Hepatitis E virus infection and acute non-traumatic neurological injury: A prospective multicentre study.

BACKGROUND & AIMS: Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury. METHODS: Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands. RESULTS: Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8-145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus. CONCLUSIONS: In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted. Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system.

Incidence and predictive factors for positive 75SeHCAT test: improving the diagnosis of bile acid diarrhoea.

AIMS: To determine the value of 75SeHCAT retention in determining bile acid diarrhoea (BAD), treatment response and predictors of a positive result. METHODS: Retrospective casenote review of consecutive patients undergoing 75SeHCAT from 2008 to 2014, including gender, age, history, clinical, and laboratory parameters. This included diseases associated with Type 1 BAD (ileal resection, Crohn's disease) and Type 3 BAD. Chi-squared test and logistic regression determined factors predictive of BAD. Subjective response to treatment with bile acid sequestrants (BAS) was analysed with respect to the 75SeHCAT result. RESULTS: Of 387 patients, 154 (39.7%) were male and average age was 50 years. Ninety-five patients (24.5%) were investigated for Type 1 BAD, 86 (22.2%) for Type 3, and 206 patients (53.2%) for Type 2 or idiopathic BAD. There was a large increase in the number performed with time but no difference in percentage positive tests. One hundred and seventy-nine patients (46.2%) had BAD. Positive result was commonest in possible Type 1 and they had most severe BAD. Ninety-nine patients had severe BAD (<5% 75SeHCAT retention), 47 moderate BAD (5% to <10% retention), and 33 mild BAD (10% to <15% retention). Predictors of a positive 75SeHCAT were right hemicolectomy (OR 4.88), cholecystectomy (OR 2.44), and Crohn's (OR 1.86). A positive 75SeHCAT predicted a good or partial response to BAS of 66.7% (mild), 78.6% (moderate), or 75.9% (severe BAD). CONCLUSION: 75SeHCAT test use increased in 2008-2014, with high positive results throughout. Ileal resection, Crohn's, and cholecystectomy independently predict BAD. 75SeHCAT predicted response to BAS.

Hepatitis E Seroprevalence in Europe: A Meta-Analysis.

UNLABELLED: There have been large numbers of studies on anti-HEV IgG seroprevalence in Europe, however, the results of these studies have produced high variability of seroprevalence rates, making interpretation increasingly problematic. Therefore, the aim of this study was to develop a clearer understanding of anti-HEV IgG seroprevalence in Europe and identify risk groups for HEV exposure by a meta-analysis of published studies. METHODS: All European HEV-seroprevalence studies from 2003 to 2015 were reviewed. Data were stratified by assay, geographical location, and patient cohort (general population, patients with HIV, solid-organ transplant recipients, chronic liver disease patients, and individuals in contact with swine/wild animals). Data were pooled using a mixed-effects model. RESULTS: Four hundred thirty-two studies were initially identified, of which 73 studies were included in the analysis. Seroprevalence estimates ranged from 0.6% to 52.5%, increased with age, but were unrelated to gender. General population seroprevalence varied depending on assays: Wantai (WT): 17%, Mikrogen (MG): 10%, MP-diagnostics (MP): 7%, DiaPro: 4%, Abbott 2%. The WT assay reported significantly higher seroprevalence rates across all cohorts (p < 0.001). Individuals in contact with swine/wild animals had significantly higher seroprevalence rates than the general population, irrespective of assay (p < 0.0001). There was no difference between any other cohorts. The highest seroprevalence was observed in France (WT: 32%, MP: 16%) the lowest in Italy (WT: 7.5%, MP 0.9%). Seroprevalence varied between and within countries. The observed heterogeneity was attributed to geographical region (23%), assay employed (23%) and study cohort (7%). CONCLUSION: Seroprevalcence rates primarily depend on the seroassy that is used, followed by the geographical region and study cohort. Seroprevalence is higher in individuals exposed to swine and/or wild animals, and increases with age.

Hepatitis E Virus: Time to Change the Textbooks.

