Antibody-mediated rejection in ABO compatible husband to wife living donor liver transplant and review of the literature.

Role of donor specific antibodies (DSAs) in liver allograft function has not been fully defined. We report an ABO compatible orthotopic liver transplant case with DSAs to donor HLA, where the patient developed immediate antibody-mediated rejection (AMR).The patient, a 43-year-old female with cirrhosis, underwent ABO-compatible living-donor liver transplant from her husband. On post-operative day (POD)1, serum transaminases were sharply elevated. Retrospective testing of pre-transplant serum demonstrated presence of strong class I and class II anti-HLA antibodies and positive T- and B-cell flow-cytometric crossmatches (FCXM). Transaminase levels improved with plasmapheresis and thymoglobulin. On POD7, her liver enzymes became elevated again and allograft biopsy stained positive for C4d. Patient was treated with intravenous immunoglobulin and rituximab and recovered over time. Pre-transplant sera of patient were retrospectively tested by C1q assay to determine the cytotoxic function of DSAs; DSAs were positive for C1q binding. Our results suggest that pre-liver transplant antibody testing may be helpful in identifying patients at risk for development of AMR.

Hepatitis E virus infection in a liver transplant recipient in the United States: a case report.

BACKGROUND: Chronic infection with hepatitis E virus (HEV) has recently been recognized in immunocompromised or immunosuppressed individuals. CASE REPORT: We report a case of concurrent HEV and human herpes virus-6 (HHV-6) infection, documented by serum HEV RNA and HHV-6 DNA, in an orthotopic liver transplant (OLT) recipient in the United States, where HEV genotype 3 infection, although prevalent, is considered to be self-limited and almost always asymptomatic. The coinfection was accompanied by elevated serum aminotransaminases, liver biopsies demonstrating chronic hepatitis, and the presence of HEV RNA in the tissue. After lowering of immunosuppressive therapy and 2 courses of valganciclovir, sequential clearance of the viruses and normalization of the serum aminotransaminases were observed. CONCLUSIONS: HEV infection can lead to chronic hepatitis in OLT recipients, and evaluation of this virus should be considered in immunosuppressed individuals with unexplained liver test abnormalities.

Durability of sustained response shown in paediatric patients with chronic hepatitis C who were treated with interferon alfa-2b plus ribavirin.

Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit (n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment.

Results of steroid-based therapy for the hepatitis C-autoimmune hepatitis overlap syndrome.

OBJECTIVE: Overlap syndromes in which persons manifest clinical, histological, or immunological features of both hepatitis C infection and autoimmune hepatitis are well described. The discordant forms of treatment for hepatitis C and autoimmune hepatitis have made medical management of these patients difficult. We report our experience in using corticosteroids as first line therapy for the hepatitis C-autoimmune hepatitis overlap syndrome. METHODS: Seven patients with this overlap syndrome (diagnosis based on the presence of serum hepatitis C antibody by RIBA and serum hepatitis C RNA by polymerase chain reaction, and serum hypergammaglobulinemia, elevated ANA or ASMA titers, or histological findings consistent with autoimmune hepatitis) were treated with prednisone with or without azathioprine or cyclosporine, and followed for a median duration of 44.5 months. RESULTS: Five patients (71%) showed improvement of median serum ALT level from 162 U/L to 38 U/L (p = 0.04) and median serum gamma-globulin from 2.1 g/dl to 1.4 g/dl (p = 0.04) by 6 months of therapy. The mean modified histological activity index score also decreased from 11.4 +/- 2.5 to 6.6 +/- 2.6 (p = 0.04) by at least 1 yr of therapy. One patient discontinued prednisone while taking azathioprine and experienced a rebound elevation of serum ALT that did not respond to retreatment with prednisone. Antiviral therapy was subsequently administered and resulted in biochemical and virologic response. Hepatitis C virus RNA remained detectable in all other patients. CONCLUSION: Corticosteroids are beneficial as a first line therapy for some patients with the hepatitis C-autoimmune overlap syndrome, resulting in appreciable biochemical and histological response but without viral eradication.

Open cardiotomy for removal of migrating transjugular intrahepatic portosystemic shunt stent combined with liver transplantation.

BACKGROUND: Transjugular intrahepatic shunts are widely used for the management of variceal bleeding. Complications such as stent misplacement or migration may occur. METHODS: We describe the management of a transjugular intrahepatic shunts stent that migrated across the tricuspid valve in a patient with Child-Pugh category C cirrhosis. RESULTS: An attempt at percutaneous retrieval of the stent was unsuccessful. Due to the unacceptably high risk for mortality from open heart surgery with cardiopulmonary bypass in the setting of cirrhosis, stent removal was deferred until the time of orthotopic liver transplantation. The procedures were performed successfully, and the patient made a good recovery. CONCLUSION: Surgical stent extraction and valve repair can be performed safely along with orthotopic liver transplantation in carefully selected patients with end-stage liver disease.

Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease.

