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.