Cost-Effectiveness Analysis of Screening for Persistent Hepatitis E Virus Infection in Solid Organ Transplant Patients in the United Kingdom: A Model-Based Economic Evaluation.

BACKGROUND: Despite potentially severe and fatal outcomes, recent studies of solid organ transplant (SOT) recipients in Europe suggest that hepatitis E virus (HEV) infection is underdiagnosed, with a prevalence of active infection of up to 4.4%. OBJECTIVES: To determine the cost-effectiveness of introducing routine screening for HEV infection in SOT recipients in the UK. METHODS: A Markov cohort model was developed to evaluate the cost-utility of 4 HEV screening options over the lifetime of 1000 SOT recipients. The current baseline of nonsystematic testing was compared with annual screening of all patients by polymerase chain reaction (PCR; strategy A) or HEV-antigen (HEV-Ag) detection (strategy B) and selective screening of patients who have a raised alanine aminotransferase (ALT) value by PCR (strategy C) or HEV-Ag (strategy D). The primary outcome was the incremental cost per quality-adjusted life-year (QALY). We adopted the National Health Service (NHS) perspective and discounted future costs and benefits at 3.5%. RESULTS: At a willingness-to-pay of £20 000/QALY gained, systematic screening of SOT patients by any method (strategy A-D) had a high probability (77.9%) of being cost-effective. Among screening strategies, strategy D is optimal and expected to be cost-saving to the NHS; if only PCR testing strategies are considered, then strategy C becomes cost-effective (£660/QALY). These findings were robust against a wide range of sensitivity and scenario analyses. CONCLUSIONS: Our model showed that routine screening for HEV in SOT patients is very likely to be cost-effective in the UK, particularly in patients presenting with an abnormal alanine aminotransferase.

Noninvasive models for predicting poor prognosis of chronic HBV infection patients precipitating acute HEV infection.

Hepatitis E virus (HEV) infection contributes to a considerable proportion of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B virus (HBV) infection. This study aimed to predict the prognosis of chronic HBV infection patients precipitating acute HEV infection. A total of 193 patients were enrolled in this study. The performances of three chronic liver disease prognostic models (CTP score, MELD score, and CLIF-C ADs) were analyzed for predicting the development of ACLF following HEV superimposing chronic HBV infection. Subsequently, the performances of five ACLF prognostic assessment models (CTP score, MELD score, CLIF-C ACLFs, CLIF-C OFs, and COSSH-ACLFs) were analyzed for predicting the outcome of those ACLF patients. Of 193 chronic HBV infection patients precipitating acute HEV infection, 13 patients were diagnosed ACLF on admission, 54 patients developed to ACLF after admission, and 126 patients had non-ACLF during the stay in hospital. For predicting the development of ACLF, CTP score yielded a significantly higher AUROC compared with MELD score and CLIF-C ADs (0.92, 0.88, and 0.86, respectively; all p < 0.05). For predicting the poor prognosis of ACLF patients, the COSSH-ACLFs yielded a significantly higher AUROC compared with CLIF-C ACLFs, CLIF-C OFs, MELD score, and CTP score (0.89, 0.83, 0.81, 0.67, and 0.58, respectively; all p < 0.05). In conclusion, the stepwise application of CTP score and COSSH-ACLFs can predict the prognosis of chronic HBV infection patients precipitating acute HEV infection.

HEV superinfection accelerates disease progression in patients with chronic HBV infection and increases mortality in those with cirrhosis.

