Icteric acute hepatitis E with no response of immunoglobulin M class anti‐hepatitis E virus antibody

A 68‐year‐old Japanese man developed icteric acute hepatitis during periodic care after undergoing gastrectomy due to early gastric cancer. The routine serological markers for hepatitis A, B and C viruses were all negative. Although the liver enzymes spontaneously recovered without any specific therapy, cholestasis was relatively prolonged and successfully treated with prednisolone. Determination of serum hepatitis E virus (HEV) RNA revealed the transient infection of HEV, and both immunoglobulin (Ig)A and IgG class anti‐HEV antibodies were detected after the disease onset, whereas those were negative when measured 3 weeks prior to the onset. In addition, the titer of serum IgA class antibody was associated with the clinical signs of hepatitis. In contrast, no IgM class antibody was detected throughout the course. This case suggests that screening only with IgM class antibody is not sufficient to detect acute HEV infection.     

Epidemiological and clinical study of sporadic acute hepatitis E caused by indigenous strains of hepatitis E virus in Japan compared with acute hepatitis A

Background We compared acute hepatitis E (AH-E) and acute hepatitis A (AH-A) to investigate the epidemiology, clinical features, and prognosis of AH-E caused by an indigenous hepatitis E virus (HEV) in Japan.Methods We enrolled 58 patients diagnosed with AH-A or AH-E (32 men and 26 women; age, 20–72 years) from December 1997 to October 2002. Phylogenetic analysis of the partial 412-nucleotide sequence of open reading frame (ORF) 2 was performed in patients with AH-E.Results Regarding the geographic distribution of the HEV genotype, genotype III was principally distributed in Honshu Island, and genotype IV in Hokkaido Island (P = 0.0034). The phylogenetic analysis of the ORF2 region revealed that there were significant geographic differences in the distribution of the HEV strains in Japan, with some strains being widespread and some, localized. In comparison with AH-A patients, those with AH-E were older (56.1 ± 10.6 vs 45.9 ± 10.8 years; P = 0.0017). The proportion of males among patients with AH-E was significantly higher (P = 0.0001). Pyrexia was often observed in AH-A, and malaise in AH-E. Laboratory data indicate that AH-E induces a weak immunological reaction, whereas jaundice appears earlier in AH-E than in AH-A. One patient with AH-E died of acute hepatic failure, but none of those with AH-A died during the study period.Conclusions Our results suggest that there are geographical differences between HEV strains in Japan, and that AH-E is more common in males and older patients than AH-A. Laboratory data indicate a weak immunological reaction and early appearance of jaundice in AH-E.     

Comparison of clinical manifestations and epidemiology between acute hepatitis A and acute hepatitis E in Taiwan

BACKGROUND AND AIMS: Acute hepatitis A (AHA) and acute hepatitis E (AHE) are endemic in developing countries. They share similar transmission routes and clinical manifestations. To compare the differences in epidemiology, clinical picture and prognosis between these two enterically transmitted forms of hepatitis, we enrolled 58 consecutive AHA or AHE patients (42 men and 16 women; age 16-74 years) from January 1990 to April 2001. RESULTS: In comparison to AHA, patients with AHE were older (56.2 +/- 15.4 vs 30.7 +/- 11.0 years, P < 0.0001), and more frequently had a history of travel within 3 months before onset of illness (68.8 vs 30.8%, P = 0.003). In laboratory data, AHE patients had lower serum levels of albumin (3.4 +/- 0.4 vs 3.8 +/- 0.4 g/dL, P = 0.016), alanine aminotransferase (1912 +/- 1587 vs 3023 +/- 1959 U/L, P = 0.015), and aspartate aminotransferase (1681 +/- 1444 vs 2374 +/- 2869 U/L, P = 0.24), but a higher serum bilirubin level (17.8 +/- 12.3 vs 8.7 +/- 5.0 mg/dL, P = 0.003) than AHA patients. Moreover, five (15.6%) patients with AHE compared with none with AHA died. This probably indicates that AHE had a worse outcome than AHA in our study. In analysis of epidemiological factors, older age of onset of illness was the only significant predicator of outcome. From an epidemiological survey, most AHE patients were imported while most AHA patients were not. However, native AHE and imported AHA did occur in Taiwan. CONCLUSION: Patients with AHE in Taiwan had older age of onset, more records of traveling history, and poorer clinical manifestations than those with AHA, and age seemed to be the most important factor to influence outcome.     

