The impact of hepatitis C virus donor and recipient status on long-term kidney transplant outcomes: University of Wisconsin experience

Singh N, Neidlinger N, Djamali A, Leverson G, Voss B, Sollinger HW, Pirsch JD. The impact of hepatitis C virus donor and recipient status on long‐term kidney transplant outcomes: University of Wisconsin experience. Abstract: The survival benefit of transplanting hepatitis C (HCV)‐positive donor kidneys into HCV‐positive recipients remains uncertain. The purpose of this study was to assess the effect of HCV‐status of the donor (D) kidney on the long‐term outcomes in kidney transplant recipients (R). We evaluated 2169 consecutive recipients of deceased‐donor kidney transplants performed between 1991 and 2007. The following HCV cohorts were identified: D?/R? (n = 1897), D?/R+ (n = 59), D+/R? (n = 118), and D+/R+ (n = 95). Patients were followed for a mean of 6.02 (standard deviation = 4.26) yr. In a mulitvariable Cox‐proportional hazards model, D+/R+ cohort had significantly lower patient survival (adjusted‐hazard ratio [HR] 2.1, 95% CI [1.4–2.9]) with respect to the reference D?/R? group, whereas mortality was not increased in D?/R+ group. The rate of graft loss was increased in both D+/R+ and D?/R+ but was comparable with each other (adjusted‐HR 1.8, 95% CI [1.4–2.5]) vs. adjusted‐HR 2.0, 95% CI [1.4–2.8], respectively). D?/R+ cohort experienced significantly higher rate of rejection (adjusted‐HR 1.7, 95% CI [1.2–2.5]) and chronic allograft nephropathy (adjusted‐HR 2.1, 95% CI [1.2–3.7]). Neither donor nor recipient HCV‐status impacted the risk of recurrent or de novo GN. Transplanting HCV‐positive kidneys as opposed to HCV‐negative kidneys into HCV‐positive recipients provided similar graft survival but compromised patient survival in the long term.     

The acquisition time of infection: a determinant of the severity of hepatitis C virus-related liver disease in renal transplant patients

Abstract: Background: The aim of this study was to compare the clinical and histopathological course of HCV infection acquired before and during or after renal transplantation. Methods: According to HCV status, 197 RT patients were divided into three groups. At the time of RT, anti‐HCV antibody was positive in 47 patients (pre‐RT HCV group). In 27 patients, in whom anti‐HCV negative at the time of RT, anti‐HCV and/or HCV RNA was found to be positive following an ALT elevation episode after RT (post‐RT HCV group). Both anti‐HCV and HCV RNA were negative at all times in remaining 123 patients (control group). Results: Liver biopsy was performed in 31 of 47 patients in pre‐RT and 24 of 27 in post‐RT HCV group after RT. Duration of follow‐up was similar in all groups with a mean of 7.1 ± 4.0 yr. Ascites and encephalopathy were seen in only post‐RT HCV group (22%). Histological grade (6.5 ± 2.7 vs. 4.1 ± 1.4) and stage (2.0 ± 1.5 vs. 0.8 ± 0.8) was significantly severe in post‐RT HCV group (p < 0.01). Three patients died due to liver failure in post‐RT HCV group. Conclusions: HCV infection acquired during or after RT shows a severe and rapidly progressive clinicopathological course, which is significantly different from pre‐transplant anti‐HCV positive patients.     

Chronic liver disease in kidney recipients with hepatitis C virus infection

BACKGROUND: The prevalence of anti-hepatitis C virus (HCV) positive test is higher among patients in dialysis and in kidney recipients than in general population. Hepatitis C virus infection is the main cause of chronic liver disease in renal transplant patients. Liver biopsy and virological analysis were performed to clarify the grade of liver damage in kidney recipients. METHODS: Renal recipients patients with at least 5 yr under immunosuppression were submitted to clinical and laboratory analysis. Patients who tested anti-HCV positive were candidates to liver biopsy with no regard to transaminase levels. RESULTS: Forty-five patients tested anti-HCV positive and 42 anti-HCV negative. Twenty-six anti-HCV and RNA-HCV positive patients were submitted to liver biopsy. Seventy-three percentage of these patients presented chronic active hepatitis, from these only one patient presented cirrhosis. Only 29% of the anti-HCV positive group presented elevated alanine aminotransferase levels. Anti-HCV positive patients presented longer previous time on dialysis and less rejection episodes than the group anti-HCV negative (p < 0.05). All anti-HCV positive patients but one tested RNA-HCV positive by polymerase chain reaction (PCR). CONCLUSIONS: In this series the prevalence of anti-HCV positive is 51.7%. Most of the patients presented liver damage in histology caused by HCV. However, we found only mild or minimal fibrosis and inflammatory activity grade, despite 10 yr of HCV infection and 5 yr of immunosuppressive treatment. Only one patient presented cirrhosis (4%). Performing serial liver biopsies in a long-term follow-up is needed to clarify the impact of HCV infection in renal transplant patients.     

