Implications of Gender on the Outcome in Patients With Autoimmune Hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is uncommon and predominantly affects females. Data on AIH from India are scanty. We retrospectively analyzed the spectrum and outcome of adults with AIH and compared it between male and female patients. METHODS: AIH was diagnosed using a simplified AIH score. For suspected seronegative AIH, the revised score was used. Standard therapies for AIH and portal hypertension were administered and response was assessed at six months. Relapse rates and five-year mortality were also evaluated. RESULTS: Of the 157 patients with AIH, 85 (male: female 25: 60) were included in the study. The median age at diagnosis was 46 (interquartile range (IQR) 32-55.5) years in males vs 45 (IQR 34.2-54) years in females (p=0.91). A similar proportion of male and female patients presented with cirrhosis, acute severe AIH, or AIH-related acute on chronic liver failure (ACLF); Extra-hepatic autoimmune diseases were less common in male patients (16% vs 35.5% p=0.02). Other laboratory and histological features were comparable in both groups. During the median follow-up period of 51 months (IQR 45-67 months). The biochemical and clinical response at six months were seen in 64% of male patients and 63.3% of female patients (p= 0.57). Of patients, 75% relapsed in the male AIH group (12 of 16 patients) after initial remission compared to 42% in the female group (p=0.02). Five-year mortality was 14.1%, and no patient developed hepatocellular carcinoma. CONCLUSION: Male and female patients with AIH have similar clinical, biochemical, and histological profiles. More male patients relapsed after an initial response to therapy.

Acute Hepatitis E Virus Infection Triggering Autoimmune Hepatitis in a Patient With Chronic Liver Disease: Case Report and the Review of the Literature.

Acute viral hepatitis E (HEV) is the most common form of acute viral hepatitis in India. It is associated with self-limiting disease in most cases. However, the chronic form of HEV is also being increasingly recognized. Other viral infections like the hepatitis A virus (HAV) have been implicated in inciting autoimmune hepatitis. HEV infection has been associated with the formation of circulating liver-directed autoantibodies, however autoimmune liver disease following acute HEV infection has been rarely reported. Here we present a case of a 72-year-old diabetic lady who presented to us with an asymptomatic rise of liver enzymes. Investigations suggested metabolic dysfunction associated with steatotic liver disease. After three months of the diagnosis, she developed acute-on-chronic liver failure and her anti-HEV came out positive. She was managed accordingly. Afterwards patient had persistent high liver enzymes, so she underwent a liver biopsy. Her liver biopsy was compatible with autoimmune hepatitis.

Capsule endoscopy for obscure gastrointestinal bleed in the tropics: A single-center experience on 350 patients.

BACKGROUND: Obscure gastrointestinal bleed (OGIB), now called small bowel bleed (SBB), comprises 5% to 10% of all gastrointestinal (GI) bleed episodes and capsule endoscopy (CE) is a tool for its evaluation. Studies on CE in a large sample of SBB patients from the tropics are limited. METHODS: We did a retrospective analysis of a prospectively maintained database of patients with SBB undergoing CE using PillCam or MiroCam CE. RESULTS: Of 350 patients (age 52.4 ± 17.4 years; 248 [70.9%] male) undergoing CE, 243 (69.4%) and 107 (30.6%) had overt and occult SBB, respectively. CE detected lesions in 244 (69.7%) patients (single lesion in 172 [49.1%]; multiple in 72 [20.6%]). The single lesions included vascular malformations (52, 14.9%), ulcer/erosion (47, 13.4%), tumor (24, 6.9%), hookworm (19, 5.4%), stricture (15, 4.3%), hemobilia (1, 0.3%) and blood without identifiable lesion (9, 2.6%). Of 72 with multiple lesions, ulcer with stricture was the commonest finding (n = 43, 12.3%). No abnormality was detected in 106 (30.3%) patients. The frequency of lesion detection was comparable among patients with overt and occult SBB (173/243, 71.2% vs. 71/107, 66.3%, respectively; p = 0.4). Younger patients (0 to 39 years) more often had multiple lesions on CE than the older (≥ 40 years) ones (26/76, 34.2% vs. 46/228, 20.2%, respectively; p = 0.001). CONCLUSION: CE has a high diagnostic yield in SBB in the tropics, regardless of the type of bleed or of CE brand and the duration of recording. Multiple lesions associated with SBB are commoner among younger (< 40 years) patients.

