Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation.

Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon-based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon-based therapy in a selected group of liver transplant recipients. Twenty-three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated-interferon alpha-2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA-undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 +/- 2.37 vs. 5.64 +/- 2.94 units before and after treatment, respectively; P =.016). However, 5 of these 11 patients had no histologic improvement in follow-up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P <.01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection.     

Intravenous interferon during the anhepatic phase of liver retransplantation and prevention of recurrence of cholestatic hepatitis C virus.

Cholestatic hepatitis C virus (HCV) infection post orthotopic liver transplantation is associated with a poor prognosis. We describe 2 patients who received interferon and ribavirin for cholestatic HCV infection with clearance of HCV RNA from the serum. Both developed signs of graft failure necessitating repeat orthotopic liver transplantation, and at surgery, interferon was administered during the anhepatic phase to prevent graft reinfection. Both patients are doing well with no evidence of recurrent viremia at 36 and 24 months of follow-up after repeat transplantation, respectively. Our results suggest that in those with cholestatic HCV infection, repeat transplantation after viral clearance is feasible and can occur without reinfection of the graft, challenging the current practice of denying retransplantation for patients with cholestatic HCV. The role of anhepatic administration of interferon deserves further examination, and this combination may provide a solution in a subset of patients with an otherwise poor prognosis.     

Hepatitis C Infection in Liver Transplantation

Hepatitis C-associated liver failure is the most common indication for liver transplantation and recurs nearly universally following transplantation. Histological evidence of recurrence is apparent in approximately 50% of HCV-infected recipients in the first postoperative year. Approximately 10% of HCV-infected recipients will die or lose their allograft secondary to hepatitis C-associated allograft failure in the medium term. While the choice of calcineurin inhibitor and/or the use of azathioprine have not been clearly shown to affect histological recurrence of hepatitis C or the frequency of rejection in hepatitis C-infected recipients, cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia and more severe histological recurrence. In contrast to nonhepatitis C-infected recipients, treatment for acute cellular rejection is associated with attenuated patient survival among recipients with hepatitis C. The development of steroid-resistant rejection is associated with a greater than five-fold increased risk of mortality in HCV-infected liver transplant recipients. In lieu of large studies in a post-transplant population therapy with pegylated interferon (+/- ribavirin) should be considered in recipients with histologically apparent recurrence of hepatitis C before total bilirubin exceeds 3 mg/dL. The role of hepatitis C immunoglobulin and new immunosuppression agents in the management of post-transplant hepatitis C infection is still evolving. Overall, HCV-infected recipients who undergo retransplantation experience 5-year patient and graft survival rates that are similar to recipients undergoing retransplantation who are not HCV-infected.     

Pediatric liver transplantation for acute liver failure

The only proven therapy for patients unlikely to recover from acute liver failure (ALF) is liver transplantation. Correct diagnosis of these individuals and rapid referral to a transplant center are crucial. We evaluated 12 pediatric patients with ALF who underwent liver transplantation (LT) at our institution during a 3-year period. The reasons for transplantation were hepatitis A (3 patients); non-A, non-E hepatitis (3); autoimmune hepatitis (1); fulminant Wilson's disease (3); Amanita phalloides (mushroom) poisoning (1); and hepatitis B and toxic hepatitis with leflunomide treatment (1). Seven of the participants were female and five were male (mean age, 9.1 +/- 4.2 years). Three received right liver-lobe grafts, one received a whole liver graft, and the remainder received left or left-lateral liver lobe grafts. All patients recovered from hepatic coma the second postoperative day. Two patients died at postoperative days 57 and 71 due to adult respiratory distress syndrome and sepsis with multiorgan failure, respectively. One patient required retransplantation because of chronic rejection 7 months after the initial transplantation. That patient died 10 days after retransplantation because of sepsis. Nine patients were healthy at follow-up (range, 2-46 months). LT is the only treatment option for ALF in patients in countries with low organ-donation rates. In this scenario, donor preparation in a limited time frame is difficult. We have been able to decrease the duration of donor preparation to approximately 4 hours (including biopsy of the donated liver tissue).     

Orthotopic liver transplantation in human immunodeficiency virus (HIV)-positive patients: outcome of 7 patients from the Bonn cohort.

