Hepatocellular Carcinoma in Patients Without Cirrhosis: The Fibrosis Stage Distribution, Characteristics and Survival.

BACKGROUND: The data on hepatocellular carcinoma (HCC) patients without liver cirrhosis is scarce. AIMS: To study the epidemiology, underlying etiology and fibrosis distribution in noncirrhotic HCC and compare the survival outcomes to cirrhotic HCC. METHODS: We conducted a retrospective study including all adult patients diagnosed with HCC at two US tertiary academic centers from 2000 to 2015. Univariable and multivariable Cox regression analyses were performed to evaluate the variables associated with patient survival. RESULTS: Two thousand two hundred and thirty-seven HCC patients were included in the final analysis, of which, 13% had no liver cirrhosis. The most common underlying liver disease in non-cirrhotic patients was cryptogenic cause (40%), followed by nonalcoholic fatty liver disease (NAFLD) (25.2%) and hepatitis C (19%). The percentage of F0-F1, F2, and F3 was 72%, 17%, and 11% (cryptogenic cause); 69%, 12%, and 19% (NAFLD); 50%, 17%, and 33% (alcohol); 33%, 39%, and 28% (hepatitis B); 20%, 40%, and 40% (hemochromatosis); and 12%, 40%, and 48% (hepatitis C), respectively. In non-cirrhotic compared to cirrhotic patients, the tumor was more likely to be larger and fell outside Milan criteria (all p < 0.001). Cirrhotic patients had significant shorter survival than non-cirrhotic patients (p < 0.001). On the multivariable analysis, having liver cirrhosis (HR 1.48; 1.21-1.82, p < 0.001), combined viral hepatitis and alcohol use (HR 1.51; 1.23-1.88, p < 0.001), morbid obesity (HR 1.31; 1.01-1.69, p = 0.040) and underweight (HR 2.06; 1.27-3.34, p = 0.004) were associated with worse patient survival. CONCLUSIONS: The fibrosis distribution in non-cirrhotic HCC differed among each etiology of liver diseases. Despite more advanced HCC, patients without cirrhosis had significantly longer survival than those with cirrhosis.

Chemopreventive Effect of Statin on Hepatocellular Carcinoma in Patients With Nonalcoholic Steatohepatitis Cirrhosis.

INTRODUCTION: To estimate the annual incidence of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis, to determine the risk factors for the development of HCC, and to evaluate the chemoprotective effect of statin use stratified by fibrosis stage. METHODS: We conducted a retrospective study at 2 US tertiary academic centers, including patients with NASH-related advanced liver fibrosis (bridging fibrosis [F3] and cirrhosis [F4]) followed between July 2002 and June 2016. Patients were followed from the date of diagnosis to the time of last abdominal imaging, liver transplantation, or HCC diagnosis. Multivariable Cox regression analysis was performed to evaluate the risk factors associated with HCC development, stratified by fibrosis stage. RESULTS: A total of 1,072 patients were included: 122 patients with F3 fibrosis and 950 patients with cirrhosis. No HCC was observed during 602 person-year follow-up among F3 patients. Among patients with cirrhosis, HCC developed in 82 patients with the annual incidence rate of 1.90 per 100 person-years (95% confidence interval [CI], 1.53-2.35). Multivariable analysis in patients with cirrhosis demonstrated that HCC development was associated with male sex (hazard ratio [HR] 4.06, 95% CI, 2.54-6.51, P < 0.001), older age (HR, 1.05, 95% CI, 1.03-1.08, P < 0.001), and CTP score (HR, 1.38, 95% CI, 1.18-1.60, P < 0.001). Statin use was associated with a lower risk of developing HCC (HR, 0.40, 95% CI, 0.24-0.67, P = 0.001). Each 365 increment in cumulative defined daily dose of statin use reduced HCC risk by 23.6%. DISCUSSION: Our findings suggest that patients with NASH and bridging fibrosis have a low risk of HCC. Dose-dependent statin use reduced HCC risk significantly in patients with NASH cirrhosis.

