Sporadic Acute Hepatitis Research Articles

A Comparison of Clinical Manifestations and Outcomes between Acute Sporadic Hepatitis A and Hepatitis E Infections in Thailand.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections often present as acute hepatitis with prodromal symptoms. These infections, transmitted via the oral-enteral route, constitute significant public health challenges, particularly in developing countries with subpar sanitary systems. The aim of the study was to describe the clinical manifestations, laboratory findings, and outcomes of hepatitis A and hepatitis E infections in Thailand. We conducted a retrospective chart review and analysis of 152 patients diagnosed with acute hepatitis A or hepatitis E from January 2007 to August 2018 at Siriraj Hospital. The hepatitis E cohort was older with a greater prevalence of comorbidities (hypertension, diabetes mellitus, chronic kidney disease, chronic hepatitis B, and post-kidney transplantation status) than the hepatitis A cohort. While the majority of hepatitis A patients presented with fever (98%) and jaundice (96%), these symptoms were less pronounced in hepatitis E patients. Furthermore, hepatitis A patients exhibited significantly higher aminotransferase and total bilirubin levels. However, clinical outcomes, such as hospitalization rates, progression to acute liver failure, and mortality, were comparable across both groups. In conclusion, although the clinical manifestations of hepatitis A and hepatitis E were similar, fever and jaundice were more prevalent and aminotransferase and bilirubin levels were higher in the HAV-infected group.

Role of Non-Hepatotropic Viruses in Acute Sporadic Viral Hepatitis and Acute-on-Chronic Liver Failure in Adults

Background and Aim: Viral infections, drugs, metabolic disorders, and autoimmune processes can cause hepatitis, which is a diffuse inflammatory condition of the liver. Hepatitis E (HEV) and hepatitis A (HAV) viruses are the most common causes of acute viral hepatitis (AVH). AVH and chronic liver failure (ACLF) patients were studied to determine whether they were infected with various hepatotropic and non-hepatotropic viruses. Patients and Methods: This prospective study was conducted on 186 adult patients with ACLF and AVH in the Department of Gastroenterology, DHQ Teaching Hospital and Mufti Mahmood Memorial Hospital, Dera Ismail Khan from September 2020 to August 2022. Our study included consecutive patients with acute viral hepatitis who had a definite viral etiology, a fever or jaundice that developed after 3 weeks, and an ALT that was 2x the upper limit of normal. There were three serological tests performed for all the patients: hepatitis (A, B, C, D, and E), Epstein-Barr virus (EBV), and non-hepatitis (CMV). Data analysis was carried out in SPSS version 26. Results: Of the total 186 samples investigated, the incidence of ACLF and AVH was 60 (32.3%) and 126 (67.7%) respectively. The prevalence of confirmed etiology such as HEV, HAV, HBV, and HCV was 98 (52.7%), 29 (15.6%), 20 (10.8%), and 2 (1.1%) respectively. The mixed viral etiology and Epstein-Barr virus was present in 18 (9.7%) and 19 (10.2%) respectively. The most prevalent cause of infection was HEV found in 76 (60.3%) AVH and 42 (70%) ACLF cases. The mortality rate among AVH patients was significantly lower 2.4% (n=3) than ACLF 23.3% (n=14). As compared to ACLF patients, AVH patients had significantly higher infections caused by non-hepatotropic viruses (24 vs. 3, p=0.001). There were significantly more mixed infections in AVH as opposed to ACLF (28 vs. 4, p<0.001). Conclusion: The present study concluded that both AVH and ACLF patients were susceptible to HEV-associated hepatitis. There were significant numbers of patients with AVH being infected with non-hepatotropic viruses including CMV and EBV. These viruses are much less common in patients with ACLF. Keywords: Epidemiology, Non-hepatotropic virus, Acute viral hepatitis, Acute chronic liver failure

Functional epitopes on hepatitis E virions and recombinant capsids are highly conformation-dependent

