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Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant patients.

ABSTRACT: Liver failure resulting from chronic hepatitis C virus (HCV) infection is a major cause for liver transplantation worldwide. Recurrent infection of the graft is universal in HCV patients after transplant and results in a rapid progression to severe fibrosis and end-stage liver disease in one third of all patients. No single clinical variable, or combination thereof, has, so far, proven accurate in identifying patients at risk of hepatic decompensation in the transplant setting. A combination of longitudinal, dimensionality reduction and categorical analysis of the transcriptome from 111 liver biopsy specimens taken from 57 HCV-infected patients over time identified a molecular signature of gene expression of patients at risk of developing severe fibrosis. Significantly, alterations in gene expression occur before histologic evidence of liver disease progression, suggesting that events that occur during the acute phase of infection influence patient outcome. Additionally, a common precursor state for different severe clinical outcomes was identified.Based on this patient cohort, incidence of severe liver disease is a process initiated early during HCV infection of the donor organ. The probable cellular network at the basis of the initial transition to severe liver disease was identified and characterized.

SUBMITTER: Rasmussen AL

PROVIDER: S-EPMC3349763 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant patients.

Rasmussen Angela L AL Tchitchek Nicolas N Susnow Nathan J NJ Krasnoselsky Alexei L AL Diamond Deborah L DL Yeh Matthew M MM Proll Sean C SC Korth Marcus J MJ Walters Kathie-Anne KA Lederer Sharon S Larson Anne M AM Carithers Robert L RL Benecke Arndt A Katze Michael G MG

Hepatology (Baltimore, Md.) 20120605 1

<h4>Unlabelled</h4>Liver failure resulting from chronic hepatitis C virus (HCV) infection is a major cause for liver transplantation worldwide. Recurrent infection of the graft is universal in HCV patients after transplant and results in a rapid progression to severe fibrosis and end-stage liver disease in one third of all patients. No single clinical variable, or combination thereof, has, so far, proven accurate in identifying patients at risk of hepatic decompensation in the transplant setting ...[more]

PMID: 22278598

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Project description:AimTo examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit.MethodsHepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction.ResultsFour cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases.ConclusionIn patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history.

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Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant patients.

Publications

Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant patients.

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