Isoniazid acetylation phenotyping in Saudi Arabs.

AIMS: The present study is designed to investigate the acetylator status in Saudi Arabs. METHODS: Isoniazid (INH) acetylation phenotyping was studied in 136 Saudi Arabs in Riyadh, Saudi Arabia, using a single plasma sample taken 3 h post-INH oral dose of 200 mg. Metabolic ratio (MR) of plasma acetyl-INH (Ac-INH) to INH was used to determine the acetylation phenotype. RESULTS: The MR had a bimodal distribution with an antimode of 1.0. The frequency distribution of slow acetylators (MR < 1.0) was 94.9% (n = 129). Using Hardy-Weinberg Law, the gene frequency (q) of the recessive allele determining slow acetylator phenotype was found to be 0.97. CONCLUSION: INH phenotyping suggests a high frequency of slow acetylators among Saudi Arabs. There was no association between the MR of plasma Ac-INH/INH and age or gender.

Treatment of chronic hepatitis C genotype IV with interferon-ribavirin combination in Saudi Arabia: a multicentre study.

Between 1996 and 1997, we conducted a multicentre study to assess the effect of combination therapy of interferon (IFN) + ribavirin on chronic hepatitis C genotype 4. Ninety-seven patients were enrolled. Sixty-eight patients (47 male and 21 female) were non-responders to previous therapy with IFN (Group I). Twenty-nine patients (19 male and 10 female) were new (Group II). Following treatment with IFN, 23% in Group I and 9% in Group II had a sustained biochemical response. Only 12% in Group I and 5% in Group II achieved a sustained virological response. Virus load was found to be the major factor determining response, followed by histology grading and staging. Like HCV genotype 1, HCV genotype 4 seems to have a poor response to therapy.

Hepatic granulomas in an arab population: a retrospective study from a teaching hospital in Riyadh.

This is a retrospective analysis of the medical records of 116 patients who presented to the gastroenterology division, department of medicine at King Khalid University Hospital (KKUH) in Riyadh, Kingdom of Saudi Arabia and subsequently had a histopathologic diagnosis of hepatic granulomas. Infections contributed to 56% and were represented mainly by schistosomiasis and to a lesser extent by tuberculosis, brucellosis and hydatid disease. Lymphomas (8%) were the major representative of noninfectious causes. The etiology of 25% of granulomas remained undetermined. Weight loss, fever, anorexia and abdominal pain were the most frequent presenting symptoms in 53, 45, 43 and 42% of patients, respectively. Ten percent of the patients were asymptomatic. Hepatomegaly and splenomegaly were the predominant physical findings in 55% and 43% of patients respectively. Hepatic granulomas in this study are mainly caused by infections. Schistosomiasis, tuberculosis and brucellosis represented the most common etiologic factors.

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.

Treatment of chronic hepatitis C genotype 4 with alpha-interferon in Saudi Arabia: a multicenter study.

BACKGROUND/AIM: Several studies have indicated that there are certain predictive factors (gender, duration of infection with HCV, cirrhosis and genotype of HCV) of a better response with alpha-interferon treatment in patients with chronic hepatitis C. The aim of this study was to evaluate these factors in Saudis and other Arab nationals with chronic hepatitis C-genotype 4-undergoing alpha-interferon treatment. METHODOLOGY: A multicenter study was conducted between 1992 and 1994 on 80 consecutive patients who were prospectively recruited and randomized in treatment and control groups. RESULTS: The results of this multicenter study indicated a low response rate to alpha-interferon with an overall response rate of 43%, of which 28% was complete. The sustained response was only 16%. Among the reasons for this low response in our study are the high percentage of patients with cirrhosis and the long infection interval, as about 80% of our HCV cases were community-acquired. CONCLUSION: Liver cirrhosis was found to be the main predetermining factor for response to interferon treatment. Genotype 4 was not a contributing factor to the difference in response rate.

Schistosomiasis as a possible risk factor for acquiring hepatitis C virus (HCV) infection among Saudis.