ABSTRACT Hepatitis E virus (HEV) is responsible for epidemic and sporadic acute hepatitis cases, especially in developing countries. Hepatitis E has become a vaccine-preventable disease in recent years with the development of a licensed vaccine. Most functional and neutralizing monoclonal antibodies (mAbs) are known to be highly sensitive to antigen conformation. In this study, a similar approach was used to characterize the conformational sensitivity of antibodies in human or mouse serum samples. Interestingly, comparative binding analysis using different antigen forms showed that the antibodies in the sera of naturally infected individuals, of human vaccinees and from mice immunized with the HEV p239 vaccine all exhibited a strong preference to particulate antigens over the monomeric form of the truncated capsid protein. The degree of discriminating the two test antigens is similar for serum samples to that for the well-characterized murine mAbs. A functional assay for assessing the inhibition of subviral particle cell entry by antibodies was used to determine the functional titers of anti-HEV antibodies in mouse sera. A good correlation was observed between the functional and binding titers in mouse sera determined using two different methods. This result supports the continued use of the enzyme-linked immunosorbent assay as the primary serological assay assuming that the coating antigen contains conformational and native-like epitopes, as in the case for HEV p239.

Full-genome characterization of the RIVM-HAV16-090-like hepatitis A virus strains recovered from Japanese men who have sex with men, with sporadic acute hepatitis A.

The major transmission mode of hepatitis A virus (HAV) in Japan is the fecal-oral route by contaminated foods. In contrast, HAV infection is well documented as a sexually transmitted disease in Europe and North America. The present study was undertaken to determine the full-genome sequence of HAV and trace the transmission route of HAV in Japanese men who have sex with men (MSM). In 2018, we encountered three Japanese MSM with acute hepatitis A co-infected with HIV for 4-12 years. Serum samples obtained from these patients were used for HAV full-genome analyses. Isolated HAV strains were segregated into subgenotype IA. The three HAV strains shared 100% identity within the 481-nucleotide partial sequence. The entire nucleotide sequence showed that the three strains were 99.97% similar to each other with only two nucleotide substitutions. At the amino acid level, the three strains differed from each other by only one or two amino acids. All three strains obtained in the present study were >99.6% identical to the 66 reported strains isolated from Taiwan and European countries during 2015-2017. In addition, these 66 strains include the RIVM-HAV16-090 (EuroPride) strain, which has been involved in HAV outbreaks among MSM worldwide. We determined for the first time the full-genome sequence of HAV isolated from Japanese MSM with acute hepatitis A and found that the strains were identical to those from MSM worldwide. Thus, these HAV strains were imported to Japan from foreign countries through MSM.

Acute sporadic hepatitis E in the Zhejiang coastal area of China: a 14-year hospital-based surveillance study

BackgroundTo examine the epidemiological trends and changes of hepatitis E virus (HEV) infection and the potential risk factors for severe infection in the Zhejiang eastern coastal area of China.MethodsWe analyzed statutory hepatitis E cases notifications and inpatient data held by the national surveillance and hospital information systems in Wenzhou, Taizhou, Ningbo, and Zhoushan cities of the Zhejiang eastern coastal area of China.ResultsNine thousand four hundred sixteen hepatitis E cases were reported from 2004 to 2017, with an average incidence of 2.94 per 100,000. The overall death rate was 0.06% (6/9416). A gradual decline of hepatitis E cases was found in the coastal areas since 2007, while a rise was identified in the non-coastal areas. Annual incidence in non-coastal cities was much higher than that in coastal cities (4.345 vs. 2.945 per 100,000, relative risk = 1.5, P value < 0.001). The mean age was 52 years old and 50.55 years with a male-to-female ratio of 2.32:1 and 2.21:1 in coastal and noncoastal areas respectively (all P > 0.05). Hepatitis E cases prevalence increased with age, highest among men in their 70s (9.02 vs. 11.33 per 100,000) and women in their 60s (3.94 vs. 4.66 per 100,000) groups for both coastal and noncoastal areas respectively. A clear seasonal pattern was observed, with a peak in March (0.4429 per 100,000) in coastal areas. 202 inpatients were documented, of which 50.50% (102/202) were severe cases. Male individuals with alcohol consumption, alcohol hepatic diseases, and superinfection were the three independent highest risks for severe infections (all with P value < 0.05).ConclusionsThis is to our knowledge the largest epidemiological study of hepatitis E cases in the eastern coastal area of Zhejiang province of China. The patterns of infection across the coastal areas were similar to those of the non-coastal areas, but the incidence was substantially lower and decreased gradually since 2007.