Hepatocellular carcinoma in nonalcoholic fatty liver disease with or without cirrhosis: a population-based study.

BACKGROUND: There are limited data regarding the factors associated with hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. We sought to determine the prevalence and factors associated with HCC in NAFLD patients with or without cirrhosis. METHODS: Adults with NAFLD (June 2015 to May 2020) were identified using the electronic health record database (Explorys Inc, Cleveland, OH) from 26 major integrated US healthcare systems. The prevalence of HCC was calculated. Multivariable analyses adjusting for covariates were performed to evaluate the associated risk factors and the presence of HCC. RESULTS: A total of 392,800 NAFLD patients were identified. Among 1110 patients with HCC, 170 (15.3%) had no cirrhosis. The prevalence of HCC in non-cirrhotic and cirrhotic NAFLD patients was 4.6/10,000 persons (95% CI 3.9-5.3), and 374.4/10,000 persons (95% CI 350.9-398.8), respectively. Age > 65 years (adjusted OR; 3.37, 95% CI 2.47-4.59), ever had elevated alanine aminotransferase (2.69; 2.14-3.37), male gender (2.57; 1.88-3.49), smoker (1.75; 1.23-2.49), and diabetes (1.56; 1.15-2.11) were associated with HCC in non-cirrhotic NAFLD (all P < 0.05). The prevalence of HCC in the non-cirrhotic with all five risk factors was 45.5/10,000 persons (95% CI 17.4-73.6). The factors associated with HCC in cirrhotic NAFLD included clinical decompensation, age > 65 years, male gender, Hispanic race, elevated alanine aminotransferase, diabetes and smoker (all P < 0.05). CONCLUSIONS: These data identified the major risk factors for the development of HCC in NAFLD patients. In the non-cirrhotics, older male patients with smoking history, diabetes and an elevated alanine aminotransferase had highest risk and may need increased judicious monitoring.

The effects of dapagliflozin on hepatic and visceral fat in type 2 diabetes patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Sodium-glucose cotransporter 2 inhibitors have shown excellent results in glucose control in type 2 diabetes mellitus (T2DM) patients, while also promoting weight loss. These mechanisms may be beneficial in the treatment of non-alcoholic fatty liver disease (NAFLD). Our study aims to investigate the effect of dapagliflozin on hepatic and visceral fat contents and related biochemical markers in T2DM with NAFLD patients. METHODS: This is a double-blinded placebo-controlled randomized, single-center study. Non-insulin-dependent T2DM patients with NAFLD were prospectively enrolled and randomly assigned to receive either dapagliflozin (10 mg/day) or placebo for 12 weeks. The primary end-point was the changes in intrahepatic lipid contents, evaluated by the liver attenuation index. RESULTS: Of 40 patients enrolled, 38 patients completed the study (dapagliflozin group, n = 18; placebo group, n = 20). Baseline demographic and laboratory findings were similar in both groups. After 12 weeks of treatment, dapagliflozin significantly decreased intrahepatic lipid contents demonstrated by an increase in liver attenuation index in comparison with the placebo treatment (5.8 ± 5.1 vs 0.5 ± 6.1 Hounsfield units, P = 0.006). Significant reduction in bodyweight, bodyfat, visceral fat/subcutaneous fat ratio, hemoglobin A1c, and alanine aminotransferase were also observed in the dapagliflozin-treated group as compared with the placebo group (all P < 0.05). There was no significant difference in adipokines including adiponectin, leptin, and tumor necrosis factor-α changes between the dapagliflozin-treated group and the placebo group (all P = nonsignificant). CONCLUSION: Dapagliflozin treatment for 12 weeks is associated with improvement in hepatic fat content, a decrease in visceral fat and bodyweight, enhanced glycemic control, and improved liver biochemistry among T2DM patients with NAFLD.

The Treatment of Unidentified Hematotoxic Snake Envenomation and the Clinical Manifestations of a Protobothrops kelomohy Bite.

