Meta-Analytic Bayesian Model For Differentiating Intestinal Tuberculosis from Crohn's Disease.

OBJECTIVES: Distinguishing intestinal tuberculosis (ITB) from Crohn's disease (CD) is difficult, although studies have reported clinical, endoscopic, imaging, and laboratory findings that help to differentiate these two diseases. We aimed to produce estimates of the predictive power of these findings and construct a comprehensive model to predict the probability of ITB vs. CD. METHODS: A systematic literature search for studies differentiating ITB from CD was conducted in MEDLINE, PUBMED, and EMBASE from inception until September 2015. Fifty-five distinct meta-analyses were performed to estimate the odds ratio of each predictive finding. Estimates with a significant difference between CD and ITB and low to moderate heterogeneity (I2<50%) were incorporated into a Bayesian prediction model incorporating the local pretest probability. RESULTS: Thirty-eight studies comprising 2,117 CD and 1,589 ITB patients were included in the analyses. Findings in the model that significantly favored CD included male gender, hematochezia, perianal disease, intestinal obstruction, and extraintestinal manifestations; endoscopic findings of longitudinal ulcers, cobblestone appearance, luminal stricture, mucosal bridge, and rectal involvement; pathological findings of focally enhanced colitis; and computed tomographic enterography (CTE) findings of asymmetrical wall thickening, intestinal wall stratification, comb sign, and fibrofatty proliferation. Findings that significantly favored ITB included fever, night sweats, lung involvement, and ascites; endoscopic findings of transverse ulcers, patulous ileocecal valve, and cecal involvement; pathological findings of confluent or submucosal granulomas, lymphocyte cuffing, and ulcers lined by histiocytes; a CTE finding of short segmental involvement; and a positive interferon-γ release assay. The model was validated by gender, clinical manifestations, endoscopic, and pathological findings in 49 patients (27 CD, 22 ITB). The sensitivity, specificity, and accuracy for diagnosis of ITB were 90.9%, 92.6%, and 91.8%, respectively. CONCLUSIONS: A Bayesian model based on the meta-analytic results is presented to estimate the probability of ITB and CD calibrated to local prevalence. This model can be applied to patients using a publicly available web application.

Efficacy and safety of entecavir versus tenofovir treatment in chronic hepatitis B patients: A randomized controlled trial.

AIM: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are considered among the most potent antiviral agents for the treatment of chronic hepatitis B infection. We aimed to compare treatment efficacy and safety of ETV and TDF in nucleoside-naïve chronic hepatitis B patients. METHODS: Inclusion criteria were compensated chronic hepatitis B patients who were either hepatitis B e antigen (HBeAg)-positive or HBeAg-negative. Exclusion criteria were co-infection with hepatitis C virus and/or HIV, concurrent malignancy, and decompensated cirrhosis. Virological, biochemical, and serological end-points at week 96 and 144 were compared. Of 400 patients, 200 patients received ETV and 200 received TDF. RESULTS: There were no significant differences between the two groups in baseline characteristics including age (41.6 ± 11.5 vs. 41.2 ± 11.6, mean baseline hepatitis B virus DNA (5.91 ± 1.79 vs. 5.94 ± 1.68 log10 IU/mL), mean baseline alanine aminotransferase (68.1 ± 64.1 vs. 76.8 ± 79.8 U/L), and cirrhosis (15.5% vs. 14.5%). At week 144 of treatment, 91 and 94% of the ETV and TDF groups, respectively, achieved undetectable hepatitis B virus DNA. In HBeAg-positive patients, HBeAg seroconversion could be achieved in 27.4% and 33.7% at week 144 for ETV and TDF groups, respectively. Quantitative hepatitis B surface antigen dropped significantly over 144 weeks of treatment period but only 1.0 to 1.5% experienced hepatitis B surface antigen loss. Safety profiles were consistent with previous reports of monotherapy. CONCLUSION: Both ETV and TDF showed potent antiviral activity against hepatitis B. Either ETV or TDF can be recommended as a treatment of choice for patients with chronic hepatitis B. Both drugs were safe and well tolerated.

Hepatocellular carcinoma screening and surveillance in 2293 chronic hepatitis B patients in an endemic area.