The outcome and clinical features of 7 HIV-positive patients who were liver transplanted at Bonn University in the era of highly active antiretroviral therapy (HAART) between 1997 and 2004, analyzed by retrospective chart review, are reported. Reasons for orthotopic liver transplantation (OLT) were end-stage liver disease due to chronic hepatitis C (n = 4) or hepatitis B (n = 1) or acute liver failure due to fulminant hepatitis B (n = 2). Immunosuppression was based on cyclosporine A and prednisone. HAART was reinitiated 1 month after transplantation, and immunosuppression was carefully adapted to account for drug-drug interactions between cyclosporine A and protease inihibitors. Prednisone was withdrawn 5 months (median) after OLT when immunosuppression had been reliably established in the presence of HAART. One patient died 95 days after OLT due intrathoracic hemorrhage, whereas 6 patients were alive at a median of 24 months. A single episode of acute rejection was observed. The spectrum of postoperative complications was no different from HIV-negative patients apart from Kaposi's sarcoma and multicentric Castleman's disease in a single patient. Recurrent hepatitis B infection was efficiently prevented, whereas hepatitis C reinfection occurred in all 4 patients who had preexisting hepatitis C. Earlier reports on fatal courses of recurrent hepatitis C infection, high rates of organ rejection, and HAART-related liver toxicity were not observed in our patients. In conclusion, even though preliminary, our data suggest that outcomes after liver transplantation of HIV-infected patients can be improved.     

C4d in Acute Rejection After Liver Transplantation—A Valuable Tool in Differential Diagnosis to Hepatitis C Recurrence

Hepatitis C is the most common indication for liver transplantation. Recurrence of HCV is universal leading to graft failure in up to 40% of all patients. The differentiation between acute rejection and recurrent hepatitis C is crucial as rejection treatments are likely to aggravate HCV recurrence. Histological examination of liver biopsy remains the gold standard for diagnosis of acute rejection but has failed in the past to distinguish between acute rejection and recurrent hepatitis C. We have recently reported that C4d as a marker of the activated complement cascade is detectable in hepatic specimen in acute rejection after liver transplantation. In this study, we investigate whether C4d may serve as a specific marker for differential diagnosis in hepatitis C reinfection cases. Immunohistochemical analysis of 97 patients was performed. A total of 67.7% of patients with acute cellular rejection displayed C4d-positive staining in liver biopsy whereas 11.8% of patients with hepatitis C reinfection tested positive for C4d. In the control group, 6.9% showed C4d positivity. For the first time we were able to clearly demonstrate that humoral components, represented by C4d deposition, play a role in acute cellular rejection after LTX. Consequently C4d may be helpful to distinguish between acute rejection and reinfection after LTX for HCV.     

Apoptosis and the expression of Fas and Fas ligand (FasL) antigen in rejection and reinfection in liver allograft specimens

BACKGROUND AND METHODS: To investigate the frequency of apoptosis and the expression of Fas/Fas ligand (FasL) in liver allografts, we examined 97 biopsy specimens from 62 patients after orthotopic liver transplantation. The results of the biopsies were as follows: acute allograft rejection (n=32); hepatitis C virus (HCV) reinfection (n=18); cytomegalovirus infection (n=5); acute rejection plus HCV reinfection (n=3); and stable graft function (n=30); and after treatment of acute rejection (n=9). RESULTS: Apoptotic cells were found in all cases examined, and their frequency increased significantly during acute rejection (0.17 vs. 9.0; P<0.05). The immunoreactivity of Fas and FasL antigen was higher in specimens with acute rejection than in those with stable graft function. Increased apoptosis, Fas, and FasL expression, however, were also seen in HCV reinfection. CONCLUSION: We conclude that apoptosis plays an important role in the hepatocellular damage observed in acute rejection and also in HCV reinfection. However, these parameters are, taken by themselves, not useful as indicators of acute rejection or HCV reinfection.     

