Sporadic Acute Hepatitis Research Articles

Abstract

In Japan up to 23% of the sporadic acute hepatitis (AH) cases remain diagnosed as non A to E (NA–E). The aim of this study was to determine the etiologic and clinical characteristics of GB virus C/hepatitis G virus (GBV-C/HGV) infection and group the isolates obtained by phylogenetic analysis. Serum samples from 72 patients with sporadic AH NA–E were investigated for the presence of GBV-C/HGV RNA by reverse transcription polymerase chain reaction (RT-PCR). PCR products were cloned, sequenced and the isolates obtained were compared with previously reported sequences. Seven out of 70 patients with the usual type of sporadic AH NA–E were positive for GBV-C/HGV RNA, suggesting that GBV-C/HGV infection accounts for ≈10% of sporadic AH NA–E patients in Japan. Patients with GBV-C/HGV infection were older (five out of seven were >45-years-old) but their acute clinical characteristics were similar to those with NA-G hepatitis. All patients, except one, had transient viremia which resolved within 2–4 weeks. One out of two patients with fulminant hepatitis (FH) NA–E was positive for GBV-C/HGV. Finally, all isolates in this study belonged to the same type, which is prevalent not only in Japan but also in Asia.

GB virus C/hepatitis G virus in Japanese patients with sporadic acute non A–E hepatitis

In Japan up to 23% of the sporadic acute hepatitis (AH) cases remain diagnosed as non A to E (NA–E). The aim of this study was to determine the etiologic and clinical characteristics of GB virus C/hepatitis G virus (GBV-C/HGV) infection and group the isolates obtained by phylogenetic analysis. Serum samples from 72 patients with sporadic AH NA–E were investigated for the presence of GBV-C/HGV RNA by reverse transcription polymerase chain reaction (RT-PCR). PCR products were cloned, sequenced and the isolates obtained were compared with previously reported sequences. Seven out of 70 patients with the usual type of sporadic AH NA–E were positive for GBV-C/HGV RNA, suggesting that GBV-C/HGV infection accounts for ≈10% of sporadic AH NA–E patients in Japan. Patients with GBV-C/HGV infection were older (five out of seven were >45-years-old) but their acute clinical characteristics were similar to those with NA-G hepatitis. All patients, except one, had transient viremia which resolved within 2–4 weeks. One out of two patients with fulminant hepatitis (FH) NA–E was positive for GBV-C/HGV. Finally, all isolates in this study belonged to the same type, which is prevalent not only in Japan but also in Asia.

Clinical and viral marker pattern of acute sporadic hepatitis in children in Madras, South India.

One hundred and twenty-seven children who presented with features of acute hepatitis during the period February 1995 to January 1996 were studied. Specific aetiologic agents were identified in 89 per cent. Of these, 67.7 per cent were due to a single virus, whereas 21.3 per cent were due to two or more hepatitis viruses. Hepatitis A virus (HAV) was the sole infecting agent in 38.6 per cent of cases, hepatitis B virus (HBV) in 13.4 per cent of cases, and hepatitis E virus (HEV) in 15.7 per cent of cases. Mixed infections were due to HAV and HBV co-infection (7.1 per cent), HAV and HEV (13.4 per cent), and the combination of HAV, HBV, and HEV (0.8 per cent). In 11 per cent, none of the markers (HAV to HEV) were identified. Acute sporadic hepatitis in children can occur due to a single hepatitis virus type or, at times, due to co-infection with a combination of two enterally transmitted viruses or enteral and parenterally transmitted viruses. Improving personal hygiene and active immunization are essential in the prevention of these viral illnesses. This study was done in a referral centre and hence we report a higher morbidity (13.4 per cent) and mortality (12.6 per cent) rate in all groups of infection. Hence, apart from the viruses, factors such as the age of the child, nutritional status, and treatment taken prior to hospitalization should be taken into consideration to predict the prognosis in a given child.

Hepatitis E virus infection in eastern India.