AIM: To determine the role of screening and surveillance of hepatocellular carcinoma (HCC) in treatment-naïve chronic hepatitis B (CHB) patients. METHODS: We recruited 2293 CHB patients (both males and females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography (AUS) and serum alpha-fetoprotein (AFP) assay every 6 mo. The diagnosis, staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score < 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis. The sensitivity and specificity were calculated on a per-patient basis. RESULTS: Among 2293 treatment-naïve CHB patients, seven cases had HCC at initial screening, giving a prevalence rate of 305 per 100000 persons; 3.3% were diagnosed with liver cirrhosis, all of which were Child-Pugh class A. With a median follow-up time of 42 (range, 3-48) mo, 10 additional cases were diagnosed with HCC, resulting in an incidence rate of 143 per 100000 persons per year. This burden was as high as that reported in other studies from East Asian countries. All HCC patients were aged ≥ 40 years. Most were at an early stage (Stage 0, A or B); 14/17 cases were successfully treated with surgical resection or radiofrequency ablation, with a high 3-year survival rate of 90%. Hemangioma was the most common focal liver lesion in CHB patients detected by AUS; the main causes of AFP elevation at the initial screening were cirrhosis, increased alanine aminotransferase level and HCC. AUS detected 16/17 HCC cases whereas AFP levels ≥ 20 µg/L at diagnosis were observed in only 7/17 patients, most with a tumor size > 5 cm. For HCC screening and surveillance, AUS had a sensitivity and specificity of 94% and 82%, respectively, whereas the sensitivity and specificity of AFP at a cut-off value of ≥ 20 µg/L were 41% and 98%, respectively. Combined use of AUS and AFP assay did not improve effectiveness. CONCLUSION: Implementation of active screening and surveillance using AUS to detect early-stage HCC in naïve CHB patients aged ≥ 40 years in an endemic area is of benefit.

Long-term use of methotrexate does not result in hepatitis B reactivation in rheumatologic patients.

BACKGROUND AND OBJECTIVE: Hepatitis B virus (HBV) infection is still prevalent in Asia, including Thailand. HBV can archive in hepatocytes for life and can reactivate after immunosuppression and chemotherapy administration. Use of immunosuppressive agents is recommended in many rheumatologic diseases and reactivation of HBV can occur. Data regarding the effect of methotrexate (MTX) on HBV reactivation is scanty. MTX is a well known cause of hepatic fibrosis but its effect on HBV reactivation is not clearly understood. There is no specific recommendation for HBV prophylaxis for patients using MTX. This study aimed to determine the prevalence of HBV seromarkers in rheumatologic patients who were treated with long-term MTX and to evaluate the hepatitis outcome in the patients with positive HBV markers. METHODS: This was a cross-sectional study at the Rheumatology Clinic, Siriraj Hospital, Bangkok, Thailand. Patients aged 15 years or older treated with MTX more than 24 weeks were invited in the study. Review of medical history, MTX prescription and dosage during the last 52 weeks, blood tests for liver function tests, HBV serology, and HBV DNA viral load were performed. The exclusion criteria included patients who were treated with biological DMARDs, drugs active against HBV, known co-infection with HCV or HIV and previous diagnosis of cirrhosis from any causes or presence of hepatocellular carcinoma. RESULTS: A total of 173 patients were enrolled (153 females, 20 males, mean age of 52.6 ± 13.6 years). The majority of patients were diagnosed with rheumatoid arthritis (67.0%), SLE (13.9%), spondyloarthopathies (8.7%) and others (10.4%). Thirty percent of them (55/173) had no previous data for HBV seromarkers. Among 118 patients who had baseline data, only one patient (0.8%) had HBsAg positive. Average duration of treatment was 9.9 years and MTX dose prescribed was 571.6 ± 240.4 mg during the last 52 weeks. Out of 173 patients, only two had clinically significant hepatitis (1.16%) and one was HBsAg positive (0.58%). Ninety-six patients (55.5%) were negative for all HBV seromarkers, 67/173 (38.7%) positive for anti-HBs antibody and 65/173 (37.6%) positive for anti-HBc IgG. Only one in 65 patients (1.5%) who had any positive HBV seromarkers had HBV DNA detectable. CONCLUSION: Prevalence of HBsAg positive rheumatologic patients treated with MTX in Thailand was only 0.58%, which was lower than the general Thai population. About one-third of the patients had exposure to HBV as demonstrated by presence of anti-HBc IgG (37.6%), but none of them had hepatitis B reactivation during 9.9 years of MTX treatment. Moreover, one case with HBsAg positive had been receiving MTX without HBV prophylaxis for 5 years but had no evidence of HBV flare and evidence of fibrosis. From our study, long-term MTX in patients exposed to HBV was safe and not associated with hepatitis flare. However, more study is needed as to whether HBV prophylaxis is required.