Fecal Microbiota Transplantation in Hepatitis B e Antigen-Positive Chronic Hepatitis B Patients: A Pilot Study.

BACKGROUND: Intestinal flora plays a critical role in immunity against hepatitis B virus (HBV). Fecal Microbiota Transplantation (FMT) may be a potential immunomodulatory therapy in patients with chronic hepatitis B (CHB). AIM: We aimed to study role of FMT in hepatitis B e antigen (HBeAg)-positive CHB patients in terms of its effect on HBeAg, HBsAg, and HBV DNA. METHODS: HBeAg-positive patients despite being on antiviral treatment for > 1 year were given six cycles of FMT via gastroscope (nasoduodenal route) at 4 weekly intervals along with antiviral therapy. Twelve out of 14 included patients in FMT arm completed six cycles. Another 15 HBeAg-positive patients who were on oral antivirals for > 1 year were taken as control-antiviral therapy (AVT) arm. Per-protocol analysis was done. RESULTS: The median (interquartile range) age in the FMT and AVT arm were 29 (25-35) and 29(24-38), respectively (P = 0.794). The median (interquartile range) duration of AVT prior to inclusion in the study was 80 (52-104) and 76 (52-114) months in FMT and AVT arm, respectively (P = 0.884). In the FMT arm, 16.7% (2/12) patients had HBeAg clearance in comparison to none in the AVT arm (P = 0.188). None of the patients in either arm had HBsAg loss. The FMT was tolerated well, 42.8% (6/14) patients reported one or more minor adverse events. CONCLUSIONS: In this non-randomized pilot study, FMT appears to be safe and potentially effective in terms of viral suppression and HBeAg clearance in patients with HBeAg-positive CHB. Further randomized controlled trials are needed in order to obtain robust conclusions.

Controlled Attenuation Parameter for Assessment of Hepatic Steatosis in Indian Patients.

BACKGROUND/AIMS: The gold standard method for measurement of hepatic steatosis is liver histology. Controlled Attenuation Parameter (CAP) can measure hepatic steatosis non-invasively. We aimed to assess the accuracy of CAP for detection of hepatic steatosis. METHODS: A total of 462 patients (May 2012-January 2017)-89 non-alcoholic fatty liver disease, 182 chronic hepatitis B, 88 chronic hepatitis C and 103 patients with other etiologies who underwent simultaneous liver biopsy and CAP estimation using Transient Elastography (TE) were included. Steatosis was graded as S0: steatosis in 0-5% of hepatocytes, S1: 6-33%, S2: 34-66% and S3: 67-100%. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the accuracy of CAP in detecting hepatic steatosis. Predictors of CAP were assessed by multivariate linear regression model. RESULTS: The mean age ± SD was 33.8 ± 11.6 years; 296 (64.1%) were males. On liver histology, steatosis grades S0, S1, S2 and S3 were seen in 331 (71.6%), 74 (16.0%), 39 (8.4%) and 18 (3.9%), respectively. The median CAP (IQR) values for S0, S1, S2, and S3 steatosis were 206 (176-252) dB/m, 295 (257-331) dB/m, 320 (296-356) dB/m, and 349 (306-363) dB/m, respectively. For estimation of ≥S1, ≥S2, and ≥S3 using CAP, AUROC were 0.879, 0.893, and 0.883, respectively. In multivariate analysis, only BMI (OR 1.18; CI, 1.11-1.26, P < 0.001) and grade of hepatic steatosis (grade 1, OR, 3.94; 95% CI, 1.58-9.84, P = 0.003; grade 2, OR 42.04; 95% CI, 4.97-355.31, P = 0.001 and grade 3, OR 35.83; 95% CI 4.31-297.61, P = 0.001) independently predicted CAP. CONCLUSIONS: CAP detects hepatic steatosis with good accuracy in Indian patients with various etiologies.

Assessment of liver fibrosis in chronic hepatitis: comparison of shear wave elastography and transient elastography.

