Hepatitis virus non-A, non-B: the cause of a major public health problem in India

Serological studies of hepatitis viruses A and B were carried out on 362 patients with acute viral hepatitis, 130 with fulminant hepatitis, and 56 with subacute hepatitis, and on samples of serum from 230 subjects during epidemics of viral hepatitis. A diagnosis of non-A, non-B viral hepatitis was made when serological tests showed that anti-HAV IgM and anti-HBc IgM were absent. Hepatitis virus non-A, non-B was the causative agent responsible for 58% of cases with acute viral hepatitis, 58% with fulminant hepatitis, 87% with subacute hepatitis, and 66% with epidemic hepatitis. A considerable proportion of patients (6-32%) were infected with both hepatitis virus non-A, non-B and hepatitis virus B. Viral hepatitis non-A, non-B is probably transmitted by infection of drinking-water and is the principal cause of hepatitis in India.     

Integrated epidethiological system for acute viral hepatitis in Italy (SEIEVA): Description and preliminary results

An integrated epidemiological system for the surveillance of acute viral hepatitis SEIEVA which linked notifications to available serology results and used a standard risk factor questionnaire is described. Results of over 1300 cases reported by 35 participating local health units (USL's) during the first 18 months of the programme are presented. Overall the annual reported incidence of acute viral hepatitis was 70 per 100,000. There were marked regional and age specific differences in the incidence of each type of viral hepatitis. The annual incidence per 100,000 of hepatitis A in southern children was 133 while in northern young adults the incidence of hepatitis B was 88 and hepatitis non-A non-B was 43. The possible roles of shellfish consumption in the transmission of non-A non-B hepatitis at all ages were highlighted.     

Acute sporadic non-A, non-B hepatitis in India

A total of 293 sporadic cases of acute viral hepatitis were identified in Kashmir, India, from April 1979 to December 1981; 44 (15%) were found serologically to be hepatitis A, 94 (32%) hepatitis B, and 155 (53%) non-A, non-B type. The non-A, non-B hepatitis observed was a disease of young adults (29.8 +/- 15 years) with slight male predominance (1.4:1). Six of the 155 non-A, non-B cases had history of prior parenteral exposure, while 51 (33%) had a recent contact with another case of jaundice, suggesting that this form of hepatitis was spread by person-to-person contact. Fulminant hepatic failure occurred in 19 cases, and six (31.5%) of the 19 cases occurred in pregnant women. None of 90 non-A, non-B cases followed up six months later had developed chronic hepatitis. The acute sporadic non-A, non-B hepatitis described in Kashmir resembles epidemic non-A, non-B hepatitis epidemiologically and seems to be distinct from the non-A, non-B hepatitis described in the West.     

The effect of underreporting on the apparent incidence and epidemiology of acute viral hepatitis

To determine if passively reported cases of acute viral hepatitis are representative of the affected population, an active surveillance system was set up that identified all persons in Pierce County, Washington, who had been diagnosed by a physician as having acute viral hepatitis in the period March 1 through August 31, 1984. In this county, this was part of an ongoing epidemiologic study of viral hepatitis that had previously included some stimulation of reporting. The active surveillance system covered all primary sources of medical care, including all private physicians who were most likely to see persons with hepatitis. Secondary sources, those that did not provide direct medical care but might be aware of new cases, were also surveyed. The results of active surveillance showed that passive reporting was about 65% complete in Pierce County. No change occurred in the number of hepatitis A cases reported, but hepatitis B cases increased by 50%, and non-A, non-B hepatitis cases increased by 138%. Most of the increase was a result of enhanced reporting from private physicians. The two risk groups most affected by underreporting were homosexual men with hepatitis B and blood transfusion recipients with non-A, non-B hepatitis. During active surveillance, the proportion of persons with hepatitis B who reported homosexual activity was 52% compared with 20% from passive surveillance. Transfusion recipients represented 24% of the non-A, non-B hepatitis reported from active surveillance compared with 9% reported from passive surveillance. Although Pierce County may not be representative of all counties in the United States, persons responsible for public health prevention programs should recognize that data acquired through passive surveillance may not accurately reflect the magnitude of the risk for specific populations or the amount of disease that can be prevented.     