Three pairs of six sporadic acute hepatitis E cases infected with three different genotype 3b hepatitis E virus strains occurred within the same economic bloc in the central region of Japan

Three pairs of six sporadic acute hepatitis E cases infected with three different genotype 3b hepatitis E virus strains occurred within the same economic bloc in the central region of Japan

Hepatitis E Virus Infection in Lung Transplant Recipients: A Case Series

BackgroundHepatitis E virus (HEV) is one of the common causes of acute and chronic viral hepatitis with a global distribution. Genotypes 1 and 2 only affect humans and produce acute hepatitis epidemics in endemic regions (Asia, Africa). In nonendemic areas (America, Europe), genotypes 3 and 4 are considered a zoonosis and cause sporadic acute hepatitis. HEV has been described in solid organ transplant recipients; however, data on lung transplant patients are limited. ObjectiveTo present the first 3 cases of HEV infection in lung transplant recipients in our unit. Case PresentationWe report 3 cases of HEV infection in post-transplant patients presenting with symptoms and alterations in liver enzymes. All patients have no history of travel outside Spain prior to observing abnormalities in the liver function. Diagnoses were made with in-home polymerase chain reaction and enzyme-linked immunosorbent assay (IgG/IgM). The first patient was not treated and died of progressive hepatic disease, with postmortem diagnosis of HEV infection complications. The other 2 patients were treated with ribavirin after the diagnosis of HEV infection. Ribavirin was discontinued in 1 patient because of anemia necessitating red blood cell transfusions. ConclusionsHEV should be considered in the differential diagnosis of patients with abnormal liver enzymes after transplant. Early detection and treatment have implications in the prevention of liver failure and mortality. Large prospective seroprevalence studies of HEV in lung transplant patients are warranted to recognize the epidemiology of this infection in lung transplant recipients.

Need for recognizing atypical manifestations of childhood sporadic acute viral hepatitis warranting differences in management.

Various atypical manifestations have been described in acute viral hepatitis (AVH). We evaluated the prevalence, clinical features, response to treatment and outcome of various atypical manifestations of AVH in children. Consecutive children (≤ 18years) with AVH due to hepatitis A, B, or E were studied while patients with acute or acute on chronic liver failure were excluded. Diagnosis of atypical manifestations was based on standard criteria. A total of 477 children with AVH (median age 7.0 (5-11) years, 74% boys) were seen; 22% (n = 106) had atypical manifestations. Prolonged cholestasis was the most common (11%), followed by ascites (7%), intravascular hemolysis (3%), relapsing hepatitis (2%), acute pancreatitis (1.3%), and thrombocytopenia (0.7%). Atypical manifestations were more common in HAV as compared to HBV (30% vs. 3%, p = 0.00) and HEV (30% vs. 15%, p = 0.07). Prolonged cholestasis was significantly more common in older children (20% in > 10years vs. 9% in 6-10years ; p = 0.009 and 5% in 0-5years of age [p < 0.000]). Ascites was more common in younger children, although not significant. All patients recovered with supportive treatment.Conclusions: Twenty-two percent of children with AVH have atypical manifestations, more often with HAV infection, and prolonged cholestasis is most common. Recognition of these manifestations ensures correct diagnosis and treatment. What is Known: • Acute viral hepatitis is a major public health problem in developing countries. • There is limited information about atypical manifestations which may lead to unnecessary investigations, delayed diagnosis and morbidity. What is New: • Atypical manifestations are common in children, seen most often with HAV infection, and prolonged cholestasis is most common. • Prompt recognition of these manifestations helps in early diagnosis, appropriate management, and preventing unnecessary investigations. • Ensure follow-up until complete recovery and not to miss underlying chronic liver disease.

Association of Toll-like receptor 4 polymorphism with hepatitis E virus-infected Indian patients.

Hepatitis E infection caused by hepatitis E virus (HEV), a major public health concern in developing countries, is responsible for sporadic and epidemic acute viral hepatitis in adults. Pathogenesis of hepatitis E infection is poorly understood. Toll-like receptors (TLRs) are the key players of innate immunity recognize pathogen-associated molecular patterns (PAMPs). Previously, we found higher TLR4 expression (at protein and gene level) with impaired cytokine response upon stimulus of PBMCs with LPS in HEV-infected patients. In view of the earlier observations of the association of polymorphisms in TLR4 genes (A299G, C399T) with liver diseases, we investigated TLR4 polymorphisms in HEV-infected patients. We observed the significant association of TLR4-399CC and CT alleles with hepatitis E (both subclinical and acute patients). Carrier frequency of TLR4-399 CT was lower in patients' categories in comparison with the controls. Higher frequency of allele TLR4-399C significantly correlated with disease progression. Acute hepatitis E patients showed the higher frequency of CG and TA haplotypes, while the rare haplotype (TG) was more frequent in controls. The other single nucleotide polymorphism (SNP) at TLR4-299 (A>G) did not show any difference. We report here for the first time the association of TLR4 polymorphism with hepatitis E and suggest that TLR 4 hyporesponsiveness during HEV infection might be related to its polymorphism.