Infectious mononucleosis in Japan: Comparison with acute viral hepatitis type A

In order to clarify the characteristics of infectious mononucleosis hepatitis (IMH) in Japan, 20 cases with IMH treated at Kamo Hospital during the past 6 years (Group I) were analysed in comparison with cases of acute viral hepatitis, especially type A. The test for heterophil antibody was positive in only two cases. During the same period 209 cases were treated for acute viral hepatitis (type A: 77 cases = Group A; type B: 61 cases; type non-A, non-B: 71 cases). In Group I the common clinical symptoms and signs were headache, sore throat and lymph node swelling; jaundice was not as common as in Group A. GOT and GPT activities increased moderately in the acute stage, but they were significantly lower than those in Group A. LDH, AP, GGT and LAP activities were disproportionately higher to GPT activity in Group I. Liver biopsy in the convalescent stage showed that lipofuscin deposition and sinusoidal mononuclear cell infiltration were more prominent in Group I, while sinusoidal neutrocyte infiltration and focal necrosis at periportal areas were more common in Group A. Differential diagnosis of the two diseases could be made using these clinical features and histological findings. However, immunological differentiation is required for specific diagnosis because some features such as fever, prolonged elevation of thymol turbidity test, atypical lymphocytes in peripheral blod and predilection for young people were observed in both groups. Furthermore, the present study indicated that IMH is no longer rare and most cases do not demonstrate heterophil antibody in Japan.     

脂微球载体前列腺素治疗急性戊型淤胆型肝炎临床评价

评价脂微球载体前列腺素治疗急性戊型淤胆型肝炎的临床疗效。52例患者随机分为脂微球载体前列腺素治疗组与对照组,疗程3周。治疗组在降低血清总胆红素、总胆汁酸、转氨酶等指标及总有效率、综合疗效等方面均优于对照组,差异有显著性。脂微球载体前列腺素是治疗急性戊型淤胆型肝炎有效、安全的药物。     

云南省大理市啮齿动物携带冠状病毒和戊型肝炎病毒的调查

目的 调查云南省大理市啮齿动物冠状病毒(Coronavirus, CoV)和戊型肝炎病毒(Hepatitis E Virus, HEV)感染率。方法 2020年8月～2021年8月在大理市4个乡镇采集啮齿动物样本,采用巢式PCR扩增CoV和HEV的保守序列基因,用生物信息学软件进行同源性与遗传进化分析。结果 共捕获76只啮齿动物属于5属6种,CoV感染动物为褐家鼠(Rattus norvegicus)和黄胸鼠(Rattus tanezumi),感染率分别为40.74%(11/27)、2.38%(1/42);HEV感染动物为褐家鼠和黄胸鼠,感染率分别为14.81%(4/27)、2.38%(1/42)。在银桥镇捕获的2只褐家鼠中同时检测到CoV和HEV,感染率为7.41%(2/27)。基于CoV的部分RNA依赖的RNA酶(RNA-dependent RNA polymerase, RdRp)的434 bp核苷酸片段分析,11株CoV阳性样本均来自褐家鼠,为α-CoV,与来自中国福建黄毛鼠(Rattus losea)RtRl/FJ2015同源性最高,为99.73%～99.74%;1株CoV阳...     