Interferon-alpha and ribavirin for the treatment of recurrent hepatitis C after liver transplantation

BACKGROUND: Initial studies utilizing interferon-alpha and ribavirin for the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation showed promising results. Here we report our single-center experience using this combination therapy. METHODS: Liver transplant recipients with recurrent HCV (elevated serum aminotransferases, positive serum HCV RNA, and biopsy-proven hepatitis without rejection) received interferon-alpha (1.5-3 million units subcutaneously three times a week) and ribavirin (400-1000 mg p.o. daily) for 12 months or more. Serum aminotransferases, HCV RNA, and severity of hepatitis were followed. RESULTS: Thirty-two patients have been treated for at least 3 months, including 13 who have been on 12 or more months of therapy. Three died from allograft failure due to recurrent HCV. Dose reductions of interferon-alpha and/or ribavirin occurred in 22 patients. Thirteen had their medications permanently discontinued for severe adverse effects. Twenty-six patients (81%) had a biochemical response (BR; normalization of serum aminotransferases) after 3 months. End-of-treatment and sustained BR were 77% and 71%, respectively. Mean viral loads decreased 68-77%; however, only three patients became serum HCV RNA negative. After 12 months of therapy, no histological improvement was observed in 11 patients who were biopsied. Patients who received mycophenolate mofetil or daclizumab had a less likelihood of achieving a BR. CONCLUSIONS: A significant number of patients did not tolerate interferon-alpha or ribavirin. Although BR was excellent and mean viral loads decreased significantly, virological clearance was poor and no histological improvement was noted. A more efficacious treatment with less adverse effects for recurrent HCV after liver transplantation is needed.     

Heart Retransplantation

Retransplants comprise only a small minority (3-4%) of heart transplants, however outcome following retransplantation is compromised. Risk factors for a poor outcome following retransplantation include retransplantation early (<6 months) after primary transplant, retransplantation for acute rejection or early allograft failure, and retransplantation in an earlier era. The incidence of rejection and infection is similar following primary transplant and retransplantation. The compromised outcomes and risk factors for a poor outcome are similar in adult and pediatric heart retransplantation. However, due to the short half-life of the transplanted heart, it is an expectation that patients transplanted in childhood may require retransplantation. Based on the data available and the opinion of the working group, indications for heart retransplantation are (i) chronic severe cardiac allograft vasculopathy with symptoms of ischemia or heart failure (should be considered) or asymptomatic moderate or severe left ventricular dysfunction (may be considered) or (ii) chronic graft dysfunction with symptoms of progressive heart failure in the absence of active rejection. Patients with graft failure due to acute rejection with hemodynamic compromise, especially <6 months post-transplant, are inappropriate candidates for retransplantation. In addition, guidelines established for primary transplant candidacy should be strictly followed.     

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。     

Hepatitis C: indication for anti-viral therapy?

Abstract  Hepatitis C infection is a frequent indication for liver transplantation. In general, recurrent graft hepatitis is assumed to be mild, but may be the cause of lethal postoperative complications in a small patient population. Out of 500 transplants in 458 patients, 123 patients were transplanted due to hepatitis C infection (26.7 %) between September 1988 and April 1994. Cumulative 1– to 6-year patient survival was similar for patients transplanted due to hepatitis C (87.0 %) and those transplanted for other indications (86.0 %). In patients with hepatitis C virus (HCV), death, in 50 % of the cases, was related to HCV recurrence and chronic rejection. Four patients (25.0 %) died because of severe infection and multiple organ failure syndrome unrelated to HCV recurrence and chronic rejection. The incidence of retransplantation was similar in HCV (9.8 %) and other patients (8.4 %). In HCV patients, 6 of 12 retransplantations (50.0 %) were performed due to HCV recurrence and chronic rejection. Of 123 HCV patients, 45 experienced histo-logically proven recurrent graft hepatitis between 2 weeks and 5.5 years after transplantation. The incidence of acute rejection was similar in both groups. The incidence of steroid-resistant rejection was, however, higher in HCV patients (29.3 %) than in those transplanted for other indications (14.5 %; P ≤ 0.05). Furthermore, there was a significant association between acute rejection and the development of recurrent graft hepatitis. In conclusion, patients with hepatitis C may be transplanted with as good patient and graft survival rates as patients transplanted for other indications. However, the combination of recurrent graft hepatitis and chronic rejection remains the most limiting factor for some of these patients, which strengthens the necces-sity for a specific anti-viral therapy.     

Respiratory Failure Associated with Human Metapneumovirus Infection in an Infant Posthepatic Transplant

This is the first reported case of respiratory failure associated with human metapneumovirus (hMPV) infection in a liver transplant recipient or in a pediatric solid transplant recipient. A 9-month-old female developed respiratory distress 8 days following a liver transplant. hMPV was detected and she required intubation followed by extracorporeal membrane oxygenation for 26 days. Immunosuppressive medications were stopped during the acute infection except for methylprednisolone as treatment for acute respiratory distress. Serial Doppler ultrasounds were used to monitor for hepatic vessel thromboses and serum liver function tests to assess for hepatic dysfunction and there was no evidence of allograft rejection. The patient recovered from the nosocomial hMPV infection with satisfactory pulmonary function and possible mild developmental delay.     

