The use of N-acetylcysteine (NAC) for non-acetaminophen-induced acute liver failure (NAI-ALF) has been increasing despite controversy in its efficacy. National guidelines are in disagreement for NAC use as standard of care; however, many healthcare centers continue to adopt the use of NAC outside of acetaminophen poisoning. While NAC may have multiple mechanisms of action in treatment of ALF, this has not translated to clinical benefit. Murine models have reported antioxidant and anti-inflammatory properties, as well as improvement in liver-specific microcirculation. Multiple case studies and series have reported positive outcomes of NAC treatment for ALF of various etiologies. While prospective studies suggested the benefit of NAC treatment, these studies have methodological and statistical shortcomings that affect the validity of the results. In this review, we aimed to summarize the existing literature on the efficacy of NAC for NAI-ALF including mechanism of action, case studies and series demonstrating outcomes, and prospective studies that have led to its current widespread use, along with the reported rate of adverse events.

Background: Nonalcoholic fatty liver disease (NAFLD) has become one of the leading etiologies of hepatocellular carcinoma (HCC), but risk factors for NAFLD-related HCC occurrence have not been defined. NAFLD is often complicated by metabolic abnormalities, and there is a bidirectional association of metabolic abnormalities with NAFLD progression. This study aimed to systematically evaluate the relationship between metabolic traits and HCC occurrence in patients with NAFLD. Method: This study reviewed eight eligible studies that included 297,956 participants, to determine the relationship between metabolic traits and the occurrence of HCC in patients with NAFLD. Results: Presence of diabetes mellitus (DM) was associated with increased risk of HCC (HR: 2.65, 95%CI: 2.02 ~ 3.49, P_{heterogeneity} = 0.589, I² = 0.0%). Stratified analysis revealed that this risk was higher in NAFLD patients with advanced fibrosis/cirrhosis (HR: 4.55, 95%CI: 2.34 ~ 8.87, P_{heterogeneity} = 0.870, I² = 0.0%). Nonetheless even in patients without cirrhosis, DM remained a high risk factor for HCC incidence (HR: 1.80, 95%CI: 1.05 ~ 3.06, P_{heterogeneity} = 0.291, I² = 10.4%). Overweight/obesity had a slight correlation with increased risk of HCC occurrence in NAFLD patients (HR: 1.31, 95%CI: 1.00 ~ 1.71, P_{heterogeneity} = 0.888, I² = 0.0%), while presence of hypertension and dyslipidemia had no correlation. Conclusion: DM and overweight/obesity are high risk factors for NAFLD-related HCC. In particular, DM increases 4-fold the risk of HCC incidence in NAFLD patients with advanced fibrosis/cirrhosis. There is a need to strengthen surveillance for HCC in NAFLD patients with DM, especially in those with advanced fibrosis/cirrhosis.

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.

Background: The impact of propranolol on patients with cirrhosis and refractory ascites is controversial. We conducted a nationwide longitudinal cohort study to compare the survival between patients with cirrhosis and refractory ascites, with and without using propranolol. Methods: Data of patients with cirrhosis and refractory ascites using propranolol, and controls matched by age and gender, were extracted from The National Health Insurance Research Database of Taiwan. The baseline demographic characteristics were compared between groups. Cox regression analysis was used to examine the predictors of mortality. Results: In this study, 1788 patients were enrolled in each group; 1304 patients (72.9%) in the propranolol group and 1445 patients (80.8%) in the control group died (P < 0.001). The mean survival was 34.3 ± 31.2 months in the propranolol group and 20.8 ± 26.6 months in the control group (P < 0.001). Propranolol (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.55–0.64, P < 0.001), statins (HR: 0.43, 95% CI: 0.34–0.56, P < 0.001), age (HR: 1.02, 95% CI: 1.01–1.02, P < 0.001), and diabetes mellitus (HR: 1.14, 95% CI: 1.05–1.24, P = 0.002) were the independent predictors for mortality. Conclusions: Use of propanolol was associated with reduced mortality, compared with controls, in this nationwide cohort of patients with cirrhosis and refractory ascites.

