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Background/Aim: Gallstone disease (GD) and nonalcoholic fatty liver disease (NAFLD) are associated with metabolic syndrome. Despite the benign nature of NAFLD, 10% of patients may develop advanced fibrosis and cirrhosis. We aimed to identify the prevalence and factors associated with NAFLD among GD patients in the Saudi population. Patients and Methods: This is a single-center, observational cohort study that included patients seen in general surgery clinics at our institution from 2011 to 2017. All liver biopsies were taken at the same time as the cholecystectomy. Demographical and clinical data were prospectively collected from the study population. Results: Of the 301 GD patients in the study, 15% had a normal body mass index (BMI), 29% were overweight, and 56% were obese. There were 143 (47.8%) patients with NAFLD, of which 125 (41.8%) showed steatosis and 18 (6%) had nonalcoholic steatohepatitis. There was a significant positive correlation between NAFLD and age (r = 0.243; P < 0.0001), and BMI (r = 0.242; P < 0.0001). Obese patients with BMI 30–40 kg/m[2] were 2.403 (P = 0.039) more likely to have NAFLD compared with normal BMI patients, and this value increased to 6.145 (P = 0.002) in patients with BMI >40 kg/m[2]. Additionally, patients with T2DM were 2.839 times (P = 0.015) more likely to have NAFLD compared with those who did not. Conclusions: The prevalence of NAFLD among GD patients is high. High BMI and diabetes are independent factors associated with NAFLD in GD patients. The results suggest that there may be a need for routine liver biopsy in selected patients during cholecystectomy. [ABSTRACT FROM AUTHOR]

Background/Aims: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. Patients and Methods: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). Results: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years; P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1-12%) and cirrhosis (range 5-23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010; P = 0.559) and hepatic steatosis (32% vs. 25% in 2010; P = 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1-2% in 2010/2012). Conclusions: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities. [ABSTRACT FROM AUTHOR]

Background: Hepatic steatosis in hepatitis C virus (HCV)-infected patients has been shown to enhance the progression of liver fibrosis and decrease the response to antiviral therapy.Aims: We aimed to determine the role of HCV genotype 4 (HCV-G4) in the prevalence of hepatic steatosis, its impact on antiviral therapy, and its associations and predictive factors in comparison to HCV-G1-infected patients.Methods: Treatment-naïve HCV patients who were started on pegylated interferon a-2b plus ribavirin therapy in two centers in Saudi Arabia were included. The severity of steatosis was assessed using the METAVIR and NAS (non-alcoholic fatty liver disease [NAFLD] activity score) scoring systems. Sustained virological response (SVR) was studied in relation to the degree of steatosis. Associations between steatosis and multiple demographic, laboratory, and virological factors were examined. HCV-G1 and HCV-G4 patients were compared.Results: A total of 116 patients (HCV-G4 85 [73.3%]; HCV-G1 31 [26.7%]) were included. The mean age was 50.4±10.7 years and 56.9% were males. In terms of steatosis grading using the NAS scoring system, 50% had steatosis grade 0, 26.7% grade 1, 14.7% grade 2, and 8.6% grade 3, while the overall staging of steatosis revealed that 43.1% had mild steatosis, 42.2% moderate, and 14.7% severe. Gamma-glutamyl transpeptidase (GGT), platelet count, body mass index (BMI), cholesterol level, presence of hyperlipidemia, liver histology stage, and grade were significantly correlated with hepatic steatosis in one or more of the statistical analyses. Twenty-two out of 55 patients (40.0%) had an SVR in the mild steatosis group, compared to 52.7% in the moderate group and 7.3% in the severe group (P=0.03). The HCV genotype did not correlate with steatosis or SVR.Conclusion: Our study confirms the high prevalence of steatosis in HCV-G4 and HCV-G1 patients, but with no difference in the grade or score of steatosis between the two genotypes. The grade of steatosis correlates with GGT, platelet count, and BMI, while the NAS score of steatosis correlates with response to antiviral therapy. [ABSTRACT FROM AUTHOR]

Toll-like receptor 3 (TLR3) plays a key role in innate immunity by recognizing pathogenic, double-stranded RNAs. Thus, activation of TLR3 is a major factor in antiviral defense and tumor eradication. Although downregulation of TLR3 gene expression has been mainly reported in patients infected with hepatitis C virus (HCV), the influence of TLR3 genotype on the risk of HCV infection, HCV-related cirrhosis, and/or hepatocellular carcinoma (HCC) remains to be determined. Single-nucleotide polymorphisms (SNPs) within the TLR3 gene and their associations with HCV-related disease risk were investigated in a Saudi Arabian population in this study. Eight TLR3 SNPs were analyzed in 563 patients with HCV, which consisted of 437 patients with chronic HCV infections, 88 with HCV-induced liver cirrhosis, and 38 with HCC. A total of 599 healthy control subjects were recruited to the study. Among the eight TLR3 SNPs studied, the rs78726532 SNP was strongly associated with HCV infection when compared to that in healthy control subjects. The rs5743314 was also strongly associated with HCV-related liver disease progression (cirrhosis and HCC). In summary, these results indicate that distinct genetic variants of TLR3 SNPs are associated with HCV infection and HCV-mediated liver disease progression in the Saudi Arabian population. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. Surface (S) protein is the major HBV antigen that mediates virus attachment and entry and determines the virus subtype. Mutations in S gene, particularly in the "a" determinant, can influence virus detection by ELISA and may generate escape mutants. Since no records have documented the S gene mutations in HBV strains circulating in Saudi Arabia, the current study was designed to study sequence variation of S gene in strains circulating in Saudi Arabia and its correlation with clinical and risk factors. Patients and Methods: A total of 123 HBV-infected patients were recruited for this study. Clinical and biochemical parameters, serological markers, and viral load were determined in all patients. The entire S gene sequence of samples with viral load exceeding 2000 IU/mL was retrieved and exploited in sequence and phylogenetic analysis. Results: A total of 48 mutations (21 unique) were recorded in viral strains in Saudi Arabia, among which 24 (11 unique) changed their respective amino acids. Two amino acid changes were recorded in "a" determinant, including F130L and S135F with no evidence of the vaccine escape mutant G145R in any of the samples. No specific relationship was recognized between the mutation/amino acid change record of HBsAg in strains in Saudi Arabia and clinical or laboratory data. Phylogenetic analysis categorized HBV viral strains in Saudi Arabia as members of subgenotypes D1 and D3. Conclusion: The present report is the first that describes mutation analysis of HBsAg in strains in Saudi Arabia on both nucleotide and amino acid levels. Different substitutions, particularly in major hydrophilic region, may have a potential influence on disease diagnosis, vaccination strategy, and antiviral chemotherapy. [ABSTRACT FROM AUTHOR]

