High prevalence of occult hepatitis B virus genotype H infection among children with clinical hepatitis in west Mexico

Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children.     

Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is not uncommon as a result of similar routes of infection. Patients who are coinfected represent a unique group with diverse serologic profiles. Combined chronic hepatitis B and C leads to more severe liver disease and an increased risk of hepatocellular carcinoma. Furthermore, coinfected patients represent a treatment challenge. No standard recommendations exist for treatment of viral hepatitis due to dual HBV/HCV infection, and therefore treatment must be individualized based on patient variables such as serologic and virologic profiles, patient's prior exposure to antiviral treatment, and the presence of other parenterally transmitted viruses such as hepatitis D virus and human immunodeficiency virus. The natural history and treatment of patients with HBV and HCV coinfection is reviewed.     

Hepatitis B Virus Infection—Current Concepts of Chronicity and Immunity

Among the three types of viral hepatitis agents—A, B and non-A, non-B—the hepatitis B virus (HBV) has been best characterized by immunologic and recombinant DNA technologies. The indefinite persistence of hepatitis B virus infection in 85% to 90% of perinatally infected infants and in about 10% of those infected later in life accounts for a worldwide epidemiologic reservoir of more than 200 million carriers who are at a high risk for the development of δ-infection, chronic liver disease and hepatocellular carcinoma. Active immunization with a safe and effective vaccine, derived from the plasma of carriers of hepatitis B surface antigen (HBsAg), is envisaged to avoid viral hepatitis type B and its chronic sequelae. In addition to serologic and immunohistochemical markers of hepatitis B virus infection, hybridization assays using cloned HBV DNA have provided new insight into the biology of this virus, its persistence and its oncogenic potential in humans and in animal models. Genetic similarities have been recognized between HBV and the antigenically distinct non-A, non-B agents implicated in some cases of transfusion-associated chronic hepatitis. Structurally this unique group of HBV and HBV-like agents are DNA viruses with functional attributes of integration and replication analogous to the retroviruses.     

输血后乙型肝炎的研究

对204例首次受血(1～2单位)的外科手术患者进行了随访,以观察输血后HBV的感染和发病。血源来自224例HBsAg阴性(RPHA法检测)的献血员,受血者于受血前及受血后6～7个月各采血1次,连同献血员献血前的血清,用同一批RIA试剂检测HBsAg、抗-HBs和抗-HBc。发现用RPHA筛选的HBsAg阴性献血员,用RIA检测时,仍有2.2％(5/224)HBsAg阳性。70例HBV易感者中,受血后13例发生HBV感染,其中2例输入HBsAg阳性血液者发生急性肝炎(2.86％),1例为黄疸型乙型肝炎,另一例为NANB肝炎;11例发生HBV感染,其中8例为输入HBV-DNA阳性血液。以上结果表明,RPHA筛选献血员仍不能杜绝输血后肝炎,RIA筛选献血员后不能杜绝亚临床感染。部分HBV感染不能排除医院内感染的可能性。     

Spread of viral hepatitis in organized children's collectives and the methods for its early diagnosis]

The authors present the results of observations over 407 children aged from 2 months to 16 years from the foci of viral hepatitis in children's collective bodies. During the quarantine a determination was made in children of the glutamic-pyroracemic, glutamic-oxalic transaminases (GPT and GOT, respectively) and of the hepatitis B antigen (HBAg). A necessity of using the enzymatic tests for the purpose of early diagnosis of viral hepatitis was shown, since 84% of the cases developing in the next focus coursed as an unicteric form without any markked clinical signs; HBAg was revealed in 6.1% of the children examined. A complex examination of the personnel and of the persons who came in contact with the patients with viral hepatitis showed the ways of spread of hepatitis B in a collective body; it was found that the viral hepatitis B infection took place both by parenteral and enteral routes. The expediency of active observation over the children, recipients of blood and plasma, with determination in them of the activity of the enzymes and HBAg for early diagnosis of parenteral infection was substantiated. It was also shown that the incidence of the unicteric forms of viral hepatitis in a focus of infection depended not on the periods of gamma-globulin administration but on the age of children who contracted the infection. Thus, the prevalence of the unicteric forms of the disease over the icteric ones in children under 3 years of age was more pronounced than in older children.     

