The association between hepatitis C infection and survival after orthotopic liver transplantation

BACKGROUND & AIMS: The effect of hepatitis C viral (HCV) infection on patient and allograft survival after orthotopic liver transplantation is controversial. Hepatitis C recurrence after transplant is inevitable, but studies to date have not found a survival difference between recipients with and without HCV. METHODS: Using data from the United Network for Organ Sharing, we performed a retrospective cohort study of 11,036 patients who underwent 11,791 liver transplants between 1992 and 1998. The hazard rates of patient and allograft survival for patients who were HCV-positive as compared with patients who were HCV-negative were assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including donor, recipient, and transplant center characteristics. RESULTS: Liver transplantation in HCV-positive recipients was associated with an increased rate of death (hazard ratio, 1.23; 95% confidence interval [CI], 1.12-1.35) and allograft failure (hazard ratio, 1.30; 95% CI, 1.21-1.39), as compared with transplantation in HCV-negative recipients. This reduction in survival persisted after adjusting for potential confounders. There was an interaction between HCV and sex (P < 0.001) with the effect of HCV on survival being most pronounced in female recipients (patient survival hazard ratio, 1.56; 95% CI, 1.35-1.81; allograft survival hazard ratio, 1.51; 95% CI, 1.34-1.70). CONCLUSIONS: HCV infection significantly impairs patient and allograft survival after liver transplantation.     

Impact of hepatitis C virus infection in renal transplant recipients.

OBJECTIVES: The impact of hepatitis C virus (HCV) infection on the success of renal transplant is controversial. We assessed the effect of HCV infection on graft and patient survival in renal allograft recipients. METHODS : We retrospectively analyzed medical records of renal allograft recipients who were transplanted between June 1990 and March 2004. Patients were divided into those positive and negative for anti-HCV antibody. Graft and patient survival were compared between the groups. RESULTS : Of 126 patients studied (median age 34.5 years, range, 16-60; 111 men), 35 were positive for anti-HCV antibody. In seven patients, the antibodies were detected for the first time after renal transplant. Mean patient and graft survival duration in the anti-HCV negative group was longer (55 [SD 2] months [95% CI, 51-58]) than in the anti-HCV positive group (50 [SD 4] months [95% CI, 43-58]) (p< 0.05). Twenty-two patients died - 8 (22.8%) in the anti-HCV positive group and 14 (15.3%) in the negative group. In the anti-HCV positive group, infections were the cause of death in 5 patients and 3 patients died of liver cell failure. In the anti-HCV negative group, corresponding figures were 13 and one. CONCLUSION: HCV infection is a bad prognostic indicator for patient and graft survival duration in renal transplant recipients. Infections are the commonest cause of death in renal transplant recipients.     

The impact of Hepatitis C virus infection on kidney transplantation outcomes: A systematic review of 18 observational studies: The impact of HCV on renal transplantation

Background

Hepatitis C virus (HCV) infection occursin 0% to 51% of dialysis patients, and manyHCV-positive patients are urged to undergo kidney transplantation. However, the outcome of renal transplantation in HCV-positive recipients is unknown.

Objectives

Our review aimed to address the outcomesof renal transplantation recipients (RTRs)following kidney transplantation.

Materials and Methods

We selected studies that used the adjusted relative risk (aRR) and 95% CI of all-cause mortality and graft loss in HCV-positive compared with HCV-negative RTRs as study endpoints. Cox proportional hazard analysis was usedin all studies to calculate the independent effects of HCV infection on RTR outcomes. Sixteen retrospective cohort studies and 2 clinical trials were selected for our review. Sixteen studies were related to patient survival, and 12 examined graft survival.

Results

The combined hazard ratio in HCV-infected recipients was 1.69-fold (1.33-1.97, p < 0.0001) and 1.56 times (1.22-2.004, p < 0.0001) greaterthan that of HCV-negative recipients for mortality and graft loss, respectively.

Conclusions

Although HCV-infected RTRs have worseoutcomes than HCV-negative RTRs,kidney transplantation is the preferred treatment for patients with HCV infection and end-stage renal disease.     

