Hepatitis A virus in the Middle East and North Africa region: a new challenge.

During the past three decades, a gradual shift in the age of infection with hepatitis A virus (HAV) from early childhood to adulthood has been observed. There is a general lack of updated data on HAV burden of disease, incidence and age-specific seroprevalence in countries of the Middle East and North Africa (MENA) region. The aim of this article is to review the published data on anti-HAV seroprevalence, an important tool to monitor infections rates, in countries of the MENA region and associated risk factors including water and socioeconomic data when available. Data on anti-HAV seroprevalence were found for 12 of 25 MENA countries. We show that MENA countries, similar to other areas in the world, have a clear shift in HAV incidence with a decline among young age groups and an increase among adults and older individuals. This would likely be associated with increased morbidity and increased risks of outbreaks among younger age groups. Consequently, the continuous surveillance of hepatitis A cases and the inclusion of hepatitis A vaccine in the expanded immunization programmes are needed in countries of the MENA.

Hepatitis C virus infection in the Middle East and North Africa "MENA" region: injecting drug users (IDUs) is an under-investigated population.

PURPOSE: Investigation of the injecting drug users (IDUs) population is becoming extremely critical and timely in light of the recent evidence that IDUs now act as the core of hepatitis C virus (HCV) epidemics in developed countries. The purpose of this article, therefore, is not only to review the epidemiology of HCV in the Middle East and North Africa (MENA) region, but also to see whether IDUs were adequately studied and whether harm reduction strategies to be applied for their protection have been set. METHODS: A literature review was carried out of articles published within the last decade on HCV infection. RESULTS: The gathered data showed that the population of IDUs is severely under-investigated throughout the whole region, possibly due to religious and cultural impediments. CONCLUSION: In order to reduce the risk of HCV infection in IDUs, a set of recommendations are advanced emphasizing the urgent need for bio-behavioral studies in this population in order to help identify the source and mode of transmission and the genotypes of HCV involved. These results may allow the development of effective and, yet, socially acceptable intervention strategies. We believe that the role which IDUs play in sustaining HCV infection is also an under-investigated topic in many developing countries. Similar reviews and, hence, interventions should be initiated in these regions.

Occult hepatitis B virus infection in HIV-infected Lebanese patients with isolated antibodies to hepatitis B core antigen.

The presence of hepatitis B virus (HBV) serological markers have been investigated in 101 Lebanese patients (69 men, 32 women; mean age 32.7 +/- 1.7 years) infected with human immunodeficiency virus type 1 (HIV-1). Seven patients (6.9%) were HBsAg carriers compared with 54 patients (53.5%) who had no evidence of exposure to HBV infection. Twenty-four patients (23.8%) had anti-HBc alone as a serological marker compared with four patients who were positive for anti-HBs alone and 12 patients (11.9%) who were anti-HBc and anti-HBs-positive. Occult HBV infection (presence of HBV DNA in the absence of HBsAg) is found to be relatively high (28.7%) in HIV-infected Lebanese patients and the overwhelming majority (83.3%) of those who were positive for anti-HBc alone had a detectable HBV DNA in their serum. However, none of our HIV-positive patients with occult HBV infection had abnormal alanine aminotransferase level, which also raises the question as to whether occult HBV plays a role in the aetiology of liver disease in HIV-infected patients. Further, studies on the association between HBV DNA levels and markers of liver function in addition to data on liver biopsy would help in answering this question.

Occult hepatitis B virus infection in Lebanese patients with chronic hepatitis C liver disease.

Occult hepatitis B virus (HBV) infection, characterised by the presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg), was investigated in 98 Lebanese patients with chronic hepatitis C liver disease and 85 control subjects recruited from eight institutions in different parts of the country. The prevalence of occult HBV infection ranged from 11.9% to 44.4% in hepatitis C virus (HCV)-infected patients and it increased with increasing severity of the liver disease. The overall rate of HBV DNA in our 98 HCV-infected patients was 16.3%. On the other hand, the rate of HBV DNA was 41.0% in anti-HBc alone positive patients compared to only 7.1% in healthy controls who were also anti-HBc alone positive (p < 0.001). Moreover, the prevalence HBV DNA increased with increasing severity of the liver disease, but this increase was only marginally significant and, perhaps, could have been significant if more patients were involved in the study. Although Lebanon is an area of low endemicity for both HBV and HCV, occult HBV infection is common in HCV-infected patients. The presence of HBV DNA, therefore, presents a challenge for the effective laboratory diagnosis of hepatitis B, particularly if polymerase chain reaction (PCR)-based HBV detection methods are not used.

