The burden of metabolic dysfunction-associated steatotic liver disease and viral hepatitis in Saudi Arabia.

BACKGROUND: Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia. METHODS: Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression. RESULTS: From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% (n = 8.34 million) to 33.11% (n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% (n = 0.54 million) to 1.53% (n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% (n = 0.21 million) to 0.73% (n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively. CONCLUSIONS: MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed.

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.

Hepatocellular Carcinoma: The Role of Immunotherapy and Transplantation in the Era of Transplant Oncology.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths worldwide. As most patients present with advanced disease, curative therapy such as surgical resection and radiofrequency ablation are rarely utilized. With the advent of immunotherapy, historical treatment approaches such as liver transplantation are being challenged. In particular, the use of immune checkpoint inhibitors (ICIs) has emerged as a safe and useful option in the treatment of HCC. However, there is concern over adverse effects, such as graft rejection and graft loss. This updated review discusses the role of immunotherapy in the pre- and post-transplantation setting and provides insights into the potential of immunotherapy as an adjunct to liver transplantation. We deliberate on the use of ICI in the setting of the Milan criteria as well as the University of California San Francisco's expanded criteria for liver transplantation. Current data suggest that ICI has utility, especially in the pretransplantation setting. Nevertheless, larger, purposefully designed clinical trials are needed to clearly identify patients who will benefit most from ICI treatment in the transplant setting and determine parameters that will minimize the risk of graft rejection and maximize the benefits of this adjunct treatment.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Diabetes mellitus is not associated with worse short term outcome in patients older than 65 years old post-liver transplantation.

BACKGROUND: Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation (LT). Hence, more patients with diabetes mellitus (DM) are undergoing LT, especially, above the age of 65. AIM: To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of 65. METHODS: We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical record. We assessed the impact of DM on short-term outcomes, one-year, post-LT based on the following variables: Survival at one year; acute cellular rejection (ACR) rates; intensive care unit (ICU) and hospital length of stay; and readmissions. RESULTS: Total of 148 patients who are 65 year or older underwent LT during the study period. The mean age is 68.5 ± 3.3 years and 67.6% were male. The median Model for End-stage Liver Disease score at time of transplantation was 22 (6-39), 39% of patients had hepatocellular carcinoma and 77.7% underwent living donor LT. The one-year survival was similar between DM patients and others, 91%. ACR occurred in 13.5% of patients (P = 0.902). The median ICU stay is 4.5-day P = 0.023. The rates of ICU and 90-d readmission were similar (P = 0.821) and (P = 0.194), respectively. CONCLUSION: The short-term outcome of elderly diabetic patients undergoing LT is similar to others. The presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.

Efficacy of generic sofosbuvir with daclatasvir compared to sofosbuvir/ledipasvir in genotype 4 hepatitis C virus: A prospective comparison with historical control.

Background and Aim: Management of genotype 4 hepatitis C virus (HCV) has shifted to interferon-free regimens with a high sustained virological response (SVR-12), especially with NS5B/NS5A inhibitor combinations such as sofosbuvir and ledipasvir (Sof-Led). The guidelines have recommended the combination of sofosbuvir and another NS5A inhibitor, daclatasvir, to manage HCV genotypes 1-3. However, its use was extended to genotype 4 HCV based on extrapolating evidence. Our aim is to assess the efficacy of generic sofosbuvir + branded daclatasvir (Sof-Dac) compared to the Sof-Led combination in treating genotype 4 HCV. Methods: This study is an open-label, 2-period, noninferiority study that compared patients receiving a combination of generic sofosbuvir 400 mg and daclatasvir 60 mg orally daily (Group 2) prospectively to a historical control (Group 1) that included patients who received a combination of sofosbuvir/ledipasvir 400/90 mg orally daily. The primary endpoint is the proportion of patients who achieved SVR-12. Results: The study included 111 patients in the (Sof-Led) Group 1 and 109 patients (Sof-Dac) Group 2. For the primary outcome, SVR-12 was achieved in 106 (95.5%) of the patients in Group 1 versus 108 (99.1%) in Group 2 (p = 0.2). In addition, all patients who achieved SVR-12 also achieved SVR-24. Conclusion: Generic sofosbuvir combined with branded daclatasvir was safe and effective for treating genotype 4 HCV compared to Sof-Led. This combination may significantly reduce the cost burden, enabling a larger pool of treated patients. Office of research affairs at KFSHRC RAC# 2171 036.