Prevention of hepatitis C recurrence after liver transplantation: An update

Hepatitis C related liver failure and hepatocarcinoma are the most common indications for liver transplantation in Western countries.Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation,being associated with accelerated progression to cirrhosis,graft loss and death.Graft and patient survival is reduced in liver transplant recipients with recurrent Hepatitis C virus(HCV) infection compared to HCV-negative recipients.Many variables may impact on recurrent HCV liver disease.Overall,excess immunosuppression is believed to be a key factor;however,no immunosuppressive regimen has been identified to be more beneficial or less harmful.Donor age limitations,exclusion of moderately to severely steatotic livers and minimization of ischemic times could be a potential strategy to minimize the severity of HCV disease in transplanted subjects.After transplantation,antiviral therapy based on pegylated IFN alpha with or without ribavirin is associated with far less results than that reported for immunocompetent HCV-infected patients.New findings in the field of immunotherapy and genomic medicine applied to this context are promising.     

Treatment of hepatitis C virus infection in patients with end-stage renal disease

Hepatitis C virus (HCV) infection is a major health problem in patients with end‐stage renal disease (ESRD). The incidence of acute HCV infection during maintenance dialysis is much higher than that in the general population because of the risk of nosocomial transmission. Following acute HCV infection, most patients develop chronic HCV infection, and a significant proportion develop chronic hepatitis, cirrhosis, and even hepatocellular carcinoma. Overall, chronic hepatitis C patients on hemodialysis bear an increased risk of liver‐related morbidity and mortality, either during dialysis or after renal transplantation. Interferon (IFN) therapy is modestly effective for the treatment of HCV infection in ESRD patients. Conventional or pegylated IFN monotherapy has been used to treat acute hepatitis C in ESRD patients with excellent safety and efficacy. Regarding chronic hepatitis C, approximately one‐third of patients can achieve a sustained virological response (SVR) after conventional or pegylated IFN monotherapy. The combination of low‐dose ribavirin and conventional or pegylated IFN has further improved the SVR rate in treatment‐naïve or retreated ESRD patients in clinical trials. Similar to the treatment of patients with normal renal function, baseline and on‐treatment HCV virokinetics are useful to guide optimized therapy in ESRD patients. Of particular note, IFN‐based therapy is not recommended at the post‐renal transplantation stage because of the low SVR rate and risk of acute graft rejection. In conclusion, ESRD patients with HCV infection should be encouraged to receive antiviral therapy, and those who achieve an SVR usually have long‐term, durable, virological, biochemical, and histological responses.     

Diabetes and Kidney Transplantation: Past, Present, and Future

Diabetes mellitus is the most common etiology for end stage renal disease (ESRD) worldwide and in the United States. The incidence of morbidity and mortality is higher in diabetic patients with ESRD due to increased cardiovascular events. Patients with type 2 diabetes who receive a renal allograft have a higher survival rate compared with patients who are maintained on chronic hemodialysis therapy, but there is scarcity of data on long-term graft outcomes. Most recently the development of new onset diabetes after transplantation (NODAT) poses a serious threat to patient and allograft survival. Pre-emptive transplantation and the use of living donors have improved overall survival. In addition, critical management of glucose, blood pressure, and cholesterol are some of the factors that can help minimize adverse outcomes in both patients with pre-existing diabetes and patients who develop NODAT. Future clinical trials are warranted to improve therapeutic medical management of these patients thus influencing graft attrition.     

