Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.

The Efficacy of Anthropometric Indicators in Predicting Non-Alcoholic Fatty Liver Disease Using FibroScan® CAP Values among the Taiwanese Population.

The controlled attenuation parameter (CAP) measurement obtained from FibroScan® is a low-risk method of assessing fatty liver. This study investigated the association between the FibroScan® CAP values and nine anthropometric indicators, including the abdominal volume index (AVI), body fat percentage (BFP), body mass index (BMI), conicity index (CI), ponderal index (PI), relative fat mass (RFM), waist circumference (WC), waist-hip ratio (WHR), and waist-to-height ratio (WHtR), and risk of non-alcoholic fatty liver disease (fatty liver). We analyzed the medical records of adult patients who had FibroScan® CAP results. CAP values <238 dB/m were coded as 0 (non- fatty liver) and ≥238 dB/m as 1 (fatty liver). An individual is considered to have class 1 obesity when their body mass index (BMI) ranges from 30 kg/m2 to 34.9 kg/m2. Class 2 obesity is defined by a BMI ranging from 35 kg/m2 to 39.9 kg/m2, while class 3 obesity is designated by a BMI of 40 kg/m2 or higher. Out of 1763 subjects, 908 (51.5%) had fatty liver. The BMI, WHtR, and PI were found to be more strongly correlated with the CAP by the cluster dendrogram with correlation coefficients of 0.58, 0.54, and 0.54, respectively (all p < 0.0001). We found that 28.3% of the individuals without obesity had fatty liver, and 28.2% of the individuals with obesity did not have fatty liver. The BMI, CI, and PI were significant predictors of fatty liver. The BMI, PI, and WHtR demonstrated better predictive ability, indicated by AUC values of 0.72, 0.68, and 0.68, respectively, a finding that was echoed in our cluster group analysis that showed interconnected clustering with the CAP. Therefore, of the nine anthropometric indicators we studied, the BMI, CI, PI, and WHtR were found to be more effective in predicting the CAP score, i.e., fatty liver.

Epidemiology of Chronic Hepatitis B Infection in the Cohort of College Students with Vaccination in Taiwan.

After the mass vaccination project in Taiwan, the prevalence of the hepatitis B virus (HBV) infection for the college-aged population of 18 to 21 years is uncertain. We aimed to investigate the prevalence of hepatitis B markers in different birth cohorts. A total of 38,075 students in universities in Kaohsiung area undergoing entrance examinations between July 2006 to September 2020 were included. Seroprevalence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) status and laboratory data were collected. The seropositive rate of HBsAg was less than 1% for students born after 1991. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly higher, and body mass index (BMI) was significantly lower in HBV carriers compared to those who were not carriers (all p < 0.001). Multivariate logistic regression showed that age, male, higher BMI, and positive HBsAg were risk factors of abnormal ALT value. A decrease in the positive rate of anti-HBs which was significantly higher in the cohort of plasma-derived vaccines than recombinant vaccines was found. We concluded that there were decreasing trends in seropositive rates of HBsAg and anti-HBs for students of the college-aged population in the Kaohsiung area. The status of HBsAg was a predictive factor of abnormal ALT levels. The period effect on anti-HBs seropositivity for DNA recombinant vaccine somehow existed.

Diagnostic performances of pepsinogens and gastrin-17 for atrophic gastritis and gastric cancer in Mongolian subjects.

