Artificial intelligence for discrimination of Crohn's disease and gastrointestinal tuberculosis: A systematic review.

BACKGROUND AND AIM: Discrimination of gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) is difficult. Use of artificial intelligence (AI)-based technologies may help in discriminating these two entities. METHODS: We conducted a systematic review on the use of AI for discrimination of GITB and CD. Electronic databases (PubMed and Embase) were searched on June 6, 2022, to identify relevant studies. We included any study reporting the use of clinical, endoscopic, and radiological information (textual or images) to discriminate GITB and CD using any AI technique. Quality of studies was assessed with MI-CLAIM checklist. RESULTS: Out of 27 identified results, a total of 9 studies were included. All studies used retrospective databases. There were five studies of only endoscopy-based AI, one of radiology-based AI, and three of multiparameter-based AI. The AI models performed fairly well with high accuracy ranging from 69.6-100%. Text-based convolutional neural network was used in three studies and Classification and regression tree analysis used in two studies. Interestingly, irrespective of the AI method used, the performance of discriminating GITB and CD did not match in discriminating from other diseases (in studies where a third disease was also considered). CONCLUSION: The use of AI in differentiating GITB and CD seem to have acceptable accuracy but there were no direct comparisons with traditional multiparameter models. The use of multiple parameter-based AI models have the potential for further exploration in search of an ideal tool and improve on the accuracy of traditional models.

FDG-PET-CT Enterography Helps Determine Clinical Significance of Suspected Ileocecal Thickening: A Prospective Study.

BACKGROUND: Ileocecal thickening (ICT) on imaging could result from diverse etiologies but may also be clinically insignificant. AIM: Evaluation of role of combined 2-deoxy-2-fluorine-18-fluoro-D-glucose(18F-FDG)-positron emission tomography and computed tomographic enterography (PET-CTE) for determination of clinical significance of suspected ICT. METHODS: This prospective study enrolled consecutive patients with suspected ICT on ultrasound. Patients were evaluated with PET-CTE and colonoscopy. The patients were divided into: Group A (clinically significant diagnosis) or Group B (clinically insignificant diagnosis) and compared for various clinical and radiological findings. The two groups were compared for maximum standardized uptake values of terminal ileum, ileo-cecal valve, cecum and overall. RESULTS: Of 34 patients included (23 males, mean age: 40.44 ± 15.40 years), 12 (35.3%) had intestinal tuberculosis, 11 (32.4%) Crohn's disease, 3 (8.8%) other infections, 1 (2.9%) malignancy, 4 (11.8%) non-specific terminal ileitis while 3 (8.8%) had normal colonoscopy and histology. The maximum standardized uptake value of the ileocecal area overall (SUVmax-ICT-overall) was significantly higher in Group A (7.16 ± 4.38) when compared to Group B (3.62 ± 9.50, P = 0.003). A cut-off of 4.50 for SUVmax-ICT-overall had a sensitivity of 70.37% and a specificity of 100% for prediction of clinically significant diagnosis. Using decision tree model, the SUVmax-ICT with a cut-off of 4.75 was considered appropriate for initial decision followed by the presence of mural thickening in the next node. CONCLUSION: PET-CTE can help in discrimination of clinically significant and insignificant diagnosis. It may help guide the need for colonoscopy in patients suspected to have ICT on CT.

Nanocrystalline SrS:Ce3+ system for the generation of white light-emitting diodes.