Clinical course of sporadic acute hepatitis E in a hepatitis B virus endemic region

ObjectivesIn China, the epidemic pattern of acute hepatitis E virus (HEV) infection has changed from waterborne outbreaks to foodborne sporadic cases. However, the clinical course of sporadic acute hepatitis E (AHE) has not been well defined. MethodsConsecutive patients with AHE who were admitted to the Jinan Infectious Disease Hospital, Jinan, Shandong Province between January 2003 and December 2014 were evaluated and followed. Demographic data, clinical manifestations, results of laboratory tests, and outcomes were recorded. Risk factors for liver failure and death were analyzed. ResultsA total of 680 patients with AHE were identified during the study period. The incidence was highest in February, March, and April, accounting for about 41% of the cases. The male to female ratio was 5.1:1 (574/106). The average age was 50.9±12.8years. The prevalence rates of prodromal fever, fatigue, loss of appetite, and jaundice were 25.6%, 85.6%, 83.8%, and 92.8%, respectively. The median (range) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, and platelet levels were 727 (8–6270) U/l, 300 (17–6226) U/l, 196.8 (8.0–1083) μmol/l, 33.0 (15.2–45.8) g/l, and 162 (10–589)×109/l, respectively. The prevalence of hepatitis B surface antigen (HBsAg) was 18.5% (126/680) and of liver cirrhosis was 9.4% (64/680). Thirteen percent (89/680) of the cases progressed to liver failure, including 4.1% (28/680) with acute liver failure (ALF) and 9.0% (61/680) with acute-on-chronic liver failure (ACLF). Among patients with HBsAg positivity or cirrhosis, 28.6% (36/126) and 36.0% (23/64), respectively, progressed to ACLF. Multiple logistic regression analysis indicated that age >53years, prodromal fever, HBsAg positivity, cirrhosis, and thrombocytopenia (platelet count <150×109/l) were independently associated with the development of liver failure, with an odds ratio (95% confidence interval) of 2.5 (1.5–4.3), 1.9 (1.1–3.2), 3.7 (2.0–6.7), 2.1 (1.1–4.2), and 5.9 (3.3–10.4), respectively. The overall mortality was 5.6% (38/680), and the mortality rates in patients with and without underlying liver disease were 9.3% (22/237) and 3.6% (16/443), respectively. Multiple logistic regression analysis indicated that hepatic encephalopathy, bilirubin >500μmol/l, international normalized ratio (INR)>2, and severe thrombocytopenia (platelet count <100×109/l) were independently associated with death, with an odds ratio (95% confidence interval) of 7.2 (2.4–21.8), 5.8 (1.9–17.2), 24.1 (7.9–73.3), and 10.8 (3.6–32.9), respectively. ConclusionsIn areas that are dual endemic for hepatitis B virus and HEV, the HEV vaccine for patients with obvious liver diseases is of significance. Thrombocytopenia is an important predictor of liver failure and mortality in sporadic AHE.

Acute hepatitis E in India appears to be caused exclusively by genotype 1 hepatitis E virus.

Hepatitis E is caused by infection with hepatitis E virus (HEV), which has four well-known genotypes. Genotypes 1 and 2 HEV have been reported from human cases in areas where the disease is highly endemic. By contrast, genotypes 3 and 4 HEV, which primarily infect several animal species worldwide, have been reported mainly from sporadic human cases in non-endemic areas such as Japan and high-income countries of Europe and North America. To determine whether genotype 3/4 HEV cause sporadic disease in India, a disease-endemic area, we determined HEV genotype in a group of patients with such disease. A part of the HEV open reading frame (ORF) 1 was amplified and sequenced from sera of 74 patients with sporadic acute viral hepatitis E from four cities in India. The sequences were compared with prototype sequences for various HEV genotypes and subgenotypes and analyzed using phylogenetic tools to determine the genotype of the isolates. For 12 specimens, a part of HEV ORF2 was also similarly analyzed. Partial ORF1 sequences of all the 74 isolates belonged to genotype 1 HEV, with 88.2% to 100% nucleotide identity with the prototypegenotype 1 isolates. Partial ORF2 sequences for all the 12 isolates also belonged to genotype 1 HEV. On phylogenetic analysis, 71 isolates clustered with prototype genotype 1a HEV;the remaining three isolates were located between subgenotypes 1a and 1c but were closer to the former. Human sporadic acute hepatitis E in India is caused almost exclusively by genotype 1 HEV.

