IL28B polymorphisms predict the virological response to standard therapy in patients with chronic hepatitis C virus genotype 4 infection.

BACKGROUND: Genome-wide association studies have recently revealed that several single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 28B genes can predict the sustained virological response (SVR) to pegylated interferon-α2a/b plus ribavirin in hepatitis C virus (HCV)-genotype 1 patients. However, data for patients infected with HCV genotype 4 (HCV-G4) are limited. AIM: We analyzed the association of IL28B SNPs (hematological, biochemical, virological, and pathological factors) with SVR in the HCV-G4 monoinfected cohort of patients. PATIENTS AND METHODS: One hundred twenty-nine treatment-naïve HCV-G4 patients undergoing treatment were recruited from three tertiary care centers in Saudi Arabia. Five IL28B SNPs (rs12979860, rs12980275, rs8105790, rs8099917, and rs72486680) were identified by polymerase chain reaction and DNA sequencing. SVR was statistically correlated with various clinical, histopathological, virological, and genetic parameters. RESULTS: SVR was significantly associated with the CC and AA alleles of rs12979860 (p = 0.008) and rs12980275 (p = 0.004), respectively. Moreover, albumin levels (p = 0.002) and platelet count (p = 0.039) showed significant differences in the SVR and No SVR groups. On multivariate analysis, the CC allele of rs12979860 (OR, 2.89; 95 % CI 1.6-6.2, p = 0.006) and albumin levels (OR, 1.2; 95 % CI 1.1-1.4, p = 0.001) independently predicted SVR. CONCLUSIONS: IL28B polymorphism (CC allele of rs12979860) predicts the sustained response to antiviral therapy in HCV-G4.

Seroprevalence of celiac disease among healthy adolescents in Saudi Arabia.

AIM: To identify the seroprevalence of celiac disease among healthy Saudi adolescents. METHODS: Between December 2007 and January 2008, healthy students from the 10(th) to 12(th) grades were randomly selected from three regions in Saudi Arabia. These regions included the following: (1) Aseer region, with a student population of 25512; (2) Madinah, with a student population of 23852; and (3) Al-Qaseem, with a student population of 16067. Demographic data were recorded, and a venous blood sample (5-10 mL) was taken from each student. The blood samples were tested for immunoglobulin A and immunoglobulin G endomysial antibodies (EMA) by indirect immunofluorescence. RESULTS: In total, 1167 students (614 males and 553 females) from these three regions were randomly selected. The majority of the study population was classified as lower middle class (82.7%). There were 26 (2.2%) students who had a positive anti-EMA test, including 17 females (3.1%) and 9 males (1.5%). Al-Qaseem region had the highest celiac disease prevalence among the three studied regions in Saudi Arabia (3.1%). The prevalence by region was as follows: Aseer 2.1% (10/479), Madinah 1.8% (8/436), and Al-Qaseem 3.2% (8/252). The prevalence in Madinah was significantly lower than the prevalence in Aseer and Al-Qaseem (P = 0.02). CONCLUSION: Our data suggest celiac disease prevalence might be one of the highest in the world. Further studies are needed to determine the real prevalence.

Epidemiology of viral hepatitis in Saudi Arabia: are we off the hook?

Some 400 million people worldwide are currently infected with the hepatitis B virus (HBV), and the infection is common in the Middle East. Another 170 million people around the globe presently live with chronic hepatitis C virus (HCV) infection. Both HBV and HCV represent a worldwide epidemic. Despite significant decline in the prevalence of HBV and HCV infection in Saudi Arabia, these viral diseases cause significant morbidity and mortality, and impose a great burden on the country's healthcare system. On the other hand, Saudi epidemiology studies have shown that the hepatitis A virus seroprevalence in the country has reduced considerably over the past two decades. The progress in mapping the epidemiological pattern of viral hepatitis in Saudi Arabia has not only aided our understanding of the disease, but has also exposed the small but relevant gaps in our identification of the intricate details concerning the disease's clinical expression. In this review, we aim to document the timeline of viral hepatitis epidemiology in Saudi Arabia, while summarizing the relevant published literature on the subject.

Seroprevalence rates of Helicobacter pylori and viral hepatitis A among adolescents in three regions of the Kingdom of Saudi Arabia: is there any correlation?