Hematotoxic snake envenomation is clinically important and has serious complications. This case report describes the clinical manifestations of a bite from a newly described species of hematotoxic snake and the outcomes of treatment using locally available antivenom and supportive management. A 39-y-old male was bitten on his right ankle by an unidentified snake. The patient developed coagulopathy, rhabdomyolysis, and clinical signs of compartment syndrome of his right leg within the first day. Eight doses (30 mL, or 3 vials per dose), or a total of 240 mL, of hemato-polyvalent antivenin (Thai Red Cross, Thailand) were given. Aggressive intravenous hydration and alkalinization of urine were performed, and a fasciotomy was performed for the treatment of suspected compartment syndrome. The patient's clinical symptoms and laboratory results indicated progressive improvement during the 5 d of hospitalization. The snake was later identified as Protobothrops kelomohy, a novel snake species with no clinical data available regarding its envenomation of humans. This case shows that P kelomohy envenomation can produce severe effects that occur both locally and systemically. The benefits of the use of polyvalent antivenom in this situation were unclear. However, with supportive treatment in conjunction with serial clinical and laboratory monitoring, the patient recovered, albeit after 7 d of hospitalization.

Omeprazole Induced Rapid Drug Reaction with Eosinophilia, Systemic Symptoms, and Cross-Reactivity in Delayed-Type Hypersensitivity Associated with Proton-Pump Inhibitors: A Case Report and Literature Review.

Background: Omeprazole, a proton pump inhibitor (PPI), is a widely used and generally safe agent for treating acid-related gastrointestinal conditions. However, drug reaction with eosinophilia and systemic symptoms (DRESSs) syndrome has been reported. Objectives: To report a case of omeprazole-induced rapid DRESS syndrome and to review the literature. Methods: Descriptive analysis of one new case and a case series from literature review. Results: We report a case of 82-year-old woman presenting with rapid-onset of DRESS syndrome. The condition was initially suspected to be caused by antibiotic, but the definite diagnosis was eventually omeprazole-induced DRESS syndrome as suggested by the enzyme-linked immune absorbent spot (ELISpot) assay along with the clinical picture. Previous literatures regarding cases of PPI-induced DRESS syndrome were pooled for descriptive analysis. Among 21 PPI cases pooled, esomeprazole was the most commonly implicated PPI (52.4%), followed by pantoprazole (19.1%), and omeprazole along with lansoprazole (both 14.3%). The issue of cross-reactivities amongst PPIs remains uncertain. Nonetheless, in situations in which a PPIs are deemed necessary, a prudent approach could be considering a switch to an alternative agent with distinct chemical structure. Conclusion: PPI is commonly used safely as an agent for acid-related gastrointestinal conditions. However, PPI-induced rapid DRESS syndrome can occur, particularly with prior exposure history. ELISpot is an in vitro test, useful in identifying the culprit agent in patients with delayed-type hypersensitivity reaction.

Imbalance of mitochondrial fusion in peripheral blood mononuclear cells is associated with liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis.

Mitochondrial dysfunction and inflammation contribute to the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH). This study aims to evaluate the potential association between mitochondrial dynamics and cell death markers from peripheral blood mononuclear cells (PBMCs) and the presence of MASH with significant liver fibrosis among metabolic dysfunction-associated steatotic liver disease (MASLD) patients. Consecutive patients undergoing bariatric surgery from January to December 2022 were included. Patients with histologic steatosis were classified into MASH with significant fibrosis (F2-4) group or MASLD/MASH without significant fibrosis group (F0-1). Mitochondrial dynamic proteins and cell death markers were extracted from PBMCs. A total of 23 MASLD/MASH patients were included (significant fibrosis group, n = 7; without significant fibrosis group, n = 16). Of the mitochondrial dynamics and cell death markers evaluated, OPA1 protein, a marker of mitochondrial fusion is higher in MASH patients with significant fibrosis compared to those without (0.861 ± 0.100 vs. 0.560 ± 0.260 proportional to total protein, p = 0.001). Mitochondrial fusion/fission (OPA1/DRP1) ratio is significantly higher in MASH patients with significant fibrosis (1.072 ± 0.307 vs. 0.634 ± 0.313, p = 0.009). OPA1 (per 0.01 proportional to total protein) was associated with the presence of significant liver fibrosis with an OR of 1.08 (95%CI, 1.01-1.15, p = 0.035), and adjusted OR of 1.10 (95%CI, 1.00-1.21, p = 0.042). OPA1 from PBMCs is associated with MASH and substantial fibrosis. Future studies should explore if OPA1 could serve as a novel non-invasive liver fibrosis marker.