Hepatitis B virus DNA in serum of 'anti-HBc only'-positive healthy Lebanese blood donors: significance and possible implications.

Transmission of HBV infection through transfusion of HBsAg-negative blood has been documented. It is evident that low levels of HBV-DNA remain detectable in serum and liver tissue of some patients who clear HbsAg, and that the detection rate is highest in individuals who are 'anti-HBc positive alone'. This study was designed to assess the frequency and clinical significance of 'anti-HBc alone' in Lebanese blood donors. A total of 5511 blood donor samples from three major hospitals representing most regions of the country were tested for anti-HBc, amongst other screening tests. Samples positive for 'anti-HBc alone' were then tested for HBV-DNA and any positive for HBV-DNA were then genotyped and investigated for hepatitis B viral load. The study showed that 203 (3.7%) of randomly selected Lebanese blood donors were confirmed as 'anti-HBc alone'. Of these, 11 (5.4%) were HBV-DNA positive as detected by nested PCR. All samples had HBV-DNA levels below 400 copies/ml and all were genotype D. It can be concluded that HBV was present, although the circulating amount of virus was below the detectable limit for the assay used. Therefore, routine screening for anti-HBc may be required in Lebanese blood donation centres as an additional preventive measure for controlling transmission of HBV via blood transfusion.

Genotypes of hepatitis C virus (HCV) among positive Lebanese patients: comparison of data with that from other Middle Eastern countries.

Recently we identified hepatitis C virus (HCV) genotype 4 as the principle genotype among Lebanese thalassaemics. In an attempt to confirm the predominance of genotype 4 in Lebanon and perhaps in the Middle East, genotyping was attempted on 142 HCV-infected Lebanese patients from five different hospitals in the country. These included 38 HCV-positive patients with symptomatic liver disease who were referred to gastroenterologists and 104 HCV-positive patients with no symptoms of liver disease: 27 patients with thalassaemia, 30 patients on haemodialysis, 32 multi-transfused and 15 intravenous drug users. HCV genotyping was performed on PCR HCV RNA-positive samples using a commercial line probe assay (LiPA; Innogenetics, Ghent, Belgium). HCV genotype 4 is found to be the predominant genotype among HCV-infected Lebanese patients (ranging from 34.2% to 53.3%) followed by 1a (ranging from 12.5% to 43.3%) and 1b (ranging from 8.0% to 34.4%). In patients with symptomatic liver disease, however, genotype 4 (34.2%) was preceded by genotype 1a (39.5%). The predominance of HCV genotype 4 in our population (45.7%) confirms the predominance of HCV genotype 4 in Lebanon and most of the Arab countries in the Middle East but contrasts with data reported from non-Arab Middle Eastern Countries as can be seen from the literature review. Implications of genotyping for clinical outcome of HCV infection, response to treatment as well as for vaccine development are discussed.

Current prevalence of hepatitis delta virus (HDV) infection and the range of HDV genotypes in Lebanon.

Recently the prevalence of hepatitis B virus (HBV) genotypes and the association between these genotypes and the clinical status of HBV-infected patients were recently investigated in the Lebanese population. The aim of the additional study reported here was to determine the current prevalence of hepatitis delta virus (HDV) infection and the range of HDV genotypes in this Lebanese population. Two hundred and fifty-eight HBsAg-positive patients (107 asymptomatic blood donors, 92 with chronic hepatitis, 24 with cirrhosis, 15 with hepatocellular carcinoma, 20 patients on haemodialysis) from ten medical centers in Lebanon were tested for antibody to hepatitis D virus (anti-HDV). Those testing positive were analysed further for HDV-RNA and for genotyping by reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). Three samples (1.2%) were anti-HDV positive and out of these, only one was HDV-RNA positive (0.6%) and was analysed as HDV genotype I. Our results point to a low endemicity of HDV in the Lebanese population which is in sharp contrast to data reported from Lebanon 20 years ago and to the situation in neighbouring Arab and non-Arab countries in the Mediterranean region. HDV genotype I seems to be the predominant genotype in Lebanon and the Middle East.

Distribution of hepatitis C virus genotypes in the Middle East.