BACKGROUND: Risk factors for acquiring hepatitis C virus (HCV) infection have been elucidated in many developed countries but the picture is still not clear in many Middle Eastern Countries including Saudi Arabia. AIM: To investigate possible risk factors for acquiring HCV among Saudis. METHODS: Various demographic and medical risk factors that might be associated with the spread of HCV among Saudis were investigated. The population studied included 20 anti-HCV-positive with chronic liver disease (CLD), 30 anti-HCV-positive patients without CLD and 272 anti-HCV-negative Saudi blood donors. All people investigated were of the same age group (>40 years of age). RESULTS: None of the demographic parameters studied (type of job, type of housing, education) was found to be significantly associated with acquiring HCV infection among our Saudi patients. On the other hand up to 40% of the anti-HCV-positive patients and irrespective of the condition of liver disease had a history of surgery, and 25% of them had a history of multiple injections. Furthermore, at least 20% of our anti-HCV-positive patients had a history of schistosomiasis which is significantly higher than schistosomiasis among the blood donors (P < 0.005). CONCLUSION: In addition to blood and blood products, schistosomiasis seems to be a possible risk factor for acquiring HCV among the Saudi population. The association between schistosomiasis and enhancement of HCV infection need to be further elucidated.

Risk of hepatitis C virus infection among household contacts of Saudi patients with chronic liver disease.

To evaluate the intrafamilial transmission of hepatitis C virus and related risk factors among the Saudi population, two groups were investigated: 1) 20 index patients with chronic liver disease and their 127 family contacts, and 2) 20 blood donors who were anti-HCV-positive but with no chronic liver disease and their 91 family contacts. After a questionnaire on the risk factors for parenteral exposure, blood samples were obtained and tested for liver biochemistry and antibody to HCV (anti-HCV) by a third-generation enzyme immunoassay (UBI HCV EIA4.0). Only two spouses of 20 index patients were anti-HCV-positive while the remaining 125 family contacts were anti-HCV-negative. None of the 91 family contacts of the 20 anti-HCV-positive blood donors was anti-HCV-positive. The two spouses were wives of index patients but had a history of blood transfusion on at least two different occasions. Our results clearly indicate the intrafamilial transmission of HCV is not the route of transmission of HCV among Saudis and our results argue against sexual transmission of hepatitis C virus despite a relatively long duration of marriage.

Diagnostic yield of upper gastrointestinal endoscopy in relation to age and gender: a study of 10112 Saudi patients.

BACKGROUND/AIMS: The availability of fiberoptic endoscopy has made it relatively easy to evaluate symptoms of upper gastrointestinal disorders with a significant degree of accuracy. MATERIALS AND METHODS: To determine the pattern of upper gastrointestinal lesions in the Saudi population with particular reference to the influence of age and gender, 10,112 patients were studied. RESULTS: No abnormal findings were detected in 26.9%. The frequency of ulcer lesions was 13.7% while non-ulcer, mucosal inflammation was diagnosed with a frequency of 33.7%. In the young (less than 20 years of age), the most common lesion was duodenal ulcer or duodenitis, whereas in the elderly (above 60 years of age), esophagitis, hiatus hernia and esophageal varices were the most frequently diagnosed. The highest mean ages were observed in the group of patients with gastric and esophageal cancers (mean ages of 58.8 and 65.1 years, respectively). There was no gender-related differences with regard to the mean age of patients in all the diagnostic categories. CONCLUSIONS: This study provides baseline data on the age distribution of major upper gastrointestinal diseases among the Saudi population. The peculiarities of upper gastrointestinal endoscopic findings in advanced age are clarified. The influence of demographic changes on the pattern of these diseases in Saudi Arabia can be evaluated against our findings in the future.

Profile of hepatitis C virus and the possible modes of transmission of the virus in the Gizan area of Saudi Arabia: a community-based study.