Efficacy and safety of pinaverium bromide as an add-on therapy in refractory dyspepsia: A randomized controlled trial.

Background and Aim: Functional dyspepsia (FD) remains a therapeutic challenge, and the efficacy of antispasmodic agents as adjunctive therapy is not well established. This study aimed to evaluate the efficacy and safety of pinaverium bromide added to omeprazole in treating refractory FD. Methods: We conducted a randomized, placebo-controlled trial in patients with refractory dyspepsia. Participants were randomly assigned to receive pinaverium (50 mg, 3 times/day, n = 36) or placebo (n = 36) in addition to omeprazole for 8 weeks. The primary endpoint was the responder rate for adequate relief. Secondary outcomes included the Global Overall Symptom Scale (GOSS), quality of life, and safety profile. Results: No statistically significant differences were observed in the adequate relief response rate between the pinaverium bromide and control group at week 2 (58.3% vs. 62.9%, P = 0.697), week 4 (62.9% vs. 78.1%, P = 0.173), week 6 (64.7% vs. 75.0%, P = 0.363), and week 8 (64.7% vs. 75.0%, P = 0.363). Additionally, there were no significant differences observed in the decline of symptom score between the two groups at week 4 (8.4 ± 7.6 vs. 7.7 ± 7.1, P = 0.702) and week 8 (10.9 ± 8.2 vs. 8.4 ± 7.2, P = 0.196). Similarly, there were no significant differences in terms of quality of life between the two groups. Adverse event rates were also comparable between the two groups. Conclusion: Pinaverium bromide was found to be safe in the treatment of refractory dyspepsia, but it did not demonstrate a significant benefit in improving symptoms.

The Long-Term Effect of Weight Loss on the Prevention of Progression to Cirrhosis among Patients with Obesity and MASH-Related F3 Liver Fibrosis.

This multi-center retrospective study examined the effect of weight loss on the prevention of progression to cirrhosis in a sample exclusively composed of patients with obesity and MASH-related F3 liver fibrosis. Adult patients with obesity and biopsy-confirmed MASH-related F3 liver fibrosis (n = 101) from two liver transplant centers in the US were included in the study. A higher proportion of patients who did not progress to cirrhosis achieved >5% weight loss at follow-up (59% vs. 30%, p = 0.045). In multivariable analysis, patients with >5% weight loss at follow-up had a lower hazard of developing cirrhosis compared to patients with no weight loss or weight gain (HR: 0.29, 95%, CI: 0.08-0.96); whereas, diabetes (HR: 3.24, 95%, CI: 1.21-8.67) and higher LDL levels (HR: 1.02, 95%, CI: 1.01-1.04) were associated with higher hazards of progression to cirrhosis. Weight loss >5% has the potential to prevent disease progression to cirrhosis in patients with obesity and MASH-related F3 liver fibrosis. The realization of this benefit requires weight loss maintenance longer than one year. Larger prospective studies are needed to determine how weight loss impacts other patient-centered outcomes such as mortality, hepatic decompensation, and hepatocellular carcinoma in patients with obesity and MASH-related F3 liver fibrosis.

Artificial Intelligence in Liver Diseases: Recent Advances.