In Mongolia, gastric cancer morbidity and mortality are high, and more than 80 percent of cases are diagnosed at an advanced stage. This study aimed to evaluate pepsinogens (PGIs) and gastrin-17 (G-17) levels and to determine the diagnostic performances for gastric cancer and chronic atrophic gastritis among Mongolian individuals. We enrolled a total of 120 subjects, including gastric cancer (40), atrophic gastritis (40), and healthy control (40), matched by age (±2) and sex. Pepsinogen I (PGI), Pepsinogen II (PGII), G-17, and H. pylori IgG levels were measured using GastroPanel ELISA kit (Biohit, Helsinki, Finland). Also, PGI to PGII ratio (PGR) was calculated. For atrophic gastritis, when the optimal cut-off value of PGI was ≤75.07 ng/ml, the sensitivity and specificity were 75% and 50%, respectively; when the optimal cut-off value of PGR was ≤6.25, sensitivity and specificity were 85% and 44.7%, respectively. For gastric cancer, when the optimal cut-off value of PGI was ≤35.25 ng/ml, the sensitivity and specificity were 47.2% and 86.8%, respectively; when the optimal cut-off value of PGR was ≤5.27, sensitivity and specificity were 75% and 60.5%, respectively. Combinations of biomarkers with risk factors could improve diagnostic accuracy (AUC for atrophic gastritis 74.8, 95% CI 64.0-85.7, p<0.001; AUC for gastric cancer 75.5, 95% CI 64.2-86.8, p<0.001). PGI, PGR biomarkers combined with the risk of age, family history of gastric cancer, and previous gastric disease could not be an alternative test for upper endoscopy but might be a supportive method which is identifying individuals at medium- and high risk of gastric cancer and precancerous lesions who may need upper endoscopy.

Persistent cryoglobulinemia after antiviral treatment is associated with advanced fibrosis in chronic hepatitis C patients.

BACKGROUND: High dosage and longer duration of antiviral treatment has been suggested to treat cryoglobulinemia patients. We aimed to investigate the efficacy of antiviral treatment in cryoglobulinemia patients and analyze the associated factors of persistent cryoglobulinemia. METHODS: Totally 148 patients after completion of anti-HCV treatment were enrolled in our study. Serum cryoglobulinemia precipitation was assessed and analyzed for the associated factors after antiviral therapy. RESULTS: Fifty-one (34.5%) out of 148 patients were positive for serum cryoglobulinemia after completion of antiviral therapy. In multivariate analysis, advanced fibrosis (Odds Ratio [OR]- 4.13, 95% Confidence Interval [95% CI]- 1.53-11.17, p = 0.005) and platelet counts (OR-0.98, 95% CI- 0.97-0.99, p = 0.010) were independently and significantly associated with persistent cryoglobulinemia. The factors associated with the persistent cryoglobulinemia in SVR patients were advanced fibrosis (OR-1.93, 95% CI- 1.02-3.65, p = 0.041) and platelet count (OR-0.98, 95% CI- 0.96-0.99, p = 0.041) by multivariate analysis. Multivariate logistic regression analysis showed persistent (OR-4.83, 95% CI- 1.75-13.36, p = 0.002) was significantly associated with advanced fibrosis in patients with cryoglobulinemia follow up after antiviral therapy. CONCLUSIONS: The prevalence of the persistent cryoglobulinemia is 34.5% after completing antiviral therapy and it is associated with advanced fibrosis, also HCV clearance.

Determining Gastric Cancer-Related Risk Factors in Mongolian Population Using ABC(D) Method: A Matched Case-Control Study.

OBJECTIVE: We aimed to identify gastric cancer-related risk factors and evaluate the efficacy of screening ABC(D) method in determining high risk  gastric cancer individuals in Mongolian population. METHODS: A total of 240 participants (120 gastric cancer patients and 120 healthy individuals) were included in this study. Data were collecting using a structured questionnaire consisting of 56 questions covering 5 categories. Serum Helicobacter pylori IgG (H. pylori IgG), pepsinogen I (PGI), and pepsinogen II (PGII) were tested in one third of all the participants (40 gastric cancer patients and 40 controls).  PGI, PGII, and H. pylori IgG levels were measured using GastroPanel enzyme-linked immunosorbent assay kit (Biohit, Helsinki, Finland). RESULTS: Habits of having leftover meals (OR 2.22, 95%CI 1.27-3.86, p<0.01), daily consumption of tea with salt (OR 1.97, 95%CI 1.18-3.30, p<0.01), smoking on an empty stomach (OR 2.44, 95%CI 1.11-5.37, p<0.05), daily consumption of vegetables (OR 0.45, 95%CI 0.27-0.76, p<0.01), and daily consumption of fruit juice (OR 0.36, 95%CI 0.15-0.85, p<0.05), family history of gastric cancer (parents OR 2.88, 95%CI 1.07-7.78, p<0.05, siblings (OR 3.09, 95%CI 1.09-8.81, p<0.05), and history of gastric diseases (OR 3.65, 95%CI 2.10-6.35, p<0.0001) were identified as protective factors. A low PGI level (<35.25ng/ml) and low PGI/II ratio (<4) were associated with gastric cancer risk. According to ABC(D) method, groups C and D had higher proportion of gastric cancer cases than group A and B (group C, OR 7.50, 95%CI 1.20-47.05, p<0.05; group D, OR 8.3, 95%CI 1.33-51.26, p<0.05). CONCLUSION: Our findings suggested that gastric cancer risk was more closely related to eating habits, smoking, family history, and precancerous lesions. ABC(D) method seems to be a plausible alternative or supplementary method for stratifying patients at high risk of gastric cancer in this country.

