Efficacy of long-term albumin therapy in the treatment of decompensated cirrhosis.

BACKGROUND AND AIMS: Decompensated liver cirrhosis has a poor prognosis, with a median overall survival of two to four years, which is worse than for many oncological disorders. These patients are highly susceptible to infections due to increased systemic inflammation leading to kidney failure and death. The aim was to study the efficacy of albumin in reducing episodes of decompensation, preventing bacterial infection, kidney dysfunction and mortality. METHOD: Study involved patients with Child B or C cirrhosis with an albumin level below 3.0 g/dL, who were administered 20% human albumin weekly with standard medical treatment (SMT) for three months or till serum albumin levels were 4.0 g/dL (whichever is earlier) and compared with age and sex-matched controls who received only SMT. The primary end-point was six-month mortality and the secondary end-points were reduction in infections, kidney dysfunction, ascites recurrence, hepatic encephalopathy (HE), gastrointestinal (GI) bleed and complications of cirrhosis. RESULTS: From September 2021 to January 2023, 88 cases and 86 controls were taken and followed up for six months. Overall, six-month survival was not statistically significant between groups (95.1% vs. 91.9%; p = 0·330). The incidence of recurrence of ascites (34.09% vs. 59.3%, p < 0.001), kidney dysfunction (6.8% vs. 24.4%, p < 0.001), HE (15.9% vs, 37.2%, p = 0.015), spontaneous bacterial peritonitis (SBP) (3.4% vs 17.4%, p = 0.002) and non-SBP infections (7.9% vs. 18.6%, p = 0.038) were significantly less in cases as compared with controls; however, GI bleed (14.8% vs. 17.4%, p = 0.632) was not statistically significant. CONCLUSION: Long-term human albumin acts as a disease-modifying treatment in patients with decompensated cirrhosis.

Exclusive Enteral Nutrition Mediates Beneficial Gut Microbiome Enrichment in Acute Severe Colitis.

BACKGROUND: Exclusive enteral nutrition (EEN) supplementation of the standard of care (SOC) augments steroid responsiveness in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study investigates EEN-driven gut microbial alterations in patients with ASUC and examines their correlations with clinical parameters. METHODS: Stool samples from patients with ASUC (n = 44) who received either EEN-supplemented SOC (EEN group; n = 20) or SOC alone (SOC group; n = 24) for 7 days were collected at baseline (day 0) and postintervention (day 7). Microbiome analysis was carried out using 16S ribosomal RNA gene sequencing followed by data processing using QIIME2 and R packages. RESULTS: Seven-day EEN-conjugated corticosteroid therapy in patients with ASUC enhanced the abundances of beneficial bacterial genera Faecalibacterium and Veillonella and reduced the abundance of Sphingomonas (generalized linear model fitted with Lasso regularization with robustness of 100%), while no such improvements in gut microbiota were observed in the SOC group. The EEN-associated taxa correlated with the patient's clinical parameters (serum albumin and C-reactive protein levels). Unlike the SOC group, which retained its preintervention core microbiota, EEN contributed Faecalibacterium prausnitzii, a beneficial gut bacterial taxon, to the gut microbial core. EEN responders showed enhancement of Ligilactobacillus and Veillonella and reduction in Prevotella and Granulicatella. Analysis of baseline gut microbiota showed relative enhancement of certain microbial genera being associated with corticosteroid response and baseline clinical parameters and that this signature could conceivably be used as a predictive tool. CONCLUSIONS: Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC.

Exclusive enteral nutrition­supplemented corticosteroid therapy in acute severe ulcerative colitis (ASUC) is accompanied by the enrichment of beneficial gut microbial genera, which correlate negatively with the disease activity scores and objective inflammatory markers in ASUC. The baseline gut microbiota in ASUC associates with and may predict corticosteroid response.

Revised Algorithmic Approach to Differentiate Between Nonspecific and Specific Etiologies of Chronic Terminal Ileitis.