Nanocrystalline SrS phosphors doped with Ce3+ ions at different concentrations (0.5, 1, 1.5 and 2 mol%) are synthesized via the solid-state diffusion method (SSDM), which is suitable for the large-scale production of phosphors in industrial applications. The as-prepared samples are characterized using an X-ray diffraction (XRD) technique, field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM) and energy-dispersive X-ray (EDX) analysis. The optical properties of these phosphors are analyzed using reflectance spectra, photoluminescence spectra and afterglow decay curves. The cubic structure of the SrS phosphor is confirmed by XRD analysis and the crystallite size calculated by Scherer's formula using XRD data shows the nanocrystalline nature of the phosphors. No phase change is observed with increasing concentrations of Ce3+ ions. The surface morphology of the prepared phosphors is determined by FESEM, which shows a sphere-like structure and good connectivity of the grains. The authenticity of the formation of nanocrystalline phosphors is examined by HRTEM analysis. Elemental compositional information for the prepared phosphors is gathered by EDX analysis. Photoluminescence studies reveal that the emission spectra of the prepared phosphor shows broad band emission centered at 458 and 550 nm due to the transition of electrons from the 5d â†’ 4f energy levels. The afterglow decay characteristics of different as-synthesized SrS:Ce3+ nanophosphors are conceptually described. Copyright © 2016 John Wiley & Sons, Ltd.

Antibiotics for inflammatory bowel disease: Current status.

There is abundant literature reporting about the use of antibiotics in inflammatory bowel disease (IBD), but their role in the management of IBD is not entirely clear. Diverse infectious organisms have been implicated in the pathogenesis of Crohn's disease. Also, infections are believed to be a trigger for flares of ulcerative colitis. The benefit of the routine use of antibiotics in IBD is equivocal. However, there are certain situations, where antibiotics have a clear role and evidence of benefit: perianal fistula, intra-abdominal abscesses in Crohn's disease, acute pouchitis and infection-related flares. However, there is a lack of supportive evidence for the routine use of antibiotics in all disease-related flares. Evidence indicates a lack of benefit of intravenous antibiotics in acute severe ulcerative colitis and only limited benefit in active ulcerative colitis. Limited evidence suggests the role of a combination of oral antibiotics in pediatric ulcerative colitis. Certain targeted antibiotic regimens have been used in IBD. In ulcerative colitis, limited evidence suggests the benefit of the use of an antibiotic cocktail directed against Fusobacterium varium. Therapy directed against Escherichia coli does not seem to have a benefit in inflammatory Crohn's disease. In Crohn's disease, antimycobacterial therapy may result in symptomatic improvement but no durable benefit. Antitubercular therapy (ATT), on the contrary, may result in fibrotic transformation, suggesting a need to avoid misdiagnosis and limit the duration of ATT in Crohn's disease. This review assesses the published literature with respect to antibiotic use and provides guidance to clinicians in appropriate antibiotic use in various situations in the setting of IBD.

Histological scores are poor predictors of short term outcomes in acute severe ulcerative colitis: An observational study.

BACKGROUND: The role of various histologic scores in predicting outcomes in acute severe ulcerative colitis (ASUC) is unexplored. METHODS: Consecutive patients of ASUC undergoing sigmoidoscopy and histological assessment by two independent pathologists for Simplified Geboes score (SGS), Robarts Histopathology Index (RHI) and Nancy histological index (NHI)] were included. Primary outcome was the role of histology in predicting need for second-line therapy or colectomy. RESULTS: Of 82 patients with ASUC (mean age: 36 years, males 47.5 %), non-response to steroids was observed in 27 (32.9 %) of cases. Sixteen patients required second-line drug therapy and 8 required colectomy. There was no significant association between the need for second-line therapy or colectomy and the baseline histological scores [NHI (p = 0.61), SGS (p = 0.116) and RHI (p = 0.109)]. All three scores performed poorly to predict the need for second-line treatment or colectomy within 28 days. There was no significant association between histological scores and steroid response (NHI (p = 0.796), SGS (p = 0.57) and RHI (p = 0.941)]. All three scores had a strong positive correlation observed between each other but not with endoscopic Mayo score. CONCLUSION: The three histologic scores (SGS, RHI and NHI) performed poorly in prediction of need for second-line treatment or colectomy in ASUC. Future studies should study the impact of histologic assessment on long term outcomes in ASUC.