Background/Aim: To assess the correlation between serum HBsAg titers and hepatitis B virus (HBV) DNA levels in patients with hepatitis B envelop antigen-negative (HBeAg -ve) HBV genotype-D (HBV/D) infection. Patients and Methods: A total of 106 treatment- naive, HBeAg -ve HBV/D patients were included; 78 in the inactive carrier (IC) state and 28 in the active hepatitis (AH) stage. HBV DNA load and HBsAg titers were tested using TaqMan real-time polymerase chain reaction (PCR) and automated chemiluminescent microparticle immunoassay, respectively. Results: The median (range) log10 HBsAg titer was significantly lower in the IC group compared with AH group, 3.09 (-1 to -4.4) versus 3.68 (-0.77 to 5.09) IU/mL, respectively; P < 0.001. The suggested cutoff value of HBsAg titer to differentiate between the two groups was 3.79 log10 IU/mL. In addition, there was a significant positive correlation between HBsAg and HBV DNA levels in the whole cohort, AH, and IC groups (r = 0.6, P < 0.0001; r = 0.591, P = 0.001; and r = 0.243, P = 0.032, respectively). Conclusion: Serum HBsAg titers may correlate with HBV DNA in treatment.naive HBeAg -ve HBV/D patients, and supports the use of HBsAg levels in clinical practice as a predictor of serum HBV DNA levels. [ABSTRACT FROM AUTHOR]

Background and Aims: Complementary alternative medicine (CAM) covers many types of treatments and procedures that are usually not included in conventional medicine and are used in addition to physician-prescribed drugs to "complement" treatment. Although liver disease is prevalent in Saudi Arabia, not much is known about CAM use among Saudi liver disease patients. Thus, this study aimed to assess the prevalence of CAM use in these patients and their attitudes toward it. Materials and Methods: Patients were recruited randomly from a tertiary care hepatology clinic at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia from February 4 to March 20, 2012. A four-page questionnaire was used to interview patients. Results: Of all the 232 participants surveyed, 55.6% have used or are using CAM to treat their liver disease with 45.0% of CAM users stating that they believe it has a positive effect on their treatment. Honey was the most used CAM treatment among the participants (39.0%). Herb use was represented by 31.8% of all users, while 13.5% used bloodletting as a treatment. Cautery was the least used CAM method (3.4%). Nearly 76.6% of CAM users were satisfied with using alternative treatments to help control their disease. Nearly 69.4% of users and nonusers stated that they believe CAM treatments to have numerous beneficial effects. Nearly 60.5% of CAM users stated that their physician had no knowledge of their CAM use. Of the factors included in linear multivariate regression analysis (including: Age, gender, and family CAM use, among other socioeconomic factors) only family CAM use was considered a significant independent factor affecting participants CAM use (Beta = 0.582, 95% CI: 0.372-0.754, P = 0.0001). Conclusion: More than half of the patients have reported CAM use. Overall, more than two-thirds of the entire sample believed that CAM treatments have numerous health benefits. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aim: Some reports in the literature have linked interferon therapy for the treatment of hepatitis C (HCV) with hearing loss. The aim of this study has been to examine the effects of interferon therapy on hearing of patients treated for HCV. Patients and Methods: Patients were recruited according to preset inclusion criteria from two centers. All patients received standard dose pegylated interferon (PEG-IFN α-2b or α-2a) plus ribavirin (RBV). All patients had pure-tone audiometry (PTA), tympanogram and distortion-product otoacoustic emission (DPOAE) before treatment, three months after initiation of treatment, and three months after completion of treatment. Results: Twenty one patients were prospectively recruited. The mean age was 45.7 years. The male to female ratio was 1.1:1. The mean PTA was 15.9 ± 5.3 before treatment, 17.4 ± 6.1 during treatment and 16.5 ± 5.1 after treatment. The differences between pre and mid, pre and post, as well as mid and post were not significantly different (P>0.05) in all audiological assessments. Conclusions: Our results indicate that PEG-IFN\RBV therapy does not have any impact on the hearing thresholds of patients with HCV. [ABSTRACT FROM AUTHOR]

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. 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. 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 = 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). 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. [ABSTRACT FROM AUTHOR]

Summary: Introduction: This is the third evaluation study of the hepatitis B virus (HBV) vaccination program, initiated in 1989 in Saudi Arabia. Aims: This study sought to assess the efficacy and long-term protection of the hepatitis B vaccine among Saudi adolescents. Methods: School students between the ages of 16 and 18 years were randomly chosen from high endemic (Aseer), intermediate endemic (Madinah), and low endemic (Al-Qaseem) areas of the country. Hepatitis B surface antigen (HBsAg), hepatitis B core IgG antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) were measured using standard techniques. Results: A total of 1355 students (689 males and 666 females) were selected randomly from the three areas. No cases of positive HBsAg or anti-HBc were detected among the study population. Five hundred and ten students (38%) showed protective anti-HBs titers (≥10mIU/ml), while 528 (39%) students had undetectable anti-HBs titers (<1mIU/ml). Conclusions: This study shows the excellent efficacy of the HBV vaccination program in Saudi Arabia 18 years after its launch. Based on this study and others, a booster dose for the adult population appears to be unnecessary. [Copyright &y& Elsevier]

The article deals with the guidelines created for the diagnosis and management of hepatocellular carcinoma (HCC) in Saudi Arabia. A committee was formed from the editors at King Khalid University Hospital after due recognition of the high prevalence of HCC in Saudi Arabia. Recommendations in the guidelines were based on the best available evidence and tailored to the needs of the patients in Saudi Arabia. It is also expected that the guidelines will improve the care of patients suffering from HCC and facilitate the performance of research in the area.

Background: Hepatocellular carcinoma (HCC) is the second commonest cancer affecting males and the eighth most common one affecting females in Saudi Arabia. Transarterial chemoembolization (TACE) is currently considered the first line therapy for multifocal HCC in selected patients. Objective: To evaluate HCC response to TACE based on triphasic computerized tomography (CT) of the liver obtained 6 weeks after the procedure. Materials and Methods: A retrospective chart review of 15 patients who underwent TACE in King Khalid University Hospital for unresectable HCC. Patients were staged according to the Child-Pugh, Okuda, and CLIP scoring systems. The first triphasic CT of the liver after TACE was evaluated for Lipiodol uptake and interval change in tumor burden. Results: The mean age was 63 years (40-82), 10 were males (66.7%), and five were females. About 11 patients had cirrhosis (73.3%). Eight patients (53.3%) were Child-Pugh class A while seven (46.7%) were Child-Pugh class B. One patient died and two were lost to follow up. Four patients had a complete response to TACE (26.7%), two had a partial response (13.3%), five showed no change (33.3%) and none showed progression of disease. Tumoral Lipiodol uptake in five patients was >75% (33.3%), in two 75-50% (13.3%) while in four patients it was <50% (26.7%). Conclusion: Our results show that TACE is an effective method of reducing the tumor burden in selected patients with unresectable HCC. [ABSTRACT FROM AUTHOR]