The seroprevalence of antibody to hepatitis C virus (anti-HCV) and the possible modes of transmission of HCV were investigated in Gizan, southern Saudi Arabia. The sample size chosen to give an adequate estimate of the seroprevalence, about 1500, was based on the assumption that 5% of the population in Gizan were anti-HCV-positive. Sera from 1482 subjects (705 males, 777 females; aged > or = 10 years) were initially screened for anti-HCV using a commercial, ubiquitin-based enzyme immunoassay. Repeatedly reactive sera were confirmed positive using second-generation immunoassays. Serum samples were also tested by ELISA for hepatitis B surface antigen (HbsAg) and antibodies to this antigen and to the hepatitis B core antigen. Of the subjects tested, 27 (1.8%) were anti-HCV-positive. Exposure to HCV was generally similar in both sexes, age-prevalence curves for anti-HCV peaking in males aged > 49 years (6.2%) and in females aged 40-49 years (5.0%). In the youngest subjects, those aged 10-19 years, the HbsAg carrier rate was significantly higher in males (10.4%) than in females (3.6%). Exposure to the hepatitis B virus was similar in both sexes (31.0% in males v. 28.6% in females). Some 7.4% and 14.8% of the 27 anti-HCV-positive cases had histories of schistosomiasis and blood transfusion, respectively. The corresponding values for the 1455 anti-HCV-negative cases investigated, 1.1% for schistosomiasis and 3.5% for blood transfusion, were much lower. The spouses and other family members of eight anti-HCV-positive index cases were investigated but none was anti-HCV-positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis C virus infection: an update.

Hepatitis C virus (HCV) infection is widely prevalent world-wide particularly in high-risk individuals including patients on hemodialysis (HD). Parenteral route seems to be the main route of transmission of this infection though other routes also exist. The high prevalence of HCV infection in patients on HD who have never received blood transfusions points to the dialysis machine as one of the likely sources of transmission of infection. The reported prevalence of anti-HCV in patients on HD in Saudi Arabia is about 68%. The natural history of HCV shows a tendency to progress to chronic liver disease including chronic active hepatitis, cirrhosis and hepatocellular carcinoma. The prevalence of anti-HCV in the general population varies from 0.5 to 3% and thus vigorous screening should be applied to all potential blood donors. A policy of public health education should be designed and implemented on the general public and health workers to reduce the non-parenteral spread of HCV. Separate HD machines should be considered for patients who are anti-HCV positive. Such preventive measures are vital because treatment of HCV with interferon has met with mixed success so far.

Hepatitis C virus genotypes in patients with chronic liver disease and haemodialysis patients from Saudi Arabia.

The genotypes of hepatitis C virus (HCV) were investigated in 28 Saudi patients (21 males, seven females; age range 23-68 years; mean 45.0 years) with histologically proven chronic hepatitis (13 chronic active hepatitis and 15 liver cirrhosis) and in 32 Saudi patients with chronic renal failure maintained on haemodialysis (22 males, 10 females; age range 18-60 years; mean 40.0 years) who also had liver disease due to HCV. Among the 28 patients with chronic liver disease genotype 4 was the predominant one (60.7%), followed by types 1b (21.4%), 1a (14.3%) and 2a (3.6%). The distribution of genotypes was similar in patients with chronic active hepatitis to those with liver cirrhosis. Among the 32 patients with chronic renal failure and maintained on haemodialysis, genotype 4 was also the dominant type (55.0%), followed by 1a (25.0%), 1b (21.9%) and 2a (3.1%). In all categories studied the prevalence of genotypes between males and females was the same. As our patients were selected from various regions of Saudi Arabia, we believe that genotype 4 is the predominant one throughout the whole kingdom.

Reduction in the prevalence of antibody to hepatitis A virus among young Saudi adults: implications for hepatitis A vaccine.

Viral etiology was investigated in 133 Saudi patients with acute hepatitis seen in King Khalid University Hospital, Riyadh. between July 1993-May 1994. Out of the 133 patients, 51 (38.3%) were diagnosed as having acute hepatitis due to hepatitis A virus (HAV). Hepatitis C virus (HCV) was the second most common etiological agent (20.3%). There were 35 patients with acute hepatitis (26.3%) in whom no viral marker for HAV, HBV, HCV, CMV or Epstein-Barr virus (EBV) was detected. Among the 51 patients with acute hepatitis due to HAV, the majority (88.2%) were children (1-12 years) and only 6 (11.8%) were adults (15-24 years). This is in contrast to patients with HCV or HBV infection where the majority were adults: 74.1% and 82.3% respectively. The diagnosis of acute hepatitis due to HAV in Saudi adults, an observation not seen earlier, indicated a change in the epidemiological pattern of HAV infection in the Saudi population. This change was confirmed by the significant reduction in the prevalence of anti-HAV in 630 Saudi subjects (1-30 years old) (50.2%) investigated in 1994 compared to that of 587 subjects of the same age group investigated in 1986 (76.5%) (P < 0.005). In the light of these results, a nation-wide survey is recommended to confirm this pattern in other areas. It is important that high-risk Saudi groups be identified and evaluated for their anti-HAV status as these groups are candidates for HAV vaccination.