BACKGROUND & AIMS: Acute HEV infection causes varying degrees of liver damage. Although liver-related death due to HEV infection alone is rare in healthy individuals, it is unclear whether HEV superinfection is associated with worse outcomes in patients with chronic HBV infection. Thus, we explored whether HEV superinfection was associated with increased incidence of liver-related death, cirrhosis, and hepatocellular carcinoma (HCC). METHODS: Serum and data were collected from 2 independent retrospective cohorts of patients with chronic HBV infection, comprising 2,123 patients without cirrhosis and 414 with cirrhosis at baseline, respectively. All the patients were negative for HEV-IgG at enrolment and HEV superinfection was defined by the presence of HEV-IgG seroconversion. RESULTS: In the non-cirrhotic cohort, 46 of 2,123 patients developed HEV superinfection. Though HEV superinfection was only associated with increased incidence of liver-related death in the overall cohort, it was a risk factor for all 3 endpoints (liver-related death, cirrhosis, and HCC) in a subgroup of 723 HBeAg-negative patients with chronic HBV infection. In addition, the 1-year mortality rate after HEV superinfection was higher in 4 patients who developed cirrhosis during the follow-up than in those who did not (50% vs. 2.4%, p = 0.001). To elucidate the perceived relationship between HEV superinfection and risk of mortality, an independent cohort of cirrhotic patients (n = 414) was further analyzed to control for the inherent increase in mortality risk due to cirrhosis. The 10 cirrhotic patients with HEV superinfection had a higher 1-year mortality rate than those without (30% vs. 0%, p <0.001). CONCLUSIONS: In both cohorts of patients with chronic HBV infection, acute HEV superinfection increases the risk of liver-related death, especially in those with cirrhosis. LAY SUMMARY: The mortality caused by acute hepatitis E virus infection is usually low in the healthy population, but it is unclear how it affects patients with chronic hepatitis B virus infection, as they already have compromised liver function. Our data show that the 1-year mortality rate is 35.7% in patients with hepatitis B-related cirrhosis who contract hepatitis E virus. Hepatitis E may accelerate disease progression in patients with chronic hepatitis B.

Hepatitis E during pregnancy: Maternal and foetal case-fatality rates and adverse outcomes-A systematic review.

Hepatitis E virus infection during pregnancy can have severe consequences for mother and child, such as vertical transmission, fulminant hepatic failure, even foetal or maternal mortality. The aim of this systematic review is to describe maternal, foetal and neonatal case-fatality rates as well as the prevalence of adverse outcomes in relation to hepatitis E virus infection during pregnancy. A systematic literature search was performed in Pubmed, Embase, Cochrane and CINAHL. Search terms included Pregnant, Women, Maternal, Infant, Foetal, Neonatal and Hepatitis E virus. Data were extracted using predefined data collection forms. All studies were quality assessed, either by the Newcastle-Ottawa Scale or by an adapted assessment scale for cross-sectional studies. We found 23 eligible studies, all observational, which were included in this systematic review with a total of 1338 cases. The median maternal, foetal and neonatal case-fatality rates were 26% (IQR 17%-41%), 33% (IQR 19%-37%) and 8% (IQR 3%-20%), respectively. Adverse outcomes such as fulminant hepatic failure, preterm labour, postpartum haemorrhage, low birth weight and vertical transmission were reported. The two studies that reported the highest prevalence of fulminant hepatic failure also reported the highest case-fatality rates. The median prevalence of fulminant hepatic failure was 45.3%. This systematic review found a high case-fatality rate among pregnant women infected with hepatitis E virus and a high rate of adverse outcomes among these women and their children. The results from this review mainly apply to hospital settings and symptomatic pregnant women from endemic countries.

The burden of hepatitis E among patients with haematological malignancies: A retrospective European cohort study.

