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.

Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

BACKGROUND: We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). METHODS: A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. RESULTS: A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. CONCLUSIONS: The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

Prevalence of metabolic dysfunction-associated steatotic liver disease in the Middle East and North Africa.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is common and closely associated with type 2 diabetes (T2D). We assessed the prevalence of NAFLD/MASLD in the general population and among patients with T2D in the Middle East and North Africa (MENA) region. METHODS: We searched PubMed and Embase for English-language articles published between 1990 and 2023 according to PRISMA. Each country's NAFLD/MASLD prevalence in the general population and in T2D patients was predicted by using a multivariable meta regression model. Input data were extracted from our systematic review, GBD and NCD Risk Factor Collaboration. Confidence intervals were constructed by using prediction intervals with the delta method. RESULTS: Meta-analytic pooling estimated the prevalence of NAFLD/MASLD as 39.43% in the general population and 68.71% among T2D patients. NAFLD/MASLD prevalence has increased from 35.42% (2008-2016) to 46.20% (2017-2020). Using GBD-2019 dataset, it was predicted that there are 141.51 million cases of NAFLD/MASLD in the MENA region. The highest number of NAFLD/MASLD cases were expected in Egypt (25.71 million), followed by Türkiye (23.33 million) and Iran (19.85 million). Estimated NAFLD prevalence exceeded 40% in 10 of 21 countries with the top countries being Kuwait (45.37%), Egypt (45.0%), Qatar (44.4%), and Jordan (43.3%). Furthermore, it was predicted that there are 24.96 million cases of NAFLD/MASLD with T2D in the MENA region. CONCLUSIONS: In the MENA region, prevalence of NAFLD/MASLD is very high and growing, necessitating an urgent need for regional public policy to deal with this growing burden.

SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024.

ABSTRACT: Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

Multicenter validation of FIB-6 as a novel machine learning non-invasive score to rule out liver cirrhosis in biopsy-proven MAFLD.

BACKGROUND AND AIMS: We previously developed and validated a non-invasive diagnostic index based on routine laboratory parameters for predicting the stage of hepatic fibrosis in patients with chronic hepatitis C (CHC) called FIB-6 through machine learning with random forests algorithm using retrospective data of 7238 biopsy-proven CHC patients. Our aim is to validate this novel score in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHOD: Performance of the new score was externally validated in cohorts from one site in Egypt (n = 674) and in 5 different countries (n = 1798) in Iran, KSA, Greece, Turkey and Oman. Experienced pathologists using METAVIR scoring system scored the biopsy samples. Results were compared with FIB-4, APRI, and AAR. RESULTS: A total of 2472 and their liver biopsy results were included, using the optimal cutoffs of FIB-6 indicated a reliable performance in diagnosing cirrhosis, severe fibrosis, and significant fibrosis with sensitivity = 70.5%, specificity = 62.9%. PPV = 15.0% and NPV = 95.8% for diagnosis of cirrhosis. For diagnosis of severe fibrosis (F3 and F4), the results were 86.5%, 24.0%, 15.1% and 91.9% respectively, while for diagnosis of significant fibrosis (F2, F3 and F4), the results were 87.0%, 16.4%, 24.8% and 80.0%). Comparing the results of FIB-6 rule-out cutoffs with those of FIB-4, APRI, and AAR, FIB-6 had the highest sensitivity and NPV (97.0% and 94.7%), as compared to FIB-4 (71.6% and 94.7%), APRI (36.4% and 90.7%), and AAR (61.2% and 90.9%). CONCLUSION: FIB-6 score is an accurate, simple, NIT for ruling out advanced fibrosis and liver cirrhosis in patients with MAFLD.

Evaluation of Quantitative Hepatitis C Virus Core Antigen Testing as a Tool for Screening and Confirmation of HCV Infection.