Perceptions regarding the impact of gender on training and career advancement among gastroenterologists in India and other South Asian countries.

BACKGROUND: There are limited studies on the impact of gender on training and career advancement in gastroenterology. AIM: The aim was to study this impact and understand the perceptions of work-life balance and beliefs regarding gender dynamics among gastroenterologists in India and other South Asian countries. METHODS: A web-based survey was conducted among trainees and attending physicians in South Asia from November 15, 2021, to March 30, 2022. The survey instrument had four components: demographic features, training, career advancement and work-life balance. RESULTS: As many as 622 gastroenterologists completed the survey, of which 467 responses were from India (mean age: 41.1 years; females: 11.5%). A higher proportion of female respondents from India believed that gender bias in recruiting and training had negatively impacted their careers (40.7% females vs. 1.5% males). Radiation hazard for fertility (11.1% females vs. 1.9% males, p < 0.001) and as a health concern (14.8% females vs. 5.1% males, p = 0.005) were significant career deterrents for females. A higher proportion of female participants from India faced a career interruption (59.3% females vs. 30.3% males, p ≤ 0.001). Common reasons were pregnancy (37%) and childcare provision (25.9%). More females believed that women were more productive than men (40.8% females vs. 16.9% males, p < 0.001) and that a salary gap existed (44.7% females vs. 29.1% males, p < 0.001). The incidence of self-perceived burnout was 63% among females and 51.6% among males (p = 0.115). CONCLUSION: Gender-related factors impact the training and career of female gastroenterologists.

Personalized Assistive Technologies for Motor-Impaired Students: A Case of Learning Process Mining.

Motor disability includes the lack of sensation, movement, or coordination, and Assistive Technologies (AT) can help overcome these challenges. Motor-disabled students need different ATs and configurations depending on courses and individual needs, and some solutions can be expensive. Some affordable AT has roots in gaming but can also be used for other purposes. However, there is little research on how they can be combined to define a personalized setting. Therefore, we performed a literature review to identify challenges and solutions to support students with motor disabilities in using information systems. The result defines a framework for identifying personalized settings. The usability of the result was demonstrated by performing a self-experimentation study of the first author, who has a motor disability. The results show its utility while learning process mining using the Graphical User Interface (GUI) and code-based tools. We identified challenges in using different User Interface (UI) elements, which can be used as a guideline for designers of process mining tools as well as other information systems to support diversity.

Cytomegalovirus in ulcerative colitis: an evidence-based approach to diagnosis and treatment.

INTRODUCTION: The detection of cytomegalovirus (CMV) in the setting of inflammatory bowel disease often creates confusion whether CMV is a 'bystander' or 'disease.' AREAS COVERED: This review discusses the clinical conundrum of CMV in ulcerative colitis, approach to discriminate infection from disease, and therapeutic considerations (immunosuppressive and anti-CMV treatment). CMV disease should be considered in corticosteroid refractory- dependent and thiopurine refractory disease. Endoscopy may reveal deep punched out ulcers, irregular ulcers, or cobble-stoning. The diagnosis rests on the presence and abundance of viral inclusion bodies on hematoxylin and eosin stain, positive immunohistochemistry, and/or positive tissue polymerase chain reaction. CMV disease is associated with worse outcomes including increased colectomy rates. EXPERT OPINION: The timing and duration of antiviral drugs in CMV disease is debatable but depends on the load of CMV in tissue. In high-grade infection, CMV needs to be treated while increasing immunosuppression may work in the setting of low-grade infection. Ganciclovir is the drug of choice for treatment of CMV disease. Tumor necrosis factor inhibitors may be useful for treating underlying disease activity in the setting of CMV. Other emerging therapies include fecal microbiota transplantation. Randomized studies are necessary to define the best timing and duration of anti-CMV therapy.

Positioning of tofacitinib in treatment of ulcerative colitis: a global perspective.