PURPOSE: To evaluate the diagnostic accuracy of shear wave elastography (SWE) and transient elastography (TE) in the evaluation of liver fibrosis in chronic hepatitis B (CHB) and C (CHC) patients taking liver biopsy as gold standard. METHODS: Ethics committee approved this prospective cross-sectional study. Between October 2012 and December 2014, consecutive CHB/CHC patients fulfilling the inclusion criteria were included-age more than 18 years, informed written consent, willing and suitable for liver biopsy. SWE, TE, and biopsy were performed the same day. Liver stiffness measurement (LSM) cut-offs for various stages of fibrosis were generated for SWE and TE. AUC, sensitivity, specificity, and positive/negative predictive values were estimated individually or in combination. RESULTS: CH patients (n = 240, CHB 172, CHC 68), 176 males, 64 females, mean age 32.6 ± 11.6 years were enrolled. Mean LSM of patients with no histological fibrosis (F0) was 5.0 ± 0.7 and 5.1+1.4 kPa on SWE and TE, respectively. For differentiating F2 and F3-4 fibrosis on SWE, at 7.0 kPa cut-off, the sensitivity was 81.3% and specificity 77.6%. For TE, at 8.3 kPa cut-off, sensitivity was 81.8% and specificity 83.1%. For F3 vs. F4, SWE sensitivity was 83.3% and specificity 90.7%. At 14.8 kPa cut-off, TE showed similar sensitivity (83.3%) but specificity increased to 96.5%. Significant correlation between SWE and TE was observed (r = 0.33, p < 0.001). On combining SWE and TE, a drop in sensitivity with increased specificity for all stages of liver fibrosis occured. CONCLUSION: SWE is an accurate technique for evaluating liver fibrosis. SWE compares favorably with TE especially for predicting advanced fibrosis/cirrhosis. Combining SWE and TE further improves specificity.

Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B.

BACKGROUND AND AIM: Liver fibrosis is an established determinant of prognosis and therapy in chronic hepatitis B (CHB). The role of fibroscan in assessing fibrosis in CHB remains unclear. Present study was designed to correlate fibroscan with liver biopsy and determine whether fibroscan can avoid liver biopsy in patients with CHB. METHODS: Fibroscan and liver biopsy were performed in 382 consecutive patients with CHB. Biopsies were reviewed by pathologist blinded to the fibroscan value. Discriminant values of liver stiffness measurement (LSM) to reasonably exclude and predict significant fibrosis were calculated from receiver operating characteristic (ROC) curves. The factors affecting LSM independent of fibrosis were assessed. RESULTS: Three hundred fifty-seven patients were included (mean age 30.1 ± 9.7 years, male : female 17 : 3). There was significant correlation between LSM and histological fibrosis (r = 0.58, P < 0.001). The area under ROC curve of LSM for significant fibrosis (F0-1 vs. F2-4), bridging fibrosis (F0-2 vs. F3-4), and cirrhosis (F0-3 vs. F4) was 0.84 (95% CI: 0.78-0.89), 0.94 (95% CI: 0.89-0.99), and 0.93 (95% CI: 0.85-1.00), respectively. LSM < 6.0 KPa could exclude significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with a negative predictive value (NPV) of 92.4% and 99.5%, respectively. Cut-off of 9 KPa could detect significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with specificity of 95% and 97%, respectively, and had a positive predictive value (PPV) of 84.3% in predicting significant fibrosis. LSM < 6 KPa and > 9 KPa matched with histological fibrosis in 227/250 (91%) patients. Therefore, fibroscan could avoid liver biopsy in 70% (250/357) patients with an accuracy > 90%. Histological fibrosis, ALT > 5 times, and age > 40 years were independent determinants of increased liver stiffness. CONCLUSIONS: Fibroscan accurately assessed fibrosis and could avoid liver biopsy in more than two-thirds of patients with CHB.