 2000;6:648-653.)     

De novo hepatitis with autoimmune antibodies and atypical histology: a rare cause of late graft dysfunction after pediatric liver transplantation

BACKGROUND: Late graft dysfunction after orthotopic liver transplantation is commonly due to chronic rejection, recurrence of primary disease, sepsis, lympho-proliferative disease, or vascular or biliary complications. Herein we describe a subset of pediatric liver transplant patients in whom late graft dysfunction was associated with autoimmune markers, bile ductular proliferation, and portal infiltrates, which progress to fibrosis. This subset of patients has not been previously described. METHODS: Six of the 115 children followed for greater than 5 years after transplantation developed this unusual form of graft dysfunction. All children were on a low-dose single immunosuppressive therapy (mean trough cyclosporine concentration 89 microg/L) and had been tapered off steroids for a median duration of 1.5 year. Liver biopsies were performed in all children to evaluate the graft dysfunction, and the histologic findings were interpreted by an experienced hepato-pathologist. All patients were tested for antibodies to hepatitis C virus, hepatitis B surface antigen, and IgM antibodies to hepatitis A. Smooth muscle antibody, antinuclear antibody, and antibody to liver/kidney microsome type 1 were sought by indirect immunofluorescence. International Autoimmune Hepatitis Group scores were calculated. All patients underwent ultrasonography with doppler studies at the onset of graft dysfunction. Three patients with marked bile duct proliferation on histology had cholangiograms. RESULTS: Histology in all patients showed mononuclear cell infiltrates in the portal area with interface hepatitis, portal fibrosis, and ductular proliferation without duct damage or loss. All six patients had positive antinuclear antibody or smooth muscle antibody titers. Viral studies for hepatitis A, B, and C were negative in all patients. On the International Autoimmune Hepatitis Group scoring system, five patients had probable autoimmune hepatitis (score of 10-15) and one had definite autoimmune hepatitis (score > 15) at the onset of graft dysfunction. All were treated with azathioprine and prednisone similar to treatment for autoimmune hepatitis. However, despite aggressive treatment, four patients developed bridging portal fibrosis resulting in graft loss in two patients. CONCLUSION: This clinical constellation is associated with worse outcome then that previously described for pediatric patients with posttransplantation de novo autoimmune hepatitis. Further studies are needed to find an optimal treatment regimen for these patients.     

Recurrent hepatitis C virus infection post liver transplantation: impact of choice of calcineurin inhibitor

Recurrence of hepatitis C virus infection following liver transplantation (LT) for hepatitis C is universal. After LT, hepatitis C is associated with accelerated fibrosis progression and reduced graft and patient survival. Furthermore, responses to antiviral therapy in patients with recurrent hepatitis C virus post‐transplant are consistently sub‐optimal. Calcineurin inhibitors (CNIs) like cyclosporine A (CsA) and tacrolimus continue to dominate immunosuppressive regimens in this population; however, there is still uncertainty as to whether either offers an advantage in terms of patient outcomes. Although tacrolimus demonstrates improved efficacy in the general LT population, differences have begun to emerge between these agents regarding diabetogenic potential, antiviral activity, and fibrosis progression in patients with hepatitis C. This review critically evaluates the existing literature, providing an overview of the reported differences, concluding that despite conflicting evidence, a potential benefit of CsA in patients with hepatitis C is supported by the data and warrants further investigation. Future studies examining the role of CNIs in hepatitis C virus‐positive LT recipients are required to accurately examine the effects of CNIs on outcomes such as fibrosis progression, survival, and effects on response to antiviral therapy, to provide robust information that allows clinicians to make an informed choice concerning which CNI is best for their patients.