INTRODUCTION: Chronic isolated terminal ileitis (TI) may be seen in Crohn's disease (CD) and intestinal tuberculosis (ITB) in addition to other etiologies that may be managed symptomatically. We developed a revised algorithm to distinguish patients with a specific etiology from a nonspecific etiology. METHODS: Patients with chronic isolated TI followed up from 2007 to 2022 were retrospectively reviewed. A specific (ITB or CD) diagnosis was made based on standardized criteria, and other relevant data were collected. Using this cohort, validation of a previously suggested algorithm was conducted. Furthermore, based on the results of a univariate analysis, a multivariate analysis with bootstrap validation was used to develop a revised algorithm. RESULTS: We included 153 patients (mean age 36.9 ± 14.6 years, males-70%, median duration-1.5 years, range: 0-20 years) with chronic isolated TI of whom 109 (71.2%) received a specific diagnosis (CD-69, ITB-40). On multivariate regression and validation statistics with a combination of clinical, laboratory, radiological, and colonoscopic findings, an optimism corrected c-statistic of 0.975 and 0.958 was obtained with and without histopathological findings, respectively. Revised algorithm, based on these, showed sensitivity, specificity, positive and negative predictive values, and overall accuracy of 98.2% (95% CI: 93.5-99.8), 75.0% (95% CI: 59.7-86.8), 90.7% (95% CI: 85.4-94.2), 94.3% (95% CI: 80.5-98.5) and 91.5%(95% CI:85.9-95.4), respectively. This was more sensitive and specific than the previous algorithm (accuracy 83.9%, sensitivity 95.5%, and specificity 54.6%). DISCUSSION: We developed a revised algorithm and a multimodality approach to stratify patients with chronic isolated TI into specific and nonspecific etiologies with an excellent diagnostic accuracy, which could potentially avoid missed diagnosis and unnecessary side effects of treatment.

Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring.

BACKGROUND/AIMS: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. RESULTS: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P=0.001) on multivariate analysis respectively. CONCLUSIONS: Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Efficacy and safety of biosimilar versus originator infliximab in patients with inflammatory bowel disease: A real-world cohort analysis.

BACKGROUND: Anti-tumor necrosis factor (anti-TNF) monoclonal antibody, infliximab, is the primary therapeutic modality for patients with Crohn's disease (CD) and ulcerative colitis (UC), refractory to conventional therapy. Biosimilars of infliximab have been shown to have equivalent efficacy to originator infliximab. We compared the safety and efficacy of infliximab biosimilar with the originator in Indian patients with inflammatory bowel disease (IBD). METHODS: Patients with IBD treated with either originator or biosimilar infliximab from January 2005 to October 2020 were included in this retrospective analysis. The safety and efficacy of originator or biosimilar infliximab in inducing and maintaining clinical remission at weeks 14 and 52 for CD and UC were evaluated. Disease activity was estimated at baseline, after induction therapy, after 1 year of treatment, and during 12 months of follow-up. RESULTS: In all, 137 patients (82 CD; 55 UC) were included, of whom 102 were on originator, and 35 patients received biosimilar. In biosimilar group, clinical response and remission rates at weeks 14 and 52 were 84.2%, 58% and 68.4%, 52.6% in CD and 81.2%, 56.2% and 68.7%, 62.5% in UC patients, respectively. Among patients who were on originator, clinical response and remission rates at weeks 14 and 52 were 79.4%, 46% and 57.1%, 43% in CD and 72%, 64.1% and 66.7%, 56.4% in UC patients, respectively. Thirty-three (24.1%) patients experienced adverse events; eighteen developed tuberculosis (TB), of whom 17 received originator and one patient received biosimilar. CONCLUSIONS: Infliximab biosimilar is comparable to originator infliximab in terms of safety profile and its efficacy in inducing and maintaining remission in patients with IBD.

Thromboembolism is associated with poor prognosis and high mortality in patients with inflammatory bowel disease: A case-control study.

BACKGROUND: The information on the risk of thromboembolism (TE) in inflammatory bowel disease (IBD) and its predictors are lacking, especially from developing countries. The present study evaluated the prevalence, predictors, and prognosis of TE in IBD. METHODS: This case-control study included 35 patients with IBD (ulcerative colitis [UC, n = 25]; Crohn's disease [CD], n = 10) and history of TE, from a cohort of 3597 patients (UC n = 2752, CD n = 845) under follow-up from 2005 to 2018. Details on demographics, extraintestinal manifestations (EIMs), patient status, type and outcomes of TE, treatment details, and disease course were compared with IBD patients without TE (age, gender, and duration of follow-up matched) in the ratio of 1:4. RESULTS: Prevalence of TE in IBD was 0.9% (UC-0.89%, CD-1.2%). Among TE patients (mean age: 34.9 ± 13.1 years, 48.6% males), median duration from diagnosis to TE was 12 (inter-quartile range [IQR]: 3-36) months, 37% had other EIMs, 94.1% had moderate/severe disease at time of TE, 62.8% had steroid-dependent/refractory disease, and 5 patients (14.2%) died because of disease-related complications. Lower limb was the commonest site (57.1%), 14.3% had pulmonary TE, and 31.4% had involvement of multiple sites. Phenotypically, more patients with TE (among UC) had steroid-dependent disease (60% vs. 25%, p = 0.001), pancolitis (76% vs. 36%, p = 0.002), chronic continuous disease course (44% vs. 19%, p = 0.009), and acute severe colitis (48% vs. 18%, p = 0.002), of which the latter three were also independent predictors of TE. CONCLUSION: Approximately 1% of patients with IBD develop thromboembolism relatively early during their disease course, and TE is associated with severe disease and higher disease-related complications including mortality.

