Sporadic Acute Viral Hepatitis Research Articles

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

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.

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.

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

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.

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?

P45: Virological characteristics of hepatitis E and A infection in acute sporadic viral hepatitis and acute exacerbation of chronic liver disease patients

Journal of Viral HepatitisVolume 21, Issue s2 p. 46-46 Poster SessionFree Access P45: Virological characteristics of hepatitis E and A infection in acute sporadic viral hepatitis and acute exacerbation of chronic liver disease patients First published: 08 October 2014 https://doi.org/10.1111/jvh.12333_44AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume21, Issues2Special Issue: Abstracts for the Viral Hepatitis Congress 2014, 9–11 October 2014, Frankfurt, GermanyOctober 2014Pages 46-46 RelatedInformation

Aetiology of Sporadic Acute Viral Hepatitis in North-East India – Differences Exist from the Rest of India

Background: Acute viral hepatitis remains a major and mostly preventable cause of morbidity and mortality in India today. Aetiology of acute viral hepatitis cannot be differentiated clinically. Most reports on sporadic, epidemic, and fulminant cases of acute viral hepatitis from India implicate Hepatitis E as the major cause. Data from the North-eastern part of India is lacking.

Identification of miR-221 and -222 as important regulators in genotype IV swine hepatitis E virus ORF3-expressing HEK 293 cells

Hepatitis E virus (HEV) has emerged as an important cause of epidemic and sporadic acute viral hepatitis worldwide, which is a major public health challenge. A better understanding of the interaction between the virus and the host cell would be very helpful for its therapy. Swine HEV (SHEV) open reading frame 3 (ORF3) is a regulatory protein that alters the activity of selected transcription factors and cytoplasmic signaling pathways. MicroRNAs (miRNAs) are potent post-transcriptional regulators of protein-coding genes and represent an interesting lead to study SHEV infection and to identify new therapeutic targets. To explore how SHEV ORF3 affects miRNAs in host cells, we used miRNA array analysis to compare the expression patterns of miRNAs in stable cell lines that expressed or did not express SHEV ORF3. We found a significant down-regulation of miR-221 and -222 in ORF3 expressing human embryonic kidney 293 cell line. Among the 116 candidate targets genes of miR-221 and -222 that we detected in silico, we demonstrated that the expression of the cyclin-dependent kinase inhibitor 1B, also named p27(kip1), was directly regulated by these miRNAs. We hypothesize that SHEV ORF3-induced miR-221/222 downregulation enhances p27(kip1) expression in HEK293 cells. This provides new avenues for future exploration of the precise roles of miRNAs in SHEV infection.

Seroprevalence of anti-hepatitis E virus (HEV) in a Korean population: comparison of two commercial anti-HEV assays

BackgroundHepatitis E virus (HEV) has emerged as an important cause of epidemic and sporadic acute viral hepatitis worldwide. This study investigated the seroprevalence of anti-HEV in a Korean population and compared the performance of two commercially available anti-HEV assays.MethodsA total 147 health-check examinees were randomly sampled as matched to the age- and sex- adjusted standard population based on the Korean National Census of 2007. Serum immunoglobulin G anti-HEV was determined by using the Genelabs assay (Genelabs, Singapore) and the Wantai assay (Wantai, Beijing, China).ResultsThe overall anti-HEV seroprevalence was 23.1% (95% CI, 16.1-30.1%) using the Wantai assay and 14.3% (95% CI, 8.3-20.3%) using the Genelabs assay. Only 12 samples (8.1%) were positive for anti-HEV as measured by both assays; agreement between the two assays was poor (kappa value of 0.315). The anti-HEV seroprevalence increased with age from 2% and 3% in the people younger than 20-years-of-age to 34.6% and 42.3% in those over 59-years-of-age by the Genelabs and Wantai assay, respectively.ConclusionsThe HEV seroprevalence in Korean population is about 20% overall, with seroprevalence increasing in this population with increasing age. There was poor concordance in the results of the Genelabs and Wantai assays, which warrants further study concerning a reliable diagnostic test for the diagnosis of hepatitis E.