Until recently, hepatitis E virus (HEV) was thought not to occur in developed countries. It is now clear that locally acquired HEV is common in such settings. HEV infection acquired in these areas differs from that in developing countries in a number of important aspects: it is caused by genotype 3 (and 4 in China and Japan), it mainly affects middle-aged/elderly males and it is zoonotic with a porcine primary host. Pig herds worldwide are infected with HEV genotype 3 and HEV has been found in the human food chain in a number of developed countries. However, the route of transmission is not fully understood, since most cases are not obviously associated with pigs/pig products. HEV can be transmitted by blood transfusion and surprisingly high numbers of asymptomatic blood donors are viremic at the time of donation: Germany 1:1,200, Netherlands 1:2,671, England 1:2,848. Our understanding of the clinical phenotype of HEV infection in humans has undergone a sea-change in recent years. Previously, HEV was thought to cause only acute self-limiting hepatitis. However, HEV may cause persistent disease in the immunocompromised. Patients with chronic HEV infection have no symptoms, but some develop rapidly progressive liver cirrhosis. The full clinical spectrum of HEV is still emerging. HEV has important extra-hepatic manifestations, which deserve further investigation. For example, HEV can cause a wide range of neurological illness. In particular, very recent data suggest that Guillain-Barré syndrome and neuralgic amyotrophy are associated with locally acquired HEV in approximately 5 and 10% of the cases, respectively.

Hepatitis E virus in developed countries: one of the most successful zoonotic viral diseases in human history?

Until recently, hepatitis E was thought to be largely confined to hyperendemic areas in Asia, Africa and Mexico. Over the last 10 years it has become clear that this is not the case, as it is surprisingly common in developed countries. In these settings, it is caused by HEV genotypes 3 and 4, and is a porcine zoonosis. It causes a range of human illness including acute and chronic hepatitis, and a spectrum of neurological injury. HEV RNA has been found in donated blood from an increasing number of countries, and in some locations with a very high incidence. The clinical phenotype and burden of disease in humans is still emerging. In contrast to previous 'received wisdom', zoonotically transmitted HEV may be one of the most successful zoonotic viral infections in human history. How did we, as a scientific community, get this so badly wrong? This review considers this question from a largely clinical perspective, explores the places HEV has been 'hiding' and the emerging clinical phenotype in humans.

The natural history of autoimmune hepatitis presenting with jaundice.

BACKGROUND: Forty percent of patients with autoimmune hepatitis (AIH) present with acute jaundice/hepatitis. Such patients, when treated promptly, are thought to have a good prognosis. OBJECTIVES: The objective of this study was to describe the natural history of AIH in patients presenting with jaundice/hepatitis and to determine whether the diagnosis could have been made earlier, before presentation. METHODS: This study is a retrospective review of 2249 consecutive patients who presented with jaundice to the Jaundice Hotline clinic, Truro, Cornwall, UK, over 15 years (1998-2013) and includes a review of the laboratory data over a 23-year period (1990-2013). RESULTS: Of the 955 patients with hepatocellular jaundice, 47 (5%) had criterion-referenced AIH: 35 female and 12 male, the median age was 65 years (range 15-91 years); the bilirubin concentration was 139 µmol/l (range 23-634 µmol/l) and the alanine transaminase level was 687 IU/l (range 22-2519 IU/l). Among the patients, 23/46 (50%) were cirrhotic on biopsy; 11/47 (23%) died: median time from diagnosis to death, 5 months (range 1-59); median age, 72 years (range 59-91 years). All 8/11 patients who died of liver-related causes were cirrhotic. Weight loss (P=0.04) and presence of cirrhosis (P=0.004) and varices (P=0.015) were more common among those who died. Among patients who died from liver-related causes, 6/8 (75%) died less than 6 months from diagnosis. Cirrhosis at presentation and oesophageal varices were associated with early liver-related deaths (P=0.011, 0.002 respectively). Liver function test results were available in 33/47 (70%) patients before presentation. Among these patients, 16 (49%) had abnormal alanine transaminase levels previously, and eight (50%) were cirrhotic at presentation. CONCLUSION: AIH presenting as jaundice/hepatitis was mainly observed in older women: 50% of the patients were cirrhotic, and liver-related mortality was high. Some of these deaths were potentially preventable by earlier diagnosis, as the patients had abnormal liver function test results previously, which had not been investigated.