Monotherapy with thiopurines in stricturing Crohn's disease: A real-life experience from low- and middle-income countries.

BACKGROUND: Stricturing Crohn's disease (CD) is difficult to manage medically with limited treatment options, anti-tumor necrosis factor (TNF) therapy being the first-line therapy. Although thiopurines are also recommended first-line treatment option for maintenance of remission in steroid-dependent CD, evidence on their use in stricturing CD is lacking. We evaluated the efficacy of azathioprine (AZA) in patients with stricturing CD. METHODS: In this retrospective cohort study (January 2005 to July 2020), patients with stricturing CD who were managed with AZA as a primary therapy for at least 6 months, and had a follow-up of at least 6 months after AZA initiation were included. Disease characteristics, complications, long-term response, and adverse events were noted. RESULTS: One hundred and fifteen patients were included (mean age 33.8±14 years, 67.8% males, median disease duration 98 months [IQR: 60-158], median follow-up duration 60 months [IQR: 50-96]). 46.1% (n=53) patients had significant anemia at presentation, and 73% (n=84) had isolated small bowel involvement. Median dose of AZA was 100 mg (equivalent to 1.5 mg/kg). Median therapy and follow-up duration (after AZA initiation) was 17 (IQR: 9-42) and 33 months (IQR 18-60), respectively. The cumulative probability of maintaining response without treatment failure at 1, 2, and 5 years was 73.1%, 40.7%, and 18.5%, respectively. Among patients with AZA failure, 15.6% received methotrexate, 13% received anti-TNFs, and 9.5% underwent surgery. Significant anemia (<10 g/dL) at presentation and steroid dependence predicted AZA failure. 31.3% patients experienced adverse events, commonest being leukopenia (n=29, 25.2%). CONCLUSION: Azathioprine demonstrated good short-term and modest long-term response rates in patients with stricturing CD.

Prospective validation of AIIMS index as a predictor of steroid failure in patients with acute severe ulcerative colitis.

BACKGROUND: Optimal outcomes in acute severe ulcerative colitis (ASUC) are related to time-bound management based upon early prediction of response to intravenous (IV) steroids. In an earlier study, we described the All India Institute of Medical Sciences (AIIMS) index (baseline Ulcerative Colitis Endoscopic Index of Severity [UCEIS] ≥ 7 and day 3 fecal calprotectin [FCP] > 1000 µg/g) for predicting failure of IV steroids. The current study is designed to validate this index in a prospective cohort. METHODS: IV steroid-naïve patients with ASUC, satisfying Truelove and Witts' criteria, hospitalized from August 2018 to July 2019 were included. Patients' assessment included baseline sigmoidoscopy, day 1 and 3 FCP, hemogram, biochemistry and day 3 C-reactive protein. All patients received IV steroids, and the primary outcome was steroid failure, defined as the need for colectomy or rescue therapy with cyclosporine (CYC)/infliximab (IFX) during admission. RESULTS: Of the 47 patients, eight were excluded (four received steroids outside, two were directly taken for surgery/infliximab therapy, one had toxic megacolon, and one had infectious colitis), and 39 patients were included (mean age: 36.1 ± 12.6 years, male: 31%). Fifteen patients (38%) failed IV steroid and required rescue therapy (IFX: 9, CYC: 2, Colectomy: 3, IFX followed by colectomy: 1). On univariate analysis, UCEIS ≥ 7 at baseline (p = 0.006), day 1 FCP (p = 0.03), day 3 FCP > 1000 µg/g (p = 0.001), Oxford criteria (p = 0.04) and AIIMS index (p < 0.001) were significantly different between steroid responders and steroid failures. On multivariate analysis, day 3 FCP > 1000 µg/g (odds ratio (odds ratio (OR)= 6.4;(95% CI =2.2-196.1) and baseline UCEIS ≥ 7 (OR) = 10.1;(95% CI = 2.1-80.2) were independent predictors. The AIIMS index predicted steroid failure with a better specificity (100% vs. 83%, p = 0.04) and positive predictive value (100% vs. 64%, p = 0.03) than Oxford criteria. CONCLUSION: AIIMS index has been validated in 39 prospective ASUC patients as an effective early predictor of steroid failure (sensitivity = 53%, specificity = 100%).

Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti-TNF therapy in tuberculosis endemic region.

BACKGROUND: Anti-tumor necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to an increased risk of tuberculosis (TB) reactivation despite latent tuberculosis (LTB) screening, especially in TB endemic regions. AIM: We evaluated the effect of stringent screening strategy and LTB prophylaxis on TB reactivation. METHODS: We performed an ambispective comparison between patients who received anti-TNF therapy after January 2019 (late cohort) and between Jan 2005 and Jan 2019 (early cohort). Late cohort patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, chest X-ray, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. RESULTS: One hundred seventy-one patients (63: ulcerative colitis/108: Crohn's disease, mean age diagnosis: 28.5 ± 13.4 years, 60% males, median follow-up duration after anti-TNF: 33 months [interquartile range: 23-57 months]) were included. Among the 112 in the early cohort, 29 (26%) underwent complete TB screening, 22 (19.6%) had LTB, 10 (9%) received chemoprophylaxis, and 19 (17%) developed TB. In comparison, in the late cohort, 100% of patients underwent complete TB screening, 26 (44%) had LTB, 23 (39%) received chemoprophylaxis, and only 1(1.7%) developed TB (p < 0.01). On survival analysis, patients in early cohort had a higher probability of TB reactivation compared with the late cohort (HR: 14.52 (95% CI: 1.90-110.61 [p = 0.01]) after adjusting for gender, age at anti-TNF initiation, concomitant immunosuppression, anti-TNF doses, and therapy escalation. CONCLUSION: The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.

Efficacy and tolerability of hyperbaric oxygen therapy in small bowel stricturing Crohn's disease: a pilot study.

BACKGROUND/AIMS: Existing therapeutic options for complicated Crohn's disease (CD) like biologics and surgery are limited by inadequate long-term efficacy, cost, and adverse effects. Tissue hypoxia is important in CD pathogenesis and may be ameliorated with hyperbaric oxygen therapy (HBOT). We assessed the efficacy and tolerability of HBOT in small bowel stricturing CD. METHODS: This pilot study included patients of small bowel stricturing CD (from April 2019 to January 2020) who underwent HBOT. These patients were refractory to conventional medical treatment or had multiple strictures not amenable to resection. Each session of HBOT was given for 60 minutes with a pressure of 1.5-2.5 atm. Clinical, biochemical responses and Short Inflammatory Bowel Disease (SIBD) questionnaire were evaluated at 2 and 6 months, and radiological response was evaluated at 6 months. RESULTS: Fourteen patients (mean age, 42.9±15.7 years; male, 50%) were subjected to 168 HBOT sessions. Thirteen patients (92.7%) had strictures and 1 patient had enterocutaneous fistula in addition. Median number of HBOT sessions was 11 (range, 3-20) which were administered over a median of 4 weeks. Most patients tolerated it well except 1 who had hemotympanum. At 2 and 6 months of follow-up, 64.2% of patients had a clinical response, 50% and 64.2% of patients had clinical remission respectively. Steroid-free clinical remission was seen in 8 (57%) of patients with radiological improvement in 50%. There was a significant improvement in SIBD scores at 2-month follow-up (59.4 vs. 44.5, P=0.03). CONCLUSIONS: HBOT can be a safe and effective therapeutic option in patients with stricturing small bowel CD refractory to conventional medical treatment.

Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis.

BACKGROUND/AIMS: Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. METHODS: Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. RESULTS: Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn's disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn's disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%. CONCLUSIONS: Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.

Real world analysis on the efficacy and safety of anti-tumor necrosis factor therapy in patients with stricturing Crohn's disease.

