Epidemiology, prevention and treatment of viral hepatitis with emphasis on new developments.

There are a large number of viruses, such as cytomegalovirus, Epstein-Barr, Herpes simplex, mumps, varicella, yellow fever, etc., known to cause inflammatory disease of the liver, but the term viral hepatitis generally refers to the five well described hepatotropic viruses which are divided into enteral and parenteral groups based on their mode of transmission. Hepatitis A and E viruses are enterically transmitted by the faecal-oral route and do not exist in a chronic carrier state. Hepatitis B, C and D viruses are parenterally transmitted, occur both in the acute and chronic forms, and, when they persist in a chronic carrier state, they serve as a reservoir for infection and give rise to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Hepatitis G virus has recently been described but its significance in the causation of human liver disease is yet to be established. Also, the most recently described TT virus in patients with post-transfusion hepatitis awaits further studies. Acute sporadic and epidemic viral hepatitis are common world-wide, mostly in the developing countries, including Ethiopia, and account for high morbidity and mortality, especially among pregnant women. Chronic infection with hepatitis B virus is a significant problem on a global scale, affecting over 300 million people. Hepatitis C virus infection is probably the most common cause of chronic viral hepatitis, end-stage liver disease and hepatocellular carcinoma in the world, especially in sub-Saharan Africa, including Ethiopia. Therefore, this article will review and highlight the relevant epidemiological, preventive and therapeutic aspects of viral hepatitis with emphasis on new developments and recent data obtained from Ethiopian studies.

Antibody levels in Ethiopian children five years after vaccination with two different doses of hepatitis B vaccine: is there a need for booster vaccine?

It was hypothesized that, following effective initial vaccination, a booster dose of hepatitis B vaccine will not be necessary in areas of hyperendemicity for hepatitis B virus (HBV) infection. A total of 314 Ethiopian children, ranging from two to 14 years old, were alternatively vaccinated with 10 and 20 micrograms hepatitis B vaccine doses, using the initial, one- and six-month schedule. Five years later, 210 of the vaccinees were retested for anti-HBV surface antibody titres. Both 10 and 20 micrograms doses of hepatitis B rDNA yeast vaccine were equally immunogenic and protective against HBV infection for at least five years despite marked reduction of mean antibody levels and geometric mean titres, with 11% of the vaccinees showing antibodies below the protective level. For firm further recommendations a longer follow-up period of vaccinees is suggested.

Phylogenetic analysis of hepatitis D viruses indicating a new genotype I subgroup among African isolates.

Genetic analysis was performed on 13 hepatitis D virus (HDV) isolates from Ethiopia, Somalia, Jordan, Kuwait, Bulgaria, Moldavia, and Sweden. The complete nucleotide sequence and genomic organization are described for the first time for two African HDV isolates. Phylogenetic analysis showed all the African isolates to be intrarelated and to form a novel group within HDV genotype I; the suggested designation for this group is IC. The genetic distance to previously described type I isolates was about 0.15. The HDV genotype I isolates (total of 22 examined) phylogenetically formed three clusters, each of them corresponding to certain geographic regions; the "western" group consisted of six HDV isolates from western Europe and the United States plus one from Kuwait; the "eastern" group consisted of two isolates from Moldavia and one each from Bulgaria, Nauru, mainland China, and Taiwan; and the "African-Middle East" group consisted of six HDV isolates from Ethiopia and one from Somalia, Jordan, and Lebanon.

HIV-1 infection in relation to educational status, use of hypodermic injections and other risk behaviours in Ethiopian sailors.