Long-term outcome of kidney transplantation in patients with hepatitis C virus infection

BACKGROUND/AIMS: The impact of HCV (hepatitis C virus) infection on the long-term outcome of kidney transplant patients is controversial. METHODOLOGY: Eighty-four renal allograft recipients who were seronegative for hepatitis B surface antigen and had been screened for antibody to hepatitis C virus (anti-HCV) were included. The outcome and survival were compared between anti-HCV-positive (n = 30, group 1) and anti-HCV-negative (n = 54, group 2) kidney transplant patients. Group 1 patients were further compared to 52 anti-HCV-positive end-stage renal disease patients (group 3) who were on chronic dialysis. RESULTS: Group 1 patients had a higher prevalence of chronic hepatitis than group 2 and group 3 patients did (67% vs. 2% and 31%). Liver-related complications and deaths between group 1 and group 2, and group 1 and group 3 patients were not significantly different. The comparisons of the long-term survival between these groups showed no significant differences, despite group 3 patients had a higher overall mortality rate. Cox regression analysis confirmed that age more than 45 years was the only independent factor that affected survival in anti-HCV-positive end-stage renal disease patients with or without kidney transplantation. CONCLUSIONS: HCV infection is not a contraindication to kidney transplantation. For anti-HCV-positive end stage renal disease patients, survival is better in younger patients, and is not influenced by kidney transplantation or continuing dialysis.     

Management of patients with hepatitis C infection and renal disease

Hepatitis C virus(HCV) infection in patients with end-stage renal disease(ESRD) is associated with more rapid liver disease progression and reduced renal graft and patients’ survival following kidney transplantation. Evaluations and management of HCV in patients with renal disease are challenging. The pharmacokinetics of interferons(IFN), ribavirin(RBV) and some direct acting antiviral(DAA), such as sofosbuvir, are altered in patients with ESRD. With dose adjustment and careful monitoring, treatment of HCV in patients with ESRD can be associated with sustained virological response(SVR) rates nearly comparable to that of patients with normal renal function. DAA-based regimens, especially the IFNfree and RBV-free regimens, are theoretically preferred for patients with ESRD and KT in order to increase SVR rates and to reduce treatment side effects. However, based on the data for pharmacokinetics, dosing safety and efficacy of DAA for patients with severe renal impairment are lacking. This review will be focused on the evaluations, available pharmacologic data, and management of HCV in patients with severe renal impairment, patients who underwent KT, and those who suffered from HCV-related renal disease, according to the available treatment options, including DAA.     

Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts.

BACKGROUND & AIMS: The present organ shortage has brought into question the suitability of hepatitis C virus (HCV)-positive grafts. This study reviewed the outcome of such transplantations in our institution. METHODS: Twenty-three HCV-positive patients who underwent orthotopic liver transplantation (OLT) for end-stage liver disease with HCV-positive grafts in 1992-1995 were studied. Only patients who survived more than 30 days were included in the analysis. Control group included 169 patients who underwent transplantation for HCV-related cirrhosis and received HCV-negative organs. RESULTS: Patients who received HCV-infected organs had a cumulative survival rate of 89% and 72% at 1 and 5 years, respectively, vs. 88% and 73% for the control group (NS). There was no difference in graft survival, incidence of cirrhosis, mean hepatitis activity index score, fibrosis, or mean activity of serum transaminases. There was a trend toward lower incidence of recurrent hepatitis C in the study group compared with control (21% vs. 23% at 1 year and 47% vs. 64% at 5 years; NS). Patients in whom the donor strain became predominant after transplantation had significantly longer disease-free survival than patients who retained their own HCV strain (P < 0.003). CONCLUSIONS: HCV-infected livers transplanted into HCV-infected recipients do not appear to convey a worse outcome in the initial years after OLT than HCV-negative grafts.     

Successful treatment of hepatitis C after kidney transplantation with combined interferon alpha-2b and ribavirin

The management of acute hepatitis C virus (HCV) infection after renal transplantation (RT) remains controversial, due to the potential risk of interferon-induced graft dysfunction. There is little experience with combined interferon and ribavirin therapy in this group of patients. We treated four consenting RT recipients who developed acute de novo HCV infection with a combination of interferon-alpha 2b and ribavirin. After 48 weeks' treatment, sustained virologic and biochemical remission were achieved in three patients infected with HCV genotypes 1a, 2, and 6a, respectively. The median time from treatment onset to ALT normalization was 8 weeks. The fourth patient was a non-responder infected with genotype 1b. Dose-dependent hemolysis was the most frequent side-effect. No patient developed allograft dysfunction. Our experience indicates that the judicious use of combined interferon and ribavirin can be considered in selected RT recipients with severe acute hepatitis C infection.     