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.

ORMDL3 regulates NLRP3 inflammasome activation by maintaining ER-mitochondria contacts in human macrophages and dictates ulcerative colitis patient outcome.

Genome-wide association studies in inflammatory bowel disease have identified risk loci in the orosomucoid-like protein 3/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) gene to confer susceptibility to ulcerative colitis (UC), but the underlying functional relevance remains unexplored. Here, we found that a subpopulation of the UC patients who had higher disease activity shows enhanced expression of ORMDL3 compared to the patients with lower disease activity and the non-UC controls. We also found that the patients showing high ORMDL3 mRNA expression have elevated interleukin-1ß cytokine levels indicating positive correlation. Further, knockdown of ORMDL3 in the human monocyte-derived macrophages resulted in significantly reduced interleukin-1ß release. Mechanistically, we report for the first time that ORMDL3 contributes to a mounting inflammatory response via modulating mitochondrial morphology and activation of the NLRP3 inflammasome. Specifically, we observed an increased fragmentation of mitochondria and enhanced contacts with the endoplasmic reticulum (ER) during ORMDL3 over-expression, enabling efficient NLRP3 inflammasome activation. We show that ORMDL3 that was previously known to be localized in the ER also becomes localized to mitochondria-associated membranes and mitochondria during inflammatory conditions. Additionally, ORMDL3 interacts with mitochondrial dynamic regulating protein Fis-1 present in the mitochondria-associated membrane. Accordingly, knockdown of ORMDL3 in a dextran sodium sulfate -induced colitis mouse model showed reduced colitis severity. Taken together, we have uncovered a functional role for ORMDL3 in mounting inflammation during UC pathogenesis by modulating ER-mitochondrial contact and dynamics.

Post-infection irritable bowel syndrome following Coronavirus disease-19: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Persistent gastrointestinal (GI) symptoms and functional gastrointestinal disorders (FGIDs) are increasingly being recognized after Coronavirus disease-19 (COVID-19). Though quite a few studies addressed irritable bowel syndrome (IBS) following COVID-19, the disorders' prevalence varies greatly. We evaluated, (i) overall frequency of post-COVID-19 IBS, (ii) relative risk of development of IBS among COVID-19 patients compared to healthy controls using systematic review and meta-analysis techniques. METHODS: Literature search was performed for studies on GI symptoms and FGIDs after COVID-19 using electronic databases (Medline, Scopus, Cochrane Central Register of Controlled Trials, Google Scholar and Web of Science) till April 28, 2023. We included studies reporting IBS after COVID-19 with any duration of follow-up and any number of subjects. Studies on pediatric population and those not providing relevant information were excluded. Relative risk of development of IBS using Rome criteria among COVID-19 patients compared to healthy controls was calculated. Analysis was done using MedCalc (Applied Math, Mariakerke, Belgium, version 7.2) and Comprehensive Meta-Analysis version 3.3.070 (Biostat Inc. Englewood, NJ 07631, USA). RESULTS: Of the available studies, 13 (four case-control) reporting on IBS after COVID-19 met inclusion criteria. Among 3950 COVID-19 patients and 991 controls, 7.2% of COVID-19 patients and 4.9% of healthy controls developed IBS. Of the four case-control studies reporting post-COVID-19 IBS, patients with COVID-19 were 2.65 (95% confidence interval [CI] 0.538 to 13.039) times more likely to have post-COVID-19 IBS as compared to healthy controls. CONCLUSIONS: Patients with COVID-19 are more likely to develop post-COVID-19 IBS than healthy controls. The heterogeneity of studies, different criteria used by various studies to diagnose post-COVID-19 IBS and some studies not meeting the six-month follow-up duration of the Rome criteria for diagnosing IBS are limitations of this systematic review.