BACKGROUND: The seroprevalence rate of Helicobacter pylori in the Kingdom of Saudi Arabia (KSA) was reported to be in the range of 50-80% among mostly symptomatic patients in non-community-based studies. However, the seroprevalence of viral hepatitis A (HAV) underwent a marked decline in the last two decades from over 50% in 1989 to 25% in 1997 among Saudi children under the age of 12 years. The aim of this paper was to study seroprevalence rates of H. pylori and HAV among the adolescent population in three regions of KSA and to determine whether there was any correlation between them. MATERIALS AND METHODS: We randomly selected 1200 16-18-year-old students from three regions around KSA. Demographic data, including socioeconomic status (SES), were recorded, and each student was tested for the presence of H. pylori-IgG antibodies and anti-HAV-IgG. RESULTS: The results indicate a high H. pylori infection rate (47%) among this age group. Boys had a higher prevalence than girls (p = .03), and the Al-Qaseem region had the highest prevalence (51%, p = .002). SES did not contribute to the high prevalence rates (p = .83). A cross-tabulation of data showed that 88 (8%) of the teenagers were seropositive and that 512 (44%) were negative for both H. pylori and HAV antibodies (χ(2) = 0.03, OR = 0.97, CI = 0.70-1.34). The agreement between H. pylori and HAV seropositivity was lower than would be predicted by chance (κ = -0.03). The variables that were independently associated with seropositivity to H. pylori were being female (OR = 0.75, 95% CI = 0.60-0.95) and living in the Madinah region (OR = 0.72, 95% CI = 0.55-0.94). CONCLUSION: The prevalence of H. pylori in this group of adolescents was high. However, there was no correlation between H. pylori and HAV infection rates. Hence, factors contributing to the transmission source and route seem to be different.

Quasispecies of genotype 4 of hepatitis C virus genomes in Saudi patients managed with interferon alfa and ribavirin therapy.

BACKGROUND AND OBJECTIVES: Many patients with hepatitis C virus (HCV) infection do not respond to antiviral treatment, possibly due to viral quasispecies. We aimed to investigate whether the quasispecies population could be used as a predictor of response to therapy in our patients. METHODS: The quasispecies of HCV genotype 4 (HCV-4) were studied in 25 naïve Saudi patients at zero, three, and six months following interferon alfa and ribavirin combination therapy. Hypervariable region 1 within the E2/NS1 gene of the virus was analyzed by the single-strand conformation polymorphism (SSCP) technique after amplification. RESULTS: Pretreatment DNA bands by SSCP (2-7 bands) were detected in all patients. In those who achieved a complete virological response within six months (viral load P=.53). Two of the four patients with pretreatment high viral load and the same or decreased composition of quasispecies bands responded to the therapy. CONCLUSION: Quasispecies in our studied patients cannot be used to predict responsiveness to treatment, but may offer an explanation for failure of most HCV-4 patients to respond to interferon alfa and ribavirin therapy.

Hepatitis B genotypes: relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia.

AIM: To identify the most common hepatitis B virus (HBV) genotype in Saudi Arabia, and correlate the prevailing genotypes with the clinical outcome of patients. METHODS: Patients were consecutively recruited from the hepatology clinics of two tertiary care referral centers. Patients were categorized into 4 different groups: group 1, patients with hepatitis B and normal liver enzymes; group 2, patients with hepatitis B and abnormal liver enzymes but without cirrhosis; group 3, patients with hepatitis B and liver cirrhosis; group 4, patients with hepatitis B and hepatocellular carcinoma. All patients had a positive hepatitis B surface antigen (HBsAg). Genotyping of HBV was performed by nested PCR-mediated amplification of the target sequence and hybridization with sequence-specific oligonucleotides. RESULTS: Seventy patients were enrolled in this study. They were predominantly male (72.9%) in their mid-forty's (mean age 47 years). Forty-nine (70%) patients were hepatitis B envelope antigen (HBeAg) negative. The majority of patients (64%) acquired HBV through unknown risk factors. Hepatitis B genotyping revealed that 57 patients (81.4%) were genotype D, 1 patient (1.4%) had genotype A, 1 patient (1.4%) had genotype C, and 4 patients (5.7%) had genotype E, while 7 patients (10%) had mixed genotype (4 patients ADG, 1 patient DE, 1 patient DF, and 1 patient ADFG). Based on univariate analysis of genotype D patients, significant predictors of advanced liver disease were age, gender, aspartate transaminase, alanine transaminase, albumin, bilirubin, and alkaline phosphatase (all P < 0.001). In multivariate analysis decreased hemoglobin (r = -0.05; 95% CI: -0.08 to -0.03; P = 0.001) and albumin levels (r = -0.004; 95% CI: -0.007 to -0.001; P = 0.002) were highly significant predictors of advanced liver disease. In patients with HBV genotype D, HBeAg negativity was found to increase across advancing stages of liver disease (P = 0.024). CONCLUSION: This study highlights that the vast majority of Saudi patients with chronic hepatitis B have genotype D. No correlation could be observed between the different genotypes and epidemiological or clinical factors. The relationship between genotype D and HBeAg status in terms of disease severity needs to be further elucidated in larger longitudinal studies.