Information on the prevalence and risk factors for HIV infection among sailors is generally scarce. The objectives of the study were to determine the prevalence and risk factors for HIV-1 infection among sailors in Ethiopia. A cross-sectional study was carried out in a population of sailors identified from their employment records. Two hundred and sixty sailors were personally interviewed to obtain information on risk factors. Blood samples were collected for the determination of antibodies against HIV-1 infection by ELISA with confirmation by Western blot. The prevalence of HIV-1 infection was 9.6% and the prevalence was observed to decrease with increasing level of education. The risk of acquiring infection was also found to increase with the use of hypodermic injections (OR = 3.42, 95% CI: 1.19 to 9.80). Fourteen percent of the studied population reported condom use. However, the use was irregular. We did not find marital status and consumption of alcohol to be associated with HIV-1 infection. The high prevalence of HIV-1 infection in this population is alarming. Specific education programmes targeted to this group need to be established in order to reduce the increasing risk of infection in this population and the spread of infection to other segments of the population.

Helicobacter pylori, gastritis and non-ulcer dyspepsia in Ethiopian patients.

The aim of this study is to find out the prevalence of Helicobacter pylori infection in patients with nonulcer dyspepsia (NUD) and asymptomatic controls and to see if there is an etiological association between gastritis, NUD and Helicobacter pylori. One hundred thirty six patients with NUD and 71 controls had six endoscopic biopsies from different sites of the gastric mucosa for histological diagnosis. Helicobacter pylori was looked for in all biopsy specimens utilizing half Gram, Giemsa and Gimenez staining techniques. Type B chronic gastritis was detected in 96% of the NUD cases and in 100% of the asymptomatic controls (P > 0.05). Helicobacter pylori was found in 82 (65%) patients with NUD and in 38 (56%) asymptomatic controls (P > 0.05). Type B chronic gastritis is almost universal in both NUD cases and asymptomatic controls. There is no difference in the prevalence of Helicobacter pylori infection between the two groups. The absence of Helicobacter pylori in a significant number of patients (36%) and controls (45%) with gastritis contradicts the etiological association between Helicobacter pylori and gastritis reported by others, suggesting that in Ethiopia there may be a chronic environmental gastritis which may not be helicobacter-related. There is no correlation between NUD and Type B gastritis, and between symptoms and Helicobacter pylori infection in this population.

Comparison of diagnostic methods for detection of Helicobacter pylori.

Of two hundred Ethiopian patients with dyspepsia, multiple biopsies were taken from the antrum of the stomach. Helicobacter pylori was cultured from 85% of duodenal ulcer and in 75% of chronic antral gastritis patients. The overall Helicobacter pylori positivity was 70%. The sensitivity, specificity, positive and negative predictive values of the tests as compared to culture were as follows, respectively: direct urease test 100%/87%/95%/100%, direct gram stain 60%/98%/99%/51%, histological gram stain 66%/97%/98%/56%, Giemsa stain 100%/97%/99%/100% and Gimenez stain 100%/87%/95%/100%. It is concluded that gram staining of direct tissue smear or histology is an insensitive method in the diagnosis of Helicobacter pylori. All the other tests, are shown to be valid. Urease test is an excellent test for provision of presumptive diagnosis of Helicobacter pylori while awaiting confirmation either by culture of histology.

Age at acquisition of Helicobacter pylori infection: comparison of a high and a low prevalence country.

Helicobacter pylori (HP) is now generally accepted as the main aetiological agent in chronic active gastritis and peptic ulcer. Infection with HP is widespread, but the routes of transmission are still unclear. Several studies have shown increasing prevalence of antibodies against HP with age. In developing countries, age at peak incidence of seroconversion is probably considerably lower than in developed countries. We performed a cross-sectional study to determine the age at maximum incidence of seroconversion to HP in a high-prevalence country (Ethiopia) and in a low-prevalence country (Sweden). Sera from 242 Ethiopian children, aged 2-14 years and from 295 Swedish children aged 1-15 years were analysed using an enzyme linked immunosorbent assay (ELISA) for detecting immunoglobulin G (IgG) antibodies. In Ethiopia, a comparison was made of a local and a reference strain for preparation of the antigen, but there was little difference in outcome. A comparison between antigen prepared from the reference strain and the pooled antigen used in the Swedish study also showed little difference. The sharpest rise in seroprevalence was found in the age range 2-4 years. Among 4-year-olds, some 60% had already seroconverted, and among 12-year-olds almost 100% had done so. In Sweden, the sharpest rise appeared between the ages of 9 and 10 years. Above 10 years of age seroprevalence was around 20%. Infection with HP is acquired in early childhood in Ethiopia, but somewhat later, although still before the teens, in Sweden. To determine properly the risk factors for infection with HP, possible exposure must be assessed around the age of seroconversion, since seropositivity may remain for a long time but environmental factors may have changed since primary infection.