INTRODUCTION: Tofacitinib has emerged as a useful drug for the treatment of ulcerative colitis (UC). AREAS COVERED: There is an unmet need for cost-effective, non-immunogenic drugs with a safe adverse effect profile to treat patients with ulcerative colitis. In the present review, we evaluate the available literature to inform the appropriate positioning of tofacitinib in the current drug landscape and identify subsets where its use should be done with caution. EXPERT OPINION: Tofacitinib is helpful in the treatment of patients where the standard conventional or biological therapies have failed or were not tolerated. With lower costs of the generic drug than the biologicals (or biosimilars), it could be an important therapy in low- to middle-income countries. The risk of infections, especially Herpes Zoster and tuberculosis, needs to be addressed before initiation. Tofacitinib should be avoided in patients with venous thromboembolism and cardiovascular disease risk factors. Due to limited evidence, the use is not recommended in pregnancy, while it should be used with caution in elderly citizens. Future trials should look into the head-to-head comparison of tofacitinib with biologicals. The role of tofacitinib in acute severe colitis needs evaluation with comparative trials with current standards of care.

SERUM PROCALCITONIN AS A PROGNOSTIC MARKER IN ACUTE SEVERE ULCERATIVE COLITIS: A PROSPECTIVE STUDY.

BACKGROUND: Procalcitonin may be increased in active ulcerative colitis (UC). We investigated the role of procalcitonin in predicting response in acute severe UC (ASUC). METHODS: Consecutive patients with ASUC diagnosed on basis of Truelove and Witts criteria were enrolled. Serum procalcitonin levels for consecutive patients were measured at admission and day 3. We assessed role of procalcitonin values at presentation and at day 3 in assessing response on day 3 (Oxford's criteria) and need for second line therapy (day 28). RESULTS: Of fifty patients (23 males, mean age: 35.98±13.8 years), 16 did not respond (day 3). Ten (20%) patients required second-line therapy. Baseline procalcitonin was significantly associated with response on day 3 (P=0.016). There was no association between day 1 or day 3 procalcitonin and need for second-line rescue therapy. CONCLUSION: Serial procalcitonin is not an effective biomarker for predicting outcomes or need for second line therapy in ASUC.

Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis.

OBJECTIVES: The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates. METHODS: Electronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes. RESULTS: Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9-89.0, I2 = 90%) as compared to a single dose (69.3, 52.4-82.3, I2 = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02-0.13, I2 = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6-96.9, I2 = 0%), spondyloarthropathy (95.6, 95% CI: 83.4-98.9, I2 = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4-94.2, I2 = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1-88.9, I2 = 85%), and vasculitis (70.5, 95% CI: 52.9-83.5, I2 = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70-90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy. CONCLUSION: Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.

Antibiotics for induction and maintenance of remission in ulcerative colitis: systematic review and meta-analysis.

Objectives: To ascertain the role of antibiotics in induction and maintenance of remission in ulcerative colitis (UC)Methods: We searched electronic databases for keywords ulcerative colitis or inflammatory bowel disease and antibiotics or antimicrobials. We performed a meta-analysis of randomized trials comparing antibiotics with control/placebo for clinical response, need for second line therapy, colectomy, and adverse effects. Subgroup analysis to clarify the mode of administration, number of antibiotics or the setting of use (acute severe UC or active non-severe UC) were also performed.Results: Thirteen trials with 785 patients were included. The pooled odds ratio of achieving clinical response with antibiotics was 1.74 (95% CI, 1.17-2.58). No differences were noted in relapse rates, need for second line therapy, colectomy or, adverse effects with the use of antibiotics. Subgroup analysis showed no differences with use of single or combination of antibiotics. Analysis of trials only in the setting of acute severe colitis did not demonstrate any benefit.Conclusion: The use of oral antibiotics in the setting of non-severe active UC could have some benefit in clinical response. The use of antibiotics is not of benefit in acute severe colitis, but oral antibiotics need to be evaluated in adult patients.

