Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis.

BACKGROUND: Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). METHODS: This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. RESULTS: Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. CONCLUSION: The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.

Burden of Anxiety, Depression and Perceived Stress in Patients with Inflammatory Bowel Disease: A Cohort Study from North India.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India. METHODS: Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. RESULTS: A total of 318 patients (255 UC, 63 CD; mean age 40.13 ± 12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10 ± 2.35; and mean HBI 2.77 ± 2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14%, 12%, and 41%, respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ = 0.083, p = 0.187), depression (ρ = 0.123, p = 0.49) and perceived stress (ρ = 0.169; p = 0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ = 0.336, p = 0.007) and poorly with depression (ρ = 0.287, p = 0.022) and perceived stress (ρ = 0.20; p = 0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p = 0.001) and hand-grip strength (OR 4.63, 95% CI 1.88-11.42; p = 0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p = 0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p = 0.009) were significant predictors of anxiety in patients with CD. CONCLUSION: Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.

Tofacitinib Versus Oral Prednisolone for Induction of Remission in Moderately Active Ulcerative Colitis [ORCHID]: A Prospective, Open-Label, Randomized, Pilot Study.

BACKGROUND: Oral corticosteroids are first-line agents to induce remission in moderately active ulcerative colitis [UC], but are associated with adverse effects. We compared the efficacy and safety of tofacitinib and prednisolone for induction of remission in moderately active UC. METHODS: This was a single-centre, prospective, open-label, randomized, active-controlled pilot study. Eligible patients [aged ≥18 years] had moderately active UC. Participants were randomly assigned to receive either prednisolone [40 mg daily, tapered by 5 mg every week] or tofacitinib [10 mg twice daily] for 8 weeks. The primary endpoint was composite remission [defined as total Mayo clinic score ≤2, with endoscopic sub-score of 0 and faecal calprotectin <100 µg/g] at 8 weeks. RESULTS: Seventy-eight patients were randomly assigned to either of the treatment groups. At week 8, the proportion of patients achieving composite remission in the tofacitinib [7/43, 16.28%] and prednisolone groups [3/35, 8.57%] were not significantly different (odds ratio [OR] 2.07, 95% confidence interval [CI] 0.49-8.70; p = 0.31). The time to achieve symptomatic remission [normal stool frequency with absence of rectal bleeding] was similar (10 days, interquartile range [IQR 7-18.75] and 10 days [IQR 5-12.5] for tofacitinib and prednisolone, respectively; p = 0.25) in the two groups. One patient each in the tofacitinib and prednisolone group discontinued treatment due to development of pulmonary tuberculosis and pustular acne, respectively. One patient receiving tofacitinib developed herpes zoster, but did not require cessation of therapy. No serious adverse events or major adverse cardiovascular events were observed. CONCLUSION: In patients with moderately active UC, there was no difference in the efficacy and safety of tofacitinib and oral prednisolone for induction of remission at 8 weeks. TRAIL REGISTRATION: Clinical Trials Registry of India [CTRI/2021/10/037641].

Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial.

INTRODUCTION: Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. METHODS: This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. RESULTS: A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. DISCUSSION: In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

Clinical and magnetic resonance imaging spectrum of complex perianal fistulizing Crohn's disease: A cohort study from northern India.

BACKGROUND: Fistulizing perianal Crohn's disease (CD) is a debilitating condition associated with significant morbidity and reduction in the quality of life. Magnetic resonance imaging (MRI) of the pelvis is the preferred imaging modality for the comprehensive assessment of the perianal fistula. There is a paucity of data from India on the MRI spectrum of complex perianal fistula in CD. METHODS: A single-centre cross-sectional analysis of patients with fistulizing perianal CD, who underwent pelvic MRI between January 2020 and December 2021, was performed. The clinical (age, sex, disease duration, disease location and behavior, disease activity [Perianal Disease Activity Index, PDAI] and treatment received) and radiological (number and location of fistulae, extensions, number and location of internal and external openings, fistula activity, presence or absence of perianal abscess and associated proctitis) characteristics of complex perianal fistula (defined according to the American Gastroenterological Association classification) were recorded. RESULTS: Of total 175 patients with CD who attended the gastroenterology clinic during the study period, 27 (15.42%) (mean age 42±15.5 years, 62.96% females and median disease duration four years) had complex perianal fistula and were included in the analysis. The mean PDAI was 5.48±2.53. The median Van Assche Index was 17 (interquartile range [IQR] 13-19). A majority (96.29%) of the fistulae were trans-sphincteric and four (14.81%) fistulae extended into the supralevator space. All fistulae were active on MRI. Concomitant perianal abscess and proctitis were seen in 59.26% (n=16) and 62.96% (n=17) of patients, respectively. Combination therapy with biologics and antibiotics/immune-suppressants were the most commonly prescribed medical therapy. Six (22.22%) patients underwent combined medical and surgical (non-cutting seton, fistulectomy, fecal diversion) treatment. CONCLUSION: The cumulative risk of the development of fistulizing perianal CD in a northern Indian cohort was similar to the western populations. Complex perianal fistulae were predominantly trans-sphincteric and commoner in females. MRI evaluation is pivotal for the delineation of fistula anatomy, assessment of disease extent and activity and the evaluation of concomitant perianal abscess and other complications.