Hepatitis C virus infection and chronic liver disease in Ethiopia where hepatitis B infection is hyperendemic.

To assess the prevalence and possible aetiological association of hepatitis C virus (HCV) with chronic liver disease and hepatocellular carcinoma (HCC), antibodies to HCV (anti-HCV) were determined by enzyme-linked immunosorbent and recombinant immunoblot assays in 500 healthy volunteer blood donors, 14 patients with chronic hepatitis, 156 cirrhotics and 68 cases of hepatocellular carcinoma (HCC) in Ethiopia. The prevalences of anti-HCV were 1.4%, 21%, 36% and 46%, respectively. There was no apparent risk factor to suggest the mode of transmission of HCV. Of the 238 patients, 65 (27%) had circulating hepatitis B surface antigen (HBsAg) (denoting current infection), 131 (55%) had antibodies to hepatitis B surface (anti-HBs) and/or core (anti-HBc) antigens (past infection) and 42 (18%) had no hepatitis B virus (HBV) marker. Anti-HCV antibodies were present in only one patient with HBsAg, in 54% with past infection and in 68% of those without HBV markers. Thus, HCV infection was uncommon in HBsAg-positive patients but significantly more common in patients with chronic liver disease and HCC who had evidence of past HBV infection or no marker for HBV infection. HCV infection appeared to be a more common cause of chronic liver disease and HCC than HBV infection in this population. However, considering the high prevalence of overall exposure to HBV infection (68% in healthy blood donors and 82% in those with chronic liver disease, including HCC), HBV is significant in terms of national preventive strategies.

Hepatitis E virus infection in pregnancy in Ethiopia.

Thirty-two pregnant and 34 nonpregnant Ethiopian women between 15 and 45 years of age with sporadic acute viral hepatitis were studied consecutively. Demographic data including family size, monthly income and nutritional status as well as hepatitis virus markers were compared in the pregnant and nonpregnant groups. Only 3 nonpregnant women had hepatitis A infection. Hepatitis B infection was diagnosed in 4 pregnant and 9 nonpregnant women. Nineteen (59%) pregnant women had hepatitis E virus (HEV) infection as compared to 7 (22%) in the nonpregnant group (Relative risk = 2.88; 95% Confidence interval = 1.4-5.9). The remaining 9 pregnant and 15 nonpregnant women had non-A, non-B, non-E (NANBNE) hepatitis. Of a total of 10 maternal deaths, 9 occurred (7 during the third trimester) in the pregnant group, 8 in association with HEV infection. Two deaths, one from each group, were due to NANBNE hepatitis. In addition to 6 foetal losses as a result of maternal death, there were 2 foetal deaths and 7 premature deliveries as a direct result of acute viral hepatitis, all but 2 associated with HEV infection. Comparison of socioeconomic and nutritional status, clinical features, mean aminotransferase and bilirubin levels did not show differences in the two groups. Thus, pregnant women are more at risk to acquire HEV infection than nonpregnant women and HEV infection in this group of Ethiopian pregnant women is associated with high maternal mortality and neonatal complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic liver disease in Ethiopia: a clinical study with emphasis on identifying common causes.