Liver diseases cause a significant burden on public health worldwide. In spite of great advances during recent years, there are still many challenges in the diagnosis and treatment of liver diseases. During recent years, artificial intelligence (AI) has been widely used for the diagnosis, risk stratification, and prognostic prediction of various diseases based on clinical datasets and medical images. Accumulative studies have shown its performance for diagnosing patients with nonalcoholic fatty liver disease and liver fibrosis and assessing their severity, and for predicting treatment response and recurrence of hepatocellular carcinoma, outcomes of liver transplantation recipients, and risk of drug-induced liver injury. Herein, we aim to comprehensively summarize the current evidence regarding diagnostic, prognostic, and/or therapeutic role of AI in these common liver diseases.

Impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients with acute gastrointestinal bleeding: an international multicenter study.

OBJECTIVES: Peptic ulcer is the most common source of non-variceal bleeding. However, it remains controversial whether the outcomes of cirrhotic patients with peptic ulcer bleeding differ from those with variceal bleeding. METHODS: Cirrhotic patients with acute gastrointestinal bleeding (AGIB) who underwent endoscopy and had an identifiable source of bleeding were retrospectively screened from an international multicenter cohort. Logistic regression analyses were performed to explore the impact of peptic ulcer bleeding on in-hospital death and 5-day failure to control bleeding. Propensity score matching (PSM) analysis was performed by matching age, gender, Child-Pugh score, and model for end-stage liver disease score between the peptic ulcer bleeding and variceal bleeding groups. RESULTS: Overall, 1535 patients were included, of whom 73 (4.7%) had peptic ulcer bleeding. Multivariate logistic regression analyses showed that peptic ulcer bleeding was not independently associated with in-hospital death (OR = 2.169, p = 0.126) or 5-day failure to control bleeding (OR = 1.230, p = 0.680). PSM analyses demonstrated that both in-hospital mortality (9.7% vs. 6.3%, p = 0.376) and rate of 5-day failure to control bleeding (6.9% vs. 5.4%, p = 0.787) were not significantly different between the two groups. CONCLUSIONS: The impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients is similar to that of variceal bleeding.

In this international multicenter study, we included 1535 patients with acute gastrointestinal bleeding (AGIB) and divided them into peptic ulcer bleeding and variceal bleeding groups. We found that only a minority of AGIB episodes in cirrhotic patients was attributed to peptic ulcer. Additionally, after adjusting for the severity of liver dysfunction, the in-hospital mortality and the rate of 5-day failure to control bleeding should be similar between cirrhotic patients with peptic ulcer bleeding and those with variceal bleeding.

Secondary Iron Overload and the Liver: A Comprehensive Review.

Iron overload is a condition involving excessive iron deposit in various organs, the liver being the main target organ for iron deposition and overload which are associated with significant liver morbidity and mortality. Iron overload can be categorized into primary and secondary causes. Primary iron overload, so-called hereditary hemochromatosis, is a well-recognized disease with available standard treatment recommendations. However, secondary iron overload is a more diverse disease with many unclear areas to be explored. Secondary iron overload is more prevalent than primary iron overload and occurs as a consequence of various causes which differ significantly across geographic regions. The main causes of secondary iron overload are iron-loading anemias, and chronic liver disease. The liver-related outcomes, patient outcomes, and treatment recommendations in these patients differ depending on the cause of iron overload. This review summarizes the causes, pathophysiology, liver-related outcomes, disease outcomes, and treatments of secondary iron overload.

Efficacy and safety of tolvaptan in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Tolvaptan has been approved for the management of cirrhosis-related complications according to the Japanese and Chinese practice guidelines, but not the European or American practice guidelines in view of FDA warning about its hepatotoxicity. This study aimed to systematically evaluate its efficacy and safety in cirrhosis. METHODS: The PubMed, EMBASE, and Cochrane library databases were searched to identify randomized controlled trials (RCTs) evaluating the efficacy and/or safety of tolvaptan in cirrhosis. Risk ratios (RRs) and weight mean differences (WMDs) were calculated. The incidence of common adverse events (AEs) was pooled. RESULTS: Eight RCTs were included. Tolvaptan was significantly associated with higher rates of improvement of ascites (RR = 1.49, P < 0.001) and hyponatremia (RR = 1.80, P = 0.005) and incidence of any AEs (RR = 1.18, P = 0.003), but not serious AEs (RR = 0.86, P = 0.410). Tolvaptan was significantly associated with reductions in body weight (WMD = -1.30 kg, P < 0.001) and abdominal circumference (WMD = -1.71 cm, P < 0.001), and increases in daily urine volume (WMD = 1299.84 mL, P < 0.001) and serum sodium concentration (WMD = 2.57 mmol/L, P < 0.001). The pooled incidences of dry mouth, thirst, constipation, and pollakiuria were 16%, 24%, 6%, and 17%, respectively. CONCLUSION: Short-term use of tolvaptan may be considered in cirrhotic patients with ascites who have inadequate response to conventional diuretics and those with hyponatremia.