Most cases of enterically transmitted non-A, non-B hepatitis in India have so far been attributed to hepatitis E virus (HEV) infection. Most of the documented studies of hepatitis have focused on the incidence of this disease in northern, western, and south central India. A small seroprevalence study was conducted in the eastern Indian city of Patna to assess the degree of HEV infection among acute sporadic hepatitis cases. Forty-two percent (24 of 57) of the cases of acute sporadic hepatitis were positive for anti-HEV antibodies. Absence of any serologic markers of hepatitis A, B, or E in 58% (33 of 57) of the cases with symptoms of acute hepatitis suggest that there may be as yet unidentified enterically transmitted viruses in this area.

Identification of a novel strain of hepatitis E virus responsible for sporadic acute hepatitis in Taiwan.

Hepatitis caused by the hepatitis E virus (HEV) is a self-limited disease and occurs most frequently as epidemic or sporadic hepatitis in developing countries. The role of HEV in sporadic acute hepatitis in areas without a history of hepatitis E epidemics is obscure. Recently, it was found that more than 10% of the patients with acute non-A, non-B, non-C hepatitis in Taiwan were associated with an acute HEV infection. Nucleotide sequences of the regions within the first open reading frame of HEV were determined in four cases and were 96.7-100% identical to each other. As compared to the isolates from China, Pakistan, Burma, India, Africa, and Mexico, the similarities were, however, only 71.7-79.3%. Phylogenetic analysis revealed that the four Taiwan isolates were categorized as a novel HEV group (the Taiwan strain), which was distinct from all of the strains isolated from other parts of the world. In addition, the isolates from China, Burma, India, and Pakistan were catalogued as the second genotype of HEV (the Asian strain), and the Mexican isolate as the third (the Mexican strain). The African isolate was more related to the Asian type and might be a subtype of the Asian strain. A simple genotyping method by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) is described. The findings also support the hypothesis that HEV may be responsible for some sporadic acute non-A, non-B, non-C hepatitis in other developed countries.

Detection of hepatitis C and E virus genomes in sera of patients with acute viral hepatitis and fulminant hepatitis by their simultaneous amplification in PCR.

A study was undertaken to investigate the role of hepatitis C virus (HCV) and hepatitis E virus (HEV), either alone or together, in the causation of sporadic acute viral hepatitis (AVH) and fulminant hepatitis (FH) by simultaneous detection of their genomes in serum samples using the reverse transcription and nested polymerase chain reaction (RT-PCR). A total of 50 patients were enrolled in the study of which 34 had AVH and 16 had sporadic FH. The serum samples were first tested for hepatitis B surface antigen (HBsAg) and immunoglobulin (Ig)M antibodies against hepatitis A virus (HAV), hepatitis B core antigen (HBcAg) and HEV and also antibodies against HCV using commercially available enzyme-linked immunosorbent assay (ELISA) kits. All samples were then subjected to RT-PCR using primers for both HCV and HEV simultaneously in the same reaction mixture. Hepatitis C or hepatitis E was diagnosed when either the antibodies or PCR or both were positive for the respective viruses. Evidence of hepatitis C was present in six of the 34 (17.6%) cases of AVH and two out of 16 (12.5%) cases of FH. Four patients in the AVH group and one of the fulminant hepatic failure (FHF) group were found to be positive by PCR and the rest by serology. But as a sole aetiological agent, HCV infection was found in only one (2.9%) case of AVH and in none of the FHF cases. Evidence of HEV infection was found in 22/34 (64.7%) and 8/16 (50%) cases of AVH and FHF, respectively. Excluding co-infection with other viruses, HEV was found to be the sole aetiological agent in 15/34 (44.1%) of AVH and 7/16 (43.7%) cases of FHF. In five (10%) (four AVH and one FHF) of the 50 cases, evidence of infection with both HCV and HEV was present. But only in two of these five cases, genomes of both HCV and HEV were co-amplified. In seven (four AVH and three FHF) out of 50 (14%) cases, no known viral agent could be detected. Our results suggest that HEV is the most common aetiological agent for both acute viral hepatitis and fulminant hepatic failure and that HCV is a rare cause of acute liver diseases although along with other viruses, evidence of either present or past HCV infection may be present in a substantial number of cases. Furthermore, advanced-stage pregnancy appears to be a potential risk factor for HEV infection and high rate of mortality in women. The study suggests that the method of simultaneous amplification of both HCV and HEV genomes could reduce the time, labour and cost involved in diagnostic work up of acute liver disease patients.