HEV-related Liver Disease in India : Why is the Disease Stormy?

Hepatitis E virus (HEV) is an important cause of epidemic and sporadic acute viral hepatitis (AVH) in many developing countries, including India. Hepatitis E, a positive-sense single-stranded RNA virus approximately 7.2 kb in length had been classified provisionally into the Caliciviridae family from 1988 to 1998 but HEV is currently placed in the genus Hepevirus and is the only member of the family Hepeviridae. Pregnant women with jaundice and AVH caused by HEV infection have worse fetal and obstetric outcome and higher maternal mortality compared to other types of viral hepatitis. Studies from various developing countries have shown that the incidence of HEV infection in pregnancy is high and a significant proportion of pregnant women can progress to fulminant hepatitis with a mortality rate varying from 30% to 100%. The incidence of hepatitis B virus (HBV) related acute liver failure is known widely in comparison to hepatitis C virus (HCV) infection in which acute liver failure (ALF) is rare. But the severe course of HEV infection causing ALF during pregnancy is unique to this virus with chronicity occurring in recipients of solid organ transplants. Various factors have been suggested to be associated with the mortality rate of the HEV in pregnant women along with the abortion of the fetus. Steroid hormones play a significant role in the viral replication through their effects on viral regulatory elements. The NF-κB signaling pathway regulating at the transcriptional level through p50 subunits has been suggested to correlate with the severe liver damage, leading to multiple organ failure and the death of both the mother and the fetus. Pregnant women in Asia suffer from folate deficiency reducing the immunocompetence to greater risk of multiple viral infections and higher viral load. The viral load of HEV was found to be significantly higher (P &lt; 0.05) in pregnant patients compared to the non-pregnant and the viral copies of HEV with fulminant hepatic failure (FHF) in pregnant women were comparatively higher when compared to the pregnant women with AVH, which may be related to the severity of the disease in these patients. Besides, reduced expression of progesterone and progesterone induced-blocking factor and the high viral load of HEV have been regarded as a cause of poor pregnancy outcome in hepatitis E infection. Vertical transmission of the HEV infection has been reported. There are published reports of abortion, death of the fetus in utero, premature delivery or death of the baby soon after birth in patients with icteric hepatitis or with ALF caused by HEV. However, studies in Europe and United States have shown the course of viral hepatitis during pregnancy resembling with the non-pregnant women. In contrast, various reports carried out in India, Iran, Africa, and Middle East have reported the incidence of ALF to be higher during pregnancy. Data on the viral load of HEV during pregnancy are limited. The study was designed to determine the viral load of HEV and its association with the disease severity in patients with ALF. A total HEV related 163 patients with ALF which included 105 pregnant, 46 non-pregnant women and girls, 12 men, and 730 patients with AVH which comprised of 220 pregnant women; 282 non-pregnant women and girls, and 228 men were included. Viral load was measured by real-time PCR. Comparison was made between the pregnant and non-pregnant women. HEV RNA was detectable in 265 patients (142 pregnant; 75 non-pregnant and 48 men) and 104 patients with ALF (64 pregnant, 34 non-pregnant and 6 men). The viral load of HEV in pregnant women with ALF and AVH was significantly higher 129,984.0±103,104.17 and 768.92±1,105.40 copies/ml, respectively compared to the non-pregnant women which was 189.2±225 and 12.73±7.8 copies/ml (P &lt; 0.0001). The viral load of HEV was also significantly higher in the pregnant patients with ALF compared to the pregnant women with AVH and also men (P &lt; 0.0001). High viral load of HEV during pregnancy could be one of the factors responsible for the severity of the infection during pregnancy.

Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms

Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis, which are mostly self-limiting. However, viral infection in immunocompromised patients and pregnant women may result in serious consequences, such as chronic hepatitis and liver damage, mortality of the latter of which reaches up to 20-30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first-line defense against virus infection. Upon HEV infection in the cell, the virus genome is recognized by pathogen recognition receptors, leading to rapid activation of intracellular signaling cascades. Expression of type I IFN triggers induction of a barrage of IFN-stimulated genes, helping the cells cope with viral infection. Interestingly, some of the HEV-encoded genes seem to be involved in disrupting signaling cascades for antiviral immune responses, and thus crippling cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by HEV have only recently begun to emerge, and in this review, we summarize known HEV evasion strategies and compare them with those of other hepatitis viruses.

Etiological characterizations of sporadic viral hepatitis in north east part of Bangladesh

These retrospective study was done to see common viral etiology of sporadic acute viral hepatitis in North East Part of Bangladesh. Consecutive patients attending in private chambers with acute or recent onset of jaundice with biochemical evidence of hepatocellular injury from January 2011 to December 2013 were enrolled. Epidemiological features and reports of viral markers i.e. HBsAg, Anti-HBc IgM, anti-HAV-IgM, Anti-HEV IgM, and Anti-HCV were retrieved. Data of 256 cases (male 195 and female 61, age ranging from 6 years to 89 years with mean 29.44 years were analyzed. Both HBsAg and anti-HBc-IgM were found positive in 98 (38.67%) cases (male 77 and female 21). Of them 39 were in 16-25 years age group. Anti-HAV IgM was found positive in 41 (16%) cases (male 30, female 11) and 27 of them were in the less than 16 years group. Anti HEV IgM was positive in 116 (45.31%) cases (male 87 and female 29). Majority (85 cases ) of HEV infection was found in 16 to 40 years age group. In this study HEV is the most frequent agent for acute sporadic viral hepatitis among adults followed by HBV. HAV is more prevalent cause of sporadic acute viral hepatitis among children.Bangladesh Med J. 2016 Sep; 45 (3): 138-140

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

BackgroundThe 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. ObjectivesWe 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 designHEV 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. ResultsNovel 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. ConclusionThe 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.

Differential Immune Responses in Mice Immunized with Recombinant Neutralizing Epitope Protein of Hepatitis E Virus Formulated with Liposome and Alum Adjuvants.

In the developing countries, Hepatitis E virus (HEV) is a predominant cause of sporadic acute hepatitis in adults and waterborne epidemics leading to high mortality in pregnant women. Vaccine development mainly focuses on the structural capsid protein open-reading-frame-2 (ORF-2) of the virus. We successfully evaluated liposome-adjuvanted recombinant neutralizing epitope protein (rNEp), a part of ORF-2, 458-607aa, in mice and rhesus macaques. We compared immune response to adjuvants alone, rNEp alone, or adjuvanted with liposome (lipo-rNEp)/alum (al-rNEp) in mice following intramuscular administration of two doses of 5 μg each. IgG anti-HEV titers (enzyme-linked immunosorbent assay), immunophenotyping (flow cytometry, CD3(+)CD4(+), CD3(+)CD8(+), CD11c(+), CD11b(+), CD19(+) cells; costimulatory markers CD80, CD86, MHC-I, MHC-II, and early activation marker CD69), and levels of Th1/Th2 cytokines (IL-2/IFN-γ/IL-4/IL-5 and additionally IL-1β/IL-6/IL-10/TNF for early time points) were determined at early (4/12/24-h postdose-1) and later time points (2 weeks post-both doses). IgG anti-HEV titers were higher in the lipo-rNEp group than al-rNEp post-both doses (p < 0.05). At early time points, cell type proportions were comparable at the site of injection; IL-Iβ levels increased in lipo-rNEp, 24 h, while IL-6 levels rose in lipo-rNEp/al-rNEp/alum-alone groups, 4 h, compared to controls. In the draining lymph nodes (DLNs), CD11c(+)CD86(+) cells increased at 24 h in liposome-alone/lipo-rNEp groups. A rise in the CD11c(+)CD69(+) cells was noted in the lipo-rNEp group compared to other groups (p < 0.05). Cytokine levels in the spleen/sera remained unchanged in all the groups (p > 0.05). At 2 weeks postdose-2, CD11c(+)MHC-II(+)/CD11b(+)MHC-II(+) cells increased in the spleen in the lipo-rNEp and al-rNEp groups, respectively. In the DLNs, CD19(+)MHC-II(+) cells increased in rNEp/al-rNEp/lipo-rNEp groups post-both doses and CD11c(+)CD86(+) cells in the lipo-rNEp group. A balanced Th1/Th2 response was evident in the lipo-rNEp, while a Th2 bias was noted in al-rNEp. Different immune response gene clustering patterns were noted in uncultured spleens from immunized mice and cultured-stimulated splenocytes. In conclusion, lipo-rNEp is a better immunogen, works through dendritic cells, and elicits a balanced Th1/Th2 response, while alum functions through macrophages and induces a Th2 response.