The author reflects on the present struggle with hepatitis C in Saudi Arabia and provides relevant insights on this national health challenge. He cites findings that the prevalence rate of antibodies to hepatitis C virus in al Saudi nationals was approximately 0.7%. He notes the need to change strategy to find and treat more patients as delaying implementation by a year can result in 68% more HCV infections in 2030 and 360 additional total deaths during 2014-2030.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of death in Saudi male patients. Local clinical and demographic data of this disease are scarce. Objectives: We sought to describe the clinical characteristics and outcomes of patients from two tertiary care centers in Saudi Arabia. Patients and Methods: Data were collected for all patients diagnosed to have hepatocellular carcinoma between June 2003 and July 2008 who had been registered in a special research database (the Saudi Observatory Liver Disease Registry (SOLID)). Data were extracted from SOLID for clinical, biochemical, radiologic parameters and outcome. Results: Data was available for 363 patients, the mean age of diagnosis was 66 years, 74% of patients were males, and Hepatitis C was the underlying cause of liver disease in 48%, while Hepatitis B in 29%. Most of the patients were diagnosed at an advanced stage, 53 % of patients had a CLIP score of 4 to 6 (advanced stage), 55% had large multi-nodular tumors and 16% had vascular invasion or extra-hepatic spread at the time of diagnosis. Most of the patients had decompensated cirrhosis; with child-pogh score B in 44% and C in 26% with presence of portal hypertension in 55%. Forty eight percent died during the study period. Predictors of poor survival in the univariate analysis were; presence of portal vein thrombosis (P = 0.03), portal hypertension (P < 0.0001), presence of ascites (P = 0.022), hepatic encephalopathy (P < 0.0001), advanced child-pough score (P < 0.0001), bilirubin > 22 (P < 0.0001) and INR > 1.2 (P = 0.02). On multivariate analysis, only the presence of portal hypertension, bilirubin > 22 and severe hepatic encephalopathy were significant with adjusted hazard ratio of 1.6 (95% CI; 1.04-2.47), 1.76 (95% CI; 1.12-2.8), and 3.18 (95% CI; 1.42-7.14) respectively. Conclusions: The data from this cohort indicates that most of patients diagnosed with HCC present at late tumor and liver disease stages, when prognosis is usually dismal. Regular cancer surveillance in cirrhotic patients might change the outcomes. Further studies with results of treatment outcomes in this community are needed. [ABSTRACT FROM AUTHOR]

Despite the implementation of various vaccination programs, hepatitis B virus (HBV) poses a considerable health problem in Saudi Arabia. Insight on HBV evolutionary history in the region is limited. We performed a comprehensive epidemiological and phylogenetic reconstruction based on a large cohort of HBV infected patients. Three hundred and nineteen HBV-infected patients with different clinical manifestations, including inactive and active chronic carriers and patients with cirrhosis and hepatocellular carcinoma (HCC), were enrolled in this study. The full-length large S gene was amplified and sequenced. Phylogenetic analysis was performed to determine the genotype and subgenotypes of the isolates. Phylogenetic tree analysis revealed that genotype D is the most dominant genotype among patients. Moreover, this analysis identified two strains with genotype E isolated from active carriers. Detailed phylogenetic analyses confirmed the presence of four HBV D subgenotypes, D1 (93%, n = 296), D2 (0.02%, n = 5), D3 (0.003%, n = 1), and D4 (0.003%, n = 1). In addition, six genotype D strains were not assigned to any existing HBV D subgenotype. The large S gene of eight strains showed signatures of genotype recombination between the genotypes D and A and between D and E. Several strains harbored medically important point mutations at the protein level. Along with the dominance of the HBV genotype D, isolation of the E genotype and several recombinant strains from patients with Saudi Arabian origin is an essential result for decisions involving therapeutic measures for patients. Development of vaccines and detection of diagnostic escape mutations at antigenic epitopes on the HBsAg will be valuable to public health authorities. Furthermore, the diversity at the nucleotide and amino acid levels and different proportions of dN/dS at the PreS1, PreS2, and HBsAg reveal the selective pressure trend from inactive status towards advanced liver diseases. • The most prevalent HBV subgenotype is D1 regardless of the clinical status of the patient. • The most prevalent HBV serotype is ayw2 as inferred from the large S gene sequence. • Only HBV isolates from HCC patients showed positive selective pressure. [ABSTRACT FROM AUTHOR]

Interleukin-37 (IL-37) has recently been recognized as a strong anti-inflammatory cytokine having anti-tumor activity against hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients. HCC is a typical inflammation-related cancer, and genetic variations within the IL-37 gene may be associated with the risk of HBV infection. Identification of the allelic patterns that genetically have a high disease risk is essential for the development of preventive diagnostics for HBV-mediated liver disease pathogenesis. In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within the IL-37 gene and disease sequelae associated with HBV infection. We genotyped ten IL-37 SNPs in 1274 patients infected with HBV and 599 healthy controls from a Saudi Arabian population. Among the selected SNPs, two SNPs (rs2723175 and rs2708973) were strongly associated with HBV infection, and six SNPs (rs2723176, rs2723175, rs2723186, rs364030, rs28947200, rs4392270) were associated with HBV clearance, comparing healthy controls and HBV infected-patients respectively. A suggestive association of rs4849133 was identified with active HBV surface antigen (HBsAg) carrier and HBV-related liver disease progression. In conclusion, our findings suggest that variations at the IL-37 gene may be useful as genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression in the Saudi Arabian population.

Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28 * and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC.