Transmission routes and clinical courses in sporadic acute hepatitis C.

Between March 1994 and March 1996 we studied transmission routes and clinical courses in eight patients with sporadic acute hepatitis C (two men, six women). Of the eight patients, three were treated for another illness 1-2 months before the onset of hepatitis, one was a parenteral drug abuser, one had an accidental needlestick injury and two had sexual contact with a partner with chronic hepatitis C virus (HCV) infection. Clinical courses included four women whose HCV RNA and alanine aminotransferase (ALT) became persistently negative without treatment, and four men and two women with the same results following interferon (IFN) treatment. It is thought that IFN therapy may prevent the progression to chronic liver disease. Results from this study might be useful in the future management of patients with sporadic acute hepatitis C.

Magnitude of hepatitis C virus infection in India: Prevalence in healthy blood donors, acute and chronic liver diseases

An enzyme immunoassay (EIA) was developed in-house for the detection of anti-hepatitis C virus (HCV) antibody against the prevailing genotypes in India. The specific reactivity of the test was compared with commercial second and third-generation EIAs and reverse transcription nested polymerase chain reaction (RT-nested PCR). Fifteen thousand nine hundred twenty-two healthy blood donors at the All India Institute of Medical Sciences (AIIMS), New Delhi, India, were screened for anti-HCV antibody. Two hundred ninety-five (1.85%) of these donors were positive. The screening was also used to determine how many patients with acute hepatitis and chronic liver diseases were positive for anti-HCV antibody. Five hundred sixty-four chronic liver disease patients were screened for anti-HCV antibody and 78 (13.83%) were found positive. Two hundred forty-seven sporadic acute viral hepatitis patients were screened for viral infection markers. Hepatitis B and E viruses (HBV and HEV) were the major etiologic agents. HCV was associated with 9% of the acute cases. Anti-HCV core IgM with HCV RNA detection were found to be helpful for the diagnosis of acute HCV infection.

Acute sporadic hepatitis in the Republic of Yemen.

The causes of acute icteric viral hepatitis were determined in 78 adult Yemeni patients. Acute hepatitis B (IgM anti-HBc positive) was the most common type (26.9%). Acute hepatitis E (IgM anti-HEV positive) occurred in 14% and was not associated with travel outside Yemen. Sixty percent of all 78 patients were positive for IgG anti-HEV as were 40% of a series of 48 healthy male blood donors and pregnant females, indicating that HEV is prevalent in Yemen. Acute hepatitis A (IgM anti-HAV positive) and hepatitis C and D were responsible for 5.1%, 6.4%, and 2.6% cases, respectively. This totals to 106%, as an infection with two viruses occurred in 6.4% cases. In 51.3% of all cases, no virological markers of acute hepatitis were detected, suggesting an as yet undiscovered agent.

The Role of Hepatitis E Virus Infection among Patients with Acute Viral Hepatitis in Southern Saudi Arabia

We investigated the etiology of acute sporadic viral hepatitis in southern Saudi Arabia in a series of 132 patients admitted with acute viral hepatitis. Of these cases, 108 (81.8%) were due to acute hepatitis A virus infection, of which 11 (8.3%) patients had been previously exposed to hepatitis E virus, and another 10 (7.6%) were chronic carriers of hepatitis B virus. Three cases (2.3%) were acute hepatitis B virus infection. The overall prevalence of hepatitis E IgG antibodies was found to be 9.1%. The remaining 21 (15.9%) patients were tested for hepatitis E IgM, EBV-VCA IgM and hepatitis C IgG antibodies by sensitive enzyme immunoassays. In none of them could hepatitis E IgM, EBV-VCA IgM or hepatitis C IgG antibodies be demonstrated, and these patients were thus considered as acute non-A, non-B hepatitis. Acute hepatitis C virus infection, however, could not be ruled out from this group. We therefore concluded that the majority of clinically apparent viral hepatitis cases were due to HAV, while HBV accounted for a small proportion of the cases. Clinically apparent HEV infection does not appear to be common in the population studied, since even those with serologic evidence of previous exposure to HEV did not recall a history suggestive of acute viral hepatitis.