Hepatitis B virus infection in medical and health care personnel.

Analysis of 51 cases of hepatitis B virus infection in health care workers admitted as patients to the liver unit over seven years showed three healthy carriers of hepatitis B virus, seven cases of fulminant hepatic persistent hepatitis, 17 cases of chronic active hepatitis (of whom 11 had cirrhosis), and five cases of hepatocellular carcinoma. To date 11 of these patients have died. Only 15 of the 51 patients had a history of direct occupational exposure and only three patients could recall specific inoculation injuries. In contrast, the source of infection was apparent in 32 of 50 consecutive cases of fulminant hepatic failure or acute hepatitis B in nonmedical staff. Since specific inoculation injuries are not the usual mode of infection ion medical staff and since only a few of the patients who are hepatitis B virus carriers will be detected by selective screening of "high-risk" patients, the overall risk of infection can be reduced only by stricter precautions in the handling of any patient''s blood and by the use of hepatitis B virus vaccines for medical staff at high risk.     

Serologic markers for hepatitis B among Marshallese accidentally exposed to fallout radiation in 1954

At least one serologic marker of prior hepatitis B infection (hepatitis B surface antigen, antibody to surface antigen, or antibody to core antigen) was found in 91.7% of 314 Marshallese tested. The prevalence of hepatitis B surface antigenemia (3.3%) in a subpopulation that had resided on Rongelap Atoll at the time of accidental exposure to radioactive fallout from a thermonuclear test in 1954 did not differ significantly from the prevalence in a selected unexposed population (10.5%).     

Incidence of hepatitis non-A,non-B compared with types A and B in hospital patients.

To establish the relative frequencies of types A, B and non-A, non-B hepatitis, stored samples of blood from all the cases of acute viral hepatitis seen over a period of 9 years in a general hospital for adults were classified according to their type by presently available serologic methods. The study included 456 episodes of hepatitis in 447 patients, distributed as follows: 114 episodes of hepatitis A (25%), 282 of hepatitis B (62%) and 60 of hepatitis non-A, non-B (13%). The episodes of non-A, non-B hepatitis were equally distributed between the sexes, suggesting a mode of transmission different from that of hepatitis A or B, which had male/female ratios of 2.4 and 3.1 respectively. The low proportion of hepatitis non-A, non-B may not reflect its real frequency, since it often escapes clinical recognition.     

Lack of evidence of hepatitis D (delta) infection in Newfoundland and Labrador.

Epidemiologic knowledge of hepatitis D virus (HDV) infection is limited. A seroepidemiologic study was undertaken to determine the prevalence of the infection in Newfoundland and Labrador. Between October 1983 and October 1985 over 200 people were recognized through routine serodiagnosis and screening as having hepatitis B seromarkers. A total of 223 serum samples from 186 of these people were tested for anti-HDV. The subjects were mainly asymptomatic carriers of hepatitis B surface antigen or patients with acute or chronic hepatitis B from the native Indian and Inuit and the non-native populations. None of the serum samples were positive for anti-HDV. The absence of anti-HDV in a substantial number of people in the province who are infected with hepatitis B virus is strong evidence that HDV infection is not prevalent in the local population, including native people.     

Non-B hepatitis in Melbourne: a serological study of hepatitis A virus infection.

A study was performed to establish the value of immune adherence haemagglutination tests for antibody to hepatitis A virus in the diagnosis of non-B hepatitis. Infection with hepatitis A virus was confirmed in 14 out of 16 patients from six families and seven out of nine patients in whom the source of infection was unknown. One additional patient, who had had two episodes of jaundice, was shown to have had an attack of hepatitis A followed by an attack of hepatitis B. In patients with acute hepatitis A antibody detectable by immune adherence haemagglutination becomes detectable three or four weeks after the onset of symptoms and reaches peak levels about five weeks later.     