Per-oral Endoscopic Myotomy and Other Applications of Third Space Endoscopy: Current Status and Future Perspectives.

INTRODUCTION: The modification of NOTES (natural orifice transluminal endoscopic surgery) by mucosal safety flap has introduced us to the world of third space endoscopy (TSE). POEM (per-oral endoscopic myotomy) for achalasia cardia being its first vista, the realm expanded so that we can now remove en bloc a subepithelial/intramural tumor by POET (per-oral endoscopic tumor resection), perform G-POEM (gastric per-oral endoscopic myotomy) for refractory gastroparesis, restore esophageal continuity in complete obstruction by performing POETRE (per-oral endoscopic tunneling for the restoration of the esophagus), divide the septum in Zenker diverticulum completely with negligible risk of perforation by Z-POEM (Zenker per-oral endoscopic myotomy) and relieve constipation in Hirschsprung disease by PREM (per-rectal endoscopic myotomy). However, the real potential of TSE became evident with the introduction of POEM with fundoplication. TSE has opened the gates of the peritoneal cavity. Improved expertise and equipment will make the role of endoscopist complimentary to the surgeon with the dawn of a new field in therapeutic endoscopy. AREAS COVERED: This review intends to comprehensively discuss the various aspects of POEM for achalasia studied so far followed by a brief discussion about other applications of TSE and the future perspectives in this exciting field.

Diagnostic accuracy of the Xpert MTB/RIF assay for abdominal tuberculosis: a systematic review and meta-analysis.

BACKGROUND: We performed a meta-analysis to determine diagnostic accuracy of Xpert MTB/RIF for diagnosis of abdominal (intestinal or peritoneal) tuberculosis (TB) in various tissues (intestinal, omental/peritoneal tissue or ascitic fluid). METHODS: Electronic databases were searched for observational studies on use of Xpert MTB/RIF in ascitic fluid, peritoneal, or omental tissue for diagnosis of peritoneal and intestinal TB. We calculated the pooled sensitivity, specificity and diagnostic odds ratio of Xpert MTB/RIF for diagnosis of peritoneal TB in comparison to composite reference standard (CRS) and culture, and in comparison to CRS for intestinal TB. RESULTS: Twenty-five observational studies were included. The pooled sensitivity and specificity as assessed with peritoneal culture from ascites as an Index test was 64% (95% Confidence Interval [C.I.] 49-76%) and 97% (95% C.I., 95-99%) respectively and with peritoneal CRS was 30% (95% C.I., 22-40%) and 100% (95% C.I., 98-100%) respectively. In the intestinal group, the pooled sensitivity and specificity of Xpert MTB/RIF was 23% (95% C.I., 16-32%) and 100% (95% C.I., 52-100%). The AUC of peritoneal culture and intestinal tissue was 0.935 and 0.499. CONCLUSION: Xpert MTB/RIF has modest sensitivity for diagnosis of peritoneal and intestinal tuberculosis but has a good specificity. PROSPERO REGISTRATION: CRD42020140545.

Prevalence of polymorphisms in thiopurine metabolism and association with adverse outcomes: a South Asian region-specific systematic review and meta-analysis.

