Tofacitinib use in ulcerative colitis: An expert consensus for day-to-day clinical practice.

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.

Comparing Myelosuppression Frequency in Indian Inflammatory Bowel Disease Patients: A Randomized Trial of Full Dose Versus Gradual Escalation of Thiopurines.

INTRODUCTION: We aimed to compare the frequency of myelosuppression in patients initiating azathioprine (AZA) at full dose versus those undergoing gradual dose escalation. METHODS: Forty patients with inflammatory bowel disease were recruited over one year and randomized into two groups of 20. Group A initiated AZA at a full dose of 2 mg/kg, while group B started at 1 mg/kg with subsequent dose increases at regular intervals. RESULTS: Seventeen patients from each group were included in the final analysis. During follow-up, two patients (11.8%) from group A and four patients (23.5%) from group B experienced relapses (p=0.65). Myelosuppression occurred in two patients (11.8%) from each group. Absolute neutrophil counts in group A tended to have lower median values than those in group B, particularly four weeks after AZA initiation. Univariate analysis identified serum proteins, albumin, and bilirubin as significantly associated with leukopenia, but these factors were not significant according to multivariate analysis. CONCLUSIONS: The incidence of myelosuppression was similar between the groups. Patients with full-dose initiation of AZA had numerically fewer relapses during the follow-up period.

Evaluation of the Utility of Amino Acid Citrulline as a Surrogate Metabolomic Biomarker for the Diagnosis of Celiac Disease.

INTRODUCTION: Citrulline is regarded as a biomarker for celiac disease (CD). Its utility for assessment and evaluation of additive predictive value for latent, potential CD and first degree relatives (FDRs) needs exploration. METHOD: Consecutive 558 index cases diagnosed as per European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) 2012 guidelines and their 1565 FDRs were evaluated over five and half year period. Serology negative FDRs at initial visit and follow ups were served as controls. HLA typing for DQ2 and DQ8 genotypes, along with plasma and dried blood spot (DBS) filter paper citrulline were evaluated. RESULTS: Median plasma citrulline values were 20.1 and 37.33 µMol/l in cases and controls (P < .001). Cut off values for Marsh grade 3a, 3b, and 3c were 35.0, 32.8, 25.26 µMol/l in CD patients and 36.51, 30.10, 25.26 µMol/l in biopsy proven FDR. Increasing trends of plasma citrulline levels with decreasing tTG-IgA levels were observed on follow up. Low plasma citrulline levels were observed with HLA DQ 2.5 genotype (P < .05). Agreement between DBS and plasma citrulline was 94.8%. CONCLUSION: Citrulline is a good surrogate biomarker for identification of histopathological grade of damage, extent of mucosal recovery and has negative correlation with tTG-IgA. It identifies the silent and latent phase of CD. DBS citrulline provides adequate information and can be used for monitoring CD patients at remote locations.

Role of linear endosonography in the diagnosis of biopsy-negative malignant esophageal strictures: Exploring the unexplored.

BACKGROUND AND AIM: Endoscopic biopsy is standard for the diagnosis of esophageal malignancy. However, few cases present with smooth stricture with repetitive negative biopsy results. We aimed to use linear endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) in the diagnosis of biopsy-negative suspected malignant esophageal strictures. METHODS: We retrospectively analyzed the data from August 2017 to December 2018 of biopsy-negative esophageal strictures. All adult patients with twice-negative biopsies and with smooth overlying esophageal mucosa on endoscopy were included. Clinical, epidemiological, endoscopic, imaging, and EUS findings were noted and analyzed. RESULTS: Eighteen patients underwent EUS for suspicion of malignant esophageal stricture. Seven were excluded as they were submucosal tumors. Eleven patients showed the presence of malignancy on EUS FNA samples. Nine were males. Computed tomography showed esophageal wall thickening in eight (16-38 mm) and esophageal mass in three patients. EUS showed loss of a normal five-layered wall structure of the esophagus in all patients. Fine-needle aspiration cytology demonstrated squamous cell carcinoma (n = 4), adenocarcinoma (n = 4), poorly differentiated carcinoma (n = 2), and neuroendocrine carcinoma (n = 1). There were no complications. CONCLUSION: EUS with FNA is effective and safe for the diagnosis of biopsy-negative malignant esophageal strictures.

Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H2 receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.

Tissue Xpert® MTB/RIF Assay in Peritoneal Tuberculosis: To be (Done) or Not to be (Done).

Introduction Peritoneal tuberculosis (PTB) is a paucibacillary disease with poor mycobacterial yield in ascitic fluid. The Xpert® MTB/RIF assay (Gene Xpert) is a new tool for the diagnosis of tuberculosis (TB) and has not yet been studied on peritoneal tissue. The present study aimed to investigate the yield of the Xpert® MTB/RIF assay on peritoneal tissue obtained at peritoneoscopy. Methods This is a retrospective study and the data were collected from hospital records. The patients who underwent peritoneoscopy along with Xpert® MTB/RIF assay on peritoneal tissue were included in this study. Those with proven PTB were considered as cases while those with other diagnoses as controls. Using the reference standard of TB diagnosis, sensitivity, specificity, and accuracy of Xpert® MTB/RIF assay were calculated. Results Total of 36 patients was analyzed in this study: 28 as cases and eight as controls. Peritoneoscopy was carried out for diagnosis and biopsy. Histopathology in cases revealed caseating granulomas in 16 while 11 had non-caseating granulomas. Nine patients showed acid-fast bacillus positivity on peritoneal tissue. The most common finding on peritoneoscopy was tubercles with adhesions (n = 14, 50%), followed by tubercles only (n = 12, 42.9%). Xpert® MTB/RIF assay was positive in 17 (60.7%) patients with a sensitivity of 60.71%, specificity of 100%, and an accuracy of 69.44%. Two patients expressed rifampicin resistance. Conclusion Xpert® MTB/RIF assay on peritoneal tissue has fair sensitivity and excellent specificity. The multidrug resistance and the ability to provide results rapidly make it clinically useful.

Cytopreparation of duodenal biopsy fixative improves detection rate of giardia in clinically suspected cases.

INTRODUCTION: Giardia intestinalis is a flagellated protozoan, frequently documented as an agent for enteric illness worldwide. Laboratory procedures for diagnosis include stool examination, antigenic detection assays and, at times, mucosal biopsy. We hypothesised that the formalin fixative used as a preservative for mucosal biopsy can be a good diagnostic sample for detecting surface mucosal and luminal infective agents such as giardia. The aim of the study was to find out the utility of processing the remaining formalin fixative as a complementary diagnostic method for detecting giardia. METHODS: This study included 200 cases of duodenal biopsies sampled over 6 months. The biopsies were picked up using clean forceps and the remaining fixative was processed using standard cytospin protocol. The cytospin preparation and formalin-fixed paraffin-embedded tissue sections were examined by two pathologists independently blinded to each others findings. RESULTS: On cytology, trophozoites of giardia were detected in 23 out of 200 cases (11.50%). The cytomorphology of pear-shaped organism with paired flagella and nuclei is very diagnostic. One case also showed presence of cryptosporidium spores. No other intestinal parasite was seen. Out of the 23 positive cytology samples, only 12 (6%) corresponding formalin-fixed paraffin-embedded tissue sections showed presence of giardia. CONCLUSION: Concurrent examination of duodenal biopsy and the formalin fixative cytopreparation in cases with high index of clinical suspicion of giardiasis proved to be a useful adjunct to biopsy diagnosis of giardiasis, which was statistically significant (P < .0001). This approach adds negligible cost and effort but with good diagnostic yield. We recommend that the formalin cytopreparation be used as a complementary technique to biopsy for cases suspected of intestinal parasitic infection.