Histological and laboratory features of patients undergoing liver biopsy at a university hospital in Central Saudi Arabia.

OBJECTIVE: To identify the most common liver pathologies seen in our center, to find the prevalence of advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C, and to correlate the histological and laboratory features of the most common diseases and compare between them. METHODS: Liver biopsy procedures performed in our Gastroenterology Unit at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia were traced from records between the years 1997-2003. Clinical, histopathological, and laboratory features were recorded. RESULTS: We identified 574 liver biopsies during the study period. Of the 502 included patients, males were 58.6%. The mean age of the patients was 43.5 years. Approximately half of the biopsies (49%) were performed for patients with hepatitis C, followed by hepatitis B, for which 17% of the biopsies were performed. Patients with hepatitis B were approximately 10 years younger than patients with hepatitis C (p = 0.01). They were 10% more likely to be males. In terms of fibrosis, only approximately 17% of patients with hepatitis B and 27% of patients with hepatitis C had advanced fibrosis. CONCLUSION: Most liver biopsies performed in our center are performed for patients with hepatitis C. Rates of advanced fibrosis in our series are significantly lower than what was previously reported in other studies.

The role of leptin in non-alcoholic fatty liver disease.

BACKGROUND: The role of steatosis in the pathogenesis of chronic liver disease (CLD) is now believed to form part of a continuum in non-alcoholic fatty liver disease (NAFLD). One of the unconventional areas in which leptin is now receiving great attention is liver diseases. Several published studies indicate that circulating leptin is increased in patients with cirrhosis, chronic HCV, and non-alcoholic steatohepatitis (NASH). AIMS: the present study aims to assess serum leptin levels in patients with NAFLD with and without HCV infection, and to correlate it with the biochemical markers and histopathology of liver diseases. PATIENTS AND METHODS: the present study included 67 Saudi subjects divided into 3 age and sex-matched groups. Group A: 22 patients with DM (8 males and 14 females, mean age 44 +/- 12.9 years). Group B: 20 patients with chronic HCV infection (7 males and 13 females, mean age 48.9 +/- 14.1 years). Group C: 25 control healthy volunteers (15 males and 10 females, mean age 40.7 +/- 12.6 years). Serum leptin, C-peptide, and insulin levels were measured by radioimmunoassay. Liver biopsy was done for the HCV group only. RESULTS: Patients with chronic HCV infection had significantly lower mean +/- SD serum leptin levels (25.6 +/- 37.2 ng/mL) compared with the diabetic and control groups, 55.7 +/- 59.0 and 81.8 +/- 41.7 ng/mL (p = 0.002 and p = 0.046 respectively). However, in the HCV group, leptin levels did not differ significantly as regard steatosis grade, and fibrosis stage. Steatosis in the HCV group patients correlated with the body mass index and hyperglycemia, but not with leptin levels. Serum leptin correlated positively with serum insulin and C-peptide levels in both the HCV and diabetic groups, but not in the control group). CONCLUSION: Serum leptin can't be used as a non-invasive marker for the predication of steatosis and fibrosis in patients with NAFLD.

Haemostatic abnormalities in liver disease: could some haemostatic tests be useful as liver function tests?

