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.

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.

Peroral endoscopic myotomy (POEM) for the treatment of achalasia: A multicenter Middle Eastern experience.

BACKGROUND: Peroral endoscopic myotomy (POEM) was proposed in 2010 as a minimally invasive procedure for the treatment of achalasia. In this article, we describe the Middle Eastern experience with the procedure in terms of efficacy, length of admission, and short- and long-term complications. METHODS: A retrospective analysis of our prospectively collected data on patients who underwent a POEM procedure was conducted between March 2019 and May 2020. The primary outcome was clinical success rate, defined as a postprocedure Eckardt score ≤3 at ≥3 months. Secondary outcomes included the length of hospital stay, presence of reflux symptoms or need for proton pump inhibitors (PPIs) ≥3 months, and adverse events. RESULTS: During the study period, 67 patients (35 females) underwent the procedure for achalasia. The participants' ages ranged from 11 to 80 years (mean 41 ± 18 years). Eckardt scores before the treatment ranged between 4 and 12 (mean 8.85 ± 1.75). Sixty-four patients (95.5%) achieved Eckardt scores of ≤3 at ≥3 months after the procedure (95% confidence interval [CI]: 91%-100%). The difference between pre- and post-procedural Eckardt scores averaged around -8 points (95% CI: -7.5 to -8.5 P < 0.0001). Adverse events were reported in 24 patients (35.8%) and included pneumoperitoneum (32.8%), reflux symptoms at 3 months (29.9%), and surgical emphysema (3%). Six patients had adverse events that led to prolongation of admission; 3% of whom had aspiration pneumonia, 3% had pneumoperitoneum, 1.5% had both, and 1.5% had an esophageal tear. CONCLUSIONS: POEM is a promising procedure for the treatment of achalasia with a high clinical success rate, short hospital admission, and a reassuring safety profile.

Revealing Hepatitis B Virus as a Silent Killer: A Call-to-Action for Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) was the first country in the Middle East to adopt the hepatitis B virus (HBV) vaccine. Despite an expanded HBV immunization program and significant progress in HBV prevention in the country, HBV infection is a significant public health burden. This review lists coordinated solutions for healthcare stakeholders, patients, and health authorities to curb HBV and its impact in KSA. It further aims to draw policymakers' attention to key priorities to bridge HBV care gaps in the country. METHODS: As part of the pre-engagement activity, medical experts across KSA were interviewed to gain a preliminary understanding of the current unmet needs in HBV management in the country. Top-recommended action points derived from the pre-engagement activity were discussed. Key priority action points to curb the impact of HBV in KSA were identified. RESULTS: The priority action points together with the challenges and unmet needs in the management and care of HBV in KSA were: (a) establish a national-level registry, (b) implement screening campaigns, (c) improve linkage of care between primary care physicians (PCPs) and specialists, and (d) increase PCP education and awareness. CONCLUSION: This work is an endeavor to set the stage for a strategic policy framework aimed at eliminating HBV in KSA. The action points/steps for the identified priorities must run parallelly across various regions in KSA, to successfully manage and further eliminate the threat of HBV.

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.

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.

Peripancreatic fluid collections, plastic stents, and different sub-types of metal stents: Where does the evidence land?