FODMAP meal challenge test: a novel investigation to predict response to low-FODMAP diet in non-constipating irritable bowel syndrome.

BACKGROUND: Though a low-FODMAP diet improves 50% irritable bowel syndrome (IBS) patients, regional dietary variations, vegetarianism, and long-term nutritional consequences challenge its implementation. We aimed developing a FODMAP meal challenge test (FMCT). We prospectively studied whether (i) high- than low-FODMAP foods produce more breath H2 among IBS patients than controls; (ii) post-meal symptoms relate to breath H2 ; and (iii) novel FMCT predicts response to a low-FODMAP diet? METHODS: Forty Rome III IBS and 20 healthy controls underwent an eight-hour H2 breath test following a low- (rice, brinjal, corn, and banana [450 Kcal]) and a high-FODMAP meal (wheat, kidney bean, pulse, and card [450 Kcal]). Breath H2 (every 15 min) and symptoms following low- and high-FODMAP meals were recorded. IBS-symptom severity scores were recorded every month for 3-months on low-FODMAP diet. RESULTS: Forty Rome III IBS (19 Rome IV positive) were comparable to 20 controls in age and gender. IBS patients (n = 39 excluding one H2 non-producer) and controls produced more breath H2 after high- (greater in IBS) than low-FODMAP meal. Post-meal symptoms were commoner in IBS (4/40 [10%] and 27/40 [67.5%] with low- and high-FODMAP, respectively [P < 0.00001]; none in healthy). IBS patients developing post-high-FODMAP meal symptoms produced greater H2 (18 PPM [IQR 10.5-23] vs 6 [0-7.2]; P < 0.001). A positive FMCT (breath H2  > 10 PPM above basal with symptoms following high-FODMAP food) had sensitivity, specificity, and diagnostic accuracy of 78.6%, 66.6%, and 75.6%, respectively, to predict low-FODMAP diet response. CONCLUSIONS: The novel FMCT predicts response to a low-FODMAP diet in IBS.

Trends and clinico-epidemiological profile of patients with Giardiasis: Five-year experience from a university hospital of northern India.

Background: Giardiasis is an important cause of diarrheal disease and is associated with morbidity in children and adults worldwide. We aimed to study the prevalence of Giardiasis, its clinical presentations, seasonal trends in detection, and coinfection with other intestinal parasites along with comparison of fecal antigen and microscopy for the detection of Giardiasis. Materials and Methods: It is a retrospective study conducted from Jan. 2017 to Dec. 2021 at our university hospital. Iodine and normal saline mounts and enzyme-linked immunosorbent assay (ELISA) were used for the detection of Giardiasis in stool samples. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of tests were computed. Results: Of 8364 patients, 432 (5.2%) had Giardiasis by microscopy and/or ELISA. Giardiasis was more common in males compared to females (318/5613 [5.6%] vs. 114/2751 [4.1%]; P = 0.003) and among those ≤10 y compared to older individuals (102/560 [18.2%] vs. 330/7804 [4.2%]; P <0.0001). Most cases were detected in the month of May to October. The most common clinical presentation was diarrhea (80.1%) and abdominal pain (72.9%) followed by malnutrition (60.2%) and loss of appetite (46.8%). Using microscopy as gold standard, sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ELISA were 95%, 91%, 91%, 95%, and 93%, respectively. Conclusion: Awareness and knowledge amongst the primary healthcare professionals and family physicians will help in early diagnosis and treatment of Giardiasis. Fecal antigen detection should be done along with microscopy for detection of Giardiasis.

Tofacitinib in Steroid-Refractory Acute Severe Ulcerative Colitis: A Retrospective Analysis.