BACKGROUND & AIMS: The burden of hepatitis E virus (HEV) infection among patients with haematological malignancy has only been scarcely reported. Therefore, we aimed to describe this burden in patients with haematological malignancies, including those receiving allogeneic haematopoietic stem cell transplantation. METHODS: We conducted a retrospective, multicentre cohort study across 11 European centres and collected clinical characteristics of 50 patients with haematological malignancy and RNA-positive, clinically overt hepatitis E between April 2014 and March 2017. The primary endpoint was HEV-associated mortality; the secondary endpoint was HEV-associated liver-related morbidity. RESULTS: The most frequent underlying haematological malignancies were aggressive non-Hodgkin lymphoma (NHL) (34%), indolent NHL (iNHL) (24%), and acute leukaemia (36%). Twenty-one (42%) patients had received allogeneic haematopoietic stem cell transplantation (alloHSCT). Death with ongoing hepatitis E occurred in 8 (16%) patients, including 1 patient with iNHL and 1 patient >100 days after alloHSCT in complete remission, and was associated with male sex (p = 0.040), cirrhosis (p = 0.006) and alloHSCT (p = 0.056). Blood-borne transmission of hepatitis E was demonstrated in 5 (10%) patients, and associated with liver-related mortality in 2 patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in 10 (47.6%) and 6 (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in 4 (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients, with an HEV clearance rate of 79.2%. Ribavirin treatment was associated with lower mortality (p = 0.037) and by trend with lower rates of chronicity (p = 0.407) when initiated <24 and <12 weeks after diagnosis of hepatitis E, respectively. Immunosuppressive treatment reductions were associated with mortality in 2 patients (28.6%). CONCLUSION: Hepatitis E is associated with mortality and liver-related morbidity in patients with haematological malignancy. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas reduction of immunosuppressive treatment requires caution. LAY SUMMARY: Little is known about the burden of hepatitis E among patients with haematological malignancy. We conducted a retrospective European cohort study among 50 patients with haematological malignancy, including haematopoietic stem cell transplant recipients, with clinically significant HEV infection and found that hepatitis E is associated with hepatic and extrahepatic mortality, including among patients with indolent disease or among stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in 5 (45.5%) patients exposed to a rituximab-containing regimen and 10 (47.6%) stem cell transplant recipients. Reducing immunosuppressive therapy because of hepatitis E was associated with mortality, while early ribavirin treatment was safe and effective.

Hepatitis E Virus Infection During Pregnancy: The Overlooked Cause of Maternal and Fetal Mortality.

BACKGROUND: Hepatitis E virus (HEV) is one the leading causes of maternal and fetal mortality. Nevertheless, in some geographical locations, especially Egypt, despite having high frequency of HEV seropositivity, HEV infection follows an asymptomatic or mild course during pregnancy. These anomalous observations have distracted attention from the importance of HEV infection in pregnant women. METHODS: While tragic cases of HEV-infected pregnant women cannot be neglected any longer. CONCLUSION: These circumstances create a strong demand for the increasing awareness of HEV infection through training programs, appropriate management of HEV infection among pregnant women, routine screening of pregnant women for timely diagnosis of HEV infection, proper treatment of HEVinfected patients, optimal preventive measures, and development of a prophylactic vaccine against HEV infection.

Epidemiology of Genotype 1 and 2 Hepatitis E Virus Infections.

Hepatitis E virus (HEV) genotypes 1 and 2 are responsible for the majority of acute viral hepatitis infections in endemic areas in South Asia and sub-Saharan Africa. In addition to frequent sporadic illnesses throughout the year, these viruses often cause large epidemics in association with monsoon rains in Asia or during humanitarian crises in Africa. Clinical hepatitis commonly involves adults more often than young children, with an overall mortality of ∼1%. However, the mortality among pregnant women is often 30% or higher. HEV infection in pregnant women frequently leads to infant mortality or premature delivery. Hepatitis E is an important, yet largely neglected, global public health problem.

Chronic Hepatitis B Increases Liver-Related Mortality of Patients With Acute Hepatitis E: A Territorywide Cohort Study From 2000 to 2016.