Atypical manifestations of hepatitis A in children

Sir,We read the article by Samanta et al. [1] on atypicalmanifestations of acute viral hepatitis A in children. This isnot the first time that these atypical manifestations havebeen reported from India. Large studies [2, 3] of 172 and149 cases each of sporadic acute viral hepatitis from twodifferent institutions from north India have been publishedearlier. The study from Chandigarh has shown that 21.5%of sporadic acute viral hepatitis (72% due to HAV) hadascites, one third of them had associated spontaneousbacterial peritonitis and five children with ascites also hadpleural effusion [2]. Similarly, prolonged cholestasis andrelapsing hepatitis were reported in 20% and 10% with acutehepatitis A (n=70),respectivelyinthestudyfromLucknow[3]. Recently in another study from Lucknow [4], wedocumented that 13% of 139 cases with sporadic acute viralhepatitis had ascites, and children with ascites had signifi-cantly low serum proteins, albumin and prolonged prothrom-bin time as compared to children without ascites.The authors have probably confused complications ofacute viral hepatitis with atypical manifestations. Acuteliver failure (ALF) is a known complication of AVH andnot an atypical manifestation. In fact 28% of their 32atypical cases are actually complications (ALF) of AVHand should not have been included as atypical manifes-tations. Further, authors have used an unusual definition ofALF that seems to be contrary to conventional definition[5]. The definition of acute liver failure (ALF) or fulminanthepatic failure (FHF) in children is not same as in adults asit is difficult to assess encephalopathy in children. The moreobjective criterion is based on coagulopathy. As per thePediatric Acute Liver Failure study group, ALF is definedas constellation of acute liver injury coupled with eithersevere coagulopathy (international normalization ratio orINR>2 or prothrombin time >20 sec) or encephalopathy inthe setting of moderate coagulopathy (INR>1.5 or pro-thrombin time >15 sec) [6].References

Ascitic Form of Sporadic Acute Viral Hepatitis in Children: A Distinct Entity for Recognition

This study looked at the frequency and differences in presentation, laboratory parameters, and outcome between ascitic acute viral hepatitis (AAVH) and nonascitic acute viral hepatitis (NAVH) in children. Diagnosis of AVH was based on clinical features, >3-fold elevation of alanine aminotransferase, viral marker positivity (IgM antihepatitis A virus, IgM antihepatitis E virus, hepatitis B surface antigen, and IgM antihepatitis B core antigen) at presentation, absence of history of liver disease, and subsequent normalization within 6 months of clinical features and liver functions including sustained resolution of ascites in AAVH on follow-up. A total of 139 children (121 children with NAVH and 18 with AAVH, 12.9%) were studied. Children with AAVH in comparison with those with NAVH were younger (median age 4 vs 8 years), had lower frequency of prodrome (22% vs 51%), lower serum albumin (median 2.8 vs 3.7 g/dL), low total serum protein (median 6.5 vs 7.4 g/dL), and prolongation of prothrombin time (median 4.8 vs 1.05 seconds); all P < 0.03. No significant differences were found in sex, height standard deviation scores, duration of symptoms, liver span or consistency, transaminases, alkaline phosphatase, and etiology of NAVH versus AAVH. Among the AAVH group clinically detectable ascites was present in 38.9% (7/18), spontaneous bacterial peritonitis in 11%, and diuretics had to be used in 44% of cases. Ascites resolved in all of the cases in 8 weeks (94.4% cases in <4 weeks) and liver functions normalized in 17%, 50%, and 33% cases in <4, 4 to 8, and >8 weeks duration, respectively. We report AAVH as a distinct entity that affects younger children. This subgroup has compromised biosynthetic liver functions irrespective of viral etiology with total recovery.

Virological evaluation of domestic water purification devices commonly used in India emphasizes inadequate quality and need for virological standards

To evaluate the performance of domestic water purification units with respect to contaminating enteric viruses. Eight domestic water purification systems widely used in India were evaluated using hepatitis E virus (HEV) as a model virus. For HEV concentration and detection, membrane filtration and real-time PCR were used respectively. Viral log reduction value (LRV) was calculated for each unit. Viral log reduction value was 0.21 for unit 6 (polyester + carbon), 1.45 for unit 4 (filter + UV), 1.52 for unit 3 (filter + chlorine), 1.70 for a carbon + exhaust indication contact disinfection unit, 2.20 for an iodine resin unit, 2.51 for a dual filter unit and 6.53 for a hollow fibre membrane unit and a gravity-fed filter unit. Thus, only the technologies employed by the latter two were efficient in complete removal of HEV. The majority of the water purifiers under use are inadequate. Virological standards in evaluating such devices need to be established urgently, in order to help manufacturers to improve the performance of such products and most importantly, to help consumers.

Viral Load, Antibody Titers and Recombinant Open Reading Frame 2 Protein-Induced Th1/Th2 Cytokines and Cellular Immune Responses in Self-Limiting and Fulminant Hepatitis E