The association between hepatitis C virus infection and renal function.

BACKGROUND: The association between hepatitis C virus (HCV) infection and chronic kidney disease (CKD) still remains controversial. We aimed to investigate whether HCV really affects renal function, and to analyze the association between clinical effects of CHC and decreased kidney function (assessed by glomerular filtration rate (eGFR) level). METHODS: An estimated 3360 patients with HCV infection and 3360 age- and sex-matched community-based control individuals without HCV were enrolled (1:1, case and control ratio) in this study between 2004 and 2016. We used the modification of diet in renal diseases to calculate eGFR. Demographic and laboratory parameters were assessed, and appropriate statistical methods were performed for the analysis. RESULTS: Multivariate logistic regression analysis revealed that serum alanine aminotransferase level (odds ratio [OR] 0.998; 95% confidence interval [CI] 0.997-0.999; P = 0.001), platelet count (OR 0.997; 95% CI 0.995-0.999; p = 0.002), and hypertension (OR 1.31; 95% CI 1.03-1.66; P = 0.027) were significantly associated with HCV infection and serum triglyceride levels (OR 1.001; 95% CI 1.00-1.002; p = 0.005), platelet count (OR 0.996; 95% CI 0.995-0.997; p < 0.001), body mass index (BMI) >25 (OR 1.43; 95% CI 1.23-1.67; p < 0.001), hypertension (OR 1.69; 95% CI 1.42-1.99; p < 0.001), hyperlipidemia (OR 1.32; 95% CI 1.02-1.71; p = 0.035), and diabetes (OR 1.33; 95% CI 1.03-1.71; p = 0.032) were significantly associated with a low eGFR (<90 mL/min/m3) in control subjects. The BMI >25 kg/m2, hypertension, and diabetes were found to be associated with low eGFR interaction with the HCV infection, via a multivariate analysis. CONCLUSION: Our study found that the patients with HCV infection are associated with a low eGFR compared with non-HCV-infected patients. This association is consistent in obese, diabetic, and hypertensive patients.

Incidence of Stomach and Esophageal Cancers in Mongolia: Data from 2009 to 2018.

INTRODUCTION: Digestive organ cancer is a major public health issue both in Asia and in Mongolia. The most prevalent cancer-related deaths in Mongolia are registered as caused by the stomach, esophagus, and liver. There is a lack of study which investigated the accurate incidence of digestive organ cancer nationwide. PURPOSE: We aimed to investigate the incidence of stomach and esophageal cancers in Mongolian population. MATERIALS AND METHODS: Epidemiologic data were collected between 2009 and 2018 through the oncology departments of hospitals and medical centers in all provinces, soums (the smallest unit of provinces), and major districts of the capital city. We used appropriate statistical methods in SPSS software. RESULTS: The incidence of esophageal cancer in last 10 years (2009-2018) was 10.09 in 100,000 populations and the highest incidence was registered in Uvs (38.13), Bayan-Ulgii (24.15), and Zavkhan (18.18) provinces, respectively. The incidence of stomach cancer was 20.33 in 100,000 populations and the highest incidences were registered in Uvs (53.01), Khovd (46.02), and Darkhan-Uul (40.50) provinces, respectively. CONCLUSION: The incidences of these cancers have increased last 10 years in some provinces. Stomach and esophageal cancers incidence in Mongolia is considerably higher compared to the other Asian countries. The nationwide targeted prevention program is needed. HOW TO CITE THIS ARTICLE: Lonjid T, Sambuu T, Tumurbat N, et al. Incidence of Stomach and Esophageal Cancers in Mongolia: Data from 2009 to 2018. Euroasian J Hepato-Gastroenterol 2020;10(1):16-21.