Background: The epidemiology of acute hepatitis A and E has been changing over the last 2 decades. The impact of concomitant chronic hepatitis B (CHB) on clinical outcomes remains unclear. We aimed to evaluate the morbidity and mortality of patients with acute hepatitis A or E with and without underlying CHB. Methods: We identified consecutive patients with acute hepatitis A or E based on hepatitis serology from the electronic medical records of the Hospital Authority of Hong Kong from January 2000 to December 2016. Hepatic events, all-cause mortality, and liver-related mortality within 30 days of the diagnosis of acute hepatitis were evaluated. Results: The cohort included 1068 cases of acute hepatitis A and 846 cases of acute hepatitis E. More patients with acute hepatitis E than those with acute hepatitis A had underlying CHB (13.5% vs 8.0%; P < .001). Patients with hepatitis E had more all-cause mortality (3.9% vs 0.6%; P < .001), liver-related mortality (2.0% vs 0.3%; P < .001), and hepatic events (2.8% vs 0.3%; P < .001) within 30 days from diagnosis. In patients with acute hepatitis E, underlying renal failure (adjusted hazard ratio [aHR], 3.90; P < .001) and age ≥50 years (aHR, 3.25; P = .036) were associated with 30-day all-cause mortality, whereas CHB (aHR, 3.34; P = .02) was associated with 30-day liver-related mortality. Conclusions: The mortality is higher in patients with acute hepatitis E than in those with hepatitis A. Coexisting CHB is the independent risk factor for liver-related mortality in patients with acute hepatitis E.

Reactive and pre-emptive vaccination strategies to control hepatitis E infection in emergency and refugee settings: A modelling study.

BACKGROUND: Hepatitis E Virus (HEV) is the leading cause of acute viral hepatitis globally. Symptomatic infection is associated with case fatality rates of ~20% in pregnant women and it is estimated to account for ~10,000 annual pregnancy-related deaths in southern Asia alone. Recently, large and well-documented outbreaks with high mortality have occurred in displaced population camps in Sudan, Uganda and South Sudan. However, the epidemiology of HEV is poorly defined, and the value of different immunisation strategies in outbreak settings uncertain. We aimed to estimate the critical epidemiological parameters for HEV and to evaluate the potential impact of both reactive vaccination (initiated in response to an epidemic) and pre-emptive vaccination. METHODS: We analysed data from one of the world's largest recorded HEV epidemics, which occurred in internally-displaced persons camps in Uganda (2007-2009), using transmission dynamic models to estimate epidemiological parameters and assess the potential impact of reactive and pre-emptive vaccination strategies. RESULTS: Under baseline assumptions we estimated the basic reproduction number of HEV in three separate camps to range from 3.7 (95% Credible Interval [CrI] 2.8, 5.1) to 8.5 (5.3, 11.4). Mean latent and infectious periods were estimated to be 34 (95% CrI 28, 39) and 40 (95% CrI 23, 71) days respectively. Assuming 90% vaccine coverage, reactive two-dose vaccination of those aged 16-65 years excluding pregnant women (for whom vaccine is not licensed), if initiated after 50 reported cases, led to mean camp-specific reductions in mortality of 10 to 29%. Pre-emptive vaccination with two doses reduced mortality by 35 to 65%. Both strategies were more effective if coverage was extended to groups for whom the vaccine is not currently licensed. For example, two dose pre-emptive vaccination, if extended to include pregnant women, led to mean reductions in mortality of 66 to 82%. CONCLUSIONS: HEV has a high transmission potential in displaced population settings. Substantial reductions in mortality through vaccination are expected, even if used reactively. There is potential for greater impact if vaccine safety and effectiveness can be established in pregnant women.

Outbreak of Hepatitis E Virus Infection in Displaced Persons Camps in Diffa Region, Niger, 2017.

Hepatitis E virus (HEV) infection in developing countries is associated with poor hygiene, lack of clean drinking water, and inadequate sanitation. In this study, we report the first case investigation and describe the present situation of HEV outbreak within displaced persons camps in the Diffa region, Republic of Niger. The investigation showed the outbreak to be closely linked to unclean water supply, low hygiene, and sanitation facility standards. Between January and September 2017, a total of 1,917 HEV suspect cases were recorded from which 736 (38.4%) have been confirmed positive for HEV by reverse transcription polymerase chain reaction and enzyme linked immunosorbent assay. Overall, 38 (1.9%) deaths were recorded, including 17 (44.7%) pregnant women. The ongoing outbreak highlights poor drinking water quality and sanitation conditions in displaced persons camps in the Diffa region. Disease containment and patient care activities, particularly for pregnant women, may have resulted in decreased transmission of infection and deaths.