It is well established that hepatitis C develops into cirrhosis of the liver and hepatocellular carcinoma (HCC) both of which are fatal diseases. The World Health Organization estimates that there are at least 21.3 million hepatitis C virus (HCV) carriers in the Eastern Mediterranean countries, which is close to the number of carriers estimated in the Americas and Europe combined. With such a high disease burden of HCV infection in this part of the world, and in light of the new evidence that genotypes may influence the outcome of antiviral therapy, the focus of this review is on the epidemiology and distribution of HCV genotypes in the Eastern Mediterranean countries. Accumulated data show that there are two main patterns for the distribution of HCV genotypes in the Middle East: in the first pattern, genotype 4 is prevalent in most of the Arab countries, and in the second pattern, genotype 1a or 1b predominates in the non-Arab countries. Results from the limited number of clinical trials on the treatment of chronic HCV genotype 4 using peginterferon alfa-2b in combination with ribavirin are encouraging. However, efforts to develop more effective antiviral therapies and the establishment of an effective HCV vaccine remain the largest challenges for the near future.

Frequency and significance of antibodies against hepatitis B core (anti-HBc) antigen as the only serological marker for hepatitis B infection in Lebanese blood donors.

During a 2-year period, blood samples from 2505 Lebanese blood donors were chosen at random, at various periods of time at one blood donation centre (Hotel Dieu de France, Beirut, Lebanon) and were screened for markers of HBV infection (HBsAg, anti-HBc and anti-HBs). The study showed HBsAg positivity of 0.6% and an overall exposure rate to HBV of 10.0%. Out of the 2505 blood donors screened, 56 (22%) were found to be 'anti-HBc alone' positive which is almost four times the HBsAg positivity. The 56 'anti-HBc alone' samples were retested by another ELISA kit commercially available and 54 samples were 'anti-HBc alone' positive by both assays. The 54 samples had no serological markers as evidence of infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Only seven (13%) out of the 54 samples were HBV DNA positive by PCR and all were HBV genotype D. All seven HBV DNA-positive samples had HBV DNA levels below 400 copies/ml. Although any circulating HBV DNA among our 'anti-HBc alone' blood donors was below the detection limit of our Amplicor Monitor assay, some of these samples had circulating virus. A national study, where a larger number of blood donors from different blood donation centres across the country will perhaps determine whether screening for anti-HBc in addition to HBsAg detection is needed in Lebanese blood donors.

Exposure rates to hepatitis C and G virus infections among HIV-infected patients: evidence of efficient transmission of HGV by the sexual route.

The importance of sexual transmission in the epidemiology of hepatitis G virus (HGV) and hepatitis C virus (HCV) was evaluated in two groups of HIV-1-positive Lebanese patients. Members of one group (90 patients) were HIV-1-infected via sexual route and denied intravenous drug (IVD) use, while members of the other group (28 patients) became HIV-1-infected parenterally and confessed frequent IVD use. The overall prevalence of HGV infection was relatively high in both groups and with no statistically significant difference between them (28% among IVD users vs 32% among the non-IVD users) despite the fact that non-IVD users were significantly older (32.7 +/- 1.7 years) than the IVD users (24.0 +/- 1.4 years) (P < 0.01). Conversely, there was a clear association between IVD use and HCV infection (25% for IVD users vs 7% for non-IVD users) despite the significantly lower age of the IVD users. These results point to the efficient transmission of HGV via the sexual route, while the transmission of HCV is mainly via the parenteral route. CD4+ lymphocyte counts were known on only 82 HIV1-infected patients. Although the number of HGV-RNA-positive patients (three) was small compared with anti-HGV-positive patients (24), a relationship was not found between CD4+ lymphocyte counts and the presence of HGV-RNA in the HIV-1-positive patients. The role of HGV in causing significant liver disease is still under dispute.

Hepatitis C virus infection in Lebanese patients with B-cell non-Hodgkin's lymphoma.

Several studies from many countries have reported a high prevalence (> 9%) of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin lymphoma (B-NHL) suggesting a possible etiological role of HCV in the development of B-NHL. Data from the United Kingdom and Turkey, however, did not confirm these observations. To determine the prevalence of HCV infection in patients with B-cell lymphoma in Lebanon, a controlled study was conducted in which 318 Lebanese patients were investigated. These included 35 patients with B-NHL, 63 patients with various malignant conditions (control group 1) and 220 patients with non-malignant conditions (control group 2). Samples were tested in duplicates for antibodies to HCV (anti-HCV) by enzyme-linked immunosorbant assay (ELISA). None of the 318 patients investigated were anti-HCV positive. Based on our findings, it can be concluded, that, there is no sufficient evidence to indicate that HCV plays role in the development of B-NHL in Lebanese patients. Predisposing factors in lymphoproliferative disorders are numerous including both genetic and environmental factors that could vary from one geographic region to another.