Crohn's disease (CD) is often complicated by strictures and associated with increased risk for surgery. Inflammatory strictures respond to medical therapy, and anti-tumor necrosis factor (TNF) therapy is often used after the failure of steroids. However, data on efficacy of anti-TNF therapy in stricturing CD is limited. We retrospectively analysed the records of patients with stricturing CD who were treated with anti-TNF therapy and were prospectively followed from January 2005 to July 2020. Treatment success was defined as continuation of anti-TNF without the requirement for steroids or parenteral nutrition, switch to other anti-TNF, endoscopic dilation, surgery and severe adverse events leading to the withdrawal of anti-TNF. Fifty-nine patients were included [50-infliximab, 9-adalimumab; mean age-30.1 ± 15 years; males-69.5%; median disease duration-124 (range 30-396) months; median follow-up duration-42 (range 8-180) months]. Ileum was the most common site of stricture (69.5%), 20.3% of patients had colonic strictures, and 64.4% had multiple strictures. 55.9% of patients were steroid dependent and 37.3% were steroid refractory. The median duration of anti-TNF therapy was 14 (range 2-96) months, and 54.2% (n = 32) patients received concomitant immunomodulators. 88% improved with induction (11.8% primary non-response), secondary loss of response was seen in 52.2%, and the cumulative probability of treatment success at 1, 2 and 5 years was 69%, 51%, and 28% respectively. Anaemia at presentation predicted poor response. Only 30% of patients retained biologics on long-term (lack of response, cost, adverse events). 16.9% had adverse events, the commonest being reactivation of tuberculosis (5.1%). Anti-TNF therapy is associated with good short-term treatment success with modest long-term response in stricturing CD.

Long-term outcomes of anti-tumor necrosis factor therapy and surgery in nonperianal fistulizing Crohn's disease.

BACKGROUND: Unlike perianal fistula, long-term outcomes of nonperianal fistulae (NPF) in Crohn's disease (CD) are not clear. We aimed to compare the outcomes of medical and surgical therapies in patients with NPF. METHODS: We retrospectively analyzed the records of patients of CD with NPF who were prospectively followed from January 2005 to December 2018. RESULTS: Of the 53 patients with NPF [mean age at presentation:29 ± 14 years; 54.7% male; median duration of follow-up: 47 months (interquartile range [IQR]:26-76 months)], enteroenteric fistula (37.8%) was the most common presentation. Of 22 patients treated with anti-tumor necrosis factor (TNF) therapy, complete response was achieved in 40.9% (n = 9). Overall probability of maintaining response was similar between the anti-TNF and surgical groups (95.2% vs 82.4%; 71% vs 76%; and 63% vs 69%% [P = 0.8] at 1, 2, and 3 years, respectively), with only 13.6% of patients treated with biologicals requiring surgery over 56 months. Twenty-one patients required upfront surgery (small bowel or ileocolonic resection with/without diversion; 28.5% emergent), with 47.6% postoperative recurrence over 36 months, of which nine patients required biologicals (77.7% response to anti-TNF therapy). Long-term outcome was comparable between medically and surgically treated patients; 6.4% developed tuberculosis on anti-TNF therapy. Two patients (3.7%) developed malignancy (one - enteroenteric, one - colovesical). CONCLUSION: Anti-TNF therapy appears to be as effective as surgery in this retrospective analysis of patients with NPFCD, and it may be indicated in the absence of abscess and other complications. These patients are at higher risk of fistula-associated malignancy, which requires a lower threshold for suspicion, especially over the long term in the presence of nonresponse to medical therapy.

Combination of sarcopenia and high visceral fat predict poor outcomes in patients with Crohn's disease.