Background: Variations at DEPDC5 gene have been recently reported as genetic markers associated with hepatocellular carcinoma (HCC) progression in chronic HCV-infected patients. This study was conducted to assess the association of DEPDC5 variants with advanced liver cirrhosis and HCC development among chronic HCV-infected patients in Saudi Arabian population., Methods: Six-hundred and one HCV-infected patients were genotyped for DEPDC5 polymorphisms (rs1012068 and rs5998152), in comparison with 592 non-infected healthy control subjects. The allelic frequency and genotype distribution of both DEPDC5 polymorphisms were determined followed by haplotype frequency estimation and multiple logistic regression analysis., Results: The frequency of the risk alleles of both rs1012068 and rs5998152 was shown to be more in healthy control subjects than in patients (p = 0.0001, OR = 0.704, CI = 0.591-0.839; p = 0.002, OR = 0.761, CI = 0. 0.639-0.907, respectively). Also, our results revealed that GT for SNP rs1012068 (OR =1.715; 95% CI 1.132-2.597; p = 0.0104) and CT for SNP rs5998152 (OR = 1.932; 95% CI 1.276-2.925; p = 0.0017) showed significant association with development of cirrhosis compared with the GG and CC genotypes, respectively. The data also revealed that subjects with the T allele of both SNPs appeared to have a lower susceptibility to HCV-related cirrhosis/HCC than those with the G allele of rs1012068 (p = 0.038, OR = 1.353, 95 % CI 1.017-1.800) and C allele of rs5998152 (p = 0.043, OR = 1.342, 95 % CI 1.010-1.784). Haplotype analysis showed that a combination of T-T alleles of rs1012068 and rs5998152 was significantly associated with liver cirrhosis (frequency = 71.3% and p = 0.027) and with cirrhosis/HCC (frequency = 71.4% and P = 0.045). Also, multiple logistic regression analysis showed that rs5998152 (OR = 2.844, 95% CI 1.333-6.069 and p = 0.007), rs1012068 (OR = 2.793, 95% CI 1.316-5.928 and p = 0.010), age (OR = 1.029, 95% CI 1.001-1.057 and p = 0.041) and HCV genotypes (OR = 0.247, 95% CI 0.097-0.630 and p = 0.003) were independently associated with chronicity of HCV infection., Conclusion: Genetic variations in DEPDC5 gene region may influence HCV-associated liver cirrhosis and/or HCC development.

Background & Aims: Several genome-wide association studies have shown that genetic variations in the chromosomal region containing interleukin-28B (IL28B) gene are associated with response to treatment in hepatitis C virus (HCV) infection. This study was conducted to examine the role of genetic variations in IL28B on disease progression in Saudi Arabian patients chronically infected with hepatitis B virus (HBV)., Methods: The study included 1128 subjects divided into four categories; 304 clearance subjects, 518 inactive carriers, 212 active carriers and 94 cirrhosis/HCC., Results: Three single nucleotide polymorphisms (SNPs), rs12979860 (OR=1.307; 95% CI 1.046-1.634, χ2=5.57 and P=0.0183), rs12980275 (OR=0.642; CI 0.517-0.798, χ2=16.17 and P=0.0001) and rs8105790 (OR=0.746; CI 0.592-0.941, χ2=6.12 and P=0.0133), were found to be strongly associated with HBV clearance. The frequency of the G allele of rs12980275 and the C allele of rs8105790 were found to be more in clearance group than in patients and could contribute to protection against the disease. On the other hand, only rs12979860 showed significant difference in distribution when inactive group was compared to other groups (OR=1.285; CI 1.030-1.603, χ2=4.95, P=0.0261). No significant association was evident for any of the variants when active carriers were compared to cirrhosis/HCC patients. Haplotype analysis showed that a combination of A-T-T-G of rs12980275, rs8105790, rs8099917, and rs7248668, respectively, was associated with clearance of the virus (frequency=67.5% and P=0.015)., Conclusion: genetic variations in IL28B gene region may influence the clearance of HBV infection., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hepatitis C virus (HCV) shows a remarkable genetic diversity, contributing to its high persistence and varied susceptibilities to antiviral treatment. Previous studies have reported that the substitution of amino acids in the HCV subgenotype 1b core protein in infected patients is associated with a poor response to pegylated interferon and ribavirin (PEG-IFN/RBV) combined therapy., Objectives: Because the role of the core protein in HCV genotype 4 infections is unclear, we aimed in this study to compare the full-length core protein sequences of HCV genotype 4 between Saudi patients who responded (SVR) and did not respond (non-SVR) to PEG-IFN/RBV therapy., Study Design: Direct sequencing of the full-length core protein and bioinformatics sequence analysis were utilized., Results: Our data revealed that there is a significant association between core protein mutations, particularly at position 70 (Arg70Gln), and treatment outcome in HCV subgenotype 4d patients. However, HCV subgenotype 4a showed no significant association between core protein mutations and treatment outcome. In addition, amino acid residue at position 91 was well-conserved among studied patients where Cys91 is the dominant amino acid residue., Conclusions: These findings provide a new insight into HCV genotype 4 among affected Saudi population where the knowledge of HCV core gene polymorphisms is inadequate.

Background: In light of the immense attention given to patient safety, this paper details the findings of a baseline assessment of the patient safety culture in a large hospital in Riyadh and compares results with regional and international studies that utilized the Hospital Survey on Patient Safety Culture. This study also aims to explore the association between patient safety culture predictors and outcomes, considering respondent characteristics and facility size., Methods: This cross sectional study adopted a customized version of the HSOPSC and targeted hospital staff fitting sampling criteria (physicians, nurses, clinical and non-clinical staff, pharmacy and laboratory staff, dietary and radiology staff, supervisors, and hospital managers)., Results: 3000 questionnaires were sent and 2572 were returned (response rate of 85.7%). Areas of strength were Organizational Learning and Continuous Improvement and Teamwork within units whereas areas requiring improvement were hospital non-punitive response to error, staffing, and Communication Openness. The comparative analysis noted several areas requiring improvement when results on survey composites were compared with results from Lebanon, and the United States. Regression analysis showed associations between higher patient safety aggregate score and greater age (46 years and above), longer work experience, having a Baccalaureate degree, and being a physician or other health professional., Conclusions: Patient safety practices are crucial toward improving overall performance and quality of services in healthcare organizations. Much can be done in the sampled organizations and in the context of KSA in general to improve areas of weakness and further enhance areas of strength.

Hepatitis B virus (HBV) infection is a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. Human leukocyte antigens (HLAs) play an important role in the regulation of immune response against infectious organisms, including HBV. Recently, several genome-wide association (GWAS) studies have shown that genetic variations in HLA genes influence disease progression in HBV infection. The aim of this study was to investigate the role of HLA genetic polymorphisms and their possible role in HBV infection in Saudi Arabian patients. Variations in HLA genes were screened in 1672 subjects who were divided according to their clinical status into six categories as follows; clearance group, inactive carriers, active carriers, cirrhosis, hepatocellular carcinoma (HCC) patients and uninfected healthy controls. Three single nucleotide polymorphisms (SNPs) belonged to HLA-DQ region (rs2856718, rs7453920 and rs9275572) and two SNPs belonged to HLA-DP (rs3077 and rs9277535) were studied. The SNPs were genotyped by PCR-based DNA sequencing (rs2856718) and allele specific TaqMan genotyping assays (rs3077, rs7453920, rs9277535 and rs9275572). The results showed that rs2856718, rs3077, rs9277535 and rs9275572 were associated with HBV infection (p = 0.0003, OR = 1.351, CI = 1.147-1.591; p = 0.041, OR = 1.20, CI = 1.007-1.43; p = 0.045, OR = 1.198, CI = 1.004-1.43 and p = 0.0018, OR = 0.776, CI = 0.662-0.910, respectively). However, allele frequency of rs2856718, rs7453920 and rs9275572 were found more in chronically infected patients when compared to clearance group infection (p = 0.0001, OR = 1.462, CI = 1.204-1.776; p = 0.0178, OR = 1.267, CI = 1.042-1.540 and p = 0.010, OR = 0.776, CI = 0.639-0.942, respectively). No association was found when polymorphisms in HLA genes were compared in active carriers versus cirrhosis/HCC patients. In conclusion, these results suggest that variations in HLA genes could affect susceptibility to and clearance of HBV infection in Saudi Arabian patients.

