Clinical and patient-reported outcomes in patients with chronic hepatitis B and C and non-alcoholic fatty liver disease from real-world practices in Saudi Arabia, Turkey and Egypt.

Patients with chronic liver disease (CLD) experience health-related quality of life (HRQoL) and patient-reported outcomes (PROs) impairments. We assessed and identified predictors of HRQoL and PROs in CLD patients from Saudi Arabia (SA), Turkey and Egypt. Patients enrolled in Global Liver Registry™ with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) were included. Clinical data and PRO questionnaires (FACIT-F, CLDQ and WPAI) were compared across countries. Linear regression identified PRO predictors. Of the 4014 included patients, 26.9% had CHB, 26.9% CHC and 46.1% NAFLD/NASH; 19.2% advanced fibrosis. Compared across countries, CHB patients were younger in Egypt (mean age [years] 41.2 ± 11.4 vs. 45.0 ± 10.3 SA, 46.1 ± 12.0 Turkey), most often employed in SA (64.8% vs. 53.2% Turkey) and had the lowest prevalence of obesity in Turkey (26.7% vs. 37.8% SA, 38.5% Egypt). In SA, CHB patients had lowest prevalence of fibrosis and comorbidities (all p < .01). There was a higher frequency of males with NAFLD/NASH in SA (70.0% vs. 49.6% Turkey, and 35.5% Egypt). Among NAFLD/NASH patients, CLDQ-NAFLD/NASH scores were highest in SA (mean total score: 5.3 ± 1.2 vs. 4.8 ± 1.2 Turkey, 4.1 ± 0.9 Egypt, p < .01). Independent predictors of worse PROs included younger age, female sex, advanced fibrosis, non-hepatic comorbidities and lack of regular exercise (all p < .05). Clinical presentation and PRO scores of CLD patients vary across SA, Turkey and Egypt. Impairment of HRQoL is associated with demographic factors, lack of regular exercise, advanced fibrosis and non-hepatic comorbidities.

Knowledge about metabolic dysfunction-associated steatotic liver disease among the medical professionals from countries in the MENA region.

INTRODUCTION AND OBJECTIVES: Given the substantial burden of metabolic dysfunction-associated steatotic liver disease (MASLD), there is an urgent need to assess knowledge and awareness levels among physicians. We assessed MASLD knowledge among healthcare providers from Saudi Arabia, Egypt, and Türkiye. MATERIALS AND METHODS: Two global surveys containing 54-59 items assessed awareness and knowledge of MASLD/NAFLD- one survey for hepatologists and gastroenterologists, the second for non-specialists (e.g. endocrinologists, primary care providers (PCPs), other healthcare professionals). Data were collected using an electronic data collection form. Knowledge scores and variables associated with higher knowledge scores were compared across all specialties. RESULTS: A total of 584 physicians completed the survey (126 hepatologists, 178 gastroenterologists (GEs), 38 endocrinologists, 242 PCPs/others). Practice guidelines were the primary source for knowledge across all specialties (43-51%), then conferences (24-31%) except PCPs/others who selected internet as the second common source (25%). Adherence to societal guidelines varied by specialty (81-84% of specialists vs 38-51% of non-specialists). Hepatologists and GEs showed similar mean knowledge scores (51-72% correct answers across three knowledge domains, p>0.05); endocrinologists outperformed PCPs/others in knowledge scores in all knowledge domains including Epidemiology/Pathogenesis (72% vs. 60%), Diagnostics (73% vs. 67%), and Treatment (78% vs. 67%) (all p<0.01). Hospital-based practice and seeing a greater number of patients with MASLD/NAFLD were identified as independent predictors of higher knowledge scores among specialists (both p<0.05). CONCLUSIONS: A knowledge gap for identification, diagnosis, and management of MASLD/NAFLD was found despite the growing burden of MASLD/NAFLD in Saudi Arabia, Egypt, and Türkiye. Education to increase awareness is needed.

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score.

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.

Hepatitis delta virus infection prevalence, diagnosis and treatment in the Middle East: A scoping review.