Inflammatory bowel disease (IBD)-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD.

BACKGROUND/AIMS: The inflammatory bowel disease (IBD)-disk is a validated, visual, 10-item, self-administered questionnaire used to evaluate IBD-related disability. The present study aimed to evaluate IBD-disk in assessment of IBD daily life burden and its relation with disease activity. METHODS: A cross-sectional study was conducted between June 2021 and December 2021. Patients with IBD were asked to complete the IBD-disk and a visual analogue scale of IBD daily-life burden (scored from 0-10, score >5 indicative of high burden). The internal consistency of IBD-disk, correlation with IBD daily life burden and disease activity (assessed by partial Mayo score and Harvey Bradshaw Index in patients with ulcerative colitis [UC] and Crohn's disease [CD], respectively) and diagnostic performance of IBD-disk to detect high burden were analyzed. RESULTS: Out of the 546 patients (mean age 40.33±13.74 years, 282 [51.6%] males) who completed the IBD-disk, 464 (84.98%) had UC and the remaining (n=82, 15.02%) had CD. A total of 311 patients (291 UC and 20 CD; 56.95%) had active disease. The mean IBD-disk total score and IBD daily life burden were 18.39±15.23 and 2.45±2.02, respectively. The IBD-disk total score correlated strongly with the IBD daily life burden (ρ=0.94, P<0.001), moderately with partial Mayo score (ρ=0.50) and weakly with Harvey Bradshaw Index (ρ=0.34). The IBD-disk total score >30 predicted high IBD daily-life burden. CONCLUSIONS: The IBD-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD and can be applied in clinical practice. (Intest Res, Published online).

Evaluation of Nutritional Characteristics Reveals Similar Prevalence of Malnutrition in Patients with Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of malnutrition and sarcopenia. AIMS: To evaluate the nutritional status of patients with IBD and determine the threshold values of different parameters of nutritional assessment to identify malnutrition. METHODS: This was a single-centre cross-sectional analysis of adult patients with IBD [ulcerative colitis (UC) and Crohn's disease (CD)] who underwent anthropometry [body mass index (BMI), mid upper arm circumference (MUAC) and triceps-fold thickness (TSF)], body composition analysis and assessment for sarcopenia [hand-grip strength and skeletal muscle index (SMI) at L3 vertebral level)]. Age- and gender-matched healthy adults served as controls. Malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. RESULTS: A total of 406 patients [336 (82.76%) UC and 70 (17.24%) CD; mean age 40.56 ± 13.67 years; 215 (52.95%) males] with IBD and 100 healthy controls (mean age 38.69 ± 10.90 years; 56 (56%) males) were enrolled. The mean BMI, MUAC, TSF thickness, fat and lean mass, hand-grip strength, and SMI at L3 vertebral level were lower in patients with IBD compared to controls. The prevalence of malnutrition was similar in UC and CD [24.40% (n = 82) and 28.57% (n = 20), respectively (p = 0.46)]. Thresholds for fat mass in females (15.8 kg) and visceral fat index in males (0.26) were both sensitive and specific to detect malnutrition. The cutoff values of MUAC and TSF thickness to identify malnutrition were 23.25 cm and 25.25 cm, and 16.50 mm and 8.50 mm, in females and males, respectively. CONCLUSION: Malnutrition and sarcopenia were common in patients with IBD, with the prevalence being similar in patients with both UC and CD.