Background: Despite the high prevalence of gastro-intestinal (GI) cancer in iron deficiency anemia (IDA), some IDA patients do not complete all the necessary GI investigations at the initial referral. As a result, existing cancers are diagnosed at a later referral with worse prognosis. The potential to detect GI cancer early depends on minimizing the delay time spent between the two consecutive referrals, where a patient did not complete investigations at the first referral, but at the second is diagnosed with positive GI cancer. This retrospective longitudinal study aims to highlight the proper methods to model these referrals. Methods: Using anonymized data of 168 episodes of care for IDA patients at an IDA clinic in a secondary care setting, continuous-time multi-state Markov chain is employed to determine the transition rates among three observed states for IDA patients at the IDA clinic, “incomplete investigations,” “negative GI cancer,” and “positive GI cancer” and to estimate the delay time. Results: Once in the state of incomplete investigations, an estimated mean delay time of 3.1 years (95% CI: 1.2, 5) is spent before being diagnosed with positive GI cancer. The probability that a “positive GI diagnosis” is next after the state of “incomplete investigation” is 17%, compared with 11% when it is followed in the state of negative GI cancer. Defining the survival as the event of not being in the state of “positive GI cancer,” the survival rate of IDA patients with negative GI cancer is always higher than those with incomplete investigations. Finally, being diagnosed with positive GI cancer is always preceded by the prediction of being considered “very high risk” at the earlier visit. Conclusion: A baseline model was proposed to represent episodes of care for IDA patients at a secondary care center. Preliminary results highlight the importance of completing the GI investigations, especially in IDA patients, who are at high risk of GI cancer and fit to go through the investigations.

Background: The purpose of this study is to assess patients' compliance to recommendations after evaluation of pancreatic cystic neoplasm (PCN) with EUS and investigate how the presence of “worrisome” characteristics including cyst's size, main pancreatic duct dilation and presence of mural nodules might affect the adherence rates of management recommendations. Methods: We performed a retrospective cohort study of patients at a private tertiary hospital who were referred for evaluation with EUS over a 5-year period (2015-2019), after the diagnosis of pancreatic cystic neoplasm during radiological imaging. Results: We included 111 patients (mean age 64.1 years, SD = 13.9) with PCN. After the EUS examination, 16 patients were referred for surgical resection, 4 patients needed no further follow up and 91 patients were recommended to follow imaging surveillance. In total, 70 (63.1%) subjects adhered to surveillance recommendations. In the group of subjects who adhered to surveillance, cyst size ≥3cm was found in 27 (38.6%) patients, main pancreatic duct diameter ≥5mm in 12 (17.1%) subjects and only 3 (4.3%) pancreatic cysts demonstrated mural nodules. However, none of the aforementioned cystic “worrisome features” was significantly correlated with increased adherence to follow up (p = 0.709, P = 0.642 and P = 0.630, respectively). Conclusions: Although the majority of patients with PCN adhered to given recommendations after EUS examination, the number of noncompliant subjects was noticeable. The presence of cystic “worrisome” features did not correlate with an increased compliance rate to suggested management plan. Further prospective studies are needed to elucidate the factors that may enhance patients' adherence.

Methods: In this retrospective study, we investigated the endoscopic and clinical features of patients with EATLs at a tertiary center, from January 2008 to October 2020. Results: From a total of 248 patients with primary intestinal lymphoma, only 11 patients were finally diagnosed with EATLs, all of which were EATL type II. Men were affected twice as commonly as women. The median patient age was 47 years. The most common initial symptom was diarrhea (63.6%). Five patients (45.4%) were at late stage (IV) at diagnosis. The endoscopic appearances were classified into four distinct types: ulcerative type (54.5%), epithelial mass type (18.2%), diffuse infiltration type (9.1%), and nodular type (18.2%). The small bowel was the most common site of involvement (72.7%). The initial endoscopic impression of lymphoma was made in only 3 patients (27.3%). Only 4 patients (36.4%) were histologically confirmed as having EATLs based on the initial biopsy specimen. Five patients (45.5%) received emergency surgery. The median overall survival (OS) was 8 months. The use of chemotherapy and the absence of emergency surgery were associated with a significantly better median OS (P < 0.05). Conclusions: EATL may show various endoscopic appearances, and its prognosis is poor. Endoscopists should obtain more knowledge of EATL in order to make an early diagnosis.

Background: Trichohepatoenteric syndrome (THES) is a very rare disorder that is characterized by intractable congenital diarrhea, woolly hair, intrauterine growth restriction, facial dysmorphism, and short stature. Our knowledge of THES is limited due to the small number of reported cases. Methods: Thirty patients diagnosed with THES, all molecularly confirmed by whole exome sequencing (WES) to have biallelic variants in TTC37 or SKIV2L, were included in the study. Clinical, biochemical, and nutritional phenotypes and outcome data were collected from all participants. Results: The median age of THES patients was 3.7 years (0.9–23 years). Diarrhea and malnutrition were the most common clinical features (100%). Other common features included hair abnormalities (96%), skin hyperpigmentation (87%), facial dysmorphic abnormalities (73%), psychomotor retardation (57%), and hepatic abnormalities (30%). Twenty-five patients required parenteral nutrition (83%) with a mean duration of 13.34 months, and nearly half were eventually weaned off. Parenteral nutrition was associated with a poor prognosis. The vast majority of cases (89.6%) had biallelic variants in SKIV2L, with biallelic variants in TTC37 accounting for the remaining cases. A total of seven variants were identified in TTC37 (n = 3) and SKIV2L (n = 4). The underlying genotype influenced some phenotypic aspects, especially liver involvement, which was more common in TTC37-related THES. Conclusion: Our data helps define the natural history of THES and provide clinical management guidelines.