Hepatitis D virus (HDV) infection is a global public health concern, especially because of its unique existence in the presence of hepatitis B virus infection. HDV infection is estimated to affect 12 million people globally. Having a clearer understanding of its prevalence in all regions of the world is essential for helping direct preventive and early interventional treatment. This mini-review assessed the literature over the last 10 years to determine the prevalence, diagnostic means and treatment guidelines available for HDV in the Middle East. The search found limited data available in 21 articles, of which 18 were studies focused on Iran. Prevalence rates ranged dramatically among the countries, and none of the 12 countries included in the search had specific HDV guidelines. This review highlights the urgent need for more precise data for the Middle East region to help establish early diagnosis and treatment options for HDV.

Development and multicenter validation of FIB-6: A novel, machine learning, simple bedside score to rule out liver cirrhosis and compensated advanced chronic liver disease in patients with chronic hepatitis C.

BACKGROUND: Non-invasive tests (NITs), such as Fibrosis-4 index (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI), developed using classical statistical methods, are increasingly used for determining liver fibrosis stages and recommended in treatment guidelines replacing the liver biopsy. Application of conventional cutoffs of FIB-4 and APRI resulted in high rates of misclassification of fibrosis stages. AIM: There is an unmet need for more accurate NITs that can overcome the limitations of FIB-4 and APRI. PATIENTS AND METHODS: Machine learning with the random forest algorithm was used to develop a non-invasive index using retrospective data of 7238 patients with biopsy-proven chronic hepatitis C from two centers in Egypt; derivation dataset (n = 1821) and validation set in the second center (n = 5417). Receiver operator curve analysis was used to define cutoffs for different stages of fibrosis. Performance of the new score was externally validated in cohorts from two other sites in Egypt (n = 560) and seven different countries (n = 1317). Fibrosis stages were determined using the METAVIR score. Results were also compared with three established tools (FIB-4, APRI, and the aspartate aminotransferase-to-alanine aminotransferase ratio [AAR]). RESULTS: Age in addition to readily available laboratory parameters such as aspartate, and alanine aminotransferases, alkaline phosphatase, albumin (g/dl), and platelet count (/cm3 ) correlated with the biopsy-derived stage of liver fibrosis in the derivation cohort and were used to construct the model for predicting the fibrosis stage by applying the random forest algorithm, resulting in an FIB-6 index, which can be calculated easily at http://fib6.elriah.info. Application of the cutoff values derived from the derivation group on the validation groups yielded very good performance in ruling out cirrhosis (negative predictive value [NPV] = 97.7%), compensated advance liver disease (NPV = 90.2%), and significant fibrosis (NPV = 65.7%). In the external validation groups from different countries, FIB-6 demonstrated higher sensitivity and NPV than FIB-4, APRI, and AAR. CONCLUSION: FIB-6 score is a non-invasive, simple, and accurate test for ruling out liver cirrhosis and compensated advance liver disease in patients with chronic hepatitis C and performs better than APRI, FIB-4, and AAR.

Clinical and virological outcomes of entecavir therapy in patients with chronic hepatitis B: A real life experience.

BACKGROUND: Entecavir (ETV) is a nucleoside analogue (NA) that is effective for treatment of chronic hepatitis B (CHB) due to its low resistance rates and potent antiviral effects. We aimed to evaluate the clinical, biochemical and virological response to ETV in patients without a prior use of nucleos(t)ide (NA-naïve) vs. those who failed prior NA use (NA-experienced) in the treatment of CHB. METHODS: Patients treated between April 2012 and December 2017 were retrospectively studied. A comparison was made between patients treated with ETV in NA-naïve Vs. NA-experienced. Complete virological response (CVR) was defined as achieving undetectable HBV-DNA level, up to 15 IU/ml, partial virological response (PVR) as 15-200 IU/ml and >200 IU/ml for no virological response (NVR) after one year of therapy. RESULTS: Overall, 148 patients were included (69 NA-naïve and 79 NA-experienced). In NA-naïve group, 51%, 17% and 32% achieved CVR, PVR and NVR vs. 17%, 9% and 75% in NA-experienced group, respectively (p < 0.001). HBsAg seroconversion was achieved in 5.8% in NA-naïve group vs. 6.3% in NA-experienced group (p = 1.00). HBeAg seroconversion was 17% in NA-naïve group and 25% in NA-experienced group (p = 0.24). There was no significant difference in alanine transaminase normalization or in mortality rate between both groups; p = 0.87 and p = 1.00 respectively. CONCLUSION: ETV therapy in CHB results in a better virological response in NA-naïve patients compared to NA-experienced. There were no differences between both groups in regards to the rate of HBsAg or HBeAg seroconversions, biochemical improvements or mortality.