Arthritis and Hepatitis

The evidence relating four clinically distinct rheumatologic syndromes to infection by the hepatitis B virus is reviewed. Acute hepatitis B is not infrequently heralded by a prodromal rash and rheumatoidlike polyarthritis. Chronic active hepatitis B more rarely is associated with transient arthritis or arthralgias. Polyarteritis nodosa may be a manifestation of hepatitis B infection in as many as 40 percent of cases, and recently the syndrome of “essential” mixed cryoglobulinemia has also been linked to infection with this virus. The finding of immune complexes of varying composition, sometimes with the viral antigen or its antibody (or both) contained in both the serum and synovial fluid suggests that these four syndromes are clinical manifestations of immune complex disease resulting from hepatitis B infection.     

Tuberculosis of the lymphatic nodes and coexisting invasion with Toxoplasma gondii]

Six cases of the peripheral lymphatic nodes tuberculosis with positive serologic reactions to Toxoplasma gondii antigen are presented. It was shown, that independently of a complex of clinical examinations histologic examination is decisive for the diagnosis of lymphatic nodes tuberculosis with coexisting toxoplasmosis. A positive serologic reaction with T. gondii antigen in patients with lymphatic nodes tuberculosis may reflect inactive infection with T. gondii. Use of anti-toxoplasmosis drugs may be not necessary in such cases.     

Hepatitis viruses: characterization and diagnostic techniques.

Two human hypatitis viruses have been identified and characterized, but one or more additional agents exist. Hepatitis B virus (HBV) is a complex 42-nm predominantly double-stranded DNA virus with distinct surface and core antigens and an endogenous DNA polymerase. Hepatitis A virus (HAV) is a 27-nm RNA virus with enterovirus-like properties. Progressively more sensitive and specific immunologic assays have been applied to the study of viral hepatitis and are available for routine diagnostic purposes. As a result we recognize distinct serologic response patterns to infection, new antigenic markers, biochemical-biophysical characteristics of the viruses, and their epidemiologic features. Recombinant DNA technology has permitted the cloning of HBV genetic material and gene products in E. coli, but the virus has not been cultivated in vitro. In contrast, successful in vitro cultivation of HAV has finally been accomplished. Application of sensitive serologic tests for HAV and HBV has revealed that "non-A, non-B" agents account for a substantial proportion of transfusion-associated hepatitis as well as hepatitis occurring in the absence of percutaneous exposure. These agents have been transmitted to chimpanzees, and several putative virus antigen-antibody systems have been described; however, a specific association between these virus antigens and non-A, non-B hepatitis has not been established.     

Etiologic structure of viral hepatitis in children based on data from an comprehensive serologic study of hospitalized patients

During a year an overall serological examination of 1,200 children hospitalized with the diagnosis of viral hepatitis was carried out with a view to establish the presence of hepatitis A and hepatitis B markers (anti-HAV IgM, HBsAg, anti-HBs, anti-HBc and anti-HBe IgM) by means of the enzyme immunoassay and radioimmunoassay. The average annual proportion of cases of hepatitis A (61.4%), hepatitis B (20.4%), hepatitis non A, non B (11.2%) and mixed infection (7.0%) among children, as well as seasonal and age-group fluctuations of this proportion, were established. The etiological structure of viral hepatitides, based on commonly accepted clinico-epidemiological diagnostic criteria, was shown to differ from their true etiological structure as determined in accordance with specific serological markers detected in this investigation.     

Outbreak of Hepatitis A on an Offshore Petroleum Platform,Alaska

An outbreak of 8 cases of hepatitis A among the 36-member crew of an offshore Alaska petroleum production platform was linked to a previous outbreak in an urban day-care center. Transmission of hepatitis A on the platform related most plausibly to refrigerated food items contaminated by a cook with mild disease. Control efforts included identifying and treating contacts of case patients who had traveled far from the platform before becoming ill. Early serologic confirmation of diagnosed cases and rapid reporting to public health authorities are essential to prevent disease transmission. Timely investigation can limit the administration of immune globulin to persons at high risk of contracting the disease.     

Hepatocellular carcinoma in urban born blacks: frequency and relation to hepatitis B virus infection.