Risk factors for vertical transmission of hepatitis E virus infection

Hepatitis E virus (HEV) infection can be vertically transmitted, but the factors that transmit the disease to foetuses are still unclear. We studied a total of 144 pregnant women with HEV infection. Cord blood and newborn samples were taken for analysis. Nutritional factors were evaluated on the basis of anthropometric parameters and biochemical factors, and HEV viral load was quantified by real‐time PCR. Sequencing of HEV‐positive samples was performed. Approximately 14.63% (6/41) of pregnant patients with acute liver failure (ALF) died before delivery. Vertical transmission was observed in 46.09% (59/128) of HEV‐IgM‐positive mothers. Approximately 23.80% (10/42) of newborns in the acute viral hepatitis group and 29.41% (5/17) in the ALF group were positive for HEV‐RNA. No significant difference was observed in the occurrence of vertical transmission in HEV groups. Viral load was found to be a significant predictor for vertical transmission of HEV infection adjusted with haemoglobin and folate in derivation cohort group. Incorporating these variables, a new score predicting vertical transmission of HEV was derived. Using these significant predictors, the probability for vertical transmission of HEV was well stratified in the validation group (P>.05). In conclusion, viral load was associated with vertical transmission of HEV infection. A valid prediction score model was generated that was verified in a validation cohort group.     

小儿急性病毒性肝炎病原学调查

为了解近几年北京地区小儿急性病毒性肝炎的病原学状况与特点，我们对北京儿童医院在1993年3月－1997年3月收治的3300例小儿急性病毒性肝炎进行了病原血清学调查。检测结果表明，急性甲肝2890例，占93．9％。急性乙肝152例，占4．6％。急性丁肝4例，占0．1％，急性戊肝20例，占0．6％。无一例急性丙肝。检测100例关于庚肝血清学，无一例阳性。病原不明者46例，占1．4％。其中双重感染187例，多重感染4例，二者在急性肝炎中占5．8％。甲乙双重感染171例，在整个双重感染中占91．4％。     

A case of acute liver failure due to hepatitis E virus,liver transplantation,and development of de novo autoimmune hepatitis

Acute hepatitis E virus (HEV) infection could lead to acute liver failure (ALF), which requires liver transplantation (LT). HEV infection could progress to chronic infection in an immunosuppressed host. De novo autoimmune hepatitis (AIH) is a rare occurrence of AIH during post‐LT immunosuppressive therapy in patients who underwent LT due to not AIH but some other etiology. Here, we report the first case of ALF due to HEV infection, the recurrence of HEV after LT that responded to ribavirin therapy, and then the development of de novo AIH showing a complete response to glucocorticoid therapy but multiple relapses after steroid withdrawal. This peculiar case suggests that HEV could have a pathogenic role in the development of the de novo AIH; additionally, this case report could help clinicians make therapeutic decisions in the post‐LT condition.     

Three male patients with sporadic acute hepatitis E in Sendai,Japan, who were domestically infected with hepatitis E virus of genotype III or IV

Recent studies indicate that hepatitis E virus (HEV) infection occurs not only in developing countries but also in industrialized nations. However, the characteristics of domestic infections of hepatitis E in Japan are not fully understood. We analyzed serum samples from 34 patients who were seen at a city hospital in Sendai, Japan, between January 1997 and December 2002, and who had been given the diagnosis of sporadic acute hepatitis of non-A, non-B, non-C etiology. Among these 34 patients, 3 (9%; all men; aged 54, 59, and 61 years) were positive for both IgG and IgM anti-HEV antibodies and for HEV RNA. The HEV isolates (HE-JAS1 and HE-JAS3) obtained from case 1 and case 3, respectively, segregated into genotype III; they had the highest nucleotide sequence identity, of 99.5% and 99.0%, with HE-JA7 and HE-JA8, respectively, both of which had been isolated in Iwate, a neighboring prefecture of Sendai. In contrast, the remaining HEV isolate (HE-JAS2), obtained from case 2, segregated into genotype IV; it had the highest nucleotide sequence identity, of 99.8% and 99.3%, with JKK-Sap and HE-JA3, respectively, both of which had been isolated in Hokkaido, Japan, although case 2 had never been to Hokkaido. Our three patients with hepatitis E had not traveled abroad in the preceding 1 year, had had no contact with pigs, and no history of blood transfusion. These results indicate that HEV should be considered as an etiological agent of acute hepatitis of non-A, non-B, non-C etiology in Japan. The risk factor(s) for acquiring domestic HEV infection in Japan needs to be clarified in future studies.The nucleotide sequences of the 3 HEV isolates reported herein have been assigned DDBJ/EMBL/GenBank accession nos. AB107366-AB107368.     