Incidence and outcome of hepatitis C virus infection after liver transplantation

Abstract The objective of this study was to determine the incidence and outcome of hepatitis C virus (HCV) infection after liver transplantation (OLT). Fifty-two transplanted patients were studied. Serum samples were examined for antibodies to HCV (anti-HCV) and HCV-RNA by PCR, before and after OLT. Patients were distributed into two groups: group 1 consisted of 24 patients (pretransplant anti-HCV positive) and group 2 consisted of 28 patients (pretransplant anti-HCV negative). One year after OLT, HCV-infected patients were evaluated by liver biopsy. HCV-RNA was detected in 28 of the 52 (53.9%) patients after OLT. Twenty-two patients in group 1 (96%) were reinfected. In group 2, acquired HCV infection was detected in six (21.4%) patients. At 6 and 12 months, one and five of six patients had seroconverted, respectively. Liver biopsy in 23 HCV-infected patients showed chronic hepatitis in 18 (78%) cases (2, chronic persistent hepatitis; 3, chronic lobular hepatitis and 13, chronic active hepatitis). Fourteen of the 23 (60.8 %) patients were asymptomatic. Most symptomatic patients had chronic hepatitis with cholestasis. Overall, 18 of 20 cases of chronic hepatitis diagnosed in OLT recipients were HCV related. Mortality beyond 6 months after OLT was slightly higher in the HCV-infected group ( P = 0.055). In conclusion, HCV reinfection is almost universal. Acquired HCV infection post-OLT is frequent. HCV-infected patients frequently develop chronic hepatitis. Most chronic hepatitis after transplantation are HCV related.     

Is alanine aminotransferase a good marker of histologic hepatic damage in renal transplant patients with hepatitis C virus infection?

INTRODUCTION: Renal transplant (RTx) patients with hepatitis C frequently show normal levels of alanine aminotransferase (ALT) and the significance of ALT in this group has not been established. AIM: To determine the value of ALT as a marker of histologic hepatic damage in RTx patients with hepatitis C virus (HCV) infection. MATERIALS AND METHODS: HCV-RNA-positive RTx patients with a liver biopsy were analyzed regarding staging and the grading of periportal and lobular necroinflammatory activity. Spearman's correlation coefficient was used to determine the correlation between ALT and histologic variables. Sensitivity, specificity and positive and negative predictive values (PPV and NPV) of ALT in the detection of septal fibrosis and interface hepatitis, and/or confluent necrosis were calculated. RESULTS: Fifty-three patients (32 men, 60%), with a mean age of 42 +/- 10 yr and time since transplant of 5 +/- 4 yr were included. Only 27 (51%) patients showed elevated ALT levels, which were associated with septal fibrosis (p = 0.001), interface hepatitis (p < 0.001) and confluent necrosis (p = 0.05). A correlation was observed between ALT and staging (r = 0.50, p < 0.001), periportal necroinflammatory activity (r = 0.59, p < 0.001) and lobular necroinflammatory activity (r = 0.50, p < 0.001). The sensitivity, specificity, PPV and NPV of ALT were 92, 61, 41 and 96%, respectively, for the detection of septal fibrosis, and 87, 77, 74 and 88% for the detection of interface hepatitis and/or confluent necrosis. CONCLUSION: ALT is a good marker of histologic hepatic lesion in HCV-infected RTx patients and, therefore, liver biopsy can be avoided in patients with persistently normal ALT.     

Hepatitis C virus infection in renal transplant patients: a comparative study with immunocompetent patients

The behavior of hepatitis C in states of immunodeficiency is poorly understood and it is still unclear whether the characteristics of hepatitis C virus (HCV) infection in renal transplant patients differ from those observed in immunocompetent subjects. The aim of this study was to compare the biochemical and histologic characteristics of chronic HCV infection between renal transplant and immunocompetent patients. Forty-one HCV-RNA-positive renal transplant patients and 41 immunocompetent controls matched for gender, age at infection and time of infection were included in the study. The groups were compared regarding laboratory and histologic variables. Renal transplant patients showed lower alanine aminotransferase (ALT) levels (p = 0.005) and higher levels of gamma-glutamyltransferase (p = 0.003), alkaline phosphatase (p < 0.001), and direct bilirubin (p < 0.001) when compared with controls. Histologic analysis revealed less intense portal (p < 0.001) and periportal (p = 0.046) inflammatory infiltrate in renal transplant patients but a larger proportion of cases with confluent necrosis (p = 0.043). No difference in the presence of septal fibrosis, hepatic steatosis, bile duct injury and siderosis was observed. However, there was a difference in the presence of lymphoid aggregates, which were less frequent in the renal transplant group (p < 0.001). In conclusion, the characteristics of hepatitis C in renal transplant patients differ from that observed in immunocompetent patients. In renal transplant patients, HCV infection is biochemically characterized by lower ALT levels and higher frequency of cholestasis. Regarding histology, despite lower frequency of lymphoid aggregates and less intense portal/periportal inflammatory infiltrate, a greater lobular damage was observed. The impact of these differences on the progression of fibrosis remains to be established.     