OBJECTIVE: Methotrexate is currently used as a treatment for refractory inflammatory bowel disease. This study sought to evaluate the hepatic effects of long-term methotrexate therapy in patients with inflammatory bowel disease and to determine whether the established guidelines for monitoring methotrexate-related hepatotoxicity with surveillance liver biopsy in patients with psoriasis or rheumatoid arthritis are applicable to these patients. METHODS: Thirty-two patients with inflammatory bowel disease receiving cumulative methotrexate doses of > or = 1500 mg were studied. Liver chemistry tests were obtained before and during therapy. Twenty patients underwent liver biopsies as recommended for methotrexate-treated patients with psoriasis; the biopsies were reviewed and graded according to Roenigk's criteria for methotrexate-induced hepatotoxicity (a grading system for methotrexate hepatotoxicity in psoriasis patients) by a liver pathologist blinded to the methotrexate dose. RESULTS: In patients who had liver biopsies, the mean cumulative methotrexate dose was 2633 mg (range, 1500-5410 mg), given for a mean of 131.7 wk (range, 66-281 wk). Nineteen of 20 patients (95%) had mild histological abnormalities (Roenigk's grade I and II), and one patient had hepatic fibrosis (Roenigk's grade IIIB). Abnormal liver chemistry tests, present in 6 of 20 (30%) patients, did not identify the patient with Roenigk's grade IIIB hepatotoxicity. CONCLUSIONS: Cumulative methotrexate doses up to 5410 mg given up to 281 wk in patients with inflammatory bowel disease are associated with little hepatotoxicity. Surveillance liver biopsies based on cumulative methotrexate doses are not warranted in these patients.

Donor liver uridine diphosphate (UDP)-glucuronosyltransferase-1A1 deficiency causing Gilbert's syndrome in liver transplant recipients.

BACKGROUND: Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert's syndrome, has been attributed to two extra (TA) bases in the TATAA-box of the promoter region of its gene, where the A(TA)6TAA allele corresponds to the normal gene and A(TA)7TAA corresponds to a gene with reduced expression. Our aim was to determine whether isolated hyperbilirubinemia in liver transplant recipients was due to Gilbert's syndrome acquired through the liver allograft. METHODS: From 305 patients followed in our Liver Transplant Clinic, five patients with isolated unconjugated hyperbilirubinemia in the absence of hemolysis, recurrent viral hepatitis, and biliary tract pathology were identified; 10 other post-orthotopic liver transplantion patients with normal liver chemistry tests were randomly selected as a control group. DNA was extracted from paraffin-embedded liver allograft tissue and peripheral lymphocytes and was genotyped for the TA repeat at the uridine diphosphate glucononosyltransferase-lA1 promoter region by polymerase chain reaction and acrylamide gel electrophoresis. Homozygosity for the (TA)7 allele was considered diagnostic of Gilbert's syndrome. RESULTS: The mean serum total bilirubin level of the study patients was 2.28 mg/dl (range 1.8-3.0), consisting predominantly of the unconjugated form; that of the control patients was 0.76 mg/dl (range 0.4-1.1). The liver tissue from all five patients in the study group possessed the homozygous A(TA)7TAA genotype that was not observed in their lymphocytes. None of the liver tissue from the control patients demonstrated homozygosity for the A(TA)7TAA allele. CONCLUSION: Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert's syndrome, may be carried by the donor liver and present with isolated unconjugated hyperbilirubinemia in liver transplant recipients.

Fulminant hepatic failure secondary to malignant melanoma: case report and review of the literature.

Malignant melanoma has a propensity to metastasize widely to many organs, involving the liver in up to one-third of cases. Fulminant hepatic failure is an unusual presentation of hepatic neoplasms, whether primary or metastatic. We describe a case of malignant melanoma with liver metastases that rapidly progressed to fulminant hepatic failure and death. Striking elevations of liver tests, particularly lactate dehydrogenase, were seen. Liver biopsy showed diffuse intrasinusoidal infiltration with melanoma cells. In patients with malignant melanoma, raised serum lactate dehydrogenase levels may suggest hepatic involvement, with extreme elevations possibly predictive of liver failure.

Intrahepatic cholestasis following liver transplantation.

Intrahepatic cholestasis following liver transplantation commonly occurs after liver transplantation and may be caused by infections, drugs such as cyclosporine and sulfonamides, and acute or chronic rejection. Less common causes such as fibrosing cholestatic hepatitis or recurrent primary biliary cirrhosis or primary sclerosing cholangitis may also be encountered. Biliary strictures may also be present. Although some disorders may be managed medically, others often require repeat liver transplantation. Prompt recognition and specific treatment can improve the outcome for liver transplant recipients.

Autoimmune hepatitis: a histological variant associated with prominent centrilobular necrosis.

A patient presented with pruritus and recent elevation of aminotransferases. The case fulfilled most of the criteria for the diagnosis of autoimmune hepatitis and achieved clinical and complete biochemical response to steroid therapy. However, the liver biopsy specimen revealed an unusual histological pattern consisting of severe centrilobular necrosis demarcated by a thin rim of hepatitic reaction. In contrast, the portal tracts appeared almost normal. This histological appearance has not been associated with autoimmune hepatitis. This presentation and the histology may represent an early pattern of autoimmune injury to the liver.