BACKGROUND: Peripancreatic fluid collections (PFCs) are a frequent complication of acute pancreatitis. Symptomatic PFCs may need to be drained, and there are multiple endoscopic accessories that can facilitate the procedure. This paper aims to compare the success rate, number of procedures required for resolution and adverse events rate for PFCs EUS-guided drainage with plastic stents and lumen-apposing metal stents (LAMS). METHODS: This is a retrospective analysis of a consecutive sample of patients that was collected from 2013 - 2019. The medical records of these patients were reviewed, and the outcomes for each type of stent (plastic vs LAMS, and different subtypes of LAMS) were compared in terms of clinical success, number of re-interventions needed, and adverse events. RESULTS: A total of 33 patients (23 males) were treated for PFCs with EUS-guided drainage and stenting. The patients' ages ranged between 14 and 85 years (mean ± SD: 43.5 ± 19 years). Overall, there was no difference between plastic stents and LAMS in terms of symptomatic recovery (P = 0. 24), but metal stents had better results with regards to radiological resolution (P = 0.03), and were associated with a higher number of necrosectomies (P = 0.029). Adverse events occurred more frequently in patients who had plastic stents, but direct comparison between the two groups showed that the difference was not statistically significant (P = 0.2). Stratification for different LAMS subtypes showed no difference in terms of symptomatic or radiological resolution (P =0.49), number of rescue procedures (P = 0.41), and adverse events (P = 0.81). CONCLUSION: Our study, along with the current available evidence, suggests a slight advantage of metal stents over plastic stents in terms of clinical success, need for rescue procedures, and incidence of adverse events. Furthermore, it provides empirical evidence that the different sub-types of LAMS perform similarly when compared against each other.

The utility of digital cholangioscopy (SpyGlass DS) in biliary and pancreatic diseases: A clinical feasibility study at two tertiary care centers in Saudi Arabia (with Videos).

BACKGROUND AND STUDY AIM: Since its inception in 2007, single-operator cholangioscopy (SOC) has gained popularity for many diagnostically and therapeutically challenging biliary and pancreatic conditions. Many studies have been published to evaluate the feasibility, usefulness, cost-effectiveness, and safety profile of the first generation. This paper is a descriptive study in which we aim to share the experience of two tertiary care centers with the novel version of SOC, SpyGlass DS. PATIENTS AND METHODS: We retrospectively reviewed the records of all the patients who went through the procedure from October 2015 - July 2019 to explore the scope of biliary and pancreatic conditions in which SOC was utilized. Technical success was defined as the ability to visualize the lesion and complete the procedure as planned, whereas clinical success was determined by the ability to achieve the desired diagnostic/therapeutic outcome. RESULTS: During the period of interest, 66 patients (34 males) went through 84 cholangioscopy procedures. Forty-four patients failed the conventional extraction methods and needed the intervention for the treatment of difficult stones, 24 patients needed a diagnostic evaluation of biliary strictures, and 3 needed an intervention to remove migrated stents. Technical success was achieved in 98.8% (83/84) of the procedures (95% CI: 96-100%). Regarding clinical success, stone breakdown and removal was achieved in 92% of the procedures (49/53; 95% CI: 85-100%). Tissue samples were successfully obtained in 95.8% (23/24) of patients with strictures (95% CI: 88-100%). The biopsy was appropriate to make a histological diagnosis in 83.3% of cases (20/24; 95% CI: 68-98%). The median number of sessions needed to achieve the deisred outcome was one (ranging between 1 and 6 sessions). CONCLUSION: The new version of SOC, SpyGlass DS, provides a feasible and an effective option for the management of difficult cholelithiasis, as well as visually evaluating and obtaining histological samples for indeterminate biliary strictures. However, data from more extensive studies are needed to establish its non-inferiority to the fiberoptic version in terms of short- and long-term outcomes, cost-effectiveness, and complications.

The utility of esophagogastroduodenoscopy and Helicobacter pylori screening in the preoperative assessment of patients undergoing bariatric surgery: A cross-sectional, single-center study in Saudi Arabia.