Clinical spectrum of elderly-onset inflammatory bowel disease in India.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India. METHODS: A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD. RESULTS: During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn's disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD. CONCLUSIONS: Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.

Correlation between magnetic resonance enterography and ileo-colonoscopy for assessment of disease activity in terminal ileal Crohn's disease.

BACKGROUND: Magnetic resonance enterography (MRE) has emerged as a novel tool for the assessment of disease activity in Crohn's disease (CD). Real world data from Indian subcontinent on performance of MRE in terminal ileal CD are lacking. METHODS: Retrospective analysis of patients with terminal ileal CD who underwent both ileo-colonoscopy and MRE was performed. Ileo-colonoscopy was considered the gold standard for assessment of disease activity. On ileo-colonoscopy, a simple endoscopic score for Crohn's disease (SES-CD) ≥2 was considered active disease; presence of ulcers indicated severe disease. MRE scoring of the disease activity was performed using magnetic resonance index of activity (MARIA) and simplified MARIA (MARIAs). The measure of agreement between ileo-colonoscopy and MRE and comparison of MARIA and MARIAs for assessment of disease activity and sensitivity of MRE to detect mucosal ulcerations were calculated. RESULTS: Seventy patients with terminal ileal CD (mean age 40.74±15.56 years; 71.4% males [n=50]) were evaluated. The sensitivities of MARIA and MARIAs scores to detect active disease were 0.76 and 0.84, respectively. The area under the receiver operating characteristic curve (AUROC) for detecting severe disease was 0.836 (p<0.0001) for MARIA and 0.861 (p<0.0001) for MARIAs. For mild active disease, there was no agreement between SES-CD and MARIA or MARIAs; however, for severe disease, the agreement was fair and moderate for MARIA and MARIAs, respectively. MARIA and MARIAs were comparable for identification of active and severe disease (κ 0.759, p<0.0001 and κ 0.840, p<0.0001, respectively). MRE was 68.18% sensitive to detect mucosal ulcers. CONCLUSION: MRE is a reliable and sensitive tool for detection of endoscopically severe, but not mild, terminal ileal CD.

Early fecal microbiome transfer after donor defecation determines response in patients with moderate to severe ulcerative colitis.

BACKGROUND: Fecal microbiome transfer (FMT) targeting gut microbiome dysbiosis is an emerging therapy for ulcerative colitis (UC). There is however no consensus on protocols for performing FMT in UC, especially in relation to time after donor feces defecation. METHODS: This is a single-center retrospective analysis of patients with moderate-severe UC (total Mayo Clinic score ≥6 and endoscopic Mayo Clinic subscore of ≥2) treated with FMT between September 2017 and December 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Fresh fecal samples from unrelated healthy voluntary donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. Time interval between donor feces defecation and FMT procedure was recorded for each FMT session and the mean time of seven sessions was designated aika. Impact of aika on clinical response and safety of FMT was evaluated. RESULTS: During the study period, 123 adult patients (mean age 33.75±11.97 years, 61.8% [n=76] males) with moderate-severe UC (mean total Mayo Clinic and endoscopic Mayo Clinic scores 7.49±1.60 and 2.50±0.50, respectively) were treated with FMT. The mean aika was 2.29±0.75 h. The aika was smaller in patients who responded to FMT as compared to non-responders (2.13±0.75 h vs. 2.71±0.76 h, p=0.0002) as well as in patients achieving clinical remission (2.15±0.76 h vs. 2.42±0.76 h, p=0.05). There was no significant impact of aika on adverse effects except for the incidence of borborygmi after FMT, which was higher in patients with aika ≤2 h. CONCLUSION: Early FMT after donor feces defecation favorably impacts the clinical response rates in patients with active UC.

Maintaining infliximab induced clinical remission with azathioprine and 5-aminosalicylates in acute severe steroid-refractory ulcerative colitis has lower cost and high efficacy (MIRACLE): a multicenter study.