Comparison of Dynamic Changes Among Various Prognostic Scores in Viral Hepatitis-Related Acute Liver Failure.

INTRODUCTION AND AIM: Multiple prognostic scores are available for acute liver failure (ALF). Our objective was to compare the dynamicity of model for end stage liver disease (MELD), MELD-sodium, acute liver failure early dynamic model (ALFED), chronic liver failure (CLIF)-consortium ACLF score and King's College Hospital Criteria (KCH) for predicting outcome in ALF. MATERIALS AND METHODS: All consecutive patients with ALF at a tertiary care centre in India were included. MELD, MELD-Na, ALFED, CLIF-C ACLF scores and KCH criteria were calculated at admission and day 3 of admission. Area under receiver operator characteristic curves (AUROC) were compared with DeLong method. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and diagnostic accuracy (DA) were reported. RESULTS: Of the 115 patients included in the study, 73 (63.5%) died. The discrimination of mortality with baseline values of prognostic scores (MELD, MELD-Na, ALFED, CLIF-C ACLF and KCH) was modest (AUROC: 0.65-0.77). The AUROC increased on day 3 for all scores, except KCH criteria. On day 3 of admission, ALFED score had the highest AUROC 0.95, followed by CLIF-C ACLF 0.88, MELD 0.81, MELD-Na 0.77 and KCH 0.52. The AUROC for ALFED was significantly higher than MELD, MELD-Na and KCH (P < 0.001 for all) and CLIF-C ACLF (P = 0.05). ALFED score ≥ 4 on day 3 had the best sensitivity (87.1%), specificity (89.5%), PPV (93.8%), NPV (79.1%), LR positive (8.3) and DA (87.9%) for predicting mortality. CONCLUSIONS: Dynamic assessment of prognostic scores better predicts outcome. ALFED model performs better than MELD, MELD, MELD-Na, CLIF-C ACLF scores and KCH criteria for predicting outcome in viral hepatitis- related ALF.

Foetomaternal outcomes of hepatitis E infection outbreak in North India.

Hepatitis E infection (HEV) in pregnant females, especially in the third trimester is associated with poor foetomaternal outcomes. However, the mechanisms of severe liver injury remain obscure. In a recent HEV outbreak in North India, six pregnant females were detected to be positive for HEV infection with concomitant hepatitis A infection in three pregnant females. None of the pregnant females were positive for hepatitis B or hepatitis C infection. The mortality was 50% in pregnant females. In an outbreak, besides, testing for hepatitis markers and understanding the pathogenesis of HEV infection in pregnancy, improving basic hygienic standards is of utmost importance.

Hepatitis E virus seroprevalence in pregnant women in Pakistan: maternal and fetal outcomes.

Hepatitis E virus (HEV) is endemic in Pakistan. Although otherwise asymptomatic, HEV infection becomes fatal in pregnancy, with considerable maternal and fetal morbidity and mortality. We conducted a descriptive study from April to October 2015 in 10 tertiary care hospitals throughout Pakistan to determine maternal and fetal morbidity and mortality in HEV-positive pregnant women with acute jaundice or raised liver function tests. Twenty-one of 135 women were HEV positive and in 3rd trimester except for 1 in 1st trimester. Overall prevalence of HEV in pregnancy was 0.19%. Ten women were artificially induced, 3 had premature labour, 4 delivered spontaneously (full term), 3 died and there was 1 intrauterine death. One woman had a home abortion before coming to hospital. There were 7 perinatal infant deaths: 4 intrauterine, 3 stillbirths and 1 abortion. Maternal mortality was significantly associated with delivery, as 17 mothers who lived went into labour spontaneously or were artificially induced, whereas 3 women who continued their pregnancy and did not deliver, died. Case fatality rate of HEV infection in pregnancy was 14.2%.