Variability of hepatitis E serologic assays in a pediatric liver transplant recipient: challenges to diagnosing hepatitis E virus infection in the United States

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis among immunocompromised individuals in developed countries. Yet the diagnosis of HEV infection in the United States remains challenging, because of the variable sensitivity and specificity of currently available tests, and the lack of a US Food and Drug Administration‐approved test. We report a case of multiple discordant HEV serology results in a pediatric liver transplant recipient with idiopathic hepatitis, and review the challenges to diagnosis of HEV infection in the United States.     

Local outbreak of hepatitis E: a rare cause of viral hepatitis in Australia

Hepatitis E is a not uncommon cause of viral hepatitis globally but is relatively rare in Australia. Here, we report a case of acute hepatitis E that was acquired in Sydney and was part of a cluster believed to be infected locally. This is to our knowledge the first known outbreak of locally acquired hepatitis E in Australia. We discuss pathogenesis, clinical features and means by which further spread of infection can be limited.     

Aetiology,clinical course and outcome of sporadic acute viral hepatitis in pregnancy

Hepatitis E causes large-scale epidemics in endemic areas. The disease, during epidemics, has increased incidence and severity in pregnant women. Sporadic acute viral hepatitis (AVH) is common in endemic areas. The relationship of sporadic AVH and pregnancy has not been well studied. Over a 3-year period we prospectively studied 76 pregnant women and 337 non-pregnant women of childbearing age with sporadic acute viral hepatitis for aetiology, clinical course and outcome of disease. The aetiology in sporadic AVH was hepatitis A virus (HAV) in six (1.5%), hepatitis B virus (HBV) in 62 (15%), hepatitis C virus (HCV) in seven (1.7%), hepatitis D virus (HDV) co-infection in six (1.5%), hepatitis E virus (HEV) in 205 (49.6%), and hepatitis non-A-to-E (HNAE) in 127 (30.7%). Sixty-five (85.5%) pregnant women and 140 (41.5%) nonpregnant women had hepatitis E. The proportion of pregnant women was 31.7% in HEV group and 5.3% in non-HEV group [P < 0.001; OR=8.3 (95%C1 4.2-16.3)]. The prevalence of HEV in pregnant women in first trimester (76.9%), second trimester (88.9%), third trimester (83.8%) and puerperium (100%) did not differ significantly (P=0.09). Forty-seven (61.8%) of the 76 pregnant women developed fulminant hepatic failure (FHF), 69.2% in HEV group and 10% in non-HEV group (P < 0.001). Thirty-four (10.1%) nonpregnant women developed fulminant hepatic failure, 10% in HEV group and 9.7% in non-HEV group (P=0.86). FHF had occurred in four (40%) of 10 patients with HE in first trimester as against 41 (74.5%) of 55 patients in second trimester and beyond (P=0.015). Amongst the major complications of fulminant hepatic failure, cerebral oedema (53.2%) and disseminated intravascular coagulation (21.3%) occurred more often in pregnant women than in nonpregnant women (29.4% and 2.8%; P=0.03 and 0.016, respectively) while infections occurred more often in nonpregnant women (36.1%) than in pregnant women (10.6%; P=0.003). Fifty (61.7%) patients with FHF died [25 (53.2%) pregnant women and 25 (69.5%) nonpregnant women (P=0.06)]. Cerebral oedema and HEV aetiology were independent variables of survival in patients with FHF. Patients with cerebral oedema had worse prognosis and patients with HEV aetiology had best chances of survival. Hence HEV was the most common cause of sporadic AVH in this endemic area. High proportion of pregnant women and increased severity of disease in pregnancy were limited to patients with hepatitis E. Sporadic AVH caused by agents other than HEV did not show any special predilection to or increased severity in pregnancy. FHF in pregnant women caused by HEV was an explosive disease with short pre- encephalopathy period, rapid development of cerebral oedema and high occurrence of disseminated intravascular coagulation and may represent a severe manifestation of a Schwartzmann-like phenomenon.     