BACKGROUND/AIM: Esophagogastroduodenoscopy (EGD) and Helicobacter pylori screening are routine parts of the preoperative assessment of patients undergoing bariatric surgery at many centers around the world. The reason for this step is to identify abnormalities that may change the surgical approach. In this study, we aim to evaluate the extent to which endoscopic findings and H. pylori testing affect the plan of care in bariatric patients. PATIENTS AND METHODS: We retrospectively reviewed the investigational processes of 356 patients planned for bariatric surgery (2014-2016) at our center. Patients were categorized into two main groups (4 subgroups) from endoscopic findings. One group included patients with normal EGD and patients who had abnormal findings that did not change the surgical approach, whereas the other included patients who had findings that changed or canceled the surgical plan. A logistic regression analysis was used to evaluate how strongly can factors such as patient demographics, BMI, comorbidities, symptomatology, and H. pylori status predict the risk of having plan-changing endoscopic abnormalities. RESULTS: The ages ranged between 15 and 66 years with a mean ± SD of 37 ± 11 years, and 56% were females. The majority of patients (75%; 95% CI: 73 - 82%) had either no findings (41%) or had abnormalities that did not change the surgical approach (34%). Only 25% (95% CI: 21-29%) were found to have pathologies that altered the surgical approach, and 0.6% of them had findings that were considered contraindications for surgery. In spite the relatively high prevalence of H. pylori in our cohort (41%; 95% CI 36-46%), the proportion of patients who had plan-changing abnormalities did not differ markedly from other studies. Gastroesophageal reflux disease (GERD) and obstructive sleep apnea symptoms were the only significant predictors of EGD findings (P = 0.009). CONCLUSIONS: GERD and sleep apnea symptoms can be strong predictors of EGD abnormalities. However, this evidence is still not enough to safely recommend changing the current practice. Therefore, until a sensitive clinical prediction score is derived and validated according to the symptoms, we suggest that EGD should continue as the standard of care in all patients undergoing bariatric surgery.

Acute Pancreatitis: An Exploratory, Cross-sectional, Single-center Study of the Epidemiological Features of the Disease in a Sample of Saudi Patients.

Epidemiological studies on Acute Pancreatitis (AP) are significantly scarce in the Saudi Arabian Literature. In this paper, we aim to explore the current trends of AP in a sample of Saudi patients. This is a cross-sectional study in which we reviewed AP-related admissions from 2014 to 2017. Data collected included demographics, clinical presentation, investigations, severity, complications, and the outcome at the end of hospitalization. During the study period, 107 patients were admitted due to AP. Fifty-seven (53%) were males. Biliary pancreatitis was the most common etiology found among our patients (39.3%; 95% CI: 30.5-48.7), followed by alcoholic pancreatitis (11.2%; 95% CI: 6.5-18.6) and hypertriglyceridemia (8%; 95% CI: 4.5-15.2). Pancreatic pseudocysts were the most common complication we found in this series (15%; 95% CI: 9.4-23). Of all the hospitalized patients in this study, eight patients (7.9%) died (95% CI: 3.8-14.1). The number of AP-related admissions and mortality rate appear to have increased as compared with the numbers in earlier national studies. The etiological groups have also changed. As compared with Western/Asian studies, however, there was almost no difference in the epidemiological patterns except for the mortality rate.

ERCP quality indicators: The experience of a high-volume tertiary care center in Saudi Arabia.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most technically demanding and high-risk procedures performed by GI endoscopists. Therefore, guidelines or position statements on various aspects of quality indicators, safety indicators and credentialing for ERCP have been developed by gastroenterology associations. In this paper, we evaluate the ERCP quality in a single, high-volume, tertiary care center in Saudi Arabia using a number of measures commonly stated by these organizations, and compare the experience of that center to the previously-published standards in this regard. PATIENTS AND METHODS: This is a descriptive, retrospective chart review of a consecutive sample taken over 12 continuous months (July 2016-June 2017). Data collected included demographic characteristics, and technical/clinical details from three time periods: preprocedure, intraprocedure, and postprocedure. Measurement parameters were all taken from the ASGE/ACG guidelines. Data was represented by the percentage of which each indicator was achieved, and the 95% proportion confidence intervals (CIs) when needed. RESULTS: From July 2016 to June 2017, 281 ERCP procedures were performed. An outstanding majority of them (95.7%) was done for therapeutic purposes, whereas 4.3% were diagnostic procedures. The sample included 206 patients, of whom 83 (40.3%) were males. The age of the participants ranged between 11 and 101 years (mean age ±â€¯SD; 51 ±â€¯19). The quality of ERCP at the center in which the study was done met the performance targets stated by the ASGE/ACG for almost all indicators. Adverse events reported in our series were lower than previous studies for pancreatitis and perforation, and slightly higher in the incidence of bleeding, cholangitis, and death. CONCLUSION: In a single, high-volume, tertiary care center in Saudi Arabia, the quality of ERCP met the performance targets stated by the ASGE/ACG for almost all indicators.