INASL Guidelines on Management of Hepatitis B Virus Infection in Patients receiving Chemotherapy, Biologicals, Immunosupressants, or Corticosteroids.

Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.

Esophageal tuberculosis: Uncommon of common.

BACKGROUND AND AIM: Esophageal involvement in tuberculosis (TB) is rare and is usually secondary. Data on esophageal TB are scarce. We aimed to analyze clinical and endoscopic features and outcomes of treatment in esophageal TB. METHODS: We retrospectively identified patients with esophageal TB from January 2014 to December 2016 at GB Pant Hospital. Well-defined granuloma with or without caseation and/or acid-fast bacilli on staining either from esophageal biopsy or the adjacent mediastinal lymph node fine-needle aspiration cytology (FNAC) specimen, along with clinical features and response to antitubercular therapy (ATT), were collectively considered to diagnose definite TB. Treatment received and response to therapy were documented and analyzed. RESULTS: A total of 19 patients had definite esophageal TB, and the median age of patients was 39 years (14-65 years) and 10 (52.6%) patients were female. The most common presenting symptom was dysphagia (n = 16, 84%) followed by odynophagia (n = 8, 42%). On endoscopy, the mid-esophagus was the most common site of involvement, and findings included ulcers (n = 17), elevated lesions (n = 9), and fistulae (n = 4) in patients. The mediastinal lymphadenopathy was present in all patients, with parenchymal lesions seen in three patients. The endoscopic mucosal biopsies were diagnostic in 11 patients, and in the remaining 8 patients, endoscopic ultrasound-guided FNAC from the mediastinal lymph nodes was diagnostic. A total of 18 patients completely responded to ATT, and 1 patient had partial response with persistent fistulae requiring additional treatment. CONCLUSION: Esophagus involvement is rare in TB; endoscopic mucosal biopsy and EUS-guided FNAC is diagnostic, and the response to ATT is excellent.

Incidentally detected asymptomatic hepatitis C virus infection with significant fibrosis: Possible impacts on management.

BACKGROUND AND AIMS: Liver biopsy may be considered in patients with hepatitis C virus (HCV) infection to assess the severity of liver injury and stage of fibrosis, thereby guiding therapeutic decisions. In addition, advanced stage also necessitates surveillance for hepatocellular carcinoma. The aim of this study was to assess whether transaminase (alanine transaminase [ALT]) levels and RNA titers correlate with the histological activity index (HAI) and fibrosis (F) stage in asymptomatic patients with incidentally detected HCV (IDHCV). PATIENTS AND METHODS: Retrospective evaluation of liver biopsies was done in 113 patients with IDHCV, diagnosed during routine screening. Decision of liver biopsy was made on the basis of age, genotype, acceptable clinical, hematological, and biochemical profiles, and willingness of the patients to undergo treatment. Serum ALT levels, HCV RNA titers, and genotypes were correlated with HAI and F stage. RESULTS: Genotyping was done in 77 of the 113 patients, of which genotype 3 was seen in 43 and genotype 1 in 25 patients. A higher fibrosis stage (Ishak's >F2) was noted in 23.8% of the biopsies. Serum ALT showed a significant correlation with the HAI score on liver biopsy (P = 0.01) but not with the stage of fibrosis (P = 0.52). HCV RNA titers did not reveal any correlation with HAI score or fibrosis stage. CONCLUSION: Serum transaminases and HCV RNA titers are poor predictors of disease severity and fibrosis. Since HCV shows a slow disease progression, higher stage may predict a worse prognosis irrespective of the low viral RNA load. Liver biopsy may help guide therapeutic decisions in IDHCV infection.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: management.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: Management.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Gluten-Free hepatomiracle in "celiac hepatitis": A case highlighting the rare occurrence of nutrition-induced near total reversal of advanced steatohepatitis and cirrhosis.