Hepatitis C virus (HCV) is a single stranded RNA virus. It affects millions of people worldwide and is considered as a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. A recent study reported that TLR4 gene polymorphisms are good prognostic predictors and are associated with protection from liver fibrosis among Caucasians. This study aims to investigate the implication of genetic polymorphisms of TLR4 gene on the HCV infection in Saudi Arabian patients. Two SNPs in the TLR4 gene, rs4986790 (A/G) and rs4986791 (C/T), were genotyped in 450 HCV patients and 600 uninfected controls. The association analysis confirmed that both SNPs showed a significant difference in their distribution between HCV-infected patients and uninfected control subjects (P < 0.0001; OR = 0.404, 95% CI = 0.281-0.581) and (P < 0.0001; OR = 0.298, 95% CI = 0.201-0.443), respectively. More importantly, haplotype analysis revealed that four haplotypes, AC, GT, GC, and AT (rs4986790, rs4986791), were significantly associated with HCV infection when compared with control subjects. One haplotype AC was more prominently found when chronic HCV-infected patients were compared with cirrhosis/HCC patients (frequency = 94.7% and P = 0.04). Both TLR4 SNPs under investigation were found to be significantly implicated with HCV-infection among Saudi Arabian population.

MHC class I polypeptide-related chain A (MICA), mapping to 6p21.33, belongs to the non-classical class I family and its expression is induced by several stress factors including viral infection. A recent genome-wide association study has identified a single nucleotide polymorphism (SNP) of MICA, rs2596542 to be significantly associated with hepatitis C-induced hepatocellular carcinoma (HCC) in a Japanese population. Therefore, this study aims to investigate whether the SNP rs2596542 plays any role in hepatitis B virus (HBV) sero-clearance or in the development of complications associated with chronic HBV such as cirrhosis and/or HCC. TaqMan genotyping assay was used to identify the association of the SNP among 584 normal healthy controls and 777 HBV-infected patients. The patient group was further categorized into inactive carriers (Group I), active carriers (Group II), cirrhosis (Group III) and cirrhosis-HCC (Group IV). Variation at this SNP was found to be significantly more frequent in control subjects than in patients (OR = 0.852; 95% C.I. = 0.730-0.994; p = 0.0415). Also, the SNP was found to have a highly significant association when the inactive carriers were compared to the rest of the patients (OR = 1.308; 95% C.I. = 1.058-1.617; p = 0.0130). The TT genotype was found to occur more frequently among active HBV carriers (groups II, III and IV) when compared to inactive HBV carriers, thus suggesting that the rs2596542-T may be recessively associated with an active HBV infection. However, no significant association was observed in the case of HBV-related cirrhosis or HCC. These findings indicate that the MICA rs2596542 has a significant role in HBV infection., (© 2013. Published by Elsevier Inc. All rights reserved.)

Background: Hepatitis B virus (HBV) affects millions of people worldwide. While some people are able to clear the virus following the first encounter, those who develop chronic infection manifest remarkable clinical heterogeneity that ranges from asymptomatic carrier state to cirrhosis and hepatocellular carcinoma. Despite extensive studies, little is known about genetic host factors that influence the outcome of chronic HBV infection. Thus, we conducted this study to investigate the genetic risk of developing active liver disease among chronic carriers of HBV., Methods: In this study, we conducted a genome-wide association study (GWAS) on a cohort of patients with chronic HBV infection., Results: One particular SNP that is 16 kb upstream of Ferredoxin 1 was found to have an association with complicated chronic HBV infection (cirrhosis and hepatocellular carcinoma) that reached GWAS significance, and was successfully validated on an independent set of samples., Conclusions: This first GWAS in an Arab population further demonstrates the utility of this approach in elucidating the genetic risk of HBV infection-related complications and highlights the advantage of conducting GWAS in different ethnicities to achieve that goal.

Background: Recently, the upper limits of normal (ULN) for alanine-aminotransferase (ALT) has been recommended to be lowered to ≤ 30 U/l in men and ≤ 19 U/l in women., Aim: To evaluate the ALT concentrations in a healthy Middle Eastern population with biopsy-proven normal liver tissue., Methods: ALT values were calculated from 175 consecutive Saudi potential living liver donors who underwent a liver biopsy as part of a stepwise pretransplant workup., Results: The mean age of the 110 potential donors with normal liver histology was 27 ± 6.2 years for men and 38.6 ± 7.1 years for women. The mean body mass index (BMI) levels were 23.0 ± 3.5 kg/m(2) for men and 24.7 ± 3.25 kg/m(2) for women, and the ALT levels were higher in male patients (22.6 ± 9 vs. 16.4 U/l ± 8, p value = 0.003). Multivariate linear regression showed that BMI and sex were independent variables that were positively associated with the levels of ALT (p < 0.0001). Moreover, when we analyzed donors according to the Prati criteria, 63 (36.0 %) of the individuals were classified into this subgroup. The mean ALT concentration was 12.9 U/l ± 4.5 in women and 19.7 U/l ± 6.9 in men, and these values were significantly lower than those obtained from subjects who did not fit the Prati criteria (19.4 U/l ± 1.8, p = 0.04 for women and 29.0 U/l ± 12.1, p = <0.0001 for men). Thus, we calculated healthy ALT values of 33 IU/l for men and 22 IU/l for women., Conclusions: The ULN for ALT levels in Middle Eastern populations should be lowered, including separate values for males and females. Furthermore, metabolic parameters were shown to have a significant effect on ALT levels.