Nonalcoholic fatty liver disease burden - Saudi Arabia and United Arab Emirates, 2017-2030.

Background/Aim: Due to epidemic levels of obesity and type 2 diabetes mellitus (DM), nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) will be driving factors in liver disease burden in the coming years in Saudi Arabia and United Arab Emirates (UAE). Materials and Methods: Models were used to estimate NAFLD and NASH disease progression, primarily based on changes in adult prevalence rates of adult obesity and DM. The published estimates and expert interviews were used to build and validate the model projections. Results: In both countries, the prevalence of NAFLD increased through 2030 parallel to projected increases in the prevalence of obesity and DM. By 2030, there were an estimated 12,534,000 NAFLD cases in Saudi Arabia and 372,000 cases in UAE. Increases in NASH cases were relatively greater than the NAFLD cases due to aging of the population and disease progression. Likewise, prevalent cases of compensated cirrhosis and advanced liver disease are projected to at least double by 2030, while annual incident liver deaths increase in both countries to 4800 deaths in Saudi Arabia and 140 deaths in UAE. Conclusions: Continued high rates of adult obesity and DM, in combination with aging populations, suggest that advanced liver disease and mortality attributable to NAFLD/NASH will increase across both countries. Reducing the growth of the NAFLD population, along with potential therapeutic options, will be needed to reduce liver disease burden.

A case series evaluating the impact of Hepatitis C eradication using direct acting antivirals on primary biliary cholangitis-associated autoimmunity.

BACKGROUND: Chronic Hepatitis C Virus (HCV) infection has been commonly linked to the development of autoimmunity, in part through activation of B cells. B cells are also postulated to play a pathogenic role in the autoimmune liver disease Primary Biliary Cholangitis (PBC). Patients with concurrent PBC and HCV infection carry an increased risk of more progressive disease, although the mechanism underlying this effect is poorly understood. Utilizing a case series of patients with concurrent PBC and HCV, the aim of this study was to evaluate for the potential impact of HCV eradication upon autoimmunity/autoantibody production. CASE PRESENTATION: A case series evaluating three patients with co-existing PBC-HCV infection receiving non-interferon based HCV treatments with direct-acting antivirals (DAA). One of three patient received Ursodeoxycholic acid (UDCA; 13 mg/kg/day) during the treatment period. Sustained virological response (SVR) to DAA's was assessed using a HCV Quantitative Nucleic Acid Test (Abbott). Autoantibodies associated with autoimmune liver diseases (including PBC) and liver biochemistry, were measured before, during and after DAA treatment (Mitogen Advanced Diagnostics Laboratory, Calgary, Canada). All patients achieved an SVR, as determined by negative HCV RNA test 12 weeks post-DAA therapy. Titres of anti-mitochondrial antibodies (AMA-M2), anti- branched-chain 2-oxo-acid dehydrogenase complex and 2-oxo glutarate dehydrogenase complex (anti-3E-BPO), and anti- tripartite motif-containing protein 21 (TRIM21/Ro52) remained unchanged, despite successful HCV eradication. Two of the three patients exhibited a transient decrease in some autoantibody titres during DAA treatment, but these returned to baseline levels post-DAA therapy. CONCLUSIONS: Within the limitations of a case series, our results suggest that HCV co-infection may not be a significant driver of PBC-related autoimmunity/autoantibody production. However, a larger n-value is required to truly assess for the effect of HCV eradication on autoantibody production.