Viral hepatitis

Three forms of viral hepatitis can be recognized: hepatitis A, hepatitis B, and hepatitis non-A, non-B. Hepatitis A is caused by a picornavirus, is transmitted by the faceal—oral route, does not become chronic, and no chronic virus carriers exist. The virus can be grown in cell cultures, and killed as well as live attenuated virus vaccines are under development. Hepatitis B is caused by an enveloped virus containing a circular, double-stranded form of DNA. The disease is transmitted parenterally through inoculation of blood or blood products containing virus or through close personal contact with a virus-positive person. Hepatitis B becomes chronic in a certain number of cases and can lead to cirrhosis and primary liver cell carcinoma. The blood and certain body secretions of individuals with a persistent or chronic infection may remain infectious for many years. The hepatitis B virus cannot be grown in cell cultures but the entire genome has been sequenced and cloned in bacterial and eukaryotic cells. An inactivated virus vaccine has been prepared from hepatitis B surface antigen present in the plasma of hepatitis B virus carriers and further vaccines are under development. The agents of hepatitis non-A, non-B have not been identified. It is possible to distinguish between a predominantly parenterally transmitted and an orally transmitted form of hepatitis non-A, non-B. The latter is reported to be caused by a picornavirus that does not, however, have any antigenic relationship with hepatitis A virus.     

Indirect immunoperoxidase method using a monoclonal antibody and clinico-pathological examination of non-A, non-B hepatitis

For the purpose of diagnosing non-A, non-B hepatitis, an indirect immunoperoxidase method using the monoclonal antibody 48-1 was carried out. Human liver biopsy specimens of 74 cases with various hepatic diseases containing non-A, non-B hepatitis were investigated by using optical microscopy. Moreover, cases with non-A, non-B hepatitis were clinico-pathologically examined. Peroxidase-positive hepatocytes were found in 13 cases of the 74 cases. The thirteen cases were as follows; 8 cases with acute hepatitis (non-A, non-B type), 2 cases with chronic hepatitis (non-A, non-B type), 2 cases with acute hepatitis (B type), 1 case with chronic hepatitis (B type). The frequency of positive peroxidase staining was high (80%) in acute hepatitis (non-A, non-B type), but it was not significant statistically. On histological examination, acidophilic condensation was frequently seen in liver specimens of cases with acute hepatitis (non-A, non-B type). Furthermore, the correlation between acidophilic condensation and peroxidase positive staining was statistically seen. It is suggested that the peroxidase staining by using monoclonal antibody 48-1 is useful for diagnosis of acute hepatitis (non-A, non-B type).     

Non-A,Non-B hepatitis; Factors involved in progression to chronicity

A cross-sectional, longitudinal study was undertaken on a group of acute non-A, non-B hepatitis patients, as well as on a control group of hepatitis B patients, in order to assess both the prevalence of the most important factors favoring infection, and the relevance of these factors in promoting evolution towards chronic liver disease. Exposures to unknown risk factors were present in 47.4% of acute non-A, non-B infections, followed by blood transfusions (17.9%), sporadic exposures (17.9%) and drug addiction (16.6%). Unknown as well as sporadic exposures showed a greater prevalence in control population if compared to non-A, non-B cases, while drug addiction was equally represented in the two groups, and blood transfusion nearly absent from control group. The risk of evolution to chronic liver disease was about 13 times greater in non-A, non-B group than in controls, with the greatest risk for drug addicts and the lowest for patients with unknown exposures. Among patients with known exposures, the lowest risk of chronic hepatitis was observed in post-transfusion and in sporadic cases, while the greatest was observed in drug addicts.Corresponding author.     

Various sero-epidemiological characteristics of viral hepatitis in general medicine: results of a pilot survey performed in Belgium

A study was made of 110 cases of viral hepatitis diagnosed by general practitioners between 31 May 1982 and 30 June 1984. Hepatitis A was diagnosed in 53 patients, hepatitis B in 18 patients, hepatitis of both types A and B in one patient, and--by exclusion--hepatitis non-A non-B in 38 patients. Hepatitis A appears to be generally acquired by contact with infected persons or by travelling in endemic regions. In more than 50% of the hepatitis B cases, a hospital stay and/or ambulatory treatment were mentioned. All patients with hepatitis A became negative for anti-HA/IgM within 9 months after the diagnosis. 30% of the patients with hepatitis B remained positive for HBs Ag 9 months after diagnosis.     