BACKGROUND: Sarcopenia and visceral fat independently predict poor outcomes in Crohn's disease (CD). However, combined influence of these parameters on outcomes is unknown, and was investigated in the present study. METHODS: This retrospective study evaluated skeletal muscle index (SMI-cross-sectional area of five skeletal muscles normalized for height), visceral and subcutaneous fat area and their ratio (VF/SC) on single-slice computed tomography (CT) images at L3 vertebrae in CD patients (CT done: January 2012-December 2015, patients followed till December 2019). Sarcopenia was defined as SMI < 36.5 cm2/m2 and 30.2 cm2/m2 for males and females, respectively. Disease severity, behavior, and long-term outcomes (surgery and disease course) were compared with respect to sarcopenia and VF/SC ratio. RESULTS: Forty-four patients [age at onset: 34.4 ± 14.1 years, median disease duration: 48 (24-95) months, follow-up duration: 32 (12-53.5) months, males: 63.6%] were included. Prevalence of sarcopenia was 43%, more in females, but independent of age, disease severity, behavior and location. More patients with sarcopenia underwent surgery (31.6% vs 4%, p = 0.01). VF/SC was significantly higher in patients who underwent surgery (1.76 + 1.31 vs 0.9 + 0.41, p = 0.002), and a cutoff of 0.88 could predict surgery with sensitivity and specificity of 71% and 65% respectively. On survival analysis, probability of remaining free of surgery was lower in patients with sarcopenia (59.6% vs 94.1% p = 0.01) and those with VF/SC > 0.88 (66.1% vs 91.1%, p = 0.1), and still lower in those with both sarcopenia and VF/SC > 0.88 than those with either or none (38% vs 82% vs 100%, p = 0.01). CONCLUSIONS: Combination of sarcopenia and high visceral fat predict worse outcomes in CD than either.

High mucosal cytomegalovirus DNA helps predict adverse short-term outcome in acute severe ulcerative colitis.

BACKGROUND/AIMS: Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC. METHODS: Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS' index (ulcerative colitis index of severity > 6 at day 1+fecal calprotectin > 1,000 µg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome. RESULTS: Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0-2,700,000] vs. 116 copies/mg [0-27,220]; P< 0.01). On multivariable analysis, mucosal CMV DNA load > 2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6-39.7; P< 0.01) and AIIMS' index (OR, 39.8; 95% CI, 4.4-364.4; P< 0.01) were independent predictors of steroid-failure and need for colectomy. The combination correctly predicted outcomes in 84% of patients with ASUC. CONCLUSIONS: High mucosal CMV DNA ( > 2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC.

Long-term outcomes in perianal fistulizing Crohn's disease in a resource-limited setting: A cohort analysis.

BACKGROUND: Perianal fistula is one of the most challenging complications of Crohn's disease (CD). We aimed to describe treatment response with surgical and medical therapies, and long-term complications. METHODS: We retrospectively analyzed records of patients with perianal fistulizing CD who were prospectively followed from January 2005 to December 2018. RESULTS: Among 807 patients, 81 (10%) had perianal fistula and 65 were included in the final analysis. The mean age of presentation was 27.4 ± 10.3 years, and 78.5% were males with a median duration of follow-up of 45 (IQR, 24-66) months. 75.4% (n = 49) had complex fistulae. 55.4% (n = 36) of patients received multiple courses (> 5 courses) of antibiotics. Complete response rates with immunomodulators, fistula surgery, biologicals, and diversion were 25%, 42.8%, 39.5%, and 45.4%, respectively. The relapse rate was highest after fistula surgery (52.6%). 44.6% of patients received medical (immunomodulators-21 and biologicals-8) whereas 46.1% received surgery as the first-line therapy. The absence of perianal abscess was associated with complete fistula closure. One patient developed malignancy and 4 (6.1%) died at the end of follow-up. Among the patients (n = 28) who received biologicals, TB reactivation occurred in one patient (3.5%). CONCLUSION: Medical therapy should be offered as first-line therapy, and immunomodulators can be considered when patients cannot afford biologicals. Surgery offers temporary improvement and is associated with high relapse rates. Absence of perianal abscess predicts long-term complete fistula closure.

Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A real-life cohort from northern India.

BACKGROUND: The decision to withdraw anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains controversial, especially in the developing world, where its long-term use is restrained by side effects and prohibitive cost. Present study evaluated the relapse rate and its predictors following anti-TNF withdrawal in a cohort of IBD patients from northern India. METHODS: Patients with IBD who received anti-TNF therapy (induction and beyond), and were under follow-up at All India Institute of Medical Sciences, New Delhi, from January 2005 to July 2018 were included. Demographic features, disease characteristics, duration, response to anti-TNF therapy, and relapse rate after its withdrawal were analyzed. RESULTS: Among 4600 patients with IBD under follow-up, 90 (1.9%) received anti-TNF therapy, of whom 11 were excluded (8-complete records unavailable; 3-received only single dose). Of 79 patients (mean age-40.1 ± 14.2 years; 53.2% males; 31 [39.2%] ulcerative colitis, 47 [59.5%] Crohn's disease; median follow-up-24 [12-39] months), 9 (11.4%) were primary non-responders, 19 (24.1%) had secondary loss of response, and 51 (64.5%) maintained clinical response on anti-TNF. Anti-TNF was withdrawn in 45 (57%) patients (major causes: financial burden-16.5%; tubercular reactivation-12.7%), of whom 33 were in clinical remission. Over a median follow-up of 26 (7.5-45) months, 15 patients (45.5%) relapsed. Most of them responded to antibiotics, steroids, or anti-TNF agents; only 3 required surgery. On Kaplan-Meier analysis, long disease duration prior to therapy was a significant predictor of relapse (hazard ratio [HR] = 1.33, p = 0.034). CONCLUSION: Almost 50% patients with IBD in clinical remission relapse within a year of anti-TNF withdrawal. However, most of these patients have a favorable disease course and respond to medical therapy.