The hepatitis E virus nonstructural polyprotein.

Hepatitis E virus (HEV) is a globally important pathogen of acute and chronic hepatitis in humans. The HEV ORF1 gene encodes a nonstructural polyprotein, essential for RNA replication and virus infectivity. Expression and processing of ORF1 polyprotein are shown in prokaryotic and eukaryotic systems, however, its proteolysis into individual proteins is still debated. While molecular or biochemical characterization of methyltransferase, protease, hypervariable region, helicase and RNA polymerase domains in ORF1 has been achieved, the role of the X and Y domains in the HEV life cycle has only been demonstrated very recently. Clinically, detection of a number of ORF1 mutants in infected patients is implicated in disease severity, mortality and drug nonresponse. Moreover, several artificial lethal mutations in ORF1 offer a potential basis for developing live-attenuated vaccines for HEV. This article intends to present the molecular and clinical updates on the HEV ORF1 polyprotein.

Hepatitis E viral infection in solid organ transplant patients.

PURPOSE OF REVIEW: The purpose of this chapter is to review the literature published in the past 10 years with focus to the best literatures published since 2015 regarding chronic hepatitis E virus (HEV) infection in patients who received solid organ transplantation. RECENT FINDINGS: Diagnosis of this disease relies primarily on identification of HEV RNA in serum and more recently in stool as way of predicting relapse and guide therapy duration. Current management focuses primarily on primary prevention and supportive care, because additional research is needed to identify efficacious pharmacologic therapy, though use of ribavirin has shown promise in case series in treatment of some genotypes. SUMMARY: Infection with HEV is a rare but significant infection in organ transplant recipients. Though initially thought to be a primarily self-limiting infection, cases of chronic and persistent infection are increasing, being recognized both in developing and developed nations as a cause of cirrhosis, and, in some cases, of fulminant hepatic failure. Clinical manifestations of this infection, including evidence of hepatocellular liver injury, are mostly indistinguishable from alternative diagnoses.

Report of novel H105R, D29N, V27A mutations in the methyltransferase region of the HEV genome in patients with acute liver failure.

BACKGROUND: The Hepatitis E virus (HEV) has been responsible for major outbreaks in the developing countries affecting millions of people and acute sporadic hepatitis worldwide. The HEV methyltransferase is important for capping the 5'-end of the viral pregenomic RNA which is critical for viral infection. OBJECTIVES: We aimed to assess the substitutional profile in the HEV methyltransferase region in patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North Indian population and associate the substitutions with the poor outcome of the disease. STUDY DESIGN: HEV RNA was detected and partial region encoding the Methyltransferase domain in the HEV genome was amplified by Reverse Transcriptase(RT-PCR). Viral load of HEV was quantified utilizing Real time PCR.32 representative samples consisting of 16 AVH and 16 ALF were directly sequenced and amino acid changes were compared using Fischer's exact (two-tailed) test. RESULTS: Novel mutations Valine27Alanine (V27A), Aspartate29Asparagine (D29N) and Histidine105Arginine (H105R) mutation corresponding to 107T>C, 115G>A and 341 A>G substitutions respectively were significantly (p<0.0001) obtained in 16/16(100%) ALF patients compared to none (0/16) of the AVH patients. HEV viral load and disease severity parameters corresponding to the samples with D29N and V27A mutations were significantly higher compared to the isolates lacking these mutations while the H105R mutation was associated with decreased viremia. CONCLUSION: The D29N and V27A mutations had significant association with the poor outcome in ALF patients suggesting key role in enhancing HEV replication while the association of H105R mutation with decreased viremia creates interest on its antiviral aspects.