Viral hepatitis and pregnancy in Kuwait

The frequency and severity of viral hepatitis among pregnant and non-pregnant women in Kuwait was studied from 1980 to 1984. 542 female hepatitis patients were investigated, of whom 52 (9.6%) were pregnant. 35 of the 52 (67.3%) cases of viral hepatitis in pregnancy were due to hepatitis B virus while 11 of 52 (21.2%) and 6 of 52 (11.5%) had acute hepatitis non-A, non-B (NANB) and hepatitis A virus infections, respectively. The frequency and severity of viral hepatitis among the pregnant women was similar to that among non-pregnant women. Hepatitis did not have a deleterious effect on pregnancy and no death was recorded. Fulminant acute NANB hepatitis was seen in only one patient, who recovered completely.     

Hepatitis C virus antibody in Hungarian blood donors, persons at risk and patients with post-transfusion hepatitis]

The authors screened blood donors, persons at high risk of infection and patients with post-transfusion hepatitis by the use of the new hepatitis C antibody test. 1.7% of persons donating blood acceptable for use according to current criteria were found positive. This ratio was markedly higher among donors displaying an elevated transaminase level. Among the various patients tested 85% of the haemophiliacs, 14% of the transfused haematology patients, and 40% of those on dialysis were found positive. In two groups of patients with post-transfusion non-A, non-B hepatitis the ratio of positives was 69% and 92%, respectively. The frequency of hepatitis C antibody was not sizably higher in the health personnel tested than that found in blood donors. The results indicate hepatitis C virus to be the main source of post-transfusion non-A, non-B hepatitis in Hungary too. As expected, HBc antibody revealing a previous contact with hepatitis B virus was found very frequent in patients with coagulopathies and in those on dialysis. A relatively high anti-HBc prevalence was found among health personnel and blood donors too. Authors intend to emphasize the need of thorough consideration of indications in hemotherapy although improvements in the screening of donations can diminish the risk of virus transmission by blood or blood derivatives.     

Fréquence de l'hépatite sporadique E en C?te d'Ivoire,vue au travers d'une sérologie encore problématique.

The first well-documented outbreak of viral hepatitis E in Africa was described in 1986 in Côte d''lvoire. Subsequently, no other outbreaks have been observed in the country. Côte d''lvoire therefore offers an excellent opportunity to evaluate the prevalence of sporadic viral hepatitis E in a country where the frequency of non-A, non-B, non-C viral hepatitis appears to be high. The study was carried out in Abidjan, the most populous city, and involved 111 hospitalized patients suffering from non-A, non-B and presumed non-C acute viral hepatitis. Screening for leptospirosis or a toxic etiology was carried out and the risk of including such patients eliminated. Diagnosis of viral hepatitis A was excluded from the absence of IgM anti-HAV antibodies. Patients with HBsAg and anti-HCV antibodies were not included in the study, although co-infection in asymptomatic HBV carriers or subsequent infection in patients who had recovered from a past HCV infection remained possible. There was a risk that some patients with late appearance of anti-HCV antibodies were included since PCR tests could not be performed. Cytomegalovirus or Epstein-Barr virus was not involved, since no specific IgMs against these viruses were detectable. Large discrepancies between the two commercial enzyme-linked immunosorbent assays (ELISAs) available for serological diagnosis of hepatitis E (Abbott and Genelabs) were observed. Among the 53 sera screened using both tests, only 20 gave positive results in both, and all such sera were confirmed using a domestic immunological test involving inhibition of labelled, well-documented anti-HEV-specific human IgG. Immunological confirmation was obtained for only half of the sera with discordant results in the commercial ELISAs. Full agreement between both commercial tests was observed for only 59% of the sera studied. The minimal incidence of sporadic viral hepatitis E among hospitalized patients in Abidjan with an acute hepatitis was estimated to be 27%.     