Between July 1986 and April 1989, 334 hospitalized adult Ethiopian patients with chronic liver disease were studied according to a protocol to define their clinical features and to identify risk factors with the aim of preventive intervention. Of these, 14 had chronic hepatitis, 208 cirrhosis and 112 hepatocellular carcinoma (HCC). Both clinical and histological diagnostic criteria were employed. A detailed questionnaire was used to document demographic and clinical data. A common clinical presentation among patients with chronic hepatitis was darkening of the face and hands with or without hypertrichosis of the face and blisters over the dorsi of the hands. This overt or latent form of porphyrea cutanea tarda (PCT) responds to chloroquine. Patients with cirrhosis of the liver commonly present for the first time with ascites, splenomegaly, haematemesis and/or melena from oesophageal varices, and mental changes due to hepatic encephalopathy. Overt or latent forms of PCT are also common features. Peculiar to these cirrhotics is the rarity of spider naevi, gynaecomastia, testicular atrophy, Dupuytren's contracture, parotid gland enlargement and clubbing of the fingers. Exhaustion, loss of appetite, rapid loss of weight, right upper quadrant and/or epigastric pain (all often of less than 6 months' duration, a big, hard, tender and grossly nodular liver with bruit, signs of portal hypertension, and/or hepatic encephalopathy, in a young male with a rapid down hill course characterize the Ethiopian patient with HCC. Serum anti-nuclear factor, anti-mitochondrial anti-bodies and anti-smooth muscle anti-bodies were absent in those with chronic hepatitis and were uncommon in the cirrhotics and HCC cases. One or more hepatitis B virus markers were found in 86% of chronic hepatitis, 88% cirrhosis and 78% HCC and the HBsAg carrier state was found in 36%, 29% and 23%, respectively. Among the HBsAg carriers, HBeAg positivity was less common than anti-HBe but anti-HDV was significantly higher than in the healthy general population. Alphafetoprotein (AFP) levels greater than 500 mg/ml were present in 16 (8%) cirrhotics and 58 (52%) patients with HCC. Histologically, 3 of the chronic hepatitis patients had progressed to cirrhosis, 8 of the cirrhotic patients had chronic active hepatitis and 85% of HCC cases occurred in a background of macronodular cirrhosis. Three cirrhotics developed HCC during follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute sporadic viral hepatitis in Ethiopia: causes, risk factors, and effects on pregnancy.

One hundred and ten consecutive cases of acute sporadic hepatitis among Ethiopian patients were studied to define viral causes, identify risk factors, and analyze demographic and clinical data. IgM antibodies to hepatitis A virus were found in nine patients (8%), and hepatitis B surface antigen and IgM antibodies to hepatitis B core antigen were found in 22 (20%); these findings were considered evidence of acute hepatitis A and hepatitis B, respectively. Sera from the remaining 79 patients were tested for antibodies to hepatitis E virus by a blocking fluorescent antibody test. Thirty-six (33%) of these patients were seropositive, as compared to 4 (7%) of 59 healthy control subjects; for 43 patients (39%), the cause of the acute sporadic hepatitis was unidentified. Twenty-one (19%) of the patients had antibodies to hepatitis C virus, as determined by ELISA. Demographic, biochemical, and clinical data (except in regard to sequelae) were comparable for the different types of infections. The study subjects included 32 pregnant women, 19 (59%) of whom had hepatitis E virus infection; these infections caused death in eight of the women (mostly in the third trimester) and 10 fetal complications. Thus, hepatitis E virus is a common cause of acute sporadic viral hepatitis in Ethiopian patients, and its occurrence during pregnancy is associated with high maternal and fetal morbidity and mortality.

Outbreak of acute hepatitis E virus infection among military personnel in northern Ethiopia.