[Figure: see text].

Use of albumin infusion for cirrhosis-related complications: An international position statement.

Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.

Impact of behavioral and psychological symptoms of Alzheimer's disease on caregiver outcomes.

This study was to determine the prevalence of behavioral and psychological symptoms of dementia (BPSD) and its association with dementia severity and to explore the association between specific BPSD and caregiver stress, burden, and depression. A cross-sectional study involving the interviewing of the primary caregivers of patients with Alzheimer's disease (AD) was conducted. Multivariable analysis was used to analyze the associations between specific symptoms of BPSD and caregiver outcomes. A total of 102 AD patients (age 79.4 ± 7.9 years, 70.6% female) and their caregivers were included. Nearly 46% had moderate-to-severe AD. Nearly all patients (99.0%) had at least one BPSD. Apathy was among the most common symptoms (74.5%), and hallucination was the only symptom associated with severity of AD (p = 0.017). After adjustment, agitation was associated with Patient Health Questionnaire-9 (PHQ-9) and Zarit Burden Interview (ZBI-22) (p = 0.021 and 0.007, respectively); sleep disorders were associated with only PHQ-9 (p = 0.049). In conclusion, the BPSD, especially agitation and sleep disorders, can give rise to difficulties for both patients and their caregivers. The prevalence of BPSD is high (99.0%), and the symptoms can start early. Routine screening of BPSD in all AD patients is advocated.

Simplified 6-month prediction scores for primary biliary cholangitis patients treated with ursodeoxycholic acid.

OBJECTIVES: To develop a prognostic score evaluating treatment response at 6 months after ursodeoxycholic acid (UDCA) initiation in primary biliary cholangitis (PBC) patients. METHODS: Adult PBC patients who were newly prescribed UDCA at our institution (n = 292) were included. Significant determinants of liver-related adverse events in the multivariable Cox model were used for score development, weighted by ß-coefficients. Discrimination ability was assessed using Harrell's C-statistic. The performance of our model was compared to the previous models. RESULTS: Our model included the following variables evaluated at 6 months: (1) alkaline phosphatase decline of less than 50% from baseline and >upper limit normal (ULN) (2 points); (2) bilirubin >ULN (2 points); (3) albumin

Effects of Metformin on Hepatic Steatosis in Adults with Nonalcoholic Fatty Liver Disease and Diabetes: Insights from the Cellular to Patient Levels.

Nonalcoholic fatty liver disease (NAFLD) patients with diabetes constitute a subgroup of patients with a high rate of liver-related complications. Currently, there are no specific drug recommendations for these patients. Metformin, a conventional insulin sensitizer agent, has been widely prescribed in patients with diabetes. Metformin treatment has been shown to be effective at alleviating hepatic lipogenesis in animal models of NAFLD, with a variety of mechanisms being deemed responsible. To date, most studies have enrolled diabetic patients who are treated with metformin, with the drug being taken continuously throughout the study. Although evidence exists regarding the benefits of metformin for NAFLD in preclinical studies, reports on the efficacy of metformin in adult NAFLD patients have had some discrepancies regarding changes in liver biochemistry and hepatic fat content. Evidence has also suggested possible effects of metformin as regards the prevention of hepatocellular carcinoma tumorigenesis. This review was performed to comprehensively summarize the available in vitro, in vivo and clinical studies regarding the effects of metformin on liver steatosis for the treatment of adult NAFLD patients with diabetes. Consistent reports as well as controversial findings are included in this review, and the mechanistic insights are also provided. In addition, this review focuses on the efficacy of metformin as a monotherapy and as a combined therapy with other antidiabetic medications.