Molecular Screening via Sanger Sequencing of the Genetic Variants in Non-Alcoholic Fatty Liver Disease Subjects in the Saudi Population: A Hospital-Based Study.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, along with steatosis and non-alcoholic steatohepatitis (NASH), and is associated with cirrhosis and hepatocellular carcinoma. Candidate gene and genome-wide association studies have validated the relationships between NAFLD, NASH, PNPLA3, TM6SF2, and HFE. The present study utilized five polymorphisms in three genes: PNPLA3 (I148M and K434E) TM6SF2 (E167K), and HFE (H63D and C282Y), based on undocumented case−control studies in the Saudi Arabian population. A total of 95 patients with NAFLD and 78 non-NAFLD subjects were recruited. Genomic DNA was isolated, and polymerase chain reaction and Sanger sequencing were performed using specific primers for the I148M, K434E, E167K, H63D, and C282Y. NAFLD subjects were older when compared to controls and showed the significant association (p = 0.0001). Non-significant association was found between gender (p = 0.26). However, both weight and BMI were found to be associated. Hardy−Weinberg equilibrium analysis confirmed that H63D, I148M, and K434E polymorphisms were associated. Genotype analysis showed only K434E variant was associated with NAFLD and non-NAFLD (OR-2.16; 95% CI: 1.08−4.31; p = 0.02). However, other polymorphisms performed with NAFLD and NASH were not associated (p > 0.05), and similar analysis was found when ANOVA was performed (p > 0.05). In conclusion, we confirmed that K434E polymorphism showed a positive association in the Saudi population.

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.

Saudi association for the study of liver diseases and transplantation position statement on the hepatology workforce in Saudi Arabia.

The field of hepatology has evolved significantly over the last two decades. Hepatology practice in Saudi Arabia (SA) was dominated by hepatitis B and C viruses but is now being overtaken by patients with non-alcoholic fatty liver disease. These patients require greater medical attention as their care is more complex compared to patients with viral hepatitis. In addition, liver transplantation (LT) has expanded significantly in SA over the last three decades. There is a necessity to increase the hepatology workforce to meet the demand in SA. The time has come to reinforce the transplant hepatology fellowship program, that was launched recently, and to develop a nurse practitioner practice model to meet these demands. In addition, SA is going through a health care reform to enhance health care delivery which may affect the financial compensation polices of various specialties including gastroenterology and hepatology. Therefore, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) established a task force to discuss the current and future demands in the hepatology workforce in SA, as well as to discuss different avenues of financial compensation for transplant hepatologists in LT centers.

Conventional Transarterial Chemoembolization Versus Drug-Eluting Beads in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma (HCC) occurs in nearly three-quarters of all primary liver cancers, with the majority not amenable to curative therapies. We therefore aimed to re-evaluate the safety, efficacy, and survival benefits of treating patients with drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) compared to the conventional transcatheter arterial chemoembolization (C-TACE). Several databases were searched with a strict eligibility criterion for studies reporting on adult patients with unresectable or recurrent HCC. The pooled analysis included 34 studies involving 4841 HCC patients with a median follow-up of 1.5 to 18 months. There were no significant differences between DEB-TACE and C-TACE with regard to complete response, partial response and disease stability. However, disease control (OR: 1.42 (95% CI (1.03,1.96) and objective response (OR: 1.33 (95% CI (0.99, 1.79) were significantly more effective for DEB-TACE treatment with fewer severe complications and all-cause mortality. The pooled-analysis did not find superiority of DEB-TACE in complete or partial response, disease stability, controlling disease progression, and 30 day or end-mortality. However, results showed that DEB-TACE is associated with a better objective response, disease control, and lower all-cause mortality with severe complications compared to C-TACE treatment. Given that the safety outcomes are based on limited studies with a potential for bias, there was no clear improvement of DEB-TACE over C-TACE treatment.