No evidence of occult hepatitis C virus (HCV) infection in serum of HCV antibody‐positive HCV RNA‐negative kidney‐transplant patients

Persistence of hepatitis C virus (HCV) in patients who cleared HCV is still debated. Occult HCV infection is described as the presence of detectable HCV RNA in liver or peripheral blood mononuclear cells (PBMCs) of patients with undetectable plasma HCV‐RNA by conventional PCR assays. We have assessed the persistence of HCV in 26 kidney‐transplant patients, followed up for 10.5 years (range 2–16), after HCV elimination while on hemodialysis. If HCV really did persist, arising out of the loss of immune control caused by institution of the regimen of immunosuppressive drugs after kidney transplantation, HCV reactivation would have taken place. Their immunosuppression relied on calcineurin inhibitors (100%), and/or steroids (62%), and/or antimetabolites (94%). An induction therapy, given to 22 patients, relied on rabbit antithymocyte globulin (59%) or anti‐IL2‐receptor blockers (32%). All patients had undetectable HCV RNA as ascertained by several conventional tests. At the last follow‐up, no residual HCV RNA was detected in the five liver biopsies, the 26 plasma, and in the 37 nonstimulated and 24 stimulated PBMCs tested with an ultrasensitive RT‐PCR assay (detection limit, 2 IU/ml). No biochemical or virologic relapse was seen during follow‐up. The absence of HCV relapse in formerly HCV‐infected immunocompromised patients suggests the complete eradication of HCV after its elimination while on dialysis.     

Rapid steroid withdrawal in hepatitis C virus-positive kidney transplant recipients

The effects of rapid steroid withdrawal (SW) on kidney transplantation (KT) outcome were investigated in 12 HCV+ patients in a prospective cohort study. These results were compared with 17 HCV+ patients who received KT in the prior 2 yr and treated with a standard prednisone taper protocol. SW patients received only 6 d of steroid treatment after transplantation. Eleven received Thymoglobulin and one Basiliximab induction treatment along with a calcineurin inhibitor and mycophenolate mofetil. Patient and graft survival was 92% in SW group (median follow-up 12 months, range 6-17), and 92 and 82% in the historic control group respectively (median follow-up 21 months, range 11-27). In the SW and control group, acute rejection rates were 9 and 18%, and mean creatinine levels at last follow-up 1.30 +/- 0.36 and 1.68 +/- 0.58 mg/dL respectively. Only two SW patients had an increase in liver function tests during follow-up (18%), compared with six patients in the control group (43%). This study demonstrates that rapid SW is safe for HCV+ KT recipients, without an increase in acute rejection episodes or liver function abnormalities in the short term.     

Outcome of liver transplantation using donors older than 60 year of age

Serrano MT, Garcia‐Gil A, Arenas J, Ber Y, Cortes L, Valiente C, Araiz JJ. Outcome of liver transplantation using donors older than 60 year of age.
Clin Transplant 2010: 24: 543–549.
© 2009 John Wiley & Sons A/S. Abstract: The impact of donor age on liver transplantation has been analyzed in several studies with contradictory results. Our aim was to evaluate graft survival and complications in the first year after liver transplantations with livers from older donors. Methods: Prospective analysis of 149 consecutive primary liver transplantations performed between 2000 and 2005. Transplantations were divided into two groups according to donor age: group A, <60 yr old (n = 102); and group B, ≥60 yr old (n = 47). Results: Chronic and acute rejection, vascular complications, and infections were not statistically different between the groups. Anastomotic biliary strictures were similar in the two groups, but non‐anastomotic biliary strictures (NABS) were clearly more frequent in the older donor group (17% vs. 4.9%; OR 3.9; p = 0.025). NABS with no arterial complication was diagnosed in 10.6% of cases in group B vs. 1% in group A (OR = 12; p = 0.012). Graft survival in the first year was 86.67% in the younger group of donors and 71.43% in the older group (p < 0.05), but patient survival was not different. Conclusions: The use of grafts from donors ≥60 yr decreased graft survival after liver transplantation and was related to a higher frequency of non‐anastomotic biliary strictures.