三重県で発生したHEV genotype 1a株による急性E型肝炎の2例

三重県で発生したHEV genotype 1a株による急性E型肝炎の2例

Role of non-hepatotropic viruses in acute sporadic viral hepatitis and acute-on-chronic liver failure in adults

Acute viral hepatitis (AVH) is mostly caused by hepatitis E (HEV) and hepatitis A (HAV) viruses in India. This study was undertaken to find out the incidence of various hepatotropic and non-hepatotropic viruses in AVH and acute-on-chronic liver failure (ACLF) patients. Six-hundred and seventy-three adult patients of AVH and ACLF were screened for acute serological markers of hepatotropic (A, B, C, D, and E) and the non-hepatotropic cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Viral etiology profile in 295 samples with confirmed etiology were HEV in 155 (52.5 %); HAV in 43 (14.5 %); HBV in 35 (11.8 %); HCV in 1 (0.3 %); mixed viral etiology in 30 (10.1 %); and non-hepatotropic viruses, cytomegalovirus, and Epstein-Barr virus in 31 (10.5 %). Two-hundred and six patients (69.8 %) were AVH and 89 (30.1 %) ACLF. HEV was the commonest cause of infection in both the groups AVH (n = 95, 46.1 %) and ACLF (n = 60, 67.4 %). Twenty-nine (9.8 %) patients died on follow up; mortality was higher in ACLF (25/89, 28 %) than AVH group (4/206, 1.94 %; p < 0.001). The mortality was higher when HEV was the cause of acute event (20/29, 68.9 %). In AVH, mixed infection was more common as compared to ACLF (27 vs. 3, p < 0.001). Non-hepatotropic viruses contributed significantly higher infections in AVH as compared to ACLF (29 vs. 2, p = 0.002) patients. HEV was an important cause of symptomatic hepatitis in both AVH and ACLF patients. Non-hepatotropic viruses like CMV and EBV were identified in a significant number of patients with AVH and much less frequently in ACLF.

Prevalence of hepatitis viruses in patients with acute hepatitis and characterization of the detected genotype 4 hepatitis E virus sequences in Mongolia.

Hepatitis E is considered to be a worldwide public health problem. Although the prevalence of hepatitis E virus (HEV) antibodies in healthy individuals is noted to be 11%, no patients with acute hepatitis E have previously been identified in Mongolia. Three hundred two consecutive patients (183 males and 119 females; median age of 22.0 [Interquartile range: 18.3-25.0] years) who were clinically diagnosed with sporadic acute hepatitis during 2012-2013 in Ulaanbaatar, Mongolia, were studied. By serological and/or molecular approaches, 77 (25.5%), 93 (30.8%), 19 (6.3%), 48 (15.9%), and 12 (4.0%) of the patients were diagnosed with acute hepatitis of types A, B, C, D (superinfection of hepatitis delta virus on a background of chronic hepatitis B virus infection) and E, respectively, while the cause of hepatitis was unknown in the remaining 53 patients (17.5%). The 12 hepatitis E patients had no history of travel abroad in the 3 months before the onset of disease, and lived separately in fixed or movable houses with water supplied via pipe, tank or well, denying transmission from a common water supply. The 12 HEV isolates obtained from the patients showed high nucleotide identities of 99.7-100%, and a representative HEV isolate, MNE13-227, was closest to the Chinese isolates of genotype 4, with the highest identity of 97.3% in the 304-nt ORF2 sequence and 92.1% over the entire genome. The present study revealed the occurrence of autochthonous acute hepatitis E in Mongolia, caused by a monophyletic genotype 4 HEV strain.

P0599 : Role of non-hepatotropic viruses in acute sporadic viral hepatitis in adults: Should the screening strategies be changed?

P0599 : Role of non-hepatotropic viruses in acute sporadic viral hepatitis in adults: Should the screening strategies be changed?