Long Term Outcomes of Liver Transplantation For Patients With Autoimmune Hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). Data on the long-term outcomes of living-related LT for AIH are limited and inconsistent. The present study aimed to assess the long-term outcomes of deceased donor LT (DDLT) and living donor LT (LDLT) for AIH. METHODS: All patients who received transplants for AIH-related cirrhosis from 2001 to 2018 were included in this study. RESULTS: Seventy-four patients (31 male, 43 female) received LT. The average follow-up was 7.9 ± 6.9 years (median = 7.2 years), average age was 34.3 ± 13.8 years, and average Model for End-Stage Liver Disease (MELD) score was 23.6 ± 8.5. Thirty-six (49.3%) patients received a graft from a living donor, and 83% of patients were maintained on steroids. The 1-, 3-, 5-, and 10-year survival rates of patients were 91%, 89%, 87%, and 82% and of grafts were 89%, 88%, 86%, and 76%, respectively. In univariate analysis, MELD score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.17; P = .028), donor age (OR per 5 years, 1.45; 95% CI, 1.07-2.02; P = .021), donor type (OR LDLT vs DDLT, 0.19; 95% CI, 0.04-0.67; P = .017), and renal function (OR glomerular filtration rate <60 vs ≥60 mL/min/m2, 7.41; 95% CI, 1.88-31.25; P = .004) were significant predictors of graft survival; however, none of the factors remained significant in multivariate analysis. CONCLUSION: We have shown the highest reported long-term survival rates in LT for AIH, including a large number of patients who underwent LDLT. Standardized management and immunosuppressive therapy, including the maintenance of a low-dose steroid protocol, may have contributed to this outcome.

Clinical Practice Guidelines for Liver Transplantation in Saudi Arabia.

The demand for liver transplantation in the Kingdom of Saudi Arabia (KSA) is associated with the country's high burden of liver disease. Trends in the epidemiology of liver transplantation indications among recipients in KSA have changed over 20 years. Non-alcoholic steatohepatitis has eclipsed the hepatitis C virus in the country due to the effective treatment strategies for HCV. Risk factors for NASH, like type 2 diabetes mellitus, obesity, and hyperlipidemia, are becoming a major concern and a leading indication for liver transplantation in the KSA. There is also a significantly increased prevalence and incidence of genetic adult familial liver diseases in KSA. New immunosuppressive agents and preservation solutions, improved surgical capabilities, and early disease recognition and management have increased the success rate of liver transplant outcome but concerns about the side effects of immunosuppressive therapy can jeopardise long-term survival outcomes. Despite this, indications for liver transplantation continue to increase, resulting in ongoing challenges to maximize the number of potential donors and reduce patient mortality rate while expecting to get transplanted. The Saudi Center of Organ Transplant is the recognized National Organ Donation Agency for transplantation, which renders important support for procurement and allocation of organs. This guidance document aims to help healthcare providers in managing patients in the liver transplant setting.

Use of COVID-19 vaccines in patients with liver disease and post-liver transplantation: Position statement of the Saudi association for the study of liver diseases and transplantation.

Patients with chronic liver disease (CLD) and liver transplant recipients are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). Although several studies demonstrated the safety and efficacy of COVID-19 vaccines in the general population, data in CLD patients and liver transplant recipients are lacking. Two COVID-19 vaccines were approved by the Saudi Food and Drug Authority and rolled out to several million recipients in Saudi Arabia. These vaccines are mRNA-based vaccine BNT162b2 from Pfizer/BioNTech and adenovirus-based AZD1222 from Oxford/AstraZeneca from three manufacturing sites (EU Nodes, Serum Institute of India, and South Korea Bio). The Saudi Association for the Study of Liver diseases and Transplantation (SASLT) has reviewed the available evidence and issued interim recommendations for COVID-19 vaccination in CLD and liver transplant recipients. Since there is no evidence contradicting the safety and immunogenicity of the currently approved COVID-19 vaccines in patients with CLD and hepatobiliary cancer and liver transplant recipients, the SASLT recommends vaccination in those patient populations. CLD and hepatobiliary cancer patients and liver transplant recipients should be prioritized depending on the risk factors for severe COVID-19. In transplant recipients, the optimal timing of vaccination remains unknown; however, immunization is recommended after the initial immunosuppression phase. Patients with CLD and liver transplant candidates or recipients should be closely monitored after COVID-19 vaccination. These patient populations should be included in future clinical trials to provide further evidence on the efficacy and safety of COVID-19 vaccines.