High Efficacy of ombitasvir/paritaprevir/ritonavir plus dasabuvir in hepatitis C genotypes 4 and 1-infected patients with severe chronic kidney disease.

BACKGROUND & AIMS: Limited data have shown high efficacy of co-formulated ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in the treatment of hepatitis C virus (HCV) genotype (GT)-4, and combined with dasabuvir (DSV) in GT1 patients, with chronic kidney disease (CKD) stages 4-5 (<30 mL/min/1.73 m2 ). We assessed real-world safety and efficacy of OBV/PTV/r ± DSV in GT1- and 4-infected patients. METHODS: In this observational cohort (n = 67), we enrolled stages 4-5 CKD treatment-naïve or Peginterferon/RBV-experienced GT4-infected patients (n = 32) treated for 12-24 weeks with OBV/PTV/r ± RBV, and plus DSV in GT1 patients (n = 35, including 3 with GT1/4 co-infection). RBV was dosed by physician discretion between 200 mg weekly and 200 mg daily. Primary endpoints were SVR12, calculated on intention-to-treat (ITT) basis, and occurrence of serious adverse events. RESULTS: The mean age of the cohort was 45.7 ± 12.7 years, 50.7% were females, 20.9% had cirrhosis, 35.8% were treatment-experienced and 97% were on haemodialysis. Three patients (F4) received 24-week treatment, 2 with GT4, and 1 with GT1a; and 19.4% were treated without RBV, including 9 GT1, and 4 GT4. Overall, 65 (97.1%) patients achieved SVR12, including 100% of those with a post-treatment follow-up (modified ITT analysis). Of the two patients without SVR12, one died from sepsis-related complications and the other from a myocardial infarction 2 weeks after completing therapy. Grades 3-4 anaemia occurred in 8.9%. CONCLUSION: A 12-week regimen of OBV/PTV/r ± DSV with or without RBV is highly effective with a favourable safety profile amongst GT4 and GT1 patients with CKD stages 4-5. SVR12 rates were high regardless of patient characteristics.

Efficacy and Safety of Simeprevir or Daclatasvir in Combination With Sofosbuvir for the Treatment of Hepatitis C Genotype 4 Infection.

INTRODUCTION: The combination of sofosbuvir (SOF) with simeprevir (SMV) or daclatasvir (DCV) is very effective in treating hepatitis C virus (HCV) infection, particularly genotype (GT) 1. However, the data on GT4 are very limited. We aimed to determine the efficacy and safety of SOF in combination with either SMV or DCV in GT4-infected patients. PATIENTS AND METHODS: In this real life, prospective, observational study, HCV (GT4) patients (n=96) were evaluated in 2 groups on the basis of the 12-week treatment regimen they received. Group 1 (n=56) patients were treated with SOF and SMV±ribavirin (RBV), whereas group 2 patients were treated with SOF and DCV±RBV (n=40). The primary efficacy endpoint was sustained virologic response 12, whereas the primary safety endpoint was drug discontinuation or occurrence of grade 3/4 adverse events. RESULTS: The mean age was 49±14.6 years (59.4% men). Cirrhosis was present in 53.6% and 35.0% of groups 1 and 2, respectively, whereas 27 patients (48.2%) in group 1 and 21 patients (52.5%) in group 2 had failed prior interferon-based treatment. The median pretreatment HCV-RNA log10 was 6.1 (3.6 to 7.0) and 6.0 (3.6 to 7.2) IU/mL in groups 1 and 2, respectively. RBV was given to 17 patients (30.4%) in group 1 and 2 patients (5%) in group 2. All patients achieved sustained virologic response 12 (100%). Adverse events occurred in 32% of patients (grade 1 and 2), but none discontinued treatment. One patient died in the SMV group (not related to treatment). CONCLUSIONS: SMV/SOF or DCV/SOF combinations are safe and highly effective in HCV-GT4 treatment. Cirrhosis and failure of prior interferon-based treatment did not influence treatment response.