Genetic compounds--Hb S, thalassaemias and enzymopathies: spectrum of interactions.

In areas with high occurrence of the red cell genetic abnormalities, i.e. sickle cell gene, alpha- and beta-thalassaemias, and glucose-6-phosphate dehydrogenase deficiency, various genes frequently co-exist in the same population. Co-inheritance of two or more abnormal genes in the same individual is frequently encountered, particularly in certain 'closed' tribes in Arabia in which consanguinity is the norm. Such genetic interactions modify the clinical presentations of the disease state. During our studies, we encountered a large number of individuals who were carriers of two or more abnormal genes. The most frequent genetic compounds were double heterozygous HbS-beta zero-thalassaemia and HbS-beta(+)-thalassaemia with associated alpha-thalassaemia or G-6-PD deficiency. Clinical history, and assessment, as well as blood analysis for haematological, biochemical, and molecular pathology determinants were carried out. The patients were classified into subgroups, based on the genetic findings. The clinical, haematological and biochemical data were assessed separately for each group. Sickle cell anaemia (Hb SS) cases, without any other abnormal gene, were used as a reference group. The results showed severe anaemia in patients with HbS/beta zero-thalassaemia and associated alpha-thalassaemia and/or G-6-PD deficiency. Patients with HbS/beta zero-thalassaemia exhibited features similar to that of the sickle cell anaemia. While sickle cell anaemia patients with alpha-thalassaemia and G-6-PD deficiency exhibited a milder presentation. This paper presents various forms of genetic associations, their influence on the clinical presentation and the laboratory parameter data, and discusses the implications of the findings.

Integration of hepatitis B vaccine into the expanded program on immunization: The Saudi Arabian experience.

Hepatitis B virus (HBV) is endemic in the Kingdom of Saudi Arabia. To prevent the chronic carriage of HBV in Saudi children, hepatitis B vaccine was added as the seventh immunogen in the expanded program on immunization (EPI). In the first year, the coverage of the first dose and third dose of HB vaccine was 90% and 73%, respectively. In a survey of 637 children, 603 (95%) were positive for antibody to hepatitis surface antigen (anti-HBs) without concomintant antibody to hepatitis B core antigen (anti-HBc) or hepatitis B surface antigen (HBsAg). A total of 592 (93%) with anti-HBs titer of > 10 IU/L were considered as responders to the vaccine. The majority (60%) of these responders had titers > 100 IU/L. Only one (0.3%) non-responder was positive for anti-HBc alone. Using historical control, the protective efficacy was estimated as 99%. Neither the gender of the recipient, schedule of the vaccination, nor the sourve of vaccine influenced the response to the vaccine. The successful integration of the HB vaccine into the EPI was due to the effectiveness of the EPI and the efficient primary health care system in Saudi Arabia.

Prevalence of antibodies to hepatitis C virus among Saudi patients with chronic liver diseases.

The prevalence of antibodies against hepatitis C virus (anti-HCV) was determined in 55 patients with chronic liver diseases including liver cirrhosis (42 patients), liver cirrhosis and hepatocellular carcinoma (8 patients), and chronic active hepatitis (4 patients). A total of 63.6% of these patients were positive for anti-HCV, a significantly higher prevalence than the rate of 3.9% observed in 488 asymptomatic volunteers. Of the 42 patients with liver cirrhosis 16 (38.1%) had positive anti-HCV without any markers of hepatitis B virus (HBV), while 12 (28.6%) had markers of neither HCV nor HBV infection. Our findings suggest that HCV infection may play a significant role in the pathogenesis of chronic liver disease in Saudi Arabia, which is an area of endemic HBV infection. Screening for anti HCV should be considered mandatory in patients with chronic liver disease (CLD) especially where the etiology appears obscure.