Changing trends in liver transplantation indications in Saudi Arabia: from hepatitis C virus infection to nonalcoholic fatty liver disease.

BACKGROUND: Several trend analyses on liver transplantation (LT) indications have been published in the U.S. and in other countries, but there are limited data on LT indication trends in Saudi Arabia (SA), especially since the availability of direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV). This study aimed to analyze trends in the frequency of LT indications among LT recipients in SA over a 19-year period and examine associations between etiologic-specific trends and clinicodemographic characteristics. METHODS: This retrospective study analyzed clinical and surgical data of adult patients (n = 1009) who underwent LT at the King Faisal Specialist Hospital & Research Center (Riyadh, SA) between 2001 and 2019. Spearman's rank correlation, Poisson regression, and Joinpoint regression analysis were employed to assess changes in LT etiologic trends. RESULTS: In the first period (2001-2010), the main LT indications were HCV (41.9%) and hepatitis B virus (HBV) (21.1%), but nonalcoholic steatohepatitis (NASH) (29.7%) surpassed HCV (23.7%) as the leading LT indication in the second period (2011-2019); and the trends were significant in correlation analyses [incidence rate ratio (IRR) = 1.09 (1.06-1.13) for NASH; IRR = 0.93 (0.91-0.95) for HCV]. In the Joinpoint regression analysis, increases in NASH from 2006 to 2012 (+ 32.1%) were statistically significant, as were the decreases in HCV from 2004 to 2007 (- 19.6%) and from 2010 to 2019 (- 12.1%). Similar patterns were observed in LT etiological comparisons before and after the availability of DAAs and within hepatocellular carcinoma stratifications. CONCLUSIONS: Trends in the epidemiology of LT indications among LT recipients in SA have changed over a 19-year period. Most notably, NASH has eclipsed HCV in the country due to the effective treatment strategies for HCV. These trends in NASH now need an aggressive public health response to minimize and avert future onset of additional clinical and economic strains on health care systems and LT centers in SA.

SASLT practice guidelines for the management of Hepatitis B virus - An update.

Infection with hepatitis B virus (HBV) remains an important public health problem with a high burden worldwide. The Saudi Association for the Study of Liver diseases and Transplantation formed a working group to develop HBV practice guidelines in Saudi Arabia. The methodology used to develop these guidelines was based on reviewing the available evidence, local data, and major international practice guidelines on the management of HBV. The aim of these guidelines is to assist healthcare providers in the management of HBV in Saudi Arabia. These updated guidelines summarize the latest local studies performed on HBV epidemiology, major changes in the prevalence of this virus, and advances in disease management.

Validating controlled attenuation parameter in the assessment of hepatic steatosis in living liver donors.