Background: Prevalence and impact of thiopurine S-methyltransferase (TPMT) and Nudix hydrolase (NUDT15) minor allele frequencies in South Asian population is unclear.Methods: We searched PubMed and Embase with keywords-TPMT and NUDT15 combined with South Asian countries. We included studies reporting frequency of TPMT and NUDT15 polymorphisms. We estimated the pooled prevalence of TPMT and NUDT15 polymorphisms and their impact on pooled odds ratio of adverse events with thiopurines.Results: We included 26 studies in our analysis. The pooled prevalence of NUDT15 and TPMT polymorphisms was 16.5% (95% CI: 13.09-20.58) and 4.57% (95% CI: 3.66-5.68), respectively. In patients with adverse effects, the pooled prevalence of NUDT15 and TPMT polymorphism was 49.51% (95% C.I. 21.69-77.64) and 9.47% (95% C.I. 5.39-16.11), respectively. The odds ratio (OR) of adverse events with presence of TPMT polymorphisms was 3.65 (95% C.I., 1.43-9.28). The pooled OR for adverse events in presence of NUDT15 polymorphism was 12.63 (95% C.I., 3.68-43.26).Conclusion: NUDT15 were reported more frequently than the TPMT polymorphisms in South Asian population and were more frequently associated with adverse events. These findings may have implications for preemptive testing amongst South Asian population and immigrants prior to starting thiopurines.

Serial measurements of faecal calprotectin may discriminate intestinal tuberculosis and Crohn's disease in patients started on antitubercular therapy.

BACKGROUND: Response to antitubercular therapy (ATT) is often used to differentiate intestinal tuberculosis (ITB) from Crohn's disease. Role of non-invasive biomarkers to predict mucosal response to ATT is unclear. MATERIALS AND METHODS: A prospective study to compare faecal calprotectin and serum C-reactive protein (CRP) levels at diagnosis, 2 and 6 months of ATT in patients with suspected ITB started on ATT was done. The patients were eventually divided into two groups: ITB or alternative diagnosis (OTH). Decline of calprotectin and CRP levels was used to compute area under the receiver operating characteristic (AUROC) to predict mucosal healing at 2 months. RESULTS: Thirty-seven patients (mean age: 34.95 ± 16.35 years, 23 males) were included and 28 (75.67%) were diagnosed as ITB while nine (24.32%) had alternative diagnosis (OTH). The median faecal calprotectin values of ITB and OTH groups at baseline, 2 months and 6 months were 216 and 282 µg/g (P = 0.466), 43 and 216 µg/g (P = 0.003), and 26 and 213 µg/g (P < 0.001), respectively. The median CRP values at baseline, 2 months and 6 months were 18 and 30 mg/L (P = 0.767), 4.7 and 15 mg/L (P = 0.025), and 3 and 10.85 mg/L (P = 0.068), respectively. The AUROC of percent decline in faecal calprotectin and serum CRP at 2 months for mucosal healing were 0.8287 [95% confidence inteval (CI) 0.6472-1] and 0.6018 (95% CI 0.4079-0.7957), respectively. CONCLUSION: Faecal calprotectin can help in assessing response to therapy in suspected ITB patients started on empirical ATT.

Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial.

OBJECTIVES: Evaluation of a combination of antibiotics as an adjuvant therapy in acute severe ulcerative colitis (ASUC). METHODS: Patients with ASUC were randomized to either infusions of placebo or intravenous ceftriaxone and metronidazole in addition to standard care. Primary outcome was response on day three according to Oxford's criteria. Secondary outcome measures included changes in partial Mayo score, CRP levels, fecal calprotectin (day three), and need for second-line therapy, hospital stay, and mortality (day 28). RESULTS: Fifty patients (25 in each group, median age: 33 years, 23 males) were included. The number of patients with fulminant disease in the antibiotic group were 16 (64%) as compared to 7 (28%) in the standard of care group. Complete response on day three was attained by 7 (28%) in the antibiotic and 6 (24%) standard of care group (p = 1.00). Three patients from the antibiotic group underwent colectomy and three received intravenous cyclosporine whereas four patients in the standard of care group received cyclosporine (p = 0.725). There was no significant difference in change in CRP, Partial Mayo score, and fecal calprotectin between the two groups on day three. CONCLUSION: Combination of intravenous ceftriaxone and metronidazole did not improve outcomes in ASUC.Acronym: AAASUC trialRegistration Number: CTRI/2019/03/018196 and NCT03794765.

Coronavirus disease (COVID-19) and the liver: a comprehensive systematic review and meta-analysis.