Antitubercular Therapy Given to Differentiate Crohn's Disease From Intestinal Tuberculosis Predisposes to Stricture Formation.

BACKGROUND AND AIM: Treatment trial with antitubercular therapy [ATT] is a common strategy in tuberculosis-endemic countries in case of a diagnostic dilemma between intestinal tuberculosis and Crohn's disease [CD]. Our aim was to determine the long-term clinical course of patients who received ATT before an eventual diagnosis of CD was made. METHODS: We performed retrospective comparison between CD patients who received ≥6 months of ATT vs those who did not receive ATT. Outcomes assessed were change in disease behaviour during follow-up, requirement of surgery and medication use. RESULTS: In all, 760 patients with CD were screened for the study and, after propensity matching for location and behaviour of disease, 79 patients in each group were compared. Progression from inflammatory [B1] to stricturing/fistulising [B2/B3] phenotype was increased among CD patients who received ATT [B1, B2, B3: 73.4%, 26.6%, 0% at baseline vs: 41.8%, 51.9%, 6.3% at follow-up, respectively] as compared with those who did not receive ATT [B1, B2, B3: 73.4%, 26.6%, 0% at baseline vs: 72.2%, 27.8%, 0% at follow-up, respectively] with an odds ratio of 11.05[3.17-38.56]. The usage of 5-aminosalocylates, steroids, immunosuppressants and anti-tumour necrosis factor was similar between both the groups. On survival analysis, CD patients who received ATT had a lower probability of remaining free of surgery [45%] than those who did not [76%] at 14 years of follow-up (hazard ratio [HR] = 3.22, 95% confidence interval [CI], 1.46-7.12, p = 0.004]. CONCLUSIONS: Crohn's disease patients diagnosed after a trial with antitubercular therapy had an unfavourable long-term disease course with higher rate of stricture formation and less chance of remaining free of surgery.

Prognostic role of serial alpha-fetoprotein levels in hepatocellular carcinoma treated with locoregional therapy.

Background and aim: To evaluate early serial AFP changes in responders and non-responders to locoregional therapy and identify differences between significant AFP decliners and non-decliners post-treatment. Methods: Case records of hepatocellular carcinoma (HCC) patients having AFP ≥20 ng/ml and treated with locoregional therapy were examined retrospectively. Patients with complete details were included. Trends of serial AFP change (from baseline to post-treatment one month) in patients showing early tumor response (complete response (CR), partial response (PR), progressive disease (PD)) as assessed on multiphasic MRI/CT liver performed at one month following treatment. Receiver operating curves were drawn to estimate the best AFP reduction cut off for differentiating between responders (CR plus PR) from non-responders (PD). AFP decliners (those with AFP level reduction greater than 20% post-treatment) were identified and comparisons of their clinical parameters, tumor response and survival rate were made with AFP non-decliners. Results: HCC patients (n = 126) had mean age of 52.8 years, male:female ratio (4:1), Child's A 94, BCLC stage A/B/C HCC 49/65/12, respectively. On 4-6 weeks' MRI/CT, 46 patients developed CR, 55 PR and 25 PD. Reduction in median AFP level (83% in CR, 19% in PR) occurred in responders while 16% increase occurred in PD patients (non-responders). A 30% AFP reduction could differentiate responders from non-responders with 70% sensitivity and 68% specificity, AUROC 74% (CI 0.64-0.85). AFP decliners showed better survival and tumor response than non-decliners. Conclusions: Serial AFP change can predict tumor response to locoregional therapy in AFP producing HCC patients. AFP decliners have better survival and tumor response than AFP non-decliners.