Background: In acute pancreatitis (AP), serum amylase, lipase and imaging help establish a diagnosis with recognised lipase superiority. Recent literature has debated serum amylase testing and proposed its elimination, but little is known about the diagnostic role of simultaneously measured serum amylase levels in patients with non-diagnostic lipase. This study examined the contribution of pancreatic enzymes and imaging and the role of simultaneously measured serum amylase in children with non-diagnostic serum lipase. Methods: Retrospective medical records review of children aged <18 years with a verified discharge diagnosis of first-attack AP between January 01, 1994, and December 31, 2016. Results: First-attack AP was confirmed in 127 children (median age, 12.5 years). The sensitivity was 90.4%, 54.3%, 42.2% and 36.4% for lipase, amylase, contrast-enhanced computed tomography and ultrasonography (US), respectively. Combination US and lipase identified 96.6% of AP cases. Simultaneous amylase and lipase measurements in 125 children showed that either was ≥3× the upper limit of normal (ULN) in 95.2%, while both were <3× the ULN in 4.8% of cases. Nondiagnostic lipase was seen in 12 (9.6%) children, and diagnosis was based on amylase level ≥3× the ULN in six children and imaging in the other six. Conclusions: Serum amylase, serum lipase and imaging should continue for the conclusive diagnosis of AP in children. Simultaneous serum amylase measurement helped diagnose AP with non-diagnostic lipase.

Background: The current international consensus report indicated that all Helicobacter pylori (H. pylori)-positive patients should be treated. This study aimed to evaluate the long-term effects and benefits of H. pylori eradication on the gastric mucosa in the elderly population. Methods: We performed a retrospective cohort study with 311 individuals aged ≥60 years, including 83 with persistent H. pylori infection (persistent group), 128 with successful H. pylori eradication (eradicated group), and 100 without H. pylori infection (control group). The results of endoscopy and mucosal histology were investigated at baseline and followed up for 5 and 10 years. Results: In the 5 to 10-year follow-up, there was a significant difference in the atrophy score among the three groups (P < 0.001); however, no significant difference was observed in the intestinal metaplasia (IM) score (P > 0.05). There was no significant difference in the cumulative incidence of gastric neoplastic lesion (GNL) between the eradicated and persistent groups during the 5 to 10-year follow-up period (P > 0.05). The baseline IM score of patients with GNL was significantly higher than that of those without GNL in the eradicated and control groups (P < 0.05). In all patients with GNL, the mean interval time between baseline and diagnosis of GLN was more than 6 years. The severity of baseline mucosal IM (odds ratio: OR 3.092, 95% confidence interval [CI]: 1.690–5.655, P < 0.001) and H. pylori infection (OR: 2.413, 95%CI: 1.019–5.712, P = 0.045) significantly increased the risk for GNL. Conclusions: Older patients with a life expectancy of less than 5 to 10 years, especially those with moderate to severe gastric mucosal IM, may not benefit from the eradication of H. pylori to prevent gastric cancer.

Background: Although several studies have reported on the prevalence of micronutrients in Saudi Arabia, most frequently vitamin D and iron, they are either old or hospital- or primary health care center-based. The objectives of our study were to provide more updated data on the prevalence rate of micronutrients deficiency among the Saudi general pediatric population and to determine if there is an association between micronutrients deficiency and undernutrition. Methods: The present study is part of a cross-sectional mass screening study, “Exploring the Iceberg of Celiacs in Saudi Arabia” conducted among school-aged children (6–16 years) in 2014–2015. A sample of 7,931 children aged 6–16 years was randomly selected. We identified thin children [body mass index (BMI) z-score <−2 SD, for age and gender], using the WHO reference 2007. A case-control study was performed, where the sera of 182 thin children (cases) and 393 normal BMI children (controls) were tested for levels of iron, ferritin, vitamin D, zinc, selenium, and copper. Results: The prevalence of thinness was 3.5%. The two most common micronutrients deficient among Saudi children with normal BMI were iron (20%) and vitamin D (78%). Vitamin D levels were significantly higher among boys as compared to girls (39.6 nmol/L vs. 31.15 nmol/L; P < 0.001). Deficiency of copper, zinc, and selenium occurred in 0.25%, 1%, and 7.4% of the children with normal BMI. Comparisons between the cases and controls did not show statistically significant differences. Conclusion: Vitamin D and iron deficiencies are still common forms of malnutrition in the Saudi community, that have remained unchanged over the past 20–30 years, while the intake of trace elements (zinc, copper, and selenium) is adequate as evident by normal serum levels in the vast majority of the investigated children. We could not observe a correlation between undernutrition and micronutrient deficiencies.