Chronic hepatitis B virus infection is far less common in urban born than in rural born southern African blacks, who also have a high incidence of hepatocellular carcinoma. A case-control study was carried out to determine the relative frequency of hepatocellular carcinoma and its relation to hepatitis B virus infection in urban born blacks. Three hundred and ninety two black patients with hepatocellular carcinoma and matched controls seen at two city hospitals were classified by questioning as urban born or rural born. The ratio of rural born to urban born blacks among the controls was 1.1:1.0 (207/185), whereas in the patients with cancer the ratio was 4.8:1.0 (324/68) (p less than 0.0001). Analysis of the prevalence of hepatitis B markers in 62 urban born and matched rural born blacks with hepatocellular carcinoma showed no differences in the frequency of current or past hepatitis B virus infection. It is concluded that urban born blacks are less likely than rural born blacks to develop hepatocellular carcinoma, but when they do the tumour is equally likely to be related to infection with hepatitis B virus. The findings lend further support to an important role for chronic hepatitis B virus infection in the aetiology of hepatocellular carcinoma.     

“Silent” Hepatitis B Virus Mutants Are Responsible for Non-A,Non-B,Non-C,Non-D,Non-E Hepatitis

Since the recent introduction of diagnostic kits for hepatitis C and E, some cases of nonA, non-B, non-C, non-D, non-E hepatitis (so-called hepatitis F) have been revealed. We attempted to demonstrate that so-called hepatitis F is caused by hepatitis B virus (HBV) variants. Polymerase chain reaction (PCR) was used to amplify serum HBV DNAs from 20 patients with acute hepatitis and 20 patients with chronic hepatitis who had been diagnosed as having so-called hepatitis F on the basis of conventional serological markers. The PCR technique successfully amplified HBV DNAs in 18 (90%) cases of acute hepatitis and 17 (85%) cases of chronic hepatitis. Sequencing of HBV DNAs of six patients (acute 3, chronic 3) revealed equally a T-to-C mutation of DR2 and an 8-nucleotide deletion of the 3′-terminus of the X gene coding region, giving rise to the generation of a C-terminally truncated X protein and probable damage to the enhancer II/core promoter elements. These mutations of the X gene coding region may lead to suppression of replication and expression of HBV DNAs. Thus virtually all cases of so-called hepatitis F appear to be caused by “silent” HBV mutants, at least in Japan.     

Hepatitis virus vaccines: present status

During the past decade there has been extraordinary progress toward the development of vaccines for the prevention of type A and type B hepatitis. The successful propagation of hepatitis A virus in cell culture in 1979 was followed by the preparation of experimental live attenuated hepatitis A vaccines that have been shown to induce antibody in marmosets and chimpanzees and protect immunized marmosets against challenge with hepatitis A virus. The first human immunization trials will begin in mid-1982. An inactivated hepatitis B vaccine that was licensed in the United States in November 1981 has been shown to be safe, immunogenic, and effective. When this vaccine becomes available for use in July 1982, it will be recommended for persons who are considered to be at increased risk of contracting hepatitis B infection. Future generations of hepatitis B vaccines may be prepared from hepatitis B surface antigen derived from DNA recombinant technology or by in vitro synthesis of HBs Ag determinants by chemical means.     

Acute hepatitis B in patients in Britain related to previous operations and dental treatment.

The frequency of transmission of hepatitis B virus infection from health service staff to patients was assessed from reports of confirmed cases of acute clinical hepatitis in 1980-3. During the four years 4505 reports (91% of the total) included replies to a question about recent operations; 153 patients (3.4%) had this history. Transfused blood or blood products were considered the source for 27 cases (0.06%). Eleven patients (0.02%) were infected in two clusters, both in cardiac surgery units; six were caused by a perfusion technician, who was a symptomless carrier, and five by a surgical registrar during the incubation period of an acute hepatitis B infection. The estimated average annual risk of a patient developing acute hepatitis B as part of a cluster caused by staff during surgical procedures was one in a million operations. For another 11 patients blood transfusion could not be excluded as a source. Where no association between surgery and hepatitis was found the incidence of a history, lay between 2.3 and 2.6%. The Hospital In-Patient Enquiry data showed that about 2.4% of the population had had operations in a six month period. These findings suggest that transmission of hepatitis B infection from staff to patients is rare in Britain and that the small risk could be eliminated by attention to measures to preserve asepsis and by immunising staff at risk.