Diminished accuracy of biomarkers of fibrosis in low replicative chronic hepatitis B.

BACKGROUND: We evaluated the diagnostic accuracy of aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), AST/alanine aminotransferase (ALT) ratio (AAR), and age-platelet index (API) for significant fibrosis (Metavir F2-4) in low-replicative (HBV DNA <20,000 IU/mL) chronic hepatitis B virus (HBV) patients. METHODS: The sensitivity, specificity, and area under the receiver-operating characteristic curve (AUROC) of HBeAg-negative, low-replicative (n = 213) and high-replicative (HBV DNA ≥20,000 IU/mL, n = 153) patients was assessed. RESULTS: Overall, 113 patients (30.9%) had F2-4 fibrosis. Of the low and high-replicative patients, 40 (18.8%) and 73 (47.7%) had F2-4, respectively (P < 0.0001). APRI ≥0.5 less frequently identified F2-4 fibrosis in low vs. high-replicative patients (48.7% vs. 69.6%, P = 0.032) and AAR identified it more frequently in low-replicative patients (37.5% vs. 19.4%, P = 0.037). FIB-4 and API were not different (P > 0.05) for identifying F2-4 fibrosis in low and high-replicative patients. Higher specificities were seen at the lowest cut-offs in low vs. high-replicative states for APRI (≥0.5, 98% vs. 68.9%), AAR (84.3% vs. 76.6%), FIB-4 (≥1.45, 97.5% vs. 87.8%) and API (>4, 94.8% vs. 93.8%). At ROC-defined thresholds, APRI (≥0.33), AAR (≥0.93), FIB-4 (≥0.70) and API (>2) showed greater AUROCs for F2-4 diagnosis in low replicative (0.80, 0.62, 0.81 and 0.71, respectively) vs. high-replicative patients (0.73, 0.52, 0.67 and 0.69, respectively). CONCLUSION: All 4 biomarkers in both, low and high-replicative HBV demonstrate modest accuracy for fibrosis diagnosis at conventional cut-offs. Lowering the cut-offs may increase the diagnostic relevance of these biomarkers, particularly for APRI and FIB-4 in low-replicative disease.

PARK2 polymorphisms predict disease progression in patients infected with hepatitis C virus.

 Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer. The present study investigated the association of single nucleotide polymorphisms (SNPs) in the PARK2 gene with the development of hepatitis C virus (HCV) infection and its progression to severe liver diseases. MATERIAL AND METHODS: A total of 800 subjects, including 400 normal healthy subjects and 400 HCV-infected patients, were analyzed in this study. The patients were classified as chronic HCV patients (group I), patients with cirrhosis (group II) and patients with hepatocellular carcinoma (HCC) in the context of cirrhosis (group III). DNA was extracted and was genotyped for the SNPs rs10945859, rs2803085, rs2276201 and rs1931223. RESULTS: Among these SNPs, CT genotype of rs10945859 was found to have a significant association towards the clinical progression of chronic HCV infection to cirrhosis alone (OR = 1.850; 95% C. I. 1.115-3.069; p = 0.016) or cirrhosis and HCC (OR = 1.768; 95% C. I. 1.090-2.867; p value = 0.020). CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients.

Genetic variability of the core protein in hepatitis C virus genotype 4 in Saudi Arabian patients and its implication on pegylated interferon and ribavirin therapy.

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.

Genetic variation in interleukin 28B and correlation with chronic hepatitis B virus infection in Saudi Arabian patients.

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.

Predictors of significant fibrosis in chronic hepatitis B patients with low viremia.