An outbreak of acute hepatitis E virus (HEV) infection occurred from October 1988 to March 1989 in military camps in northern Ethiopia. The epidemic was waterborne and entirely confined to military men, of whom 423 hospitalized, icteric patients were studied. The clinical course was mild and short, without any fulminant hepatitis or death. All sera tested for anti-HAV-IgM were negative and among 54 (13%) patients who were positive for HBsAg, 7 (2%) were positive for anti-HBc IgM. On the other hand, 28 of 30 (93%) patients had antibodies against hepatitis E virus (anti-HEV) in contrast to 1 of 29 (3%) asymptomatic controls (P less than .01). The need for an easily available, inexpensive serologic test for HEV infection, protection of water supplies from fecal contamination, adequate chlorination and/or boiling of drinking water, and health education about personal and environmental hygiene, especially in communities at high risk, is emphasized.

Immunogenicity, reactogenicity and comparison of two doses of recombinant DNA yeast-derived hepatitis B vaccine in Ethiopian children.

Hepatitis B virus infection and its sequelae, chronic hepatitis, cirrhosis of the liver and primary hepatocellular carcinoma (PHC), are important medical problems in Ethiopia. There is a possibility to prevent these by mass immunization of neonates and children. To achieve this, the cost of the hepatitis B vaccine must be possible within the limited health budget of the country. This study, therefore, was conducted to find out comparative safety and immunogenicity of two doses, 10 mcg and 20 mcg, of recombinant DNA yeast-derived hepatitis B vaccine in children, 2-14 years old. Three hundred and fourteen non-immune children, from an initial sample of 380 children, were grouped into those below and those above 8 years of age. Each group was further subdivided into boys and girls and each group was given either 10 mcg or 20 mcg hepatitis B vaccine, alternately, using the 0-1-6 months schedule. Anti-HBs titres were determined at one, two and seven months. Side effects were recorded by parents for three days following each injection. Comparison of seroconversion rates (97-100%) and anti-HBs geometric mean titres (3421-6336) of boosted vaccinees in the different sex, age and dose groups showed no significant differences. There were minor side effects recorded in 76 children. Therefore, the 10 mcg and 20 mcg doses of recombinant DNA yeast-derived hepatitis B vaccine are equally safe and highly immunogenic in children 3-14 years of age.

Immunogenicity of hepatitis B vaccine simultaneously administered with the expanded programme on immunisation (EPI).

To assess the immunogenicity of hepatitis B vaccine simultaneously administered with the Expanded Programme on Immunisation (EPI) vaccines, a total of 300 consecutive infants, ranging in age between 6 weeks and 6 months, were alternatively assigned to the revised EPI and to EPI plus plasma-derived hepatitis B vaccine (Hevac B Pasteur). Four dosages (2 mcg or 0.5 ml each) of hepatitis B vaccine were given intramuscularly. HBsAg, anti-HBc, and anti-HBs were determined at day 0 and at day 210 in both groups by radioimmunoassay methods. The anti-HBs titre levels and geometric mean titres (GMTs) were determined at day 180 and day 210. There were three new hepatitis B virus infections in the control group and none in the study group by day 210. The seroconversion rates in the study group were 66% at day 180 and 84% at day 210, the respective GMTs being 116 and 940. Although the duration of observation is short (7 months) and the difference in the rate of infection between the two groups is not statistically significant (P greater than 0.05), the immunogenicity of the vaccine appears to be good. The simultaneous administration of hepatitis B vaccine and the EPI vaccines is logistically ideal. However, we suggest a further study using a larger dose of the Hevac B Pasteur vaccine to find out if a higher seroconversion rate than the 84% observed in this study could be achieved.

The demographic, social and clinical presentations of one hundred Ethiopian patients with human immunodeficiency virus (HIV) infection.