HCV in patients with end-stage renal disease

Chronic hepatitis C virus (HCV) infection remains an important cause of liver disease in patients with end-stage renal disease (ESRD) and conversely, renal failure has a significant impact on morbidity and mortality throughout the natural history of chronic HCV and its treatment. With improved awareness within dialysis units of the potential for spread and the institution of preventative measures, the prevalence of HCV infection in the hemodialysis-dependent population has continued to decline since 1995. Use of HCV (+) donor kidneys is associated with an increase in the prevalence of liver disease, but when compared with continued hemodialysis, transplantation using these kidneys is associated with improved survival. Overall, survival in patients with chronic HCV infection appears to be better after renal transplantation when compared with maintenance hemodialysis, and transplant should be considered for these patients. Data support the use of interferon and the improved efficacy of pegylated interferon formulations for treatment of chronic HCV infection in ESRD patients, although tolerability continues to be troublesome. The newest and most promising data regarding the treatment of HCV in ESRD involve the combination of reduced dose ribavirin with interferon or pegylated interferon suggesting similar enhancements in sustained virologic response (SVR) as seen in non-ESRD patients, but caution is advised, as all studies to date used ribavirin plasma concentration monitoring in patient with ESRD. Finally, with regard to postrenal transplant treatment of HCV infection, there is no evidence to support treatment with interferon-based therapy and pretransplant treatment remains the best option whenever possible.     

Hepatitis C infection associated with renal disease and chronic renal failure

Screening of blood products and attention to stricter infection control measures in hemodialysis units have reduced the incidence of hepatitis C virus (HCV) infection among dialysis patients. HCV can be transmitted via transplanted organs. Renal transplantation may accelerate the course of liver disease, which has an impact on patient and graft survival. Interferon (IFN) alfa monotherapy has produced promising results during treatment but disappointing long-term results in patients with HCV-associated glomerulonephritis. Dialysis patients with HCV infection respond well to IFN-based therapy, and there appears to be clinical benefit in clearing HCV in renal transplantation candidates. Larger prospective trials are required to fully determine the role of IFN in these patient groups, including the potential use of IFN plus ribavirin and pegylated IFNs. IFN therapy in renal transplantation patients is not recommended because of potential graft rejection.     

Hepatitis C infection in potential recipients with normal liver biochemistry does not preclude renal transplantation

The hepatitis C virus (HCV) may be an important cause of chronic liver disease in renal transplant recipients. We investigated retrospectively the incidence and outcome of HCV infection in long-term renal transplant recipients and patients on hemodialysis. Stored, pretransplant sera of transplant recipients with normal liver biochemistry at surgery were tested for hepatitis C by a second-generation enzyme immunoassay. Hemodialysis patients were tested by a first-generation enzyme-linked immunosorbent assay (ELISA) against c100-3. We studied 252 renal transplant recipients and 58 hemodialysis patients followed for 65±10 months and 26±6 months, respectively. Fifteen percent (38/252) of the transplant recipients were HCV positive as were 3/58 (5%) of the hemodialysis patients. Over liver disease occurred in 22/252 (8.7%) transplant recipients and none in the hemodialysis group. Thirty-six percent (8/22) of transplant recipients with overt liver disease were HCV positive. No HCV-positive patients died of liver failure. Of six biopsies in the HCV-positive transplant group, two had histological evidence of CAH. CAH was seen in six of eight biopsies in the HCV-negative transplants and two of these latter patients progressed to cirrhosis. No hemodialysis patients had clinical or histological evidence of chronic liver disease. Two HCV-negative transplant patients died of liver failure, while no deaths related to liver disease occurred in hemodialysis patients regardless of HCV status. We conclude that hepatitis C may cause chronic hepatitis in renal transplant patients. However, chronic liver disease in HCV-positive renal transplant recipients appears to be a clinically and histologically benign entity. HCV-positive potential renal allograft recipients with normal liver biochemistry should not be excluded from renal transplantation.     