The liver plays a central role in haemostasis, being the site of synthesis of most of the clotting factors, coagulation inhibitors and fibrinolytic parameters, in addition to its clearance of activated clotting and fibrinolytic factors. Nonetheless, no haemostatic test(s) is included among the routine liver function tests and this study aims to probe this possibility. The liver disease group (n=258) included acute hepatitis (n=25), chronic viral hepatitis (n=128), hepatitis B (HB) carriers (n=25), liver cirrhosis (n=67), and hepatocellular carcinoma (HCC) (n=13). The prothrombin time was significantly prolonged in acute hepatitis, liver cirrhosis and HCC. However, the reptilase time was prolonged in all the groups except in HB carriers, while the thrombin time was prolonged only in the HCC group. Antithrombin III and protein C levels exhibited significant reduction in acute hepatitis, liver cirrhosis and HCC. On the other hand, protein S levels (total and free) were reduced significantly in all the patients groups, including HB carriers when compared with healthy controls. Derangement of haemostatic tests is a common feature in liver disease, being most significant in acute hepatitis, liver cirrhosis and hepatocellular carcinoma. The most sensitive markers of hepatocyte malfunction are protein S (total and free) and the reptilase time as they were abnormal, in the mildest liver affections, when other biochemical tests as well as other haemostatic tests were normal. Further studies are needed to see whether these two tests qualify for inclusion among the routine liver function tests.

Biochemical and radiological predictors of malignant biliary strictures.

AIM: Differentiation of benign biliary strictures (BBS) from malignant biliary strictures (MBS) remains difficult despite improvement in imaging and endoscopic techniques. The aim of this study was to identify the clinical, biochemical and or radiological predictors of malignant biliary strictures. METHODS: We retrospectively reviewed all charts of patients who had biliary strictures (BS) on endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous cholangiography (PTC) in case of unsuccessful ERCP from March 1998 to August 2002. Patient characteristics, clinical features, biochemical, radiological and biopsy results were all recorded. Stricture etiology was determined based on cytology, biopsy or clinical follow-up. A receiver operator characteristic (ROC) curve was constructed to determine the optimal laboratory diagnostic criterion threshold in predicting MBS. RESULTS: One hundred twenty six patients with biliary strictures were enrolled, of which 72 were malignant. The mean age for BBS was 53 years compared to 62.4 years for MBS (P=0.0006). Distal bile duct stricture was mainly due to a malignant process 48.6% vs 9% (P=0.001). Alkaline phosphates and AST levels were more significantly elevated in MBS (P=0.0002). ROC curve showed that a bilirubin level of 84 micromol/L or more was the most predictive of MBS with a sensitivity of 98.6%, specificity of 59.3% and a positive likelihood ratio of 2.42 (95% CI=0.649-0.810). Proximal biliary dilatation was more frequently encountered in MBS compared to BBS, 73.8% vs 39.5% (P=0.0001). Majority of BBS (87%) and MBS (78%) were managed endoscopically. CONCLUSION: A serum bilirubin level of 84 micromol/L or greater is the best predictor of MBS. Older age, proximal biliary dilatation, higher levels of bilirubin, alkaline phosphatase, ALT and AST are all associated with MBS. ERCP is necessary to diagnose and treat benign and malignant biliary strictures.

Malignant biliary strictures. Diagnosis and management.

OBJECTIVE: To identify the cause, methods of diagnosis and management of malignant biliary strictures in our institution and compare with studies from other communities. METHODS: From March 1998 through to August 2002, we reviewed 1000 files of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) at the Gastroenterology unit, King Khalid University Hospital in Riyadh, Kingdom of Saudi Arabia for malignant biliary strictures (MBS). Clinical, laboratory data, method of diagnosis and management were recorded. RESULTS: Seventy-two patients (72/1000) with MBS were encountered. Forty one (57%) were males and 31 (43%) were females and the majority were Saudi nationals (82%). Jaundice and right upper quadrant pain were the most frequent symptoms in 84.7% and 52.8% of patients. Cholangiocarcinoma was present in 31 (43%) and pancreatic adenocarcinoma in 23 (31.9%) patients. Other malignancies found included gallbladder carcinoma in 5 patients (6.9%), ampullary carcinoma in 5 (6.9%), metastatic liver carcinoma in 4 patients (5.6%), hepatocellular carcinoma in 2 (2.8%) and lymphoma in 2 (2.8%). The diagnosis was entertained mainly by ERCP (93%). Endoscopic palliation was carried out in 77.8% of patients, percutaneous transhepatic drainage in 13.9% and surgery in 6 (8.3%). The mean survival was higher for the endoscopic compared to the percutaneous transhepatic and surgery groups (6.9 +/- 4.13, 4.27 +/- 4.29 and 3.67 +/- 2.65 months). CONCLUSION: In non-resectable tumors, ERCP is the optimal method of diagnosis and palliation of MBS.