BACKGROUND AND AIM: The data on the prevalence and predictors of significant fibrosis (≥F2, METAVIR) in chronic hepatitis B virus (HBV) patients with low viremia are limited. We aimed to assess both the prevalence predictors of ≥F2 fibrosis in hepatitis B envelope antigen-negative patients with HBV DNA <20,000 IU/mL. METHODS: Hepatitis B envelope antigen-negative patients (n=213) with mean HBV DNA <2000 IU/mL (n=97) and HBV DNA 2000 to 20,000 IU/mL (n=116) were included and all had liver biopsy. Variables significantly associated with ≥F2 fibrosis on an univariate analysis were included in a multivariate logistic regression model. RESULTS: Overall, 40 (18.8%) patients had ≥F2 fibrosis, with no difference between those with mean HBV DNA <2000 IU/mL (19.6%) compared with patients with HBV DNA of 2000 to 20,000 IU/mL (18.1%; P=0.782). Fibrosis ≥F2 was similar in patients with HBV DNA <2000 versus 2000 to 20,000 IU/mL in relation to varying alanine aminotransferase thresholds (P>0.05), and was less frequent in persistently normal alanine aminotransferase patients (13.6%) when compared with those with elevated or fluctuating levels (25.3%, P=0.030). Fewer patients under 40 years of age had ≥F2 fibrosis (12.5%) as compared with older ones (28.2%; P=0.004). Logistic regression analysis identified higher aspartate aminotransferase [odds ratio (OR), 6.21; 95% confidence interval (CI), 2.48-15.54; P<0.0001], lower albumin (OR, 0.86; 95% CI, 0.78-0.95; P=0.002), platelet count (OR, 0.99; 95% CI, 0.98-0.99; P=0.013), and age (OR, 1.05; 95% CI, 1.01-1.09; P=0.024) as independent predictors of significant fibrosis. CONCLUSIONS: A small but significant minority of HBV patients with low viremia harbor significant fibrosis, although its rate is not different in those with viremia above or below 2000 IU/mL. Our findings may guide in decisions regarding liver biopsy and treatment in this category of patients.

Variations in DEPDC5 gene and its association with chronic hepatitis C virus infection in Saudi Arabia.

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.

Genome-wide association study of chronic hepatitis B virus infection reveals a novel candidate risk allele on 11q22.3.

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.

Long-term health and economic benefits of switching to tenofovir alafenamide versus continuing on entecavir in chronic hepatitis B patients with low-level viremia in Saudi Arabia.

BACKGROUND: Despite the success of current treatments, many chronic hepatitis B (CHB) patients still live with low-level viremia [LLV] resulting in liver disease progression. This study evaluated the long-term health and economic impact of switching to tenofovir alafenamide (TAF) from entecavir (ETV) in Saudi Arabia (SA) in chronic hepatitis B (CHB) LLV patients. METHODS: A hybrid decision tree Markov state-transition model was developed to simulate a cohort of patients with CHB LLV treated with ETV and switched to TAF over a lifetime horizon in SA. While on treatment, patients either achieved complete virologic response (CVR) or maintained LLV. CVR patients experienced slower progression to advanced liver disease stages as compared to LLV patients. Demographic data, transition probabilities, treatment efficacy, health state costs, and utilities were sourced from published literature. Treatment costs were sourced from publicly available databases. RESULTS: Base case analysis found that over a lifetime horizon, switching to TAF versus remaining on ETV increased the proportion of patients achieving CVR (76% versus 14%, respectively). Switching to TAF versus remaining on ETV resulted in a reduction in cases of compensated cirrhosis (-52%), decompensated cirrhosis (-5%), hepatocellular carcinoma (-22%), liver transplants (-12%), and a 37% reduction in liver-related deaths. Switching to TAF was cost-effective with an incremental cost-effectiveness ratio of $57,222, assuming a willingness-to-pay threshold of three times gross national income per capita [$65,790/QALY]. CONCLUSIONS: This model found that switching to TAF versus remaining on ETV in SA CHB LLV patients substantially reduced long-term CHB-related morbidity and mortality and was a cost-effective treatment strategy.

Double Trouble: How Microbiome Dysbiosis and Mitochondrial Dysfunction Drive Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are closely related liver conditions that have become more prevalent globally. This review examines the intricate interplay between microbiome dysbiosis and mitochondrial dysfunction in the development of NAFLD and NASH. The combination of these two factors creates a synergistic situation referred to as "double trouble", which promotes the accumulation of lipids in the liver and the subsequent progression from simple steatosis (NAFLD) to inflammation (NASH). Microbiome dysbiosis, characterized by changes in the composition of gut microbes and increased intestinal permeability, contributes to the movement of bacterial products into the liver. It triggers metabolic disturbances and has anti-inflammatory effects. Understanding the complex relationship between microbiome dysbiosis and mitochondrial dysfunction in the development of NAFLD and NASH is crucial for advancing innovative therapeutic approaches that target these underlying mechanisms.