Sporadic acute hepatitis caused by hepatitis E virus in Egyptian adults.

Sporadic acute hepatitis caused by hepatitis E virus in Egyptian adults.

Hepatitis E Virus: Another Addition to the Existing Alphabet of Human Hepatitis Viruses

Hepatitis E Virus: Another Addition to the Existing Alphabet of Human Hepatitis Viruses

Pattern of Hepatitis A and Hepatitis B Virus Markers in Cases of Acute Sporadic Hepatitis and in Healthy School Children from North West India

The pattern of viral markers in acute sporadic hepatitis in 329 children and those in 334 healthy school children from North West India were studied. Hepatitis A was found to be the commonest infection in sporadic cases (78 per cent). Of these, 86 per cent were under 10 years and 50 per cent less than 5 years of age. Hepatitis B was positive in 8 per cent, non-A non-B in 13 per cent, A as well as B in 1 per cent, and none had Delta virus infection. Viral markers in healthy school children showed anti-HAV IgG positivity in 96 and 85 per cent in those belonging to low and high socio-economic groups, respectively, indicating past infection. HBsAg was positive in 1 per cent of cases. Viral hepatitis is an important public health problem in children and warrants active immunization.

Acute sporadic hepatitis E virus infection in southern China

Background/Aims: The hepatitis E virus is responsiblefor epidemic and sporadic hepatitis in northwestern China, but its role as a cause of acute sporadic hepatitis in southern China has not been reported. Methods: We applied the most practical current methods for diagnosis of hepatitis E virus infection, IgM and IgG anti-HEV detection by enzyme linked immunosorbent assay, to investigate the prevalence of hepatitis E virus infection among acute sporadic hepatitis. Results: Anti-HEV IgM was found in 1 of 26 (3.8%), 4 of 20 (20.0%), 4 of 19 (21.1%), and 51 of 142 (35.9%), with acute hepatitis A, B, C and non-ABC, respectively. Anti-HEV IgM was not detectable in healthy subjects, while IgG anti-HEV was found in 14 of 77 healthy subjects (18.2%) and was long-lasting. Ninety-one cases without any evidence of hepatitis A, B or C infections and anti-HEV IgM were tentatively classified as non-A, B, C, D, E (non-ABCDE) hepatitis. By comparison with non-ABCDE, cases with hepatitis E were more frequently icteric and exhibited higher alanine aminotransferase levels (92.2% vs. 45.1%, 770 iu/l vs 377 iu/l, respectively. p<0,005). Chronic cases were not observed in hepatitis E virus infections. However, 14 of 91 (15.4%) cases with non-ABCDE developed to chronicity ( p<0.005). Conclusions: Hepatitis E virus infection is sporadic aswell as endemic in southern China. Only IgM anti-HEV but not IgG anti-HEV can be used as an appropriate marker of acute hepatitis E virus infection. Superinfection of hepatitis E virus with other types of hepatitis viruses is frequent in this area. While the disease was associated with more severe clinical manifestations, patients usually recovered completely.

Acute sporadic hepatitis E virus infection in southern China

Acute sporadic hepatitis E virus infection in southern China

Protracted viremia during acute sporadic hepatitis E virus infection

Background/Aims: Hepatitis E virus (HEV) is associated with epidemic and sporadic hepatitis in developing countries. The disease is largely self-limited with no long-term sequelae. The source of HEV for maintenance of the disease in an endemic area is unknown. This study investigated the occurrence and duration of viremia in patients with acute sporadic HEV infection. Methods: In 26 of 37 patients with sporadic acute non-A, non-B viral hepatitis, HEV infection was diagnosed based on positivity for immunoglobulin M anti-HEV and/or presence of viremia as shown by reverse-transcription polymerase chain reaction. In 4 patients, fecal samples were analyzed for presence of virus using polymerase chain reaction. Multiple samples were studied at varying times in 20 patients. Results: Viremia was detected in 19 of 26 patients. Two patients had viremia in the absence of immunoglobulin M anti-HEV. Four patients had protracted viremia of 45–112 days' duration. One patient showed fecal virus shedding up to the 52nd day of illness. Conclusions: Protracted viremia and prolonged fecal shedding of HEV were shown in a small group of patients. These patients may serve as temporary virus carriers responsible for continuous contamination of the sewage water.