INTRODUCTION: Steroid-refractory acute severe ulcerative colitis (ASUC) patients are at the highest risk of colectomy. Among the available options, cyclosporine and infliximab have similar efficacy but infliximab is a costly drug and cyclosporine has multiple side effects like kidney injury, neurotoxicity, and dyselectrolytemia. Surgical management is often associated with higher morbidity. Newer oral small molecules like Janus kinase inhibitors are the ideal molecules to bridge the gap. Tofacitinib has already been extensively evaluated in patients with moderate to severe UC; however, data on ASUC treated by tofacitinib are limited. METHODS: We retrospectively analyzed the data of patients with ASUC who were admitted to our hospital's luminal gastroenterology unit between January 2021 and July 2023. Patients with ASUC who were managed with tofacitinib were included in the study. RESULTS: Eight patients with ASUC were identified who did not respond to intravenous hydrocortisone and were treated with tofacitinib. The mean age was 39 ± 15 years and 87.5% were female. The median duration of illness was 24 months (interquartile range (IQR): 12-120 months). Seven of eight patients (87.5%) responded to oral tofacitinib 10 mg twice a day by the fifth day of treatment. The median follow-up period was six months (IQR: 1-12 months). One patient required colectomy and one patient had varicella zoster reactivation requiring treatment discontinuation. CONCLUSION: Tofacitinib is an attractive alternative to the currently available salvage therapy for steroid-refractory ASUC; however, long-term efficacy and risk remain to be explored.

Budd Chiari Syndrome with Portal Vein Thrombosis Managed Successfully with Direct Intrahepatic Portosystemic Shunt: A Case Report and Review of the Literature.

Budd -Chiari syndrome (BCS) is a hepatic vascular disorder which affects hepatic veins or inferior vena cava. Portal vein thrombosis (PVT) occurs in around 15%-25% of patients with BCS. The presence of PVT in patients with BCS makes it more difficult to intervene radiologically. We present a case of a BCS-related chronic liver disease that presented with a history of variceal upper gastrointestinal bleeding and worsening ascites. The patient had thrombosed hepatic veins (HV) and partial right portal vein thrombosis. He was started on anticoagulation, and treatment for portal hypertension was initiated. Given the inaccessibility of all the HVs for trans-jugular intrahepatic portosystemic shunts (TIPS), the patient underwent direct intrahepatic portosystemic shunts (DIPS). Next-generation sequencing identified the factor V Leiden mutation. Following DIPS, the patient's ascites disappeared, and liver function tests improved. On a nine-month follow-up, the patient was symptom-free with a patent DIPS. DIPS has been widely used in patients with BCS with thrombosed hepatic veins, but there are only a few case reports on the feasibility of DIPS in BCS patients with PVT. This is one of the very few case reports where a patient with BCS-PVT was successfully managed with DIPS.

Gastrointestinal involvement in post-acute Coronavirus disease (COVID)-19 syndrome.

PURPOSE OF REVIEW: Ten percentage of patients with coronavirus disease (COVID)-19 report having gastrointestinal (GI) symptoms as severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) not only infects the pulmonary but also the GI tract. GI infections including that due to viral infection is known to cause postinfection disorders of gut-brain interaction (DGBI); hence, we wish to review the long-term GI consequences following COVID-19, particularly post-COVID-19 DGBI. RECENT FINDINGS: At least 12 cohort studies, four of which also included controls documented the occurrence of post-COVID-19 DGBI, particularly IBS following COVID-19. The risk factors for post-COVID-19 DGBI included female gender, symptomatic COVID-19, particularly GI symptoms, the severity of COVID-19, the occurrence of anosmia and ageusia, use of antibiotics and hospitalization during the acute illness, persistent GI symptoms beyond 1 month after recovery, presence of mental health factors, The putative mechanisms for post-COVID-19 DGBI include altered gut motility, visceral hypersensitivity, gut microbiota dysbiosis, GI inflammation, and immune activation, changes in intestinal permeability, and alterations in the enteroendocrine system and serotonin metabolism. SUMMARY: Long-term sequelae of SARS-CoV2 infection may persist even after recovery from COVID-19. Patients with COVID-19 are more likely to develop post-COVID-19 IBS than healthy controls. Post-COVID-19 IBS may pose a substantial healthcare burden to society.