The demographic, social and clinical presentation of 100 HIV positive patients hospitalized in Tikur Anbessa Hospital, Addis Ababa, Ethiopia, between 1986 and 1989 are described. The mean age is 38.2 years with a range of 16 to 58. Over 75% of the patients are under 40 years. They came from ten different regions of Ethiopia. Only 82% of the patients fulfil the provisional World Health Organization clinical case definition of AIDS (acquired immunodeficiency syndrome). Tuberculosis is the commonest infection, presenting in unusual and aggressive ways. However, response to chemotherapy is similar to that in HIV-negative patients. It is recommended that all patients with unusual and aggressive tuberculosis should be screened for HIV and Mantoux-positive HIV carriers should receive INH prophylaxis. Also, all non-Hodgkin's lymphoma cases should be tested for HIV. Kaposi's sarcoma was not seen (see Addendum). As HIV infection is spreading rapidly and diagnostic facilities are limited, physicians and other health workers must develop a high index of suspicion to test for HIV among high risk groups, such as prostitutes, individuals having contacts with prostitutes, single, divorced and unemployed women living in towns and truck drivers, when they present with significant weight loss, unexplained and prolonged fever and diarrhoea, lymphadenopathy and oral thrush. Also, facilities and expertise for diagnosing opportunistic infections should be available in hospitals to prolong the lives of patients with AIDS.

Ceftriaxone in the treatment of septicaemia due to multiple drug resistant bacteria.

Ceftriaxone, a highly effective, B-Lactamase resistant broad spectrum parenteral cephalosporin was used in the treatment of 26 consecutive patients with clinically and/or bacteriologically resistant infections at the Addis Ababa University Tikur Anbessa and Ethio-Swedish Paediatric Teaching Hospitals. The patients who had failed to respond to a combination of two or more previously appropriate antibiotics were treated with ceftriaxone administered in two divided doses (daily 50-100 mg/kg) in children and a single dose of 2-3 gm in adults for an average duration of 9.9 days. Of the 21 evaluable cases 16 (76%) were cured, three died and two developed superinfection with Pseudomonas and Staphylococcus species. Primary pathogenic bacteria were eradicated from all the 21 bacteraemic patients on the third day of therapy. Twelve of the 21 patients had serious underlying conditions. Except for the two superinfections, the results of the trial confirm that ceftriaxone is a very potent and effective agent in the treatment of resistant bacteraemic infections. No significant adverse effect of the drug was encountered during the therapy.

Age-specific prevalence of hepatitis A virus antibody in Ethiopian children.

Three groups of individuals in Ethiopia, with different socioeconomic status, were studied demographically and serologically to determine the age-specific prevalence of antibody to hepatitis A virus (anti-HAV). A total of 959 subjects, 89% of whom were children under 15 years of age, were tested for anti-HAV by radioimmunoassay. Evidence of infection started early, found in 50% of the population before 5 years of age, increased rapidly with age and became universal after 15 years of age. A comparison of anti-HAV prevalences between 2 socioeconomic groups (children of health professionals versus children of lower income group) revealed a significant difference (p less than 0.01). These data show that HAV infection in Ethiopia is widespread and that environmental and socioeconomic factors play a major role in its transmission. The widespread prevalence of anti-HAV and anti-HBs also suggest that non-A, non-B virus(es) may be a major cause of the commonly observed sporadic cases of acute viral hepatitis in adult Ethiopians.

Laparoscopic evaluation of ascites and other abdominal conditions in Ethiopia.

The purpose of this study is to evaluate the appropriateness of laparoscopic examination in Ethiopia where chronic liver diseases and tuberculous peritonitis commonly present with ascites. A total of 240 patients were examined consecutively. The indications were ascites (62%) hepatomegaly (29%), splenomegaly (22%), oesophageal varices (31%), abdominal masses (6%) and miscellaneous conditions (5%). Laparoscopic findings included cirrhosis with or without primary hepatocellular carcinoma (PHC) in 72% and tuberculous peritonitis in 6% of 232 successfully examined cases. Biopsies were possible in 165 cases. When all 144 patients with ascites were separately analyzed, 82% were due to cirrhosis of the liver with or without PHC and 9% tuberculous peritonitis. There was a good correlation between laparoscopic and histological diagnosis. Though invasive, the procedure carries low morbidity and the diagnostic yield is high. The laparoscope, therefore, should be considered as an appropriate technology for developing countries.