Background/aim: This study aims to investigate whether the SNPs of CXCR1 gene, could predict the likelihood of viral persistence and/or disease progression., Material and Methods: We investigated the association of two different SNPs (rs2234671, and rs142978743) in 598 normal healthy controls and 662 HBV patients from a Saudi ethnic population. The HBV patients were categorized into inactive carriers (n = 428), active carriers (n = 162), cirrhosis (n = 54) and Cirrhosis-HCC (n = 18) sub-groups. Genetic variants in CXCR1 were determined by polymerase chain reaction (PCR)-based DNA direct sequencing., Results: The frequency of the risk allele 'C' for the SNP, rs2234671 was found to be insignificant when the patient group was compared to the uninfected control group, however, a significant distribution of the allele 'C' of rs2234671 was observed among active HBV carriers + cirrhosis + cirrhosis - HCC vs. inactive HBV carriers with an OR = 1.631 (95% C.I. 1.016-2.616) and p = 0.032. However, no significant association was observed for rs142978743 when the distribution of risk allele was analyzed among the different patient groups (i.e. inactive carriers, active carriers, cirrhosis and HCC). Furthermore, the most common haplotype, Haplo-1 (AG), was found to have an insignificant frequency distribution between HBV cases and controls, while the same haplotype was found to be significantly distributed when active carriers + cirrhosis + cirrhosis - HCC patients were compared to inactive HBV carriers with a frequency of 0.938 and p = 0.0315. Haplo-2 (AC) was also found to be significantly associated with a frequency of 0.058 and p = 0.0163., Conclusion: The CXCR1 polymorphism, rs2234671 was found to be associated with chronic HBV infection and may play a role in disease activity.

Background and Objectives: Hepatitis C virus (HCV) genotype (G) knowledge is essential for determining type, duration and rate of response to antiviral therapy, possible route of HCV transmission, and future vaccine development. Our aim was to study HCV genotypes and to provide precise data on genotype distribution in both genders and different age groups amongst Saudi patients., Design and Setting: Genotype data from molecular laboratories at four different tertiary care hospitals in Riyadh from January 2006 until December 2010 were collected and analyzed., Patients and Methods: Consecutive data on genotype, sex and age was collected from 1013 Saudi patients. Genotyping was done by selective hybridization of amplicons to HCV genotype-specific oligonucleotides., Results: We found G1 in 262 patients (25.9%), G2 in 44 (4.4 %), G3 in 29 (2.9 %), G4 in 608 (60%), and 3 patients (0.3%) each of G5 and G6. In addition, 64 (6.3%) patients had mixed genotypes, mostly G4 and G1. On subtyping in 191 G1 patients, 67 (35.1%) were G1a, and 124 (64.9 %) G1b. Age distribution showed that 18 (1.7%) were 0-20 years, 173 (17.1 %) 21-40 years, 521 (51.4%) 41-60 years and 301(29.7%) > 60 years. There was no significant difference in frequency of G1, G3 and G4 among the two genders., Conclusion: G1 and G4 are the predominant genotypes in Saudi patients infected with HCV (85.9%), with a similar distribution among the two sexes and no significant changes in genotype distribution over the past decade.

Hepatitis B virus (HBV) is the major causative agent of chronic liver complications including cirrhosis and hepatocellular carcinoma (HCC). Individuals infected with HBV show a wide spectrum of disease manifestations ranging from asymptomatic carriers to HCC. TLR3 is part of the innate immune system that recognizes double-stranded RNA (dsRNA) and provides early immune response to exogenous antigens. The genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in the TLR3 could be considered as factors for the susceptibility to viral pathogens including HBV. Due to lack of knowledge on the role of TLR3 polymorphisms in HBV infection, this study investigated the distribution of nine SNPs in the TLR3 gene and its association with Saudi Arabian patients infected with HBV. A total of 707 patients and 600 uninfected controls were examined for different parameters including the nine SNPs (rs5743311, rs5743312, rs1879026, rs5743313, rs5743314, rs5743315, rs111611328, rs78726532 and a newly identified SNP located at position 184322913 of chr4). The association analysis confirmed that only one SNP, rs1879026 (G/T), showed a significant difference (P = 0.0480; OR = 0.809, 95% CI = 0.655-0.999) in the distribution between HBV carriers and uninfected controls. While, the rest of the SNPs showed no significant association with regards to HBV infection or in the progression to cirrhosis of the liver and HCC. Furthermore, haplotype analysis revealed that one haplotype GCGA (rs1879026, rs5743313, rs5743314, and rs5743315, respectively), was associated significantly with HBV infection in this population. These findings indicate that genetic variations in the TLR3 gene could affect the outcome of HBV infection among Saudis., (Copyright © 2012 Wiley Periodicals, Inc.)

Background and Objectives: Although usually asymptomatic, many chronic hepatitis C patients have extrahepatic manifestations and impaired health-related quality of life (HRQOL), while hepatitis B virus (HBV) patients have normal or nearly normal HRQOL. The aim of this study was to investigate HRQOL in Saudi patients infected with hepatitis C virus (HCV) in comparison with patients infected with HBV in an effort to document the prevalence of and find factors associated with reduced HRQOL in these patients., Design and Setting: A prospective study that enrolled patients attending a tertiary care referral hepatology clinic in Riyadh from the period of February to July 2008., Patients and Methods: Consecutive patients who had a confirmed diagnosis of hepatitis C or hepatitis B were asked to fill out the SF-36 questionnaire. Information on epidemiological, educational, economic, and social parameters was collected. All clinical, laboratory, and available histological data were recorded., Results: Two hundred and twenty patients (107 with hepatitis B and 113 with hepatitis C) satisfied the inclusion criteria and participated in this study. Overall, 45% were men, and the average age was 41.6 (18.1) years. Patients with HCV had significantly lower scores in "physical functioning," "role limitations due to physical functioning," "social functioning," and "bodily pain." No significant differences in other parameters were observed. Various epidemiological and laboratory parameters were correlated with different HRQOL domains., Conclusions: Saudi hepatitis C patients showed significantly lower HRQOL scores in various domains compared to hepatitis B patients.

Background: The estimated prevalence of nonalcoholic fatty liver disease (NAFLD) in Saudi Arabia is 7% to 10%. Despite the high prevalence of risk factors including diabetes, obesity, and hyperlipidemia, no recent epidemiological studies have measured the disease burden. We aimed to determine the characteristics of Saudi NAFLD patients attending a university hospital, and study factors affecting alanine aminotransferase (ALT) levels., Design and Setting: A prospective study among patients referred for ultrasonography in King Khalid University Hospital in Riyadh, Saudi Arabia from February to May 2009., Patients and Methods: NAFLD was defined as an appearance of fatty liver on routine abdominal ultrasound in the absence of coexisting liver disease and alcohol consumption. Patients were classified into normal and high ALT (ALT >60 U/L) level groups for analysis., Results: The prevalence of NAFLD was 16.6% (218/1312). Patients with normal ALT had the mean (SD) age of 45.9 (10.6) years and the mean body mass index of 34.5 (7.9) kg/m2. Forty percent of the 151 patients with normal ALT had diabetes, 66.2% were obese, and 29.1% had hypertension. Forty-three patients (23%) had high ALT levels. These patients had significantly lower age (P=.003) and fasting blood sugar (P=.03) than the normal ALT group. Non-diabetic patients (odds ratio 0.30, 95% CI 0.1-0.8), men (female OR 0.23, 95% CI 0.1-0.5), lower cholesterol (P=.001), high-density lipoprotein (P=.006), and low-density lipoprotein (P=.008) levels were more likely to be observed among patients with high ALT levels. In a multivariate analysis, younger age (OR 0.96, 95% CI 0.93-0.99), being male (OR 0.23, 95% CI 0.09-0.57), and a lower cholesterol level (OR 0.55, 95% CI 0.37-0.82) were significant predictors of high ALT levels., Conclusion: Based on the high prevalence of obesity and diabetes, the prevalence of NAFLD will continue to be high, unless awareness is inculcated among the local population.