Etiology of Acute Sporadic Hepatitis in Adults in Senegal and Tunisia

Markers for acute hepatitis A, B, C and E virus infections were examined in the sera of 72 patients suffering from acute hepatitis in Senegal and Tunisia. Hepatitis B was responsible for 36% and hepatitis C for 21% of the cases. Acute hepatitis A was not diagnosed. HEV infection was not observed in Senegal and represents only 4% of the acute hepatitis cases in Tunisia.

The role of hepatitis E virus in acute sporadic non-A, non-B hepatitis.

Hepatitis E virus (HEV) is the cause of enterically transmitted non-A, non-B (NANB) hepatitis. Water-borne epidemics have been reported in many developing countries primarily affecting young and middle-aged adults. To determine the role of HEV in acute sporadic NANB hepatitis, we have studied the profiles of anti-HEV IgG in the sera of patients previously diagnosed for NANB hepatitis. We tested the sera of 53 patients with acute NANB hepatitis and 100 healthy people as a control group for anti-HEV IgG. Thirty-nine of the 53 patients (73.3%) and none of the control group were positive for HEV infection, according to results shown by ELISA. This result suggests that HEV is a common cause of acute sporadic NANB hepatitis in Turkey. Further studies are needed in the other regions to determine the true prevalence of HEV infection in Turkey.

Virus isolate-specific antibodies against hypervariable region 1 of the hepatitis C virus second envelope protein, gp70.

Hypervariable region 1 (HVR1), located in the N‐terminal region of a putative second envelope glycoprotein (gp70) of hepatitis C virus (HCV), contains immunological B‐cell epitopes which might be neutralizing epitopes. To clarify whether B‐cell epitopes within HVR1 are common among virus isolates or specific for the homologous virus isolate, we examined the reactivities of sera from 53 patients with chronic hepatitis or hepatocellular carcinoma/liver cirrhosis against two different HVR1 peptides (HVR11‐1 and HVR1 Y‐l) derived from patient I with sporadic acute hepatitis and an asymptomatic carrier Y, respectively, using our original assay system for the detection of anti‐HVR1 antibody. All patients examined had a history of blood transfusion. Most sera showed no reactivity with either HVR1 1‐1 or HVR1 Y‐l peptide. Only seven and fourteen serum samples reacted significantly, although weakly, with HVR1 1‐1 and HVR1 Y‐l peptides, respectively, compared with the serum from patient I or asymptomatic carrier Y. The blood transfusions of most reactive cases had occurred more than thirty years earlier. Six cases reacted with both HVR1 1‐1 and HVR1 Y‐l peptides, but further analysis revealed that only three cases reacted weakly with the peptide for either epitope I or II, identified within HVR11‐1, These results indicate that the B‐cell epitopes within HVR1 are fairly specific for the homologous virus isolate, and this may represent a serious difficulty in the development of a vaccine against HCV.

HEPATITIS E

With the introduction of new, albeit noncommercial, diagnostic tests for the detection of HEV, our understanding of this virus has been greatly enhanced. With these tests, it has been possible to begin a delineation of the process of pathogenesis in infected humans. These tests have also shown us that, at least in some individuals, an IgG response to HEV is long lasting and may confer immunity, and it may be possible to develop a recombinant vaccine against HEV. Contrary to past results, HEV appears to be the most common cause of acute sporadic hepatitis in pediatric populations in endemic regions. HEV has been shown to be a positive-sense single-stranded RNA virus that has been tentatively classified as a calicivirus, although its nonstructural proteins exhibit sequence similarity to rubella virus and furoviruses. Despite these advances in our understanding of HEV, it is still necessary to depend on exclusion of hepatitis caused by other viruses to diagnose a hepatitis E infection; however, this situation should change with the anticipated release of commercially available diagnostic tests.