Shift of hepatitis E virus RNA from hepatocytes to biliary epithelial cells during acute infection of rhesus monkey

Hepatitis E virus (HEV) has been considered to be the major cause of enterically transmitted non-A, non-B hepatitis in developing countries. However, little is known about viral replication and localization in the liver. The aim of this study was to examine the distribution of HEV-infected cells in experimentally infected animals. Seven captured wild rhesus monkeys were inoculated intravenously with faecal extract derived from a Myanmar strain of HEV. Animals were killed at different time-points of clinical illness: during early infection, during prehepatitis with viral-like particles in bile, during acute hepatitis and during convalescence. Intrahepatic localization of HEV was analysed using non-isotopic thymine dimer in situ hybridization (NITDISH). Both plus and minus strands of HEV RNA were found in hepatocytes during the early infection period. Staining in the submembranous cytoplasmic region of hepatocytes was observed. In the prehepatitis period, both plus and minus strand HEV RNAs appeared in the canalicular side of isolated bile epithelial cells. Subsequently, HEV RNA became universally distributed in the cytoplasm of medium-size bile epithelial cells. After recovery, HEV RNA disappeared.     

Role of transfusion-transmitted virus in acute viral hepatitis and fulminant hepatic failure of unknown etiology

BACKGROUND AND AIM: The role of the newly described transfusion-transmitted virus (TTV), a circular single-stranded DNA virus, has been investigated in acute liver disease, comprising 36 patients with acute viral hepatitis (AVH) and 25 with fulminant hepatic failure (FHF), including 50 volunteer blood donors as controls. METHODS: Detection of TTV DNA sequences was carried out by polymerase chain reaction (PCR) using primers derived from the UTR(A) region of the TTV genome. The clinical course and biochemical profile when infected with TTV alone or coinfected with other classical hepatotropic viruses were analyzed. All patients were first evaluated for liver function profile and for the presence of various hepatotropic viruses using serological tests and PCR in serologically negative patients. RESULTS: Transfusion-transmitted virus DNA was detected in 80.6% (29/36) of the AVH cases and in 76% (19/25) of the FHF cases, which were significantly higher levels (P < 0.05) than the 52% (26/50) observed in volunteer blood donors. No significant difference in symptoms, clinical course, liver function and risk factor profile between TTV-positive and TTV-negative patients could be observed in both AVH and FHF patients. TTV was found to coexist with both parenterally and non-parenterally transmitted hepatotropic viruses in similar frequency in both AVH and FHF patients. Further, there was no significant difference in the mortality rates between TTV-positive and TTV-negative FHF patients. Also, there was no difference between patients coinfected by TTV and other hepatotropic viruses and those with TTV infection alone. CONCLUSION: Thus, it appears that TTV, although it exists in a very high frequency in the Indian population, appears to have no significant etiological role in AVH and FHF.     

Kinetics of hepatitis B virus load and haemodialysis: a prospective study

The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been an important goal in the management of patients on regular dialysis but infected patients continue to enter the dialysis system. It is evident that HBV viraemia in hepatitis B surface antigen (HBsAg)-positive patients on dialysis is low but it remains unclear whether haemodialysis per se can contribute to viral load reduction in such patients. HBV DNA was determined in 40 HBsAg-positive patients on maintenance haemodialysis immediately before and at the end of a 4-h haemodialysis session. The same measurements were repeated 48 and 72 h later. Twenty (50%) of 40 HBsAg-positive patients had detectable HBV DNA in serum. Detectable HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in the majority of patients after haemodialysis, although the difference was not significant (29 390 +/- 48 820 vs 23 862.8 +/- 4 350 copies/mL, NS). There was a strong relationship between mean HBV DNA levels before dialysis and absolute reduction of HBV DNA during haemodialysis sessions (r = 0.75, P = 0.0001). No difference occurred in the magnitude of change in HBV DNA titre when comparing cellulosic to synthetic membranes. Haemodialysis per se leads to a reduction in HBV load in HBsAg-chronic carriers on maintenance dialysis. This phenomenon could explain the low viral loads in these patients. Prospective studies are in progress to identify the mechanisms responsible for reduction in HBV load during haemodialysis.