INTRODUCTION: Hepatic steatosis (HS) negatively impacts transplant outcomes in living liver donors. To date, liver biopsy is preferred for HS evaluation. This study aims to evaluate the measurement of controlled attenuation parameter (CAP) as a diagnostic tool of HS in living liver donors. METHODS: Candidates recruited to this study, conducted from April 2016 to February 2020, were potential donors who had undergone transient elastography using Fibroscan® and CAP measurements at liver segments VI and VII, followed by liver biopsy. The HS grades from liver biopsy were classified as S0 (<5%), S1 (5-33%), S2 (33-66%), and S3 (>66%). For CAP, they were S0 (≤218dB/m), S1 (218-249dB/m)), S2 (250-305dB/m)), and S3 (>305dB/m)). The CAP measurements were compared with the liver biopsy results. RESULTS: Of the 150 potential donors [male, 73.3%; mean age, 30.0±7.0 years; body mass index (BMI), 24.7±3.5kg/m2], 92 (61.3%) had no or mild HS, while 58 (38.7%) and 10% had moderate to severe HS based on CAP and liver biopsy, respectively. Subjects with moderate to severe HS per CAP were mostly males (0.014), and had higher BMI (p = .006), alanine aminotransferase (ALT) (.001), gamma-glutamyl transferase (.026), and high-density lipoprotein (.008). On multivariate analysis, high ALT (OR, 1.051; 95% CI, 1.016-1.087; p = .004) was a predictor of significant HS. The sensitivity, specificity, positive and negative predictive values of CAP to detect significant HS were 93.3%, 67.4, 24.1%, and 98.9%, respectively. CONCLUSION: The high sensitivity and negative predictive values of CAP make it a good screening test to exclude significant HS in potential living liver donors which, in turn, can help avoid unnecessary liver biopsies.

Efficacy and safety of once daily tacrolimus compared to twice daily tacrolimus after liver transplantation.

BACKGROUND: Once daily tacrolimus regimen was found to exhibits similar bioavailability, safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients. AIM: To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients. METHODS: MEDLINE, EMBASE, CENTRAL databases were searched for clinical trials until December 2020. Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection, Serum creatinine, graft loss, or death. Two reviewers independently selected studies, collected data and assessed risk of bias. The results are reported as risk ratio with 95% confidence interval (CI) for dichotomous data. RESULTS: Seven studies included with 965 patients. All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool. Biopsy-proven acute rejection was reported in four studies, and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups (risk ratio: 1.06, 95%CI: 0.84-1.34, n = 758, I2 = 0%) and also we found no significant difference between both groups for renal outcome (serum creatinine; mean difference, 0.001 mg/dL, 95%CI: -0.042 to 0.043, n = 846, I2 = 18.6%). Similarly, there was similar number of adverse events such as hypertension, headache, back pain, blood related disorders, infections and nausea observed in both groups. CONCLUSION: The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.

Clinical and economic burden of nonalcoholic steatohepatitis in Saudi Arabia, United Arab Emirates and Kuwait.

BACKGROUND AND AIMS: The Middle East (ME) has a high prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), driven by obesity and type-2 diabetes mellitus (T2DM). Studies in Saudi Arabia (KSA) and United Arab Emirates (UAE) predict an escalating impact of NAFLD/NASH, particularly advanced fibrosis due to NASH (AF-NASH), increasing cases of cirrhosis, liver cancer and death. The scale of this burden in other ME countries is unknown with no reports of NAFLD/NASH healthcare resource utilization (HCRU) or costs. We estimated the clinical and economic burden of NAFLD/NASH in KSA, UAE and Kuwait. METHODS: Markov models populated with country-specific obesity and T2DM prevalence data estimated numbers and progression of NAFLD/NASH patients from 2018 to 2030. Model inputs, assumptions and outputs were collected from literature, national statistics, and expert consensus. RESULTS: Over 13 years, the KSA model estimated cases increasing as follows: patients with fibrosis F0-3 doubled to 2.5 m, compensated and decompensated cirrhosis and hepatocellular carcinoma trebled to 212,000; liver failure or transplant patients increased four-fold to 4,086 and liver-related death escalated from < 10,000 to > 200,000. Similar trends occurred in UAE and Kuwait. Discounted lifetime costs of NASH standard-care increased totaling USD40.41 bn, 1.59 bn and 6.36 bn in KSA, UAE (Emiratis only) and Kuwait, respectively. NASH-related costs in 2019 comprised, respectively, 5.83%, 5.80% and 7.66% of national healthcare spending. CONCLUSIONS: NASH, especially AF-NASH, should be considered a higher priority in ME Public Health policy. Our analyses should inform health policy makers to mitigate the enormity of this escalating regional burden.