Recognizing the significant prevalence of hepatocellular carcinoma (HCC) in Saudi Arabia, and the difficulties often faced in early and accurate diagnoses, evidence-based management, and the need for appropriate referral of HCC patients, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) formed a multi-disciplinary task force to evaluate and update the previously published guidelines by the Saudi Gastroenterology Association. These guidelines were later reviewed, adopted and endorsed by the Saudi Oncology Society (SOS) as its official HCC guidelines as well. The committee assigned to revise the Saudi HCC guidelines was composed of hepatologists, oncologists, liver surgeons, transplant surgeons, and interventional radiologists. Two members of the task force served as guidelines editors. A wide based search on all published reports on all aspects of the epidemiology, natural history, risk factors, diagnosis, and management of HCC was performed. All available literature was critically examined and available evidence was then classified according to its strength. The whole document and the recommendations were then discussed in detail by members and consensus was obtained. All recommendations in these guidelines were based on the best available evidence, but were tailored to the patients treated in Saudi Arabia. We hope that these guidelines will improve HCC patient care and enhance the multidisciplinary care needed for these patients.

Background: Alpha-fetoprotein (AFP) levels for the diagnosis of hepatocellular carcinoma (HCC) may vary by geographical region and racial background. No data exists for this test in the Middle Eastern population. In addition, there is limited data on the impact of virological status on AFP levels., Methods: In a multicenter, case-control study involving 206 cases, 199 cirrhotic and 197 chronic hepatitis controls, we assessed the utility of AFP in the diagnosis of HCC (sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and positive likelihood ratios (LR). PPV and NPV were evaluated for three additional HCC prevalence rates (5, 10, and 20%)., Results: The best discriminating AFP value was 11.7 ng/ml. The sensitivity ranged from 32 to 79.5% at different AFP levels with the specificity increasing sequentially from 47.7 to 98.5%. Sensitivity of AFP at the best cut-off level for hepatitis C virus (HCV), hepatitis B virus (HBV) and non-viral etiology for HCC was 73.7, 65.6, and 59.5%, respectively. Specificity at this level for HCV, HBV, and non-viral etiology was 36.6, 30.1, and 29.4%, respectively. AFP cut-off levels of 102, 200, and 400 ng/ml showed similar sensitivity (39.8, 35.9, and 32%, respectively) and specificity (96, 98.5, and 98.5% respectively). Positive LR for AFP at >11.7, >20, >102, >200, >400 ng/ml were 2.8, 3.3, 9.9, 23.8, and 21.2, respectively., Conclusions: In cirrhotic patients, AFP has a poor screening and diagnostic value for HCC. Underlying viral etiology fails to influence the diagnostic accuracy of this test. An AFP level greater than 100 ng/ml has a high degree of specificity and may be used as a confirmatory test.

Background and Objectives: There are few reports on hepatitis C virus genotype 4 (HCV-4) recurrences after orthotopic liver transplantation (OLT). Therefore, we undertook a study to determine the epidemiological, clinical and virological characteristics of patients with biopsy-proven recurrent HCV infection and analyzed the factors that influence recurrent disease severity. We also compared disease recurrence and outcomes between HCV-4 and other genotypes., Patients and Methods: All patients who underwent OLT (locally or abroad) for HCV related hepatic cirrrhosis from 1991 to 2006 and had recurrent HCV infection were identified. Clinical, laboratory and pathological data before and after OLT were collected and analyzed., Results: Of 116 patients who underwent OLT for hepatitis C, 46 (39.7%) patients satisfied the criteria of recurrrent hepatitis C. Twenty-nine (63%) patients were infected with HCV genotype 4. Mean (SD) for age was 54.9 (10.9) years. Nineteen of the HCV genotype 4 patients (65.5%) were males, 21 (72.4%) received deceased donor grafts, and 7 (24.1%) developed > or =1 acute rejection episodes. Pathologically, 7 (24.1%) and 4 (13.8%) patients had inflammation grade 3-4 and fibrosis stage 3-4, respectively. Follow-up biopsy in 9 (31%) HCV genotype 4 patients showed stable, worse and improved fibrosis stage in 5, 2 and 2 patients, respectively. Of the 7 patients in the recurrent HCV group who died, 6 were infected with genotype 4 and 4 of them died of HCV-related disease., Conclusion: This analysis suggests that HCV recurrence following OLT in HCV-4 patients is not significantly different from its recurrence for other genotypes.

Aim: To determine the seroprevalence of Hepatitis A (HAV) amongst Saudi children and compare it with previously reported prevalence data from the same population., Methods: A total of 1357 students were randomly selected between the ages of 16 and 18 years (689 males and 668 females) from three different regions of Saudi Arabia (Madinah, Al-Qaseem, and Aseer) and tested for anti-HAV-IgG., Results: The overall prevalence of anti-HAV-IgG among the study population was 18.6%. There was no difference between males and females but there was a significant difference in the seroprevalence (P = 0.0001) between the three different regions, with Madinah region showing the highest prevalence (27.4%). When classified according to socioeconomic status, lower class students had a prevalence of 36.6%, lower middle class 16.6%, upper middle class 9.6%, and upper class 5.9% (P = 0.0001). Comparing the current study results with those of previous studies in 1989 and 1997 involving the same population, there was a marked reduction in the overall prevalence of HAV from 52% in 1989, to 25% in 1997, to 18.6% in 2008 (P < 0.0001)., Conclusion: Over the last 18 years, there has been a marked decline in the prevalence of HAV in Saudi children and adolescents. The current low prevalence rates call for strict adherence to vaccination policies in high-risk patients and raises the question of a universal HAV vaccination program.