Timing of reinfection and mechanisms of hepatocellular damage in transplanted hepatitis C virus[ndash ]reinfected liver

Pathogenic mechanisms and dynamics of hepatitis C virus (HCV) reinfection in orthotopic liver transplantation (OLT) are poorly defined. This study focuses on these aspects by studying 55 frozen biopsy specimens from transplant recipients with various histological diagnoses obtained from 4 days to 4 years post-OLT and 10 patients with HCV-related chronic hepatitis. The percentage of HCV-infected hepatocytes, number and distribution of CD8 and natural killer cells, and rates of hepatocellular apoptosis and proliferation were quantified by immunohistochemistry. HCV antigens were detected in 37% of biopsy specimens obtained within 20 days and 90% of biopsy specimens obtained from 21 days to 6 months after OLT. The number of HCV-infected hepatocytes was never less than 40% in acute hepatitis specimens and never greater than 30% in the other cases. Hepatocellular apoptosis was high in biopsy specimens of acute hepatitis and moderate in those from transplant recipients with normal histological characteristics, but still greater than in specimens of chronic active hepatitis. Proliferation correlated significantly with apoptosis. Lymphocyte infiltration was high and similar among cases of acute hepatitis, chronic hepatitis, and rejection. These data: (1) show that the detection of liver HCV antigens is sensitive enough to be used in clinical practice as a diagnostic tool to detect infection of the transplanted liver and might be useful, combined with conventional histological evaluation to detect hepatitic damage, for therapeutic decision making; (2) suggest direct cytotoxicity of HCV, as well as immunologic mechanisms possibly prevalent in chronic hepatitis and rejection, at least in the phase of acute massive liver infection; and (3) show that hepatocellular apoptosis and regeneration might be active enough to lead to replacement of the entire transplanted liver in 2 weeks. (Liver Transpl 2002;8:10-20.)     

Hepatitis C etiology of liver disease is strongly associated with early acute rejection following liver transplantation.

Although recurrent hepatitis C (HCV) occurs universally after liver transplantation (LT), its tempo and severity are variable and unpredictable. Diagnosis and treatment of early acute rejection (EAR) likely affect the course of recurrent HCV disease. We have studied a contemporary cohort of LT recipients to reexamine risk factors for EAR. We hypothesized that HCV etiology may represent a significant risk factor for EAR for many reasons. First, recurrent disease commonly causes biochemical abnormalities prompting allograft biopsy. Second, overlapping histologic features of acute rejection and recurrent HCV ambiguity may result in diagnostic ambiguity. Finally, the biology of hepatitis may precipitate an antidonor response in addition to an antiviral response. Records of 285 adult recipients undergoing primary LT for cirrhosis between January 1, 1999, and December 31, 2002, were retrospectively reviewed. EAR was defined as a biopsy-proven or an empirically treated episode within 6 months of LT. Cox proportional hazards analysis identified donor, recipient, transplant, and posttransplant characteristics associated with EAR; Kaplan-Meier analysis was used to assess rejection by etiology. HCV cirrhosis was the etiology for 51% of all LT recipients. There were 135 episodes of EAR (127 biopsy proven) in 117 recipients for an overall incidence of 41%. Patient groups with HCV and cholestatic / autoimmune disease groups exhibited the highest incidence of rejection at 49%. Recipient gender, ethnicity, etiology, LT year, and posttransplant immunosuppression levels were risk factors for EAR in univariate analysis; HCV etiology and female gender remained robust risk factors in multivariate analysis. Interferon-based therapy did not impact the incidence or timing of EAR. In conclusion, HCV etiology is strongly associated with EAR. HCV allograft reinfection may create an immunologic environment predisposed to EAR. Alternatively, the association of HCV and EAR may result from an increased frequency of allograft biopsy and may be further exacerbated by inability to accurately diagnose EAR in the setting of recurrent HCV.     

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.     

