Hepatitis E virus in patients with acute severe liver injury

AIM: To examine the incidence of hepatitis E(HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit.METHODS: Hepatitis 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 isoften 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.RESULTS: Four 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.CONCLUSION: In 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.

Predictive value of symptoms and demographics in diagnosing malignancy or peptic stricture

AIM:To determine which features of history and demographics predict a diagnosis of malignancy or peptic stricture in patients presenting with dysphagia.METHODS:A prospective case-control study of 2000 consecutive referrals(1031 female,age range:17-103 years) to a rapid access service for dysphagia,based in a teaching hospital within the United Kingdom,over 7 years.The service consists of a nurse-led telephone triage followed by investigation(barium swallow or gastroscopy),if appropriate,within 2 wk.Logistic regression analysis of demographic and clinical variables was performed.This includes age,sex,duration of dysphagia,whether to liquids or solids,and whether there are associated features(reflux,odynophagia,weight loss,regurgitation).We determined odds ratio(OR) for these variables for the diagnoses of malignancy and peptic stricture.We determined the value of the Edinburgh Dysphagia Score(EDS) in predicting cancer in our cohort.Multivariate logistic regression was performed and P < 0.05 considered significant.The local ethics committee confirmed ethics approval was not required(audit).RESULTS:The commonest diagnosis is gastro-esophageal reflux disease(41.3%).Malignancy(11.0%) and peptic stricture(10.0%) were also relatively common.Malignancies were diagnosed by histology(97%) or on radiological criteria,either sequential barium swallows showing progression of disease or unequivocal evidence of malignancy on computed tomography.The majority of malignancies were esophago-gastric in origin but ear,nose and throat tumors,pancreatic cancer and extrinsic compression from lung or mediastinal metastatic cancer were also found.Malignancy was statistically more frequent in older patients(aged >73 years,OR 1.1-3.3,age < 60 years 6.5%,60-73 years 11.2%,> 73 years 11.8%,P < 0.05),males(OR 2.2-4.8,males 14.5%,females 5.6%,P < 0.0005),short duration of dysphagia(≤ 8 wk,OR 4.5-20.7,16.6%,8-26 wk 14.5%,> 26 wk 2.5%,P < 0.0005),progressive symptoms(OR 1.3-2.6:progressive 14.8%,intermittent 9.3%,P < 0.001),with weight loss of ≥ 2 kg(OR 2.5-5.1,weight loss 22.1%,without weight loss 6.4%,P < 0.0005) and without reflux(OR 1.2-2.5,reflux 7.2%,no reflux 15.5%,P < 0.0005).The likelihood of malignancy was greater in those who described true dysphagia(food or drink sticking within 5 s of swallowing than those who did not(15.1%vs 5.2% respectively,P < 0.001).The sensitivity,specificity,positive predictive value and negative predictive value of the EDS were 98.4%,9.3%,11.8% and 98.0% respectively.Three patients with an EDS of 3(high risk EDS ≥ 3.5) had malignancy.Unlike the original validation cohort,there was no difference in likelihood of malignancy based on level of dysphagia(pharyngeal level dysphagia 11.9% vs mid sternal or lower sternal dysphagia 12.4%).Peptic stricture was statistically more frequent in those with longer duration of symptoms(> 6 mo,OR 1.2-2.9,≤ 8 wk 9.8%,8-26 wk 10.6%,> 26 wk 15.7%,P < 0.05) and over 60 s(OR 1.2-3.0,age < 60 years 6.2%,60-73 years 10.2%,> 73 years 10.6%,P < 0.05).CONCLUSION:Malignancy and peptic stricture are frequent findings in those referred with dysphagia.The predictive value for associated features could help determine need for fast track investigation whilst reducing service pressures.

Hepatitis E virus: Western Cape, South Africa

AIM To conduct a prospective assessment of anti-hepatitis E virus(HEV) Ig G seroprevalence in the Western Cape Province of South Africa in conjunction with evaluating risk factors for exposure.METHODS Consenting participants attending clinics and wards of Groote Schuur, Red Cross Children's Hospital and their affiliated teaching hospitals in Cape Town, South Africa, were sampled. Healthy adults attending blood donor clinics were also recruited. Patients with known liver disease were excluded and all major ethnic/race groups were included to broadly represent local demographics. Relevant demographic data was captured at the time of sampling using an interviewer-administered confidential questionnaire. Human immunodeficiency virus(HIV) status was self-disclosed. HEV Ig G testing was performed using the Wantai? assay.RESULTS HEV is endemic in the region with a seroprevalence of 27.9%(n = 324/1161) 95%CI: 25.3%-30.5%(21.9% when age-adjusted) with no significant differences between ethnic groups or HIV status. Seroprevalence in children is low but rapidly increases in early adulthood. With univariate analysis, age ≥ 30 years old, pork and bacon/ham consumption suggested risk. In the multivariate analysis, the highest risk factor for HEV Ig G seropositivity(OR = 7.679, 95%CI: 5.38-10.96, P < 0.001) was being 30 years or older followed by pork consumption(OR = 2.052, 95%CI: 1.39-3.03, P < 0.001). A recent clinical case demonstrates that HEV genotype 3 may be currently circulating in the Western Cape.CONCLUSION Hepatitis E seroprevalence was considerably higher than previously thought suggesting that hepatitis E warrants consideration in any patient presenting with an unexplained hepatitis in the Western Cape, irrespective of travel history, age or ethnicity.