Objectives: Hepatitis E virus (HEV) is the predominant cause of water-borne epidemics, sporadic acute viral hepatitis (AVH) in adults and fulminant hepatic failure (FHF) among pregnant women and other adults in India. This preliminary study was designed to examine the association of viral load and certain host immune responses with uneventful recovery or progression to FHF. Methods: Viral load, anti-HEV antibody titers, rORF2p-induced Th1/Th2 cytokines levels and cellular immune responses were assessed in 47 patients with self-limiting hepatitis E and 14 FHF-E cases. The controls included 16 anti-HEV-IgM and IgG-negative healthy individuals. Results: In AVH category, the viral load was 2.4 × 10⁴ ± 1.92 × 10⁴ copies/ml while except for one, all FHF patients were negative for HEV RNA; anti-HEV-IgM and IgG titers were higher in the FHF group. Lymphocyte proliferative response to rORF2p was comparable in both groups. As compared to AVH, significantly higher levels of both Th1 (IFN-γ, IL-2 and TNF-α) and Th2 (IL-10) cytokines were recorded in FHF patients. Analysis of sequential samples differentiated FHF recovered and fatal patients with respect to IFN-γ and IL-12. Conclusion: The results document increased Th1/Th2 responses and anti-HEV titers in FHF patients that warrant in-depth immunological studies.

Spectrum of acute viral hepatitis in Southern India

Background: The incidence of hepatitis-A among adults in India is on the decline as majority develops protective immunity to it by late adolescence. Most of these studies are from northern India. Clinical spectrum of sporadic acute viral hepatitis from southern India has not been well documented. Methods: A prospective hospital based study was conducted in a large military hospital in southern India. 224 consecutive patients with acute viral hepatitis were studied for their presentation, etiology and clinical features. Result: Hepatitis-E was detected in 102 (45.4%), hepatitis A in 74 (33%) and hepatitis B in 28 (12.5%) patients. Acute hepatitis C was detected in two patients. 15 patients had a mixed infection. Hepatitis A constituted 41.2% and 31.3% of all cases in the age groups 11–20 and 21–30 years respectively. Cholestasis was present in 68 (30.4%) patients with hepatitis E accounting for most (61.8%) cases. There were four (1.8%) cases of acute liver failure. Two cases were due to hepatitis E and one case each was due to hepatitis A and hepatitis B. A relapsing course was seen in four cases due to hepatitis-A. Conclusion: Hepatitis A remains a significant cause of sporadic acute viral hepatitis in young adults in southern India.

Does co‐infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children?

This study looked at the frequency of co-infection with multiple hepatotropic viruses and the effect of such infection on the course and outcome of acute sporadic viral hepatitis (AVH) and fulminant hepatic failure (FHF) in children. Consecutive children up to 15 years of age presenting with AVH or FHF between January 1998 and July 2002 were evaluated prospectively. The following viral markers were assessed in all children: immunoglobulin M (IgM) anti-hepatitis A virus (HAV), IgM anti-hepatitis E virus (HEV), hepatitis B surface antigen (HBsAg), IgM anti-hepatitis B core (HBc), and anti-hepatitis C virus (HCV). A total of 149 children were included in the study, 122 with AVH and 27 with FHF. Co-infection with multiple viruses was detected in 30 (24.6%) AVH patients (A+E in 24, A+B in three, and E+B, A+C and A+E+B in one each) and seven (26%) FHF patients (A+E in five, and A+B and E+B in one each). The majority of single infections were due to HAV (AVH 70/92, FHF 14/20) followed by HEV (AVH 9/92, and FHF 5/20). HEV infection was associated with infection with another agent in 88% of patients with AVH (odds ratio 53, 95% confidence interval 15-186, P<0.0001). Frequency of anicteric state, prolonged cholestasis, relapsing hepatitis, ascites, hemolysis and mortality rates were similar in the single and multiple infection groups for both AVH and FHF patients. Co-infection with multiple viruses is observed in one-quarter of patients with sporadic AVH in childhood. Such infection does not produce a more severe disease. HEV positivity is a strong marker for multiple infections.

Molecular detection and sequence analysis of a new hepatitis E virus isolate from Pakistan

Sporadic and epidemic acute viral hepatitis E in many developing countries is caused by hepatitis E virus (HEV). The HEV genome has been classified into three major genotypes. However, extensive diversity has been noted among HEV isolates from patients with acute hepatitis in China and Taiwan. Some reports indicated that multiple genotypes of HEV could cocirculate in the same area; even distinct genotypes of HEV could exist in the same patient. Pakistan is a highly endemic area for hepatitis E. So far only two Pakistan HEV isolates Sar-55 (87-Pakistan-A) and Abb-2B (88-Pakistan-2B) have been characterized, and the nucleotide sequences of these two HEV isolates show only 90% homology. In this study, a third HEV isolate from Pakistan (87-Pakistan-B) is reported. The sequences of a 438-bp fragment from ORF-2 and a 259-bp fragment from the ORF-1-3 region of this new HEV isolate were obtained and sequenced. The sequence analysis showed that this new HEV isolate was very closely related to the Sar-55 but different from the Abb-2B HEV isolate. These results indicated that the Sar-55 (87-Pakistan-A) genotype is the main endemic HEV strain in the Sargodha area. These data will be useful for HEV epidemiological studies, diagnosis and vaccine development.

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.