BACKGROUND/AIMS: Infliximab (IFX) has been used to induce and maintain remission in patients with severe steroid-refractory ulcerative colitis (UC). Long-term use of biologics in developing countries is limited by high cost and frequent side effects. An optimal maintenance strategy in these patients needs to be established. METHODS: A retrospective analysis of maintenance of clinical remission with combination of azathioprine (AZA) and 5-aminosalicylates (5-ASA) in patients with severe steroidrefractory UC where IFX (5 mg/kg intravenously at weeks 0, 2, 6) had been used only as an induction therapy was done at 2 centers in India. Primary outcome was the proportion of patients maintaining corticosteroid-free sustained clinical remission (SCR) at the end of study period. Rates of relapse and cost of therapy were also analyzed. RESULTS: Of the 137 patients who received rescue IFX induction therapy, 77 (56.2%) achieved clinical remission (mean age 34.81 ± 13.32 years, 68.83% males, median follow-up 4 years, range 3 months to 6 years) and were included. Cumulative corticosteroid-free SCR was maintained in 68%, 59%, 42%, and 35% patients at 1, 2, 4, and 6 years respectively. Sixty-seven relapses were observed in 33 patients. Majority of the relapses (45/67, 67.16%) occurred within first 2 years of follow-up. Two relapses were managed with re-induction with IFX, one required colectomy, whereas all other responded to repeat course(s) of corticosteroids. Annual per capita maintenance therapy with 5-ASA and AZA was cheaper by US$ 4,526 compared to maintaining remission with IFX. CONCLUSIONS: Clinical remission achieved with IFX induction therapy in severe steroid-refractory UC can be sustained over long time with a combination of AZA and 5-ASA.

Trends of inflammatory bowel disease at a tertiary care center in northern India.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is increasingly being reported from India and other Asian countries. This study looks into the changing trends of IBD at a tertiary care center in north India over last two decades. METHODS: Retrospective analysis of a prospectively maintained database of patients diagnosed with IBD between January 1991 and December 2015 was conducted. The study period was divided into five times cohorts (1991-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015). RESULTS: During the study period, 2,467 patients (UC [n = 2,137, 86.6%], CD [n = 330, 13.3%], mean age 38.5 ± 13.3 years; 55.9% males) were registered. The proportion of patients with CD increased (ratio of UC to CD declined from 15.7:1 to 4:1). The mean age at diagnosis decreased for UC (45.7 ± 12.1 years in 1991-1995 vs. 37.6 ± 13.0 years in 2011-2015; P= 0.001) and remained consistent for CD (41.3 ± 13.6 years in 1996-2000 vs. 41.3 ± 16.9 years in 2011-2015, P= 0.86). Patients with proctitis in UC and isolated ileal disease in CD increased over the study period (P= 0.001 and P= 0.007, respectively). Inflammatory CD increased (P= 0.009) whereas stricturing CD decreased (P= 0.01) across all cohorts. There was a trend towards less severe presentation of both UC and CD. The use of thiopurines (P= 0.02) and biologics increased (P= 0.001) with no significant change in trends for requirements of surgery (P= 0.9). CONCLUSIONS: Increasing prevalence of CD, younger age at diagnosis, diagnosis at an earlier and milder stage, greater use of thiopurines and biologics were observed.

Clinical Predictors of response to Faecal Microbiota Transplantation in patients with active ulcerative colitis.

BACKGROUND: Fecal Microbiota Transplantation (FMT) has been shown to be effective for induction of remission in patients with active ulcerative colitis (UC). At present, clinical factors impacting the response to FMT in UC remain unclear. METHODS: Patients with active UC treated with multisession FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22, were analysed. Response to FMT was defined as achievement of corticosteroid free clinical remission at week 30. Patient and disease characteristics were evaluated to determine the predictors of response to FMT. RESULTS: Out of 140 patients with active UC treated with FMT, 93 patients [mean age 34.96±11.27 years, 62.36% males (n=58), mean Mayo clinic score 8.07±2.00] who completed the multi-session FMT protocol were analysed. Fifty-seven (61.29%) patients achieved clinical remission. Younger age (OR for age 0.93, 95% CI 0.89-0.97, p=0.001), moderate (Mayo clinic score 6-9) disease severity (OR 3.01, 95% CI 1.12 to 8.06, p=0.025) and endoscopic Mayo score 2 (OR 5.55, 95% CI 2.18-14.06, p<0.001) were significant predictors of remission on univariate analysis. Younger age, disease extent E2 and endoscopic mayo score 2 (OR 0.925, 95% CI 0.88-0.97, