Background & Aims The safe discontinuation of nucleos(t)ide analogue therapy remains challenging in chronic hepatitis B. We investigated the potential role of quantitative hepatitis B surface antigen, hepatitis B core‐related antigen and hepatitis B virus RNA at the end of treatment in predicting off‐therapy relapse. Methods Patients who fulfilled the stopping criteria of the Asian Pacific Association for the Study of the Liver guideline were enrolled. Virological relapse was defined as hepatitis B virus DNA level greater than 2000 IU/mL, and clinical relapse was defined as virological relapse plus alanine aminotransferase level of more than twice the upper limit of normal. Results Ninety‐two patients participated. The combination of end‐of‐treatment hepatitis B core‐related antigen and hepatitis B virus RNA levels was most predictive of clinical relapse. Multivariate analysis revealed that end‐of‐treatment hepatitis B core‐related antigen and hepatitis B virus RNA were independently associated with clinical relapse. During follow‐up, no patients with undetectable hepatitis B core‐related antigen (<3.0 log10 U/mL) and hepatitis B virusRNA (<2.0 log10 copies/mL) at end of treatment developed clinical relapse, in comparison with 22.9% and 62.5% patients with detectable levels of one or both biomarkers respectively. End‐of‐treatment quantitative hepatitis B surface antigen was linked to a likelihood of hepatitis B surface antigen clearance. Conclusions The combined hepatitis B core‐related antigen and hepatitis B virus RNA assays at end of treatment were highly predictive of subsequent clinical relapse. These novel biomarkers could potentially be used to identify patients who could safely discontinue nucleos(t)ide analogue therapy.

Background: NAFLD is common in primary care. Liver fibrosis stage 2 or higher ( ≥ F2) increases future risk of morbidity and mortality. We developed and validated a score to aid in the initial assessment of liver fibrosis for NAFLD in primary care. Methods: Data from patients with biopsy-proven NAFLD were extracted from the NASH Clinical Research Network observational study (n = 676).Using logistic regression and machine-learning methods, we constructed prediction models to distinguish ≥ F2 from F0/1. The models were tested in participants in a trial ("FLINT," n = 280) and local patients with NAFLD with magnetic resonance elastography data (n = 130). The final model was applied to examinees in the National Health and Nutrition Examination Survey (NHANES) III (n = 11,953) to correlate with long-term mortality. Results: A multivariable logistic regression model was selected as the Steatosis-Associated Fibrosis Estimator (SAFE) score, which consists of age, body mass index, diabetes, platelets, aspartate and alanine aminotransferases, and globulins (total serum protein minus albumin). The model yielded areas under receiver operating characteristic curves ≥ 0.80 in distinguishing F0/1 from ≥ F2 in testing data sets, consistently higher than those of Fibrosis-4 and NAFLD Fibrosis Scores. The negative predictive values in ruling out ≥ F2 at SAFE of 0 were 88% and 92% in the two testing sets. In the NHANES III set, survival up to 25 years of subjects with SAFE < 0 was comparable to that of those without steatosis (p = 0.34), whereas increasing SAFE scores correlated with shorter survival with an adjusted HR of 1.53 (p < 0.01) for subjects with SAFE > 100.

Background and Aims. Tissue-invasive gastrointestinal cytomegalovirus (TI-GI CMV) disease is common in immunocompromised patients, but the increasing prevalence in immunocompetent patients has been reported. This study compared the clinical manifestations, endoscopic features, treatment outcomes, and predictors for inhospital mortality of TI-GI CMV between immunocompromised and immunocompetent patients. Methods. Patients with HIV infection, malignancy, or receiving immunosuppressive agents (chemotherapy, high dose, or long-term corticosteroids) were defined as the immunocompromised group. Demographic and inhospital mortality data were obtained and retrospectively analyzed. Results. A total of 213 patients (89 immunocompetent) with histologically confirmed TI-GI CMV were enrolled. Immunocompetent patients were older (70 vs. 52 years; p < 0.001 ), had more GI bleeding as a presenting symptom (47.2% vs. 29.0%; p = 0.010 ), and shorter symptom onset (2 vs. 14 days, p = 0.018 ). Concomitant extra-GI involvement was only seen in the immunocompromised group (6.5% vs. 0%; p = 0.02 ). Diffuse GI tract (14.5% vs. 4.5%; p = 0.032 ) and esophageal involvement (14.5% vs. 5.6%; p = 0.046 ) were more frequent in the immunocompromised, while small bowel involvement was more frequent in the immunocompetent group (19.1% vs. 8.1%; p = 0.029 ). An overall inhospital mortality was 27.7%. There was no significant difference in inhospital survival probability between the two groups (Peto-Peto test, p = 0.65 ). ICU admission (hazard ratio [HR] 7.21; 95% CI 2.55-20.36), sepsis or shock (HR 1.98; 95% CI 1.08-3.66), malnutrition (HR 2.62; 95% CI 1.05-7.01), and receiving chemotherapy (HR 5.2; 95% CI 1.89-14.29) were independent factors for inhospital mortality. Antiviral treatment for more than 14 days was the only protective factor to improve survival (Peto-Peto test, p < 0.001 ). Conclusions. Immunocompetent and immunocompromised patients with TI-GI CMV disease had distinct clinical and endoscopic characteristics. There was no significant difference in the inhospital mortality between the two groups. The factors for mortality were ICU admission, sepsis/shock, malnutrition, and receiving chemotherapy. Early diagnosis and initiation of antiviral treatment might improve the survival probability.

BackgroundNon-invasive models and methods to substitute liver biopsy in chronic hepatitis B (CHB) patients were investigated but their roles as predictors of significant liver histology for diagnosis of HBeAg-negative CHB patients who had indication for liver biopsy according to The American Association for the Study of Liver Diseases (AASLD) and The Asian Pacific Association for the Study of the Liver (APASL) guidelines are still unknown. This study was designed to identify predictors of significant liver necroinflammation as defined by a Histology Activity Index of necroinflammatory score ≥ 4 or Metavir necroinflammatory activity score ≥ 2 and significant liver fibrosis as defined by a Metavir fibrosis score ≥ 2 in HBeAg-negative CHB patients that had a hepatitis B virus (HBV) DNA level ≥ 2,000 IU/ml and age ≥ 40 years or elevated alanine aminotransferase level between 1–2 times the upper limit of normal.MethodsTwenty-two patients were prospectively included and performed liver biopsies. Clinical and laboratory parameters including age, gender, underlying disease, family history of cirrhosis or hepatocellular carcinoma, body mass index (BMI), HBV DNA level, HBsAg level, liver function test, complete blood count, aspartate aminotransferase-to-platelet ratio index and transient elastography were collected and analyzed with liver histology profiles.ResultsFive patients (23%) had significant liver inflammation and 7 patients (32%) had significant liver fibrosis. Factors associated with significant liver inflammation were a lower BMI and higher alkaline phosphatase level while a factor associated with significant liver fibrosis was lower age. On multivariate analysis, only HBV DNA level > 5.5 log IU/ml could predict significant liver fibrosis (odds ratio 28.012, 95% CI, 1.631-481.240, p = 0.022) and its sensitivity, specificity, positive predictive value and negative predictive value were 71.4%, 93.3%, 83.3% and 87.5% respectively.ConclusionsAn HBV DNA level of > 5.5 log IU/ml was able to predict significant liver fibrosis for treatment of HBeAg-negative CHB patients that had indication for liver biopsy as recommended by AASLD and APASL guidelines.