急性病毒性肝炎的病例对照研究与分型转归研究

对两所医院162例急性病毒性肝炎患者进行了血清学分型和流行病学研究,并对发病的一些危险因素按成组和配对方法进行了病例对照研究。结果甲肝为37.0%,乙肝为40.7%,非甲非乙型肝炎为19.8%。经单因素和多因素Logistic回归分析,甲肝发病主要与肝炎接触史(OR=10.56)和不洁饮食史(OR=4.25)有关;乙肝与肝炎接触史(OR=4.30)和家庭成员既往肝炎史(OR=5.66)有关;非甲非乙型肝炎与肝炎接触史(OR=3.82)、输血史(OR=16.67)和既往肝炎史(OR=6.56)有关。甲肝、乙肝和非甲非乙型肝炎的转慢率分别为0%、12.1%和16.7%。     

Hepatitis in dialysis units in the United Kingdom: a Public Health Laboratory Service Survey.

A prospective study of hepatitis that began in 1968 and continues to include more than half the dialysis units in the United Kingdom shows that type B infection has been completely controlled in such units since the last outbreak ended in 1973. Though occasionally a single patient has developed hepatitis B surface antigenaemia in the course of dialysis or after transplantation, the infection has not spread to other patients or staff in the survey units. A detailed analysis of the results in 1974-75 shows clustering of patients with raised aminotransferase levels in about one-fifth of the units but, unlike past outbreaks of hepatitis B, these clusters are not accompanied by clinical hepatitis among staff. The possibility that some of the clusters are caused by hepatitis viruses other than type A or B is discussed. It is concluded that, when reliable tests for type non-A non-B infections become available, the continued existence of the survey will allow prompt assessment of any viral hepatitis problems that may still exist in UK units.     

Trends of hepatitis B and hepatitis C mortality in Canada, 1979-1997

Mortality data from Statistics Canada were analyzed to measure the temporal trends and burden of illness attributed to viral hepatitis in Canada. Analysis of age-standardized mortality rates from 1979 to 1997 showed an increasing trend in mortality for both hepatitis B and non-A, non-B hepatitis (NANBH), most of which are attributed to hepatitis C infections. Hepatitis B and NANBH age-standardized mortality rates increased respectively, from 0.03 and 0.12 deaths per 100,000 population in 1979 to 0.26 and 0.41 deaths per 100,000 in 1997. Male mortality rates were consistently higher than female for both diseases. Among deaths from chronic liver disease, over 1,000 deaths were estimated to have been caused by hepatitis B and hepatitis C annually. Although the hepatitis B or NANBH recorded deaths largely underestimate the true burden of HBV and HCV in Canada, the temporal trends are useful as they reflect changes in the impact of both diseases.     

Hepatitis: Current Status of Etiology and Prevention

Transmission of both type A and type B hepatitis to nonhuman primates is a major advance that has expedited development of tests for antibody and preparation of a type B inactivated vaccine, now under trial. The antibody tests have led to improved immune serum globulins for preventing infections. Recently a “non-A, non-B” variety has emerged as the primary cause of hepatitis in patients given multiple transfusions.     

Advances in the research on non-A, non-B hepatitis: hepatitis C virus. Multicenter anti-HCV studies

In the introduction, a brief overview is given on the clinical aspects and classification of non-A, non-B hepatitis and on the discovery of hepatitis C virus. Using a recombinant hepatitis C virus antigen in an ELISA test system, for the demonstration of the antibody to hepatitis C virus, a new possibility became available in the serological diagnosis of non-A, non-B hepatitis. According to the previous hepatitis C virus antibody studies performed in Western Europe and in Hungary, the results of the present multicentre study also show that hepatitis C virus infection is frequent mainly in the post-transfusion chronic non-A, non-B hepatitis (87%) and in haemophiliacs (86%). In addition, antibody to hepatitis C virus occurs in open-heart surgery (27%) as well as in haemodialysed patients (20%), furthermore, it can be found in other forms of liver disease of various aetiology, e. g. in chronic HBsAg-positive hepatitis (33%), autoimmune liver diseases (20%) and chronic alcoholic hepatitis (14%) as well. The parenterally transmitted non-A, non-B hepatitis, practically the hepatitis C virus-related liver disease often leads to cirrhosis or even carcinoma. As its treatment is unsolved question yet, the prevention seems to be of great importance, the preventive measures of post-transfusion hepatitis C virus infection is listed.     

Risk factors for acute non-A, non-B hepatitis and their relationship to antibodies for hepatitis C virus: a case-control study.