Elevated interleukin-4 levels predicted advanced fibrosis in chronic hepatitis C.

BACKGROUND: Cytokine imbalance has been associated with chronic hepatitis C virus (HCV) infection. We hypothesized that cytokines have an important role in fibrosis development in HCV infection. METHODS: Data of 92 patients were analyzed retrospectively. Fluorescent Bead immunoassay was used to measure the following serum cytokine levels: Interferon γ, tumor necrosis factor α, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-12. Various statistical analyses were used as appropriate. RESULTS: Of the 92 HCV-infected patients, 49 (53.3%) were male, 23 (25%) patients had advanced (fibrosis grades 3-4) fibrosis, and the mean age of the study population was 51.9 ± 9.4 years. Elevation of baseline IL-4 level (>490 pg/mL) was associated with liver fibrosis grade by χ test (odds ratio [OR] = 2.99; 95%, CI = 1.02-8.78; p = 0.042) and multivariate logistic regression (OR = 4.26; 95% CI = 1.13-16.02; p = 0.032). Also, IL-4 had strong diagnostic value in advanced liver fibrosis by using area under receiver operating characteristics curve analysis. Assessment of fibrosis score was consequently developed from our findings and compared with other noninvasive serum markers to assess liver fibrosis. CONCLUSION: This study provides evidence that increased IL-4 expression predicted advanced liver fibrosis in treatment of naive HCV-infected patients. The newly developed "FIL4" score had good predictive value for advanced fibrosis before treatment and this value was even strong in HCV-genotype 1b patients.

Elevated serum ferritin level associated with hepatic steatosis and fibrosis in hepatitis C virus-infected patients.

BACKGROUND: Serum ferritin is an indicator of iron accumulation in a human body, and it is frequently elevated in patients with systemic inflammatory state in chronic hepatitis C (CHC). Iron accumulation is associated with hepatic fibrosis, steatosis, and unfavorable outcome in CHC patients. We studied the status of elevated serum ferritin level and its association with the liver fibrosis or steatosis in Taiwanese CHC patients. METHODS: Seven hundred and thirty-eight Taiwanese CHC patients were consecutively included in this study. Laboratory analysis, four indexes of fibrosis (FIB4), histological assessment of fibrosis, and steatosis were assessed by appropriate elevation of serum ferritin level. RESULTS: Three hundred and one patients (40.8%) had elevated serum ferritin level (sex-specific threshold >1.5 × upper limit of normal). Serum iron level (odds ratio [OR], 1.02; 95% CI, 1.01%-1.03%, p < 0.001), female gender (OR, 1.49; 95% CI, 1.07%-2.08%, p = 0.018), serum gamma-glutamyl transferase level (OR, 1.007; 95% CI, 1.003%-1.01%, p < 0.001), steatosis grade (OR, 1.56; 95% CI, 1.13%-2.16%, p = 0.006), and FIB4 ≥3.25 (OR, 1.63; 95% CI, 1.18%-2.27%, p = 0.003) indexes were associated with high serum ferritin level by multivariate logistic regression analysis. Patients with steatosis (>5%) were associated with older age (OR, 1.01; 95% CI, 1.00%-1.03%, p = 0.015), body mass index (OR, 1.10; 95% CI, 1.05%-1.15%, p < 0.001), and elevated serum ferritin level (OR, 1.001; 95% CI, 1.00%-1.001%, p = 0.024) by multivariate logistic regression analysis. Serum ferritin level also associated with high FIB4 (≥3.25) (OR, 1.001; 95% CI, 1.001%-1.002%, p = 0.010) when multivariate model adjusted together with advanced liver fibrosis by biopsy. CONCLUSION: Elevated serum ferritin level was noted in 40.8% of Taiwanese CHC patients, and the serum ferritin level was associated with liver steatosis and high FIB4.