Recurrent hepatitis C after liver transplantation: clinical and therapeutical issues

Hepatitis C virus (HCV) reinfection after liver transplantation is almost constant, assessed by the persistence of HCV RNA in 90% of cases. Acute hepatitis appeared in 75% of patients at a median of 4 months' post-transplantation. The 5-year actuarial rate of acute and chronic hepatitis on the graft is 75% and 60%, respectively. The rate of HCV cirrhosis on the graft is variable from 8 to 25% at 5 years. After transplantation, HCV viraemia is dramatically increased and correlates with the occurrence of acute hepatitis on the graft. Intrahepatic levels of HCV are high at the time of acute hepatitis, and decrease with constitution of chronic graft hepatitis lesions, implying an immunological response to the viral infection. A relationship between genotype 1b and the prevalence of HCV hepatitis on the graft has been suggested in European but not American series. The influence of the age of the recipient, quasispecies, viral compartmentalization, immunosuppressive treatment, and of HLA matching is being evaluated. The 5-year patient survival is around 65-80%. However, the occurrence of cirrhosis with a risk of graft failure may decrease the 10 and 15-year patient survival. Attempts to give prophylactic post-transplant antiviral treatment are under evaluation. Antiviral treatment of post-transplant graft lesions with combination therapy interferon–ribavirin gave promising results but indications and duration of treatment should be evaluated.
In conclusion, HCV reinfection is frequent, but medium-term survival is good. However, the long-term graft and patient survival remains unknown, and efficient prevention and treatment of HCV graft is mandatory.     

Interferon-Based Treatment of Hepatitis C Virus Infection Reduces All-Cause Mortality in Patients With End-Stage Renal Disease: An 8-Year Nationwide Cohort Study in Taiwan

The long-term survival of end-stage renal disease (ESRD) patients with hepatitis C virus (HCV) infection who received interferon treatment has not been extensively evaluated.The HCV cohort was the ESRD patients with de novo HCV infection from 2004 to 2011; they were classified into treated and untreated groups according to interferon therapy records. Patients aged <20 years and those with a history of hepatitis B, kidney transplantation, or cancer were excluded. The control cohort included ESRD patients without HCV infection matched 4:1 to the HCV cohort by age, sex, and year of ESRD registration. We followed up all study participants until kidney transplantation, death, or the end of 2011, whichever came first. We assessed risk of all-cause mortality by using the multivariate Cox proportional hazard model with time-dependent covariate.In the HCV cohort, 134 patients (6.01%) received interferon treatment. Compared with the uninfected control cohort, the treated group had a lower risk of death (hazard ratio 0.47, 95% confidence interval [CI] 0.22–0.99). The untreated group had a 2.62-fold higher risk (95% CI 1.24–5.55) of death compared with the treated group. For the HCV cohort without cirrhosis or hepatoma, the risk of death in the treated group was further markedly reduced (hazard ratio 0.17, 95% CI 0.04–0.68) compared with that in the control cohort.For ESRD patients with HCV infection, receiving interferon treatment is associated with a survival advantage. Such an advantage is more prominent in HCV patients without cirrhosis or hepatoma.     

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).     

Outcome of Patients with Diabetic Nephropathy after Kidney Transplantation

ABSTRACT During the period 1973–1983, 1014 patients with end stage renal failure received a kidney graft at the Helsinki University Central Hospital. As a consequence of diabetic nephropathy, 163 of them (16%) developed renal failure. Ten diabetic (6%) and 72 non-diabetic (9%) patients received grafts from a living donor. One-year patient survival did not differ between diabetic and non-diabetic patients (76% and 79%, respectively). From the second post-transplant year onwards patient survival was worse in diabetic than in non-diabetic patients. The two groups did not differ with respect to graft survival. Sixty-two diabetic patients (38%) died during the follow-up period, with myocardial infarction as the most common cause of death (31%), followed by infection (15%) and cerebral stroke (13%). Seven myocardial infarctions out of 19 occurred within three months of transplantation. However, significantly more fatal and non-fatal myocardial infarctions were observed in post-transplant patients who had returned to dialysis therapy than in patients with a functioning kidney graft. Blindness did not influence the outcome of transplantation. Nor did the transplantation significantly affect the course of this diabetic complication. In conclusion, although the early success rate of kidney transplantation in our study population was acceptable, the later outcome was poor, mainly due to advanced disease-related complications.     

