Pin-Chao Wang

Male sex, hiatus hernia, and Helicobacter pylori infection associated with asymptomatic erosive esophagitis

Background and Aims:  Asymptomatic erosive esophagitis (AEE) is an easily forgotten subgroup of gastroesophageal reflux disease due to its lack of warning symptoms, despite having the risk of developing complications, such as bleeding, stricture, or even esophageal adenocarcinoma.

Severity of fatty liver on ultrasound correlates with metabolic and cardiovascular risk

Non‐alcoholic fatty liver disease is associated with an increased risk of metabolic and cardiovascular diseases. Whether the severity of fatty liver on ultrasound correlates with metabolic or cardiovascular risk remains unclear. A total of 1000 people receiving health examinations were enrolled, and 126 were excluded due to the presence of HBsAg, anti‐HCV, known hepatic disorders or alcohol use (>140 g/wk). Significant fatty liver consisted of moderate and severe fatty liver on ultrasound. The definition of central obesity was modified to a waist circumference of >90 cm in men and >80 cm in women. Framingham risk score was used to estimate the risk of cardiovascular disease. A total of 874 subjects (485 women and 388 men with a mean age of 52.07 ± 11.68 years) were included in the final analysis. By using logistic regression analyses stratified by gender, the odds ratio for the prevalence of diabetes mellitus, metabolic syndrome and risk of cardiovascular disease increased with increasing fatty liver status in both genders (p ≤ 0.001). The difference was not only present between individuals with fatty liver vs. non‐fatty liver but also between the mild fatty liver and significant fatty liver groups (p < 0.05). In conclusion, the severity of fatty liver on ultrasound could be useful for the risk stratification of metabolic syndrome, diabetes mellitus and cardiovascular disease in clinical practice.

Baseline hepatitis B surface antigen quantitation can predict virologic response in entecavir-treated chronic hepatitis B patients

BACKGROUND/PURPOSE Several anti-viral drugs are approved for the treatment of hepatitis B virus (HBV) infection. However, whether quantitative hepatitis B surface antigen (qHBsAg) can predict the therapeutic response during long-term entecavir treatment remains unclear. METHODS Fifty-five chronic hepatitis B (CHB) patients who received entecavir for more than 2 years were enrolled. The serum qHBsAg level was measured by HBsAg II quant immunoassay. A significant decline in the qHBsAg level was defined as > 1 log reduction from baseline to 6 months of entecavir treatment. RESULTS Of the 55 patients (41 males and 14 females with a mean age of 48.3 ± 11.4 years), 23 patients were positive for hepatitis B e antigen (HBeAg). The median treatment period was 34 months, and ranged from 26 months to 43 months. A total of 288 serum samples were used to determine the qHBsAg levels. At year 3 of entecavir therapy, one (1.8%) patient had HBsAg seroclearance. A high qHBsAg level was defined as greater than 10,000 IU/mL. Patients with a high baseline qHBsAg level had a lower rate of virologic response at year 1 (37.5% vs. 89.7%, p < 0.001) and year 2 (56.2% vs. 94.9%, p = 0.001). In this study population, 14.5% had a significant decline of the qHBsAg level. A significant decline could not predict HBeAg loss in HBeAg-positive or virologic response in all patients. CONCLUSION The baseline serum qHBsAg level can predict virologic response in entecavir-treated CHB patients. However, a significant decline in the qHBsAg level cannot predict serologic or virologic response of entecavir treatment.

Different risk factors between reflux symptoms and mucosal injury in gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is diagnosed based on typical symptoms in clinical practice. It can be divided into two groups using endoscopy: erosive and nonerosive reflux disease (NERD). This study aims to determine the risk factors of reflux symptoms and mucosal injury. This was a two‐step case‐control study derived from a cohort of 998 individuals having the data of reflux disease questionnaire (RDQ) and endoscopic findings. Those with minor reflux symptoms were excluded. The first step compared symptomatic GERD patients with healthy controls. The 2nd step compared patients with erosive esophagitis with healthy controls. In this study, the prevalence of symptomatic GERD and erosive esophagitis were 163 (16.3%) and 166 (16.6%), respectively. A total of 507 asymptomatic individuals without mucosal injury of the esophagus on endoscopy were selected as healthy controls. Compared with healthy controls, multivariate analyses showed that symptomatic GERD patients had a higher prevalence of hypertriglyceridemia [odds ratio (OR), 1.83; 95% confidence interval (CI) 1.13–2.96] and obesity (OR, 1.85; 95% CI 1.08–3.02). By contrast, male sex (OR, 2.24; 95% CI 1.42–3.52), positive Campylo‐like organism (CLO) test (OR, 0.56; 95% CI 0.37–0.84), and hiatus hernia (OR, 14.36; 95% CI 3.05–67.6) were associated with erosive esophagitis. In conclusion, obesity and hypertriglyceridemia were associated with reflux symptoms. By contrast, male sex, negative infection of Helicobacter pylori, and hiatus hernia were associated with mucosal injury. Our results suggested that risk factors of reflux symptoms or mucosal injury might be different in GERD patients. The underlying mechanism awaits further studies to clarify.

Association of Insulin Resistance with Alanine Aminotransferase Activity in Patients with Nonalcoholic Fatty Liver Disease

Abstract Objective Elevated liver enzymes have been recognized as a predictor for the development of metabolic syndrome and type 2 diabetes mellitus in patients with nonalcoholic fatty liver disease (NAFLD). However, the association of insulin resistance with alanine aminotransferase (ALT) activity remains largely unknown. Patients and Methods A total of 454 subjects attending the health examination center were enrolled from September 2005 through December 2006. Of them, 203 patients (male/female, 113/90; mean age, 50.9 years) were identified to have NAFLD. Their insulin resistance index was determined using the homeostasis model assessment (HOMA-IR). Elevated ALT level was defined as > 30 IU/L for male and > 19 IU/L for female subjects according to the new cut-off values. Results There were 113 subjects in the elevated ALT group and 90 in the normal ALT group. Age, gender and the prevalence of diabetes mellitus, hypertension and smoking history were comparable between these two groups. The elevated ALT group had higher readings for body mass index, triglyceride, total cholesterol, low-density lipoprotein cholesterol, insulin and HOMA-IR than the normal ALT group using univariate analyses. Multivariate logistic regression analyses showed that only log(HOMA-IR) was positively associated with elevated ALT level in the NAFLD patients (adjusted odds ratio, 5.04; 95% confidence interval, 1.56–16.27). Conclusion Our data showed that there was an association between insulin resistance and serum ALT levels in NAFLD patients, independent of other metabolic factors. However, further longitudinal studies are needed to clarify the causal relationship between insulin resistance and increased ALT activity in patients with NAFLD.

Factors affecting the diagnostic accuracy of ultrasonography in assessing the severity of hepatic steatosis.

BACKGROUND/PURPOSE Ultrasonography has long been recognized as a useful tool for detecting hepatic steatosis in clinical practice. However, whether it can assess the severity of hepatic steatosis and which factors affect its diagnostic accuracy remain unclear. METHODS A total of 171 patients with various causes of hepatitis undergoing liver biopsies were retrospectively reviewed. The clinical, serologic data and ultrasonographical findings were recorded. Hepatic steatosis was graded as negative, mild, moderate, or severe by ultrasonography and histology. Histology was used as gold standard and the agreement rates were calculated. RESULTS Our data showed that the agreement rate of ultrasonography was 61.4% in assessing the severity of hepatic steatosis and 74.3% in diagnosing hepatic steatosis compared with histology (crude kappa=0.46 vs. 0.46). Using univariate analyses, body mass index and histology activity index score were associated with the agreement in assessing the severity of hepatic steatosis (p=0.008 and 0.035), whereas Ishak fibrosis score had a trend association (p=0.066). Multivariate analyses indicated that age, body mass index, and Ishak fibrosis score could affect the agreement (odds ratio=0.72, 0.89, and 1.41; 95% confidence interval=0.54-0.97, 0.83-0.97, and 1.1-1.8). CONCLUSION Ultrasonography could assess the severity of hepatic steatosis with moderate accuracy. Obese patients are difficult ultrasonographically. In addition, age and hepatic fibrosis could affect the performance of ultrasonography in assessing the severity of hepatic steatosis.

Cirrhosis has no impact on therapeutic responses of entecavir for chronic hepatitis B

