Non-alcoholic Steatohepatitis in Asians: Current Perspectives and Future Directions.

Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty liver disease (NAFLD), which, apart from excess fat in the liver, may be characterised by some level of inflammatory infiltration and fibrogenesis, occasionally progressing to liver cirrhosis or hepatocellular carcinoma (HCC). The objective of the current review is to elucidate the rising prevalence, the role of microbiome and genetics in pathogenesis, diagnostic challenges, and novel treatment alternatives for NASH. Newer diagnostic techniques are being developed since using liver biopsy in a larger population is not a reasonable option and is primarily restricted to clinical research, at least in developing countries. Besides these technical challenges, another important factor leading to deviation from guideline practice is the lack of health insurance coverage in countries like India. It leads to reluctance on the part of physicians and patients to delay required tests to curb out-of-pocket expenditure. There is no cure for NASH, with liver transplantation remaining the last option for those who progress to end-stage liver disease (ESLD) or are detected with early-stage HCC. Thus, lifestyle modification remains the only viable option for many, but compliance and long-term adherence remain major challenges. In obese individuals, bariatric surgery and weight reduction have shown favourable results. In patients with less severe obesity, endoscopic bariatric metabolic therapies (EBMT) are rapidly emerging as less invasive therapies. However, access and acceptability remain poor for these weight reduction methods. Therefore, intense research is being conducted for potential newer drug classes with several agents currently in phase II or III of clinical development. Some of these have demonstrated promising results, such as a reduction in hepatic fat content, and attenuation of fibrosis with an acceptable tolerability profile in phase II studies. The developments in the management of NASH have been fairly encouraging. Further well-designed long-term prospective studies should be undertaken to generate evidence with definitive results.

Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): a randomised, placebo-controlled, double-blind, phase 3 study.

BACKGROUND: Etrolizumab is a gut-targeted anti-ß7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab for maintenance of remission in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, placebo-controlled, double-blind, phase 3 study (LAUREL) across 111 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. During open-label induction, participants received subcutaneous etrolizumab 105 mg once every 4 weeks. Participants who had clinical response at week 10 (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) proceeded into the double-blind maintenance phase and were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or matched placebo until week 62. Randomisation was stratified by baseline concomitant treatment with corticosteroids, treatment with immunosuppressants, baseline disease activity, and week 10 remission status. All participants and study site personnel were masked to treatment assignment. The primary endpoint was remission at week 62 (MCS ≤2, with individual subscores ≤1, and rectal bleeding subscore of 0) among patients with a clinical response at week 10, measured in the modified intention-to-treat population (all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02165215, and is now closed to recruitment. FINDINGS: Between Aug 12, 2014, and June 4, 2020, 658 patients were screened for eligibility and 359 were enrolled into the induction phase. 214 (60%) patients had a clinical response at week 10 and were randomly assigned to receive etrolizumab (n=108) or placebo (n=106) in the maintenance phase. 80 (74%) patients in the etrolizumab group and 42 (40%) in the placebo group completed the study through week 62. Four patients in the placebo group did not receive study treatment and were excluded from the analyses. At week 62, 32 (29·6%) of 108 patients in the etrolizumab group and 21 (20·6%) of 102 in the placebo group were in remission (adjusted treatment difference 7·7% [95% CI -4·2 to 19·2]; p=0·19). A greater proportion of patients reported one or more adverse events in the placebo group (82 [80%] of 102) than in the etrolizumab group (70 [65%] of 108); the most common adverse event in both groups was ulcerative colitis (16 [15%] patients in the etrolizumab group and 37 [36%] in the placebo group). Ten (9%) patients in the etrolizumab group and eight (8%) in the placebo group reported one or more serious adverse events. No deaths were reported in either treatment group. INTERPRETATION: No significant differences were observed between maintenance etrolizumab and placebo in the primary endpoint of remission at week 62 among patients who had a clinical response at week 10. Etrolizumab was well tolerated in this population and no new safety signals were identified. FUNDING: F Hoffmann-La Roche.

Endoscopic ultrasound-guided pelvic and prostatic abscess drainage: experience in 30 patients.

BACKGROUND: Endoscopic ultrasound (EUS)-guided drainage is an effective treatment for many abscesses in the abdomen. We review our experience with EUS-guided drainage of pelvic abscesses. METHODS: Thirty consecutive patients who underwent EUS-guided pelvic abscess drainage were evaluated after excluding three patients with distance to transducer >2 cm or organized abscess. RESULTS: Thirty patients (25 male) aged 60 ± 4.5 years (mean ± SD) had 4 prostatic abscesses, 7 perisigmoid abscesses, and 19 perirectal abscesses with mean ± SD sizes of 2.5 ± 0.3, 4.7 ± 0.6, and 5.4 ± 0.4 cm, respectively. Surgery was the most common predisposing factor (n = 14, 46.6 %) followed by diverticulitis (n = 5, 16.6 %). Interventions included aspiration only (2 prostatic and 3 perisigmoid), aspiration and dilatation (2 patients in each group), and dilatation and stenting (2 perisigmoid and 17 perirectal). Five (16.6 %) patients needed re-intervention, and two (6.6 %) needed surgery. There were no recurrences. Technical success of EUS-guided pelvic abscess drainage overall was 90.9 % (30/33) and was 93.3 % (27/30) in patients in whom EUS-guided drainage was attempted, with 16.5 % (n = 5) re-intervention rate. CONCLUSION: EUS-guided drainage has an excellent success rate in drainage of pelvic abscesses.