Regression of hepatic fibrosis is increasingly becoming a reality, both in clinical as well as experimental models. Reversal or near-total regression of marked liver steatohepatitis and fibrosis, however, remains a rare event. We report the case of a 20-year-old female presenting with diarrhea due to celiac disease and biopsy proven cirrhosis with portal hypertension who had a remarkable clinical improvement in response to a gluten free diet (GFD). A follow-up liver biopsy 9 months after the initiation of GFD revealed a remarkable regression of both fibrosis as well as steatosis. Villous atrophy, as seen in patients with celiac disease, could lead to a deprivation of trophic factors leading to liver injury and subsequent cirrhosis. A gluten-free dietary regimen can produce a reversal of fibrosis leading to the amelioration of symptoms associated even with advanced liver disease.

Rectal tuberculosis after infliximab therapy despite negative screening for latent tuberculosis in a patient with ulcerative colitis.

Tumor necrosis factor-α inhibitors are now considered as standard therapy for patients with severe inflammatory bowel disease who do not respond to corticosteroids, but they carry a definite risk of reactivation of tuberculosis. We present a case in which a patient with inflammatory bowel disease developed a de novo tuberculosis infection after the start of anti-tumor necrosis factor-α treatment despite showing negative results in tuberculosis screening. Although there are many case reports of pleural, lymph nodal and disseminated tuberculosis following infliximab therapy, we present the first case report of rectal tuberculosis following infliximab therapy.

Short-term prognosis of potential celiac disease in Indian patients.

BACKGROUND: Progression of potential celiac disease (PCD) to overt celiac disease (CD) has been described in some studies from the Western Hemisphere. There are no Asian data on this aspect of CD. OBJECTIVE: We aimed to study the short-term histological course of PCD in Indian patients. METHODS: Patients with PCD were prospectively identified by screening relatives of patients with CD, the diarrheal subtype of irritable bowel syndrome (IBS-D) and patients with iron deficiency anemia (IDA). Patients with serology that was positive for immunoglobulin A antibodies against tissue transglutaminase (IgA anti-tTG) were subjected to endoscopy with duodenal biopsy. PCD was defined as a Marsh-0 to Marsh-II lesion on duodenal biopsy, along with positive IgA tTG serology. Retesting for serology and histology was done at 6-month intervals, for 12 months. RESULTS: We diagnosed 57 patients (23 male) of mean age 28.7 years (range: 4-73 yrs) as having PCD. Of these 57 patients, 28 were identified by screening 192 first-degree relatives of 55 index cases of CD, while the remaining 29 had either IBS-D or IDA. Duodenal biopsy showed Marsh-0, Marsh-I and Marsh-II changes in 28, 27 and 2 patients, respectively. At 6 months, 12 patients became seronegative. The remaining 45 patients continued to be seropositive at the 12-month time point. Histological progression to Marsh-III occurred in only four patients, while progression from Marsh-0 to either Marsh-I or Marsh-II occurred in six patients and one patient, respectively; but 14 patients with Marsh-I did show regression to Marsh-0. Of the two patients who were initially Marsh-II, one remained so upon follow up and one showed regression to Marsh-0. CONCLUSIONS: Our data suggested that despite the fact that nearly 80% of the patients diagnosed to have PCD continue to remain seropositive for tTG 12 months later, histological progression to Marsh-III occurred in only 7% of patients over the same time period. These observations do not justify starting a gluten-free diet in all patients with PCD, in India.

Indian Society of Gastroenterology consensus statements on Crohn's disease in India.

In 2012, the Indian Society of Gastroenterology's Task Force on Inflammatory Bowel Diseases undertook an exercise to produce consensus statements on Crohn's disease (CD). This consensus, produced through a modified Delphi process, reflects our current recommendations for the diagnosis and management of CD in India. The consensus statements are intended to serve as a reference point for teaching, clinical practice, and research in India.