Infection with hepatitis B and C viruses and human retroviruses (HTLV-I and HIV) among high-risk Lebanese patients.

Three groups of Lebanese patients (haemophiliacs, patients on cycled cancer chemotherapy who were regularly receiving blood transfusions, and intravenous drug users) and a control group of healthy blood donors were checked for markers of infection with hepatitis viruses (B and C) and human retroviruses (HIV and HTLV-I). Compared with the controls, all three groups of patients were more likely to be seropositive for antibody to hepatitis C virus (anti-HCV), and the haemophiliacs and cancer patients (but not the relatively young drug users) were more likely to be seropositive for hepatitis B virus (HBV). All the haemophiliacs and cancer patients found to be carrying the surface antigen of HBV (HBsAg) and/or to be seropositive for anti-HCV had given the same result when tested before the screening of blood and blood products for HBsAg and anti-HCV became routine practice in Lebanon (a decade before the present study). The four intravenous drug users (IVDU) found seropositive for HBV (two cases) or anti-HCV (two cases) had seroconverted in the 2 years prior to the present study. In addition to highlighting the problem of HCV infection among IVDU, the present results emphasise the need for the careful screening of donated blood for all blood-borne viruses, and for the exclusive use of disposable equipment in the management of cancer patients. The anti-HBV vaccination of IVDU is recommended but only the results of further clinical evaluation will show whether the similar vaccination of patients on cycled cancer chemotherapy is of value. Although none of the patients or controls was found positive for anti-HIV-1, anti-HIV-2 or anti-HTLV-I, the routine screening of blood and blood products for these viruses (particularly for HIV) should remain mandatory.

HTLV-I and HTLV-II infections in volunteer blood donors and high-risk groups in Lebanon.

A serosurvey for Human T-cell Lymphotropic virus type 1 (HTLV-I)/HTLV-II was conducted in 1,900 blood donors, 120 pregnant women and 436 high-risk group patients in Beirut, Lebanon. One of the 1,900 blood donors was anti-HTLV-I/II-seroreactive on screening by enzyme immunoassay (EIA) but was indeterminate by Western blot and negative by polymerase chain reaction. None of the other 556 subjects studied was seroreactive by EIA. The credibility of the zero prevalence of HTLV-I/II infection among the Lebanese blood donors is supported by the absence of seroreactivity of antibodies in the multiply transfused patients. It seems therefore that the prevalence of HTLV-I/II appears to be less than 1 in 2,456 in the Lebanese population and hence, HTLV-I/II infection does not appear to require routine screening in Lebanon.

Hepatitis-C-virus genotypes and hepatitis-G-virus infection in Lebanese thalassaemics.

Exposure to hepatitis C virus (HCV), hepatitis G virus (HGV) and the carrier 'rate' for hepatitis B virus (HBsAg) were investigated in thalassaemia patients in Lebanon, a group that has not been studied in the past. The HCV genotypes and their distribution in the 395 thalassaemics, all of whom had been registered at the Chronic Care Center (CCC) in Hazmieh since 1996, were also studied. Of the 55 samples (14%) found positive for anti-HCV, 19 were also positive for HCV RNA. The 19 samples of HCV RNA were mostly of genotype 4 (37%), followed by 1a and 3a (21% each), lb (16%) and 2b (5%). Most (14; 74%) of the 19 HCV-RNA-positive samples, but only 13 (36%) of the 36 samples that were negative for HCV RNA although anti-HCV-positive, were positive for anti-HGV. Among 100 anti-HCV-negative samples, eight (8%) were anti-HGV positive. Only one (0.28%) of all 395 patients investigated was found to be HBsAg-positive. All of the HBV- and HCV-positive patients had initially been found positive in 1996, when they were first registered at the CCC, and none of the remaining patients had seroconverted since. As none of the patients had been checked for anti-HGV until the present study, the history of their exposure to HGV was unknown. These results emphasise the importance of screening all blood donations collected in Lebanon for HBsAg and anti-HCV. This and stringent infection-control measures are necessary steps to limit the spread of HBV, HCV and perhaps HGV to thalassaemics.

Hepatitis G virus (HGV) infection in Saudi dialysis patients and healthy controls.