Background: Hepatic granuloma (HG) has a high reported incidence in Saudi Arabia (14.6%). We aimed to identify the incidence of HG in our centres and review its presenting features and underlying aetiology., Methods: A total of 5531 liver biopsies were screened through a computer database over 13 years. Sixty-six (1.2%) patients fulfilled our inclusion criteria. The patients were then divided into three groups according to the aetiology. Group 1, tuberculosis (n=26); Group 2, viral hepatitis B and C (n=11); and Group 3, idiopathic (n=9). The demographical data and the clinical and biochemical features of all the groups were analysed., Results: Infections comprised of 72.2% of HG. The incidence of tuberculosis was 42.6%, viral hepatitis 16.3% and idiopathic 14.8%. Fever (47.5%), weight loss (42.6%) and fatigue (45.9%) were commonly found symptoms. Fever and weight loss were significantly more frequently presenting symptoms in Group 1 than in Groups 2 and 3 (P=0.0002, 0.04, 0.001 and 0.02 respectively). The mean bilirubin levels in Group 1 were significantly lower than in Groups 2 and 3 (P=0.04 and 0.03 respectively). The mean albumin levels were significantly lower in Group 3 compared with Group 2 (P=0.002), and Group 1 had lower levels compared with Group 2 (P=0.018)., Conclusion: The incidence of HG is much lower than reported previously from this region. Tuberculosis and viral hepatitis are the most common causes and, contrary to previous reports, schistosomiasis is rare. Fever and weight loss distinguished tuberculous HG.

Objective: To assess the patients awareness of their medical conditions, identify the factors affecting their awareness, and assess patient's satisfaction with their doctors explanations of medical conditions., Methods: A cross-sectional study was conducted in October 2005 in the outpatient clinics of King Khalid University Hospital in Riyadh, Kingdom of Saudi Arabia. A self-administered questionnaire was used for data collection. The statistical package for Social Science was used for analysis., Results: Five hundred and one patients were included in the study. The mean age was 45.6 +/- 16.8. Fifty-five percent were female and 29% were highly educated. Most of the patients (64.1%) knew their diagnoses. This was significantly associated with the educational level; chronicity of the disease, and the awareness of other issues related to their illness such as complications and name of their medications (p<0.05). Few patients (20%) knew complications of their diseases. Seventy percent of patients were satisfied with their doctors' explanation of their disease. Knowing the diagnosis (p=0.001) and the disease complications (p=0.014) were associated significantly with patients' satisfaction., Conclusion: These figures are less than what they should be. Physicians must be advised of the importance of proper patient education. In addition, the lack of proper education by physicians demonstrated in this study should be compensated for by an increase in non-physician based education tools.

Objectives: Biliary complications remain a major concern in living-donor liver transplant. They can lead to patient and graft loss. In this study, we retrospectively analyzed patients' records to identify factors that increase the frequency of biliary complications in living-donor liver transplant with an aim toward decreasing this frequency., Materials and Methods: We performed 53 living-donor liver transplants between November 2002 and September 2007. Five cases were excluded because of graft or patient loss within 2 weeks resulting in 48 cases available for analysis. The effect of the following variables on the frequency of biliary complications was analyzed: recipient age, liver lobe used, number of graft bile ducts, number of biliary anastomoses, type of biliary anastomosis, and bile duct diameter 4 mm or smaller., Results: Biliary complications were seen in 14 cases (29.1%). These included 9 biliary strictures, 3 bile leaks, and 2 bile leaks eventually healing as biliary strictures. The presence of more than 1 graft bile duct increased the frequency of biliary complications (P = .03). The other variables did not have a statistically significant effect on the frequency of biliary complications., Conclusions: The rate of complications in our experience is comparable to that already published. The presence of more than 1 bile duct in the graft is a risk factor for biliary complications in living-donor liver transplant. A review of the data suggests additional risk factors.

Background: Saudi Arabia is a leading country in the Middle East in the field of deceased-donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT). We present out experience with DDLT and LDLT at King Faisal Specialist Hospital and Research Center (KFSHRC) for the period from April 2001 to January 2007., Patients and Methods: We performed 122 LT procedures (77 DDLTs and 45 LDLTs) in 118 patients (4 re-transplants) during this period of time., Results: The number of adult and pediatric procedures was 107 and 11, respectively. The overall male/female ratio was 66/52 and the median age of patients was 43 years (range, 2-63 years). In the DDLT group, the median operating time was 8 hours (range, 4-19), the median blood transfusion was 6 units (range, 0-40), and the median hospital stay was 13 days (range, 6-183). In the DDLT group, after a mean follow-up period of 760 days (range, 2-2085), the overall patient and graft survival rate was 86%. In the LDLT group, the median operating time was 11 hours (range, 7-17), the median blood transfusion was 4 units (range, 0-65), and the median hospital stay was 15 days (range, 7-127). In the LDLT group, and after a mean follow-up period of 685 days (range, 26- 1540), the overall patient and graft survival rates were 90% and 80%, respectively with no significant difference in patient and graft survivals between groups. Biliary complications were significantly higher in LDLT compared to DDLT (P<0.05). Vascular complications were also significantly higher in LDLT compared DDLT (P<0.05)., Conclusions: Both DDLT and LDLT are being successfully performed at KFSHRC with early experience indicating a higher rate of biliary and vascular complications in the LDLT group.

Objective: To evaluate the prevalence of Helicobacter pylori (H. pylori) among Saudi medical students., Methods: Volunteer medical students were randomly selected in the College of Medicine, King Saud University, Riyadh, Saudi Arabia from January 2005 to May 2005. A urea breath test (UBT) was performed for each medical student. Important demographic data was recorded. Each student had to answer a questionnaire on upper gastrointestinal (UGI) symptoms before the UBT., Results: A total of 120 students were recruited (73 males [61%] and 47 females [39%]) with a mean age of 22.2 years (age varied from 18 to 28 years). The prevalence of H. pylori was surprisingly low at 35%, compared to a previously reported high prevalence among the Saudi population (80%). Thirty-one percent of medical students reported >or= 1 UGI symptom with no significant differences between the positive and negative UBT results. Although there was a trend, there was no significant prevalence difference between the preclinical and the clinical group of students., Conclusion: We found a low prevalence of H. pylori in our young university medical student's population. The low prevalence of H. pylori in this young population may have important clinical and economic implications.

Background: We tested the clinical utility of the platelet count, the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the AST to platelet ratio index (APRI) score in predicting the presence or absence of advanced fibrosis and cirrhosis in patients with chronic hepatitis C in Saudi Arabia., Methods: Liver biopsy procedures performed on chronic hepatitis C patients in our gastroenterology unit at King Khalid University Hospital were traced from records between the years 1998 to 2003. The hospital computer database was then accessed and detailed laboratory parameters obtained. By plotting receiver operating characteristic curves (ROC), three selected models (platelet count, AST/ALT ratio, and the APRI score was the one associated with the highest area under the curve (AUC)=0.812 (95% CI, 0.756-0.868) on the ROC curves, compared to the platelet count and AST/ALT ratio, which yielded an AUC of 0.783 (0.711-0.855) and 0.716 (0.642-0.789), respectively., Conclusion: The APRI score seemed to be the best predictive variable for the presence or absence of advanced fibrosis in Saudi hepatitis C patients.

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.

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.