The effect of antiviral therapy on serum lipid profiles in chronic hepatitis C.

BACKGROUND: Low lipid profile is associated with hepatitis C virus (HCV) infection. Chronic HCV infection is the main cause of liver injury and serum lipid levels during antiviral treatment. We aimed to evaluate the effect of antiviral treatment on the change of lipid profiles during HCV treatment. METHODS: Total 863 patients who complete the interferon-based therapy in Kaohsiung Medical University Hospital were included in this study. The lipid profile measured and evaluated in baseline and after 6 months of the treatment. RESULTS: Sustained virological response (SVR) was achieved in 81.2% of all patients. The baseline triglycerides (TG) levels in the SVR group and non SVR groups were similar. The TG levels at 6 months after cessation of the treatment was significantly elevated in SVR group (102.9±57.0 mg/dL, p=0.0001) but did not elevated in non SVR group (94.5±45.6 mg/dL, p=0.690) compared with baseline TG levels. After adjusting patients by four indexes for fibrosis (FIB4) in cut-off point 3.25, serum TG levels significantly increased in low FIB4 group (103.2±57.9 mg/dL, p=0.0001) but not in high FIB4 group (98.1±49.6 mg/dL, p=0.095) after 6 months end of the treatment. Serum TG level was increased greater in patients who had low FIB4 score and patients who achieved SVR (baseline 89.1±34.8 mg/dL; 6 months after treatment 104.3±59.3 mg/dL, paired T test p=0.0001). CONCLUSION: The clearance of the HCV RNA is the main determinant of the increase of lipids after PegIFN/RBV treatment. However advanced fibrosis also has an effect in increase of lipids after the treatment.

Association between cryoglobulinemia and liver fibrosis in chronic hepatitis C patients.

BACKGROUND AND AIM: The prevalence of mixed cryoglobulinemia is 15-50% in chronic hepatitis C (CHC) patients, and these patients are in an increased risk of liver fibrosis and cirrhosis, but it is controversial. This study aimed to reveal the prevalence of mixed cryoglobulinemia in Asian population and to determine the relationship between presence of serum cryoglobulinemia and liver fibrosis in CHC patients with or without liver biopsy. METHODS: In total, 2255 treatment-naïve patients retrospectively enrolled in our study. Serum cryoglobulinemia precipitation, liver biopsy, and four indexes of fibrosis (FIB4) were assessed to detect the associated factors. RESULTS: Three hundred sixty-four (32%) out of 1135 liver biopsy patients and 341 (30.4%) out of 1120 non-biopsy patients were positive for serum cryoglobulinemia. Multivariate analysis revealed that male gender, hepatitis C virus RNA, platelet and advanced fibrosis (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.05-1.87, P = 0.021) were significantly associated with the presence of cryoglobulinemia in the liver biopsy proven patients. The presence of serum cryoglobulinemia (OR 1.43, 95% CI 1.04-1.96, P = 0.026) was associated with advanced liver fibrosis (F3 and F4) by multivariate logistic regression analysis. In patients without liver biopsy, FIB4 (OR 1.72, 95% CI 1.30-2.27, P = 0.0001) was associated with the presence of serum cryoglobulinemia, and also cryoglobulinemia (OR 1.74, 95% CI 1.32-2.30, P = 0.0001) was associated with high FIB4 (≥ 3.25) patients. CONCLUSION: The prevalence of the presence of serum cryoglobulinemia is 30.4-32% in CHC patients and associated with advanced fibrosis in liver biopsy proven patients and high-FIB4 (≥ 3.25) patients without liver biopsy.