BACKGROUND: Liver function derangements have been reported in coronavirus disease (COVID-19), but reported rates are variable. METHODS: We searched PubMed and Embase with terms COVID and SARS-COV-2 from December 1, 2019 till April 5, 2020. We estimated overall prevalence, stratified prevalence based on severity, estimated risk ratio (RR), and estimated standardized mean difference (SMD) of liver function parameters in severe as compared to non-severe COVID. Random effect method utilizing inverse variance approach was used for pooling the data. RESULTS: In all, 128 studies were included. The most frequent abnormalities were hypoalbuminemia [61.27% (48.24-72.87)], elevations of gamma-glutamyl transferase (GGT) [27.94% (18.22-40.27)], alanine aminotransferase (ALT) [23.28% (19.92-27.01)], and aspartate aminotransferase (AST) [23.41% (18.84-28.70)]. Furthermore, the relative risk of these abnormalities was higher in the patients with severe COVID-19 when compared to non-severe disease [Hypoalbuminemia-2.65 (1.38-5.07); GGT-2.31 (1.6-3.33); ALT-1.76 (1.44-2.15); AST-2.30 (1.82-2.90)]. The SMD of hypoalbuminemia, GGT, ALT, and AST elevation in severe as compared to non-severe were - 1.05 (- 1.27 to - 0.83), 0.76 (0.40-1.12), 0.42 (0.27-0.56), and 0.69 (0.52-0.86), respectively. The pooled prevalence and RR of chronic liver disease as a comorbidity was 2.64% (1.73-4) and 1.69 (1.05-2.73) respectively. CONCLUSION: The most frequent abnormality in liver functions was hypoalbuminemia followed by derangements in gamma-glutamyl transferase and aminotransferases, and these abnormalities were more frequent in severe disease. The systematic review was, however, limited by heterogeneity in definitions of severity and liver function derangements. Graphical depiction of the summary of meta-analytic findings a) pooled prevalence of abnormalities b) Risk ratio of abnormality in severe versus non-severe COVID-19 c) standardized mean difference (SMD) between severe and non-severe group and d) pooled prevalence for parameters based on severity stratification for bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), albumin, globulin and acute hepatic injury (AHI) . Also estimates for overall/total liver disease (TLD) and chronic liver disease (CLD) amongst COVID-19 patients are depicted in a, b, d. For d) In addition to severity stratification, Overall (all studies for a particular estimate) and combined (only those studies which reported severity) estimates are provided.

Risk of hepatitis with various reintroduction regimens of anti-tubercular therapy: a systematic review and network meta-analysis.

Objective: To compare risk of hepatotoxicity between various regimens for reintroduction of antitubercular therapy (ATT) in patients with previous episode of ATT hepatitis.Methods: We searched various databases (PubMed, Embase, CENTRAL, Scopus, WoS and LILACS) for studies comparing ATT reintroduction regimens using terms 'drug-induced liver injury' and 'antitubercular drugs' AND 'reintroduction'. The reintroduction regimens i.e concomitant (all drugs introduced together), sequential (reintroduction of one drug in full dose followed by another) or incremental (one drug in a low dose and then higher dose followed by next drug) were compared using Bayesian approach for network meta-analysis with random-effect model. Cochrane revised tool was used to assess risk of bias in included studies (RoB 2.0).Results: Four randomized studies with 577 patients were eligible for analysis. Compared with concomitant regimen (baseline comparator), incremental regimen appeared to have lower risk of ATT hepatitis (odds ratio [OR] 0.24; 95% CrI 0.017, 1.2) as also the sequential regimen (OR 0.33; 95% CrI 0.033, 1.7). Rifampicin first and isoniazid first reintroduction regimens were similar via-a-vis recurrence of hepatotoxicity.Conclusion: The sequential and incremental regimen may be better than concomitant regimen in reducing risk of ATT hepatitis although the odds did not achieve statistical significance.