BACKGROUND: Hepatitis C is a common viral infection worldwide. Finding the most effective diagnostic methods with low cost is always needed for laboratory improvement. In this study, we evaluated the performance of a quantitative chemiluminescent hepatitis C virus core antigen (HCV cAg) test by comparing it with the HCV confirmatory antibody line immunoblot assay (HCV Ab-LIA) test as well as the HCV quantitate reverse transcription-polymerase chain reaction (qRT-PCR) test. METHODS: A total of 394 samples were enrolled in the retrospective study. Of these, 225 samples were tested using HCV Ab screening and confirmatory Ab-LIA along with chemiluminescent HCV core Ag testing, while 169 samples were tested using qRT-PCR for HCV RNA and chemiluminescent HCV core Ag testing. RESULTS: Out of these, 225 positive samples tested by HCV Ab screening test were analyzed using the confirmatory Ab LIA and HCV cAg assays, a total of 183 samples (81.3 %) were confirmed to be Ab-positive, and among those, 77 samples (42.1%) were also positive for HCV cAg. Thirty-eight samples (20.76%) were HCV Ab indeterminate, and all of them were HCV cAg negative. Four samples (1.8%) were HCV Ab LIA-negative and negative for HCV cAg. Moreover, 169 samples were measured for qRT-PCR HCV viral load and quantitative HCV cAg test. One hundred and three samples were positive for HCV RNA, while 66 were negative. Among the positives, 96/103 samples were HCV cAg positive and 7/103 samples were negative. Out of the negatives, 4/66 samples were HCV cAg positive but 62/66 samples were negative. The HCV cAg results were concordant with the qRT-PCR results in 158 samples (93.5%); however, 11 samples (6.5%) were found to be discrepant. The sensitivity, specificity, positive predictive value, and negative predictive value of the quantitative HCV cAg were found to be 93%, 94%, 96%, and 90%, respectively. The overall coefficient of correlation between the HCV RNA levels and HCV cAg data was determined to be r2 = 0.9. CONCLUSIONS: The HCV cAg test showed a high correlation with the HCV RNA levels and may potentially be used as a more cost-effective alternative to the HCV RNA qRT-PCR test.

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.

Nonalcoholic Fatty Liver Disease in Asia, Africa, and Middle East Region.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. The global prevalence of the disease varies according to the geographical region. Despite having distinct models for the western patterns of NAFLD, Africa, Asia, and the Middle East regions exhibited varying prevalence rates of NAFLD. The disease burden is anticipated to significantly increase in these areas. Furthermore, with an increase in NAFLD risk factors in these regions, the disease burden is expected to rise even more. Policies at the regional and international levels are required to address such growing burden of NAFLD consequences.

Clinical and patient-reported outcome profile of patients with hepatitis B viral infection from the Global Liver Registry™.

Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p < 0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p < 0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p < 0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real-life Global Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.

The future health and economic burden of obesity-attributable type 2 diabetes and liver disease among the working-age population in Saudi Arabia.

BACKGROUND: Obesity and type 2 diabetes (T2DM) are increasing in Saudi Arabia (SA). Among other conditions, these risk factors increase the likelihood of non-alcoholic fatty liver disease (NAFLD), which in turn increases risks for advanced liver diseases, such as non-alcoholic steatohepatitis (NASH), cirrhosis and cancer. The goal of this study was to quantify the health and economic burden of obesity-attributable T2DM and liver disease in SA. METHODS: We developed a microsimulation of the SA population to quantify the future incidence and direct health care costs of obesity-attributable T2DM and liver disease, including liver cancer. Model inputs included population demographics, body mass index, incidence, mortality and direct health care costs of T2DM and liver disease and relative risks of each condition as a function of BMI category. Model outputs included age- and sex-disaggregated incidence of obesity-attributable T2DM and liver disease and their direct health care costs for SA's working-age population (20-59 years) between 2020 and 2040. RESULTS: Between 2020 and 2040, the available data predicts 1,976,593 [± 1834] new cases of T2DM, 285,346 [±874] new cases of chronic liver diseases, and 2,101 [± 150] new cases of liver cancer attributable to obesity, amongst working-age people. By 2040, the direct health care costs of these obesity-attributable diseases are predicted to be 127,956,508,540 [± 51,882,446] USD. CONCLUSIONS: The increase in obesity-associated T2DM and liver disease emphasises the urgent need for obesity interventions and strategies to meaningfully reduce the future health and economic burden of T2DM, chronic liver diseases and liver cancer in SA.

Hepatic fibrosis changes in patients with chronic hepatitis C infection who respond to direct-acting antivirals.