Objective As the efficacy of a direct antiviral agent is reduced in cirrhotic chronic hepatitis C patients, prolonged duration of treatment or addition of ribavirin is recommended to improve the rates of sustained virological response. However, the impact of cirrhosis on the efficacy of antiviral treatment for chronic hepatitis B (CHB) remained unclear. Patients and methods This retrospective cohort study screened entecavir (ETV)-treated CHB patients in Taipei Tzu Chi Hospital from January 2007 till October 2014. The diagnosis of cirrhosis was made on the basis of clinical/imaging or histologic findings. The primary endpoints were hepatitis B e antigen (HBeAg) loss in HBeAg-positive patients and undetectable hepatitis B virus (HBV) DNA in the overall study population. Initial virological response is defined as undetectable HBV DNA at 1-year ETV treatment. Results A total of 381 (262 men; mean age: 49.6±12.9 years) CHB patients were recruited for the final analysis. Of these, 138 were cirrhotic. In 143 HBeAg-positive patients, there was no difference in the rates of 1- and 2-year HBeAg loss between cirrhotic and noncirrhotic patients (P=0.226 and 0.729, respectively). In the overall population, the rate of 1-year undetectable HBV DNA was higher in patients with cirrhosis than those without cirrhosis (76.1 vs. 64.2%, P=0.016). The rate of 2-year undetectable HBV DNA was not different between these two groups. Using multivariate logistic regression analysis, baseline HBV DNA levels (P=0.006) and HBeAg status (P=0.007), were associated with initial virological response, but not cirrhosis. Conclusion Therapeutic responses of ETV are not decreased in cirrhotic CHB patients. Thus, cirrhotic CHB patients can be treated with ETV without the need for dose adjustment.

Serum vitamin D level not correlated with hepatitis B virus replication in patients with chronic hepatitis B virus infection

Vitamin D is an important immune modulator in chronic liver diseases. The study aims to investigate the relationship between vitamin D and hepatitis B virus replication.

Fibrosis index based on four factors better predicts advanced fibrosis or cirrhosis than aspartate aminotransferase/platelet ratio index in chronic hepatitis C patients

BACKGROUND/PURPOSE Liver biopsy is the gold standard to determine the severity of hepatic fibrosis despite its risk and invasiveness. The aspartate aminotransferase/platelet ratio index (APRI) could noninvasively predict the severity of hepatic fibrosis in chronic hepatitis C (CHC) patients. Whether fibrosis index based on four factors (FIB-4) could better predict the severity of hepatic fibrosis than APRI in CHC patients remains inconclusive. METHODS This retrospective study enrolled 1473 CHC patients (784 men and 689 women) with liver biopsy and clinical data including age, aspartate aminotransferase, alanine aminotransferase, and platelet count. FIB-4 and APRI were calculated with a formula using the four clinical parameters. Hepatic fibrosis was staged using the Metavir classification system. RESULTS The areas under the receiver operating characteristics of FIB-4 for the diagnosis of significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (F4) were 0.816 [95% confidence interval (CI), 0.795-0.836], 0.827 (95% CI, 0.806-0.849), and 0.849 (95% CI, 0.830-0.867), respectively, compared with those of APRI-0.799 (95% CI, 0.778-0.819), 0.791 (95% CI, 0.770-0.812), and 0.802 (95% CI, 0.781-0.922). In addition, the areas under the receiver operating characteristics of FIB-4 were significantly greater than those of APRI for patients with advanced fibrosis and cirrhosis, respectively (p < 0.0001). CONCLUSION FIB-4 could predict hepatic fibrosis in CHC patients. By adding two parameters (age and alanine aminotransferase), FIB-4 better predicts advanced fibrosis and cirrhosis than APRI in CHC patients.

High-Density Lipoprotein Cholesterol Negatively Associated with Nonalcoholic Fatty Liver Disease in Non-Diabetic and Normal Weight Adults

Goals and Background: Although non-alcoholic fatty liver disease (NAFLD) is closely associated with obesity and diabetes mellitus, it is not rare in non-diabetic and normal weight subjects. Which factors are associated with the presence of NAFLD in this special population remains unclear. Materials and Methods: A total of 207 non-diabetic (fasting plasma glucose＜126 mg/dL and without previous diabetic history) and normal weight (body mass index＜24 kg/m^2) individuals attending a health examination center were enrolled since September 2005 to December 2006. All the subjects were negative for serum hepatitis B surface antigen and antibody against hepatitis C virus, and consumed alcohol less than 140 g/week. Insulin resistance index was determined using homeostasis model assessment (HOMA-IR). Results: 70 subjects (33.8%) were identified to have ultrasonographic NAFLD, and remaining 137 (66.2%) served as controls. There was no significant difference in age and gender distribution between two groups. In nondiabetic and normal weight individuals, patients of NAFLD had raised body mass index, HOMA-IR, triglyceride, total cholesterol and low-density lipoprotein cholesterol, but reduced high-density lipoprotein cholesterol (HDL-C) as compared to controls by univariate analyses. Multivariate logistic regression analyses showed a negative association between HDL-C and the presence of NAFLD (odds ratio, 0.93; 95% confidence interval, 0.89-0.98; P＜0.01). Conclusions: Serum HDL-C level has a negative association with NAFLD in non-diabetic and normal weight adults, independent of other metabolic factors or insulin resistance.