Acute Liver Failure Due to Hepatitis E Virus Infection Is Associated with Better Survival than Other Etiologies in Indian Patients.

BACKGROUND AND AIM: Hepatitis E virus (HEV) is a global disease and an important cause of acute liver failure (ALF) in the Indian subcontinent. The aim of this study was to assess the differences in the course of HEV-ALF as compared to other etiologies of ALF. METHODS: We compared the clinical course, complications, and outcomes of HEV-ALF with other etiologies. We assessed the prognostic factors and compared existing prognostic scores in HEV-ALF patients. RESULTS: One thousand four hundred and sixty-two ALF patients were evaluated between January 1986 and December 2015. HEV was the etiology of ALF in 419 (28.7%) cases, whereas non-A non-E hepatitis, HBV and anti-tuberculosis therapy (ATT) were the etiologies in 527 (36.0%), 128 (8.8%), and 103 (7.0%) cases, respectively. The frequency of cerebral edema in HEV-ALF (41.3%) was lower than that in non-A non-E ALF (52.9%; P < 0.001) and HBV-ALF (52.8%; P = 0.024). Infection and seizures were significantly less in patients with HEV-ALF compared to non-A non-E and HBV-ALF (P = 0.038 and 0.022, respectively). The survival of HEV-ALF patients was significantly better (55.1%, P < 0.001) than patients of other etiologies-including ATT (30.0%), non-A non-E (38.1%) and HBV (35.9%). In HEV-ALF patients, age, female sex, cerebral edema, prothrombin time >60 s, infection, and total bilirubin were observed as independent predictors of outcome on multivariate logistic regression analysis. Model for end-stage liver disease, acute liver failure study group model and King's College Hospital criteria had poor discriminative accuracy for outcome (area under receiver operator characteristic curve 0.63-0.64) in HEV-ALF. CONCLUSIONS: Hepatitis E virus-associated ALF has a better outcome than ALF of other etiologies.

A Single Lineage of Hepatitis E Virus Causes Both Outbreaks and Sporadic Hepatitis in Sudan.

Few studies have reported sporadic hepatitis E virus (HEV) infections during non-outbreak periods in Africa. In this study, the prevalence of HEV infection in Sudan was investigated in 432 patients with acute hepatitis from 12 localities in North Kordofan, and from 152 patients involved in smaller outbreaks of hepatitis in the neighbouring Darfur. HEV infection was diagnosed in 147 (25%) patients: 98 from Kordofan and 49 from Darfur. The mortality was 10%; six of the patients who died from the infection were pregnant women. HEV RNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR) in 38 (26%) patients: 22 from Kordofan and 16 from Darfur. Partial open reading frame (ORF) 1 and ORF2 were sequenced from HEV from nine and three patients, respectively. Phylogenetic analysis showed that the Sudanese strains belonged to genotype 1 (HEV1), and confirmed the segregation of African HEV1 strains into one branch divergent from Asian HEV1. It also revealed that the Sudanese strains from this study and from an outbreak in 2004 formed a separate clade with a common ancestor, distinct from strains from the neighbouring Chad and Egypt. This HEV strain has thus spread in a large area of Sudan, where it has caused both sporadic hepatitis E and outbreaks from at least 2004 and onwards. These data demonstrate that hepatitis E is a constant, on-going public health problem in Sudan and that there is a need for hepatitis E surveillance, outbreak preparedness, and general improvements of the sanitation in these remote areas of the country.

[Hepatitis E and pregnancy].

Hepatitis E virus (HEV) infection among pregnant women is severe, often leading to fulminant hepatic failure and death, with mortality rates up to 15-25%. Studies suggest that differences in genotypes/subgenotypes, hormonal and immunological changes during pregnancy may contribute to the severe consequences for pregnant women with HEV. Although the increased mortality among pregnant women predominantly is seen in developing countries where genotype 1 is endemic, there are also large differences in mortality among pregnant women within these countries. The reason for this is not clear.