BACKGROUND: Clearance of hepatitis C virus (HCV) can potentially slow or reverse liver fibrosis and cirrhosis. Studies of fibrosis changes after treatment with direct-acting antivirals (DAAs) are limited. OBJECTIVES: We aimed to assess the impact of DAAs on fibrosis in HCV treatment responders. DESIGN: Retrospective cohort study. SETTING: Tertiary care centers. PATIENTS AND METHODS: This study included adult patients who received DAA treatment for HCV (naïve and experienced) from June 2015 to January 2019 who were treatment responders. Biochemical and hematological data and noninvasive fibrosis markers were recorded at baseline and follow-up. MAIN OUTCOME MEASURES: Aspartate aminotransferase/platelet ratio index (APRI), fibrosis-4 score (FIB-4) and liver stiffness measurements (LSM) at baseline and follow-up. SAMPLE SIZE AND CHARACTERISTICS: 172 HCV treatment responders, mean (SD) age 54.1 (14.1) and body mass index 28.8 (6.5) kg/m2 at baseline; 96 (55.8%) were females. RESULTS: Fifty-eight (33.7%) patients were HCV treatment-experienced. Most patients were genotype 4 (n=125, 73%) and the mean follow-up was 141 (57.9) weeks. Compared with baseline, changes in alanine aminotransferase (P<.001), aspartate aminotransferase (P<.001), and albumin (P=.01) were statistically significant. Changes in LSM (15.09 kPa [11.4] vs. 10.19 kPa [7.4], P<.001), APRI (0.81 [0.7] vs. 0.34 [0.2], P<.001), and FIB-4 (1.99 [1.4) vs.1.35 [0.9], P<.001), and AST/ALT ratio (0.86 [0.32] vs. 0.95 [0.41], P=.015) were statistically significant. Differences in many of the same parameters were statistically significant between patients with low fibrosis (F0-F1) (n=59, 34.3%) and significant fibrosis (≥F2) (n=113, 65.7%). CONCLUSIONS: Our findings confirm that clearance of HCV with DAAs is associated with significant improvement in fibrosis as assessed by noninvasive liver fibrosis measures, which supports the concept of post-treatment fibrosis regression. Long follow-up studies are needed to assess the impact on morbidity and mortality. LIMITATIONS: Absence of histological correlation with these noninvasive scores. No assessment of fibrosis changes based on HCV geno-type or treatment regimen. CONFLICT OF INTEREST: None.

Validation of the EVendo score for the prediction of varices in cirrhotic patients.

Background: Screening endoscopy for varices may be deferred when the calculated EVendo score is ≤3.90. This novel score has not been validated in an external cohort. This study aimed to assess the performance of the EVendo score and compare it with the Baveno VI criteria. Methods: We identified and calculated this score in all cirrhotic patients who underwent screening endoscopy for the first time with laboratory tests and liver stiffness measurements within 6 months of the endoscopy date. Results: In total, 103 patients were included. An EVendo score of ≤3.90 identified patients with no gastroesophageal varices (GEV) and varices needing treatment (VNT) with sensitivities of 82% and 83% and specificities of 57% and 34%, respectively. The negative predictive value for VNT was 94%. A comparison with the Baveno VI criteria in Child-Turcotte-Pugh-A patients showed spared endoscopy and missed VNT rates with EVendo score cutoffs of ≤3.9 and ≤4.5 and the Baveno VI criteria of 25%, 33%, and 16.6% and 1.7%, 1.7%, and 0%, respectively. Conclusions: EVendo score is reliable in clinical practice for predicting GEV and VNT. The number of spared endoscopies was higher than that with the Baveno VI criteria; however, there were more missed VNT cases.

A Global Survey of Physicians Knowledge About Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally. METHODS: NAFLD knowledge surveys containing 54 and 59 questions covering 3 domains (epidemiology/pathogenesis, diagnostics, and treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs), and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% high-income Global Burden of Disease super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). RESULTS: Hepatologists saw the greatest number of NAFLD patients annually: median 150 (interquartile range, 60-300) vs 100 (interquartile range, 35-200) for GEs, 100 (interquartile range, 30-200) for ENDOs, and 10 (interquartile range, 4-50) for PCPs (all P < .0001). The primary sources of NAFLD knowledge acquisition for hepatologists were international conferences (33% vs 8%-26%) and practice guidelines for others (39%-44%). The Internet was the second most common source of NAFLD knowledge for PCPs (28%). NAFLD knowledge scores were higher for hepatologists than GEs: epidemiology, 62% vs 53%; diagnostics, 80% vs 73%; and treatment, 61% vs 58% (P < .0001), and ENDOs scores were higher than PCPs: epidemiology, 70% vs 60%; diagnostics, 71% vs 64%; and treatment, 79% vs 68% (P < .0001). Being a hepatologist or ENDO was associated with higher knowledge scores than a GE or PCP, respectively (P < .05). Higher NAFLD knowledge scores were associated independently with a greater number of NAFLD patients seen (P < .05). CONCLUSIONS: Despite the growing burden of NAFLD, a significant knowledge gap remains for the identification, diagnosis, and management of NAFLD.

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.