Incidence and clinical relevance of recurrent hepatitis C infection after orthotopic liver transplantation

Abstract From September 1988 to November 1992 318 liver transplants were performed at our hospital. Of these patients 68 had end-tage cirrhosis due to non-A, non-B, hepatitis, 44 of whom (64.7%) had hepatitis C virus RNA in the serum. Of this subgroup 35 patients (79.5%) were also anti-HCV positive. Postoperatively most recipients remained anti-HCV positive and after 1 year more than 90% had HCV RNA in the serum. About 40% developed a mild, chronic hepatitis and 50% were carriers of HCV without histo-pathological signs. Two patients suffered from a temporary severe acute hepatitis and one patient had a fulminant liver failure due to reinfection. In general, in liver recipients transplanted for end-tage HCV hepatitis there was a high incidence of reinfection with HCV. The clinical course, however, was less severe than in hepatitis B recurrence.     

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.     

Liver Transplant Pathology: Review of Challenging Diagnostic Situations

Histopathologic assessment of allograft liver biopsies has an important role in managing patients who have undergone liver transplantation. In this review, several topics are discussed that create diagnostic problems in transplant pathology, with emphasis on pathologic features and differential diagnosis. The topics discussed are acute cellular rejection, late acute rejection (centrizonal/parenchymal rejection), chronic rejection, plasma cell hepatitis, idiopathic posttransplant chronic hepatitis, fibrosing cholestatic hepatitis, selected viral infections (cytomegalovirus, Epstein-Barr virus, and hepatitis E), and acute antibody-mediated rejection.     

c-Kit-positive mast cells in portal tracts cannot be used to distinguish acute cellular rejection from recurrent hepatitis C infection in liver allografts

Cirrhosis secondary to chronic hepatitis C virus (HCV) is the most common indication for liver transplantation. Recurrence of HCV infection in the liver allograft occurs at a high rate. The differentiation of recurrent HCV infection from acute cellular rejection (ACR) represents a difficult challenge in transplantation pathology. The c-Kit receptor is a tyrosine kinase membrane protein encoded by the c-Kit proto-oncogene, which is expressed on mast cells and on hematopoietic stem and progenitor cells. Mast cells are important effector cells of a broad range of immune responses. Recently, c-Kit+ mast cells were shown to form part of the inflammatory infiltrate in acute liver allograft rejection. A strong relationship was found between c-Kit+ cell densities and increasingly severe rejection. The present study sought to determine whether the presence of c-Kit+ cells could be used to distinguish between ACR and recurrent HCV in liver allografts. Immunohistochemical staining for c-Kit was performed on 20 transplant biopsy specimens from 10 patients with mild to moderate ACR and 10 other patients with recurrent hepatitis C. The number of c-Kit+ cells per portal tract varied with the density of the overall inflammatory infiltrate. There was no significant difference between the number of c-Kit+ cells in the biopsy specimens that carried a diagnosis of ACR and those from patients who had been diagnosed as having recurrent HCV. It was concluded that immunohistochemical staining for the presence of c-Kit+ mast cells cannot be used to differentiate between ACR and recurrent HCV infection in liver allograft biopsy specimens.     

Liver transplantation for autoimmune hepatitis: fulminant versus chronic hepatitis presentation

AIMS: The aim of this study was to analyse long-term outcomes of patients with liver transplantation for autoimmune hepatitis and to determine if fulminant/subfulminant hepatic failure (FSHF) at presentation was a predictor of outcome after ortothopic liver transplantation. PATIENTS AND METHODS: Between April 1990 and October 2002, 18 patients with autoimmune hepatitis underwent 21 liver transplants. Three patients were excluded because of coexisting causes of hepatitis. Seven patients had FSHF and eight patients had chronic disease. The initial immunosuppressive regimen was cyclosporine based in 80%, and all but one patient received steroids or azathioprine. RESULTS: Mean age at time of transplant was 44.2+/-15.5 years. Patients were followed for 38.9+/-29.6 months. Five patients (33.3%) had seven episodes of acute rejection (two steroid-resistant). Three patients developed chronic rejection. One patient displayed histologically proven recurrent autoimmune hepatitis. Actuarial patient and graft survival rates at 1 and 5 years were 80% and 56% and 78.6% and 51%, respectively. No differences in the clinical characteristics of the patients, rates of acute or chronic rejection episodes, end biliary or arterial complications were observed between FSHF and chronic autoimmune hepatitis. The study suggests a better survival for autoimmune FSHF (P=.003). CONCLUSIONS: Liver transplant is indicated for patients displaying autoimmune chronic liver disease and FSHF with similar clinical courses at however, patients with FSHF at presentation had better survivals.