Renal transplantation in chronic hepatitis C

Abstract   Hepatitis C virus (HCV) infection is present in 2–70% of patients receiving hemodialysis. The major risks for transmission are transfusions and nosocomial spread within dialysis units and the incidence has declined dramatically following the introduction of universal precautions and blood and organ donor screening. Renal transplantation confers an overall survival benefit in HCV+ hemodialysis patients, with similar 5-year patient and graft survival to those without HCV infection. However, long-term studies (more than 10 years) have reported increased liver-related and sepsis-related mortality in HCV-infected recipients. Attempts to eradicate HCV prior to transplant have been disappointing. Interferon is poorly tolerated in patients with end-stage renal disease and ribavirin is contraindicated because of universal severe hemolysis related to reduced renal clearance. Interferon is associated with unacceptable rates of allograft dysfunction and loss (attributed to interferon-induced rejection).     

Life expectancy of adult liver allograft recipients in the UK

BACKGROUND: Liver transplantation is a very successful therapy for those with end stage disease. Although there are numerous data on patient and graft survival after liver transplantation, life expectancy and possible loss of life (compared with a normal matched population) in those who survive remains unknown. AIMS: To assess the life expectancy and life years lost of adult liver allograft recipients, compared with an age and sex matched UK population to provide patients with more information and to improve the use of a scarce resource. METHODS: Using the National Transplant Database held by UK Transplant, on over 3600 adult liver allograft recipients transplanted between 1985 and 2003, we analysed survival of all adults who survived more than six months after transplantation and compared survival after transplantation with national age and sex matched controls to assess life years lost. RESULTS: Estimated median survival time of the analysis cohort of 2702 adult liver allograft recipients was 22.2 years (95% confidence interval 19.3-25.6), with an estimated loss of seven life years compared with an age and sex matched population. CONCLUSIONS: Overall, female recipients have a longer life expectancy and lose fewer life years than male recipients. While younger recipients have a longer life expectancy, they also lose more life years. Those transplanted for cancer, hepatitis C virus infection, and alcoholic liver disease had the greatest loss of life years.     

Kidney transplantation from an HIV‐positive cadaveric donor

Kidney transplantation is the gold‐standard therapy for select HIV‐positive patients with ESRD. Since the Italian Ministry of Health defined the guidelines for organ donation from HIV‐positive persons in 2018, we report the first case of renal transplantation from an HIV‐positive cadaveric donor in two HIV‐positive recipients in Italy. The donor was a 50‐year‐old male, deceased due to post‐anoxic encephalopathy, with a history of HIV infection in HAART, undetectable viral load, and HCV‐related chronic hepatitis that had been previously treated. The first recipient was a 59‐year‐old female with a prior history of drug addiction, and she suffered from ESRD secondary to HIV nephropathy. The patient followed preoperative HAART with a good viral response and undetectable HIV viral load. She also had a history of HCV‐related chronic hepatitis that had been successfully treated. The right kidney was uneventfully transplanted. The patient developed an asymptomatic reinfection of endogenous BK virus. The second recipient was a 41‐year‐old male with ESRD secondary to polycystic kidney disease. The patient was HIV‐positive in HAART, with a good viro‐immunologic response and an undetectable HIV viral load. He suffered from a severe form of hemophilia A and HCV‐related chronic hepatitis, which had been previously treated with undetectable HCV RNA. The left kidney was uneventfully transplanted. At the end of follow‐up, both patients had a healthy condition with stable renal function, a persistently good viral response and undetectable HIV and HCV viral loads. These encouraging preliminary results seem to confirm the safety and effectiveness of kidney transplantation from select HIV‐positive donors.