BACKGROUND: Viral hepatitis is a global health problem with a high mortality rate. End stage renal disease (ESRD) patients have a high prevalence of Hepatitis B and C virus infection. Present study was done to identify the prevalence and course of a new isolate Hepatitis G virus (HGV) infection in Saudi dialysis patients. METHODS: The pattern of viral hepatitis infection (HBV. HCV and HGV) was investigated in 109 Saudi patients with ESRD and 100 healthy Saudi blood donors. Donated blood was tested for markers of Hepatitis B, C and G viruses. Liver functions were measured and blood picture and liver biopsies were also performed at regular intervals. RESULTS: Out of the 109 ESRD patients 68 (62.4%) were positive for at least one viral marker: 59 (54.1%) were positive for HCV, six (5.5%) were positive for HGV and three (2.8%) were positive for HBsAg. Four of the six HGV positive patients were also co-infected with HCV. Eight (8%) of the blood donors were positive for at least one viral marker. Elevated ALT levels (>4 times normal) were recorded in four out of the six HGV-positive patients including three co-infected with HCV. CONCLUSIONS: Our results are in agreement with similar studies from different countries and also raise the question about the causal relationship between HGV and liver disease among dialysis patients.

Seroepidemiology of hepatitis B virus infection in Saudi children 8 years after a mass hepatitis B vaccination programme.

OBJECTIVES: On October 1 1989, a programme was begun in Saudi Arabia in which the HBV vaccine was added as the 'seventh' primary immunogen of the Extended Programme of Immunization (EPI). In 1990, another programme was launched by the Ministry of Health to vaccinate all school children. Eight years after this mass vaccination programme, the efficacy of HBV vaccine was evaluated in a community-based study. METHODS: A community-based study was carried out in Saudi children in urban and rural areas, covering all the regions of Saudi Arabia. After informed consent, blood samples were obtained and tested for HBV markers. RESULTS: Among 4791 vaccinated Saudi children aged 1-12 years, only 15 were found to be HbsAg-positive (0.31%). HbsAg-positivity was 0.16% in children vaccinated at birth compared with 0.7% in those vaccinated at school entry. The overall HbsAg carrier rate dropped from 6.7% in 1989 to 0.3% in 1997 (P<0.00001). Similarly, there was a significant reduction in the prevalence of anti-HBc from 4.2% in 1989 to 0.46% in 1997 (P<0.00001). The overall seroconversion rate to HB vaccine among 4087 Saudi children up to 12 years of age was about 77%. Seroconversion rate in those vaccinated at birth was 77% compared with 71% in those vaccinated at school entry. After 8 years of receiving the third vaccine dose, close to 65% of the children had an anti-HBs titre of more than 10 IU/l compared with about 28% who had an anti-HBs titre of more than 100 IU/l after the same period. CONCLUSION: The result of this study demonstrates the tremendous impact of the mass HB vaccination programme on the seroepidemiology of HBV infection in Saudi Arabia. The ultimate goal of preventing HBV-related chronic liver disease and hepatocellular carcinoma in Saudi Arabia is foreseeable in the near future.

Hepatitis A in Saudi Arabia: A comparative sero-epidemiological study.

Full text is available as a scanned copy of the original print version.

Hepatitis G virus (HGV) and liver diseases.

Recently, a new flavi-like virus, provisionally named hepatitis GBV-C or hepatitis G virus (HGV), has been described and was initially thought to be the major etiological agent of non-A-E hepatitis. HGV does not induce an immune response that is consistently detectable by using recombinant proteins from prokaryotic expression and hence prevalence studies have been conducted by using polymerase chain reaction (PCR)-based system. HGV-RNA has been detected in many human populations. This article reviews what has been investigated about HGV from normal blood donors, patients with liver disease, patients at risk of acquiring the infection to possible perinatal and sexual transmission of the virus. Based on the conclusions that can be drawn from these studies conducted so far, the association between HGV infection and liver disease is still not certain. It is possible that HGV might play a role in other diseases not involving the liver, but at the present time HGV can be considered as an orphan flavivirus still looking for a human disease.

Fine-needle aspiration cytology of primary Kaposi's sarcoma of lymph nodes in an immunocompetent man.

This case report describes the fine-needle aspiration (FNA) findings of primary lymphadenopathic Kaposi's sarcoma (KS) in a 44-year-old African heterosexual male who is immunocompetent and has no clinical or serological evidence of the acquired immunodeficiency syndrome (AIDS) or the endemic form of KS. The cytological findings emphasize the role of FNA in the diagnosis of KS and draw the attention to the fact that a diagnosis of KS in an African man is not synonymous with the diagnosis of AIDS or endemic/African KS. A description of other spindle cell intranodal lesions which may mimick KS is given with a discussion of the differential diagnoses that should be considered in such cases by the cytopathologist.