Enterolith at the ileocecal valve mimicking a subepithelial mass.

A 32-year-old woman presented with chronic constipation for three years. Colonoscopy revealed a 2.5 cm subepithelial tumor-like lesion at the ileocecal (IC) valve with protrusion of the lesion into the lumen. A CT scan of the abdomen showed an oval-shape laminated calcified lesion adhered to the IC valve and several gallstones. An exploratory laparotomy to enterotomy with stone extraction and open cholecystectomy was performed. Operative findings showed stone erosion into the ileal wall with the lesion being covered with colonic mucosa. Pathologic examination of stones from the intestinal wall revealed an enterolith. The case exemplifies the infrequent cause of a subepithelial lesion of the gastrointestinal tract and a rare presentation of an enterolith as a subepithelial lesion within the terminal ileal wall.

Utilization of Health Care Services and Common Disease Diagnoses among University Students: An Analysis of 35,249 Students from Thailand.

The health care services for university students are important to improve student health and well-being. Analyzing the database of health conditions in the health service system will identify common health problems, which could be useful in further appropriate and specific health service planning. This study aims to investigate the utilization of health care services and common disease diagnoses among university students enrolled at Chiang Mai University during the academic year of 2018. A retrospective study was carried out using health data from the electronic health records (EHR) database of the university hospital. Ethical procedures were followed. Out of the overall 35,249 students in the academic year 2018, 17,284 students (49.03%) had visited an outpatient department (65,150 outpatient department visits), and 407 students (1.15%) had been admitted to the hospital (458 inpatient department admissions). The proportions of utilization between each field of education and training were similar across both groups. The top five categories of diagnosis, for both outpatient department visits and inpatient department admissions, differed between gender. Some of the most common diseases included trauma and injury conditions, respiratory diseases, and mental health. The conclusion of the study is that integration of a health promotion program with preventive methods, especially regarding traffic injury, transmitted diseases, mental health support, and safe environments are essential for university students. A general overview of utilization and common diseases among university students, which is still lacking in the literature, could be useful as a platform to enhance health care services for common diseases.

Randomised clinical trial: the effects of pregabalin vs placebo on functional dyspepsia.

BACKGROUND: Currently, central neuromodulators are among the therapeutic options for the treatment of functional dyspepsia (FD). Pregabalin, a gabapentinoid, is a neuromodulator that could potentially improve visceral hypersensitivity in FD patients. AIM: To assess the efficacy and safety of pregabalin for the treatment of FD METHODS: We performed a randomised placebo-controlled study including FD patients who did not respond to proton pump inhibitors. Patients were randomly assigned to receive pregabalin (75 mg daily) or placebo for 8 weeks. The primary outcome was an adequate relief response rate. The secondary outcomes were improvement in quality of life, pain scores in divided categories, and safety profile. RESULTS: Of 72 patients enrolled, 34 received pregabalin and 38 received placebo. The self-reported adequate relief rates in the pregabalin and placebo groups were 70.6% and 42.1% at week 4 (P = 0.02), and 70.6% and 44.7% at week 8 (P = 0.03), respectively. The reduction in global symptoms in the pregabalin and placebo groups were 11.7 ± 10.6 and 3.7 ± 8.9 points at week 4 (P < 0.01) and 15.1 ± 12.2 and 8.0 ± 10.2 points at week 8 (P = 0.01), respectively. Pregabalin improved the overall quality of life (P = 0.03). The most common adverse event with pregabalin was dizziness, occurring in 51.6% of patients. CONCLUSIONS: Pregabalin led to significant alleviation of dyspeptic symptoms, especially in patients with predominant epigastric pain . Thaiclinicaltrials.org #TCTR20200404002.