A case-control study was carried out comparing 333 case subjects with non-A, non-B hepatitis and 1095 hospital control subjects. Of 333 case subjects, 197 (59%) were positive for hepatitis C antibody (anti-HCV). Excluding blood transfusion and intravenous drug use, surgical intervention and dental therapy were strongly associated with anti-HCV-positive cases: in particular, obstetric and gynecology surgical intervention was found to be strongly associated with HCV positivity (odds ratio [OR] = 32; 95% confidence interval [CI] = 7, 147). Raw shellfish consumption was a risk factor for anti-HCV-negative cases (OR = 2.2; 95% CI = 1.0, 5.1), thus suggesting an enterically transmitted virus in sporadic non-A, non-B hepatitis in Italy.     

The aetiology of acute viral hepatitis in the western region of Saudi Arabia

Of the 1050 sera of acute viral hepatitis patients admitted to the Infectious Diseases Hospital in Jeddah, Saudi Arabia, over a one-year period, 40.9% were due to hepatitis A, 21.5% to hepatitis B, and 37.6% to non-A, non-B (NANB) hepatitis. The mean age for hepatitis A patients was 4 +/- 2.4 years, with no sex preponderance. The mean ages for hepatitis B and NANB were 26.1 +/- 11.9 and 28.8 +/- 14.2 years, respectively. A male to female ratio of 2:1 was noticed for both. 10% of HBsAg patients were positive for anti-delta. 32% of NANB cases were excluded on the bases of possessing specific IgM against cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV) or Treponema pallidum. Only 9% of NANB cases had a history of blood transfusion. In conclusion, nearly all cases of acute jaundice in Saudi children are due to hepatitis A, whereas hepatitis B and NANB generally occur in adults. Other viruses such as CMV, HSV, and EBV are highly prevalent and must be excluded in all cases of NANB hepatitis.     

Hepatitis of viral origin in Leporidae: introduction and aetiological hypotheses.

In less than ten years, two very serious viral hepatic diseases have spread through Leporidae populations (rabbits and hares) in numerous countries. In May 1989, the Office International des Epizooties designated this new disease of rabbits "viral haemorrhagic disease" and entered it as a List B disease in the International Animal Health Code. Clinically, the disease is very similar to the European brown hare syndrome. However, numerous uncertainties prevail today on the true nature of the viruses of the two species. Although they are related, the viruses appear to be different and cross infection between species has given contradictory results. Hepatitis of Leporidae have probably existed in Europe for several years, although their viral aetiology has been demonstrated only recently. The acute form has occurred in hares in Northern Europe since approximately 1980, while the inapparent (or ignored) form has been present in rabbits in Czechoslovakia since 1975. These diseases of Leporidae are true viral hepatitis which, in their fulminating forms, bear a remarkable resemblance to human viral hepatitis (B and non-A non-B) with regard to clinical symptoms, pathological lesions and mode of transmission. The dominant faecal-oral transmission observed for types A and E hepatitis would explain the particular susceptibility of family-kept rabbits, as they are fed potentially contaminated fodder. As the clinically similar fulminating hepatitis in human beings is caused by a diversity of viruses (both RNA and DNA), the disease in Leporidae might also be caused by different viruses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reactivity of 48-1 antibody with human liver tissue

Reactivity of monoclonal antibody (48-1), produced by the Epstein-Barr Virus (EBV) transformation method using lymphocytes from a chimpanzee infected with non-A, non-B hepatitis, on human liver biopsy specimens from 240 cases was studied. By means of indirect immunoperoxidase study (Secondary Antibody: Horseradish peroxidase labeled anti-human IgM.F(ab')2), the cases with non-A, non-B acute hepatitis showed a high positive reaction (15/24), while those cases with A-type and B-type hepatitis showed almost no reaction, suggesting that this 48-1 antibody strongly related to human non-A, non-B hepatitis. As for staining pattern, cytoplasms of some hepatocytes and large-size histiocytes were stained diffusely in pellet form, and were found scattered in each lobule. In addition, an EM study was made on positive cases using an immunoperoxidase method. However, a definite finding on peroxidase-reactive products was not obtained. We believe that this antibody (48-1) obtained by the EBV method would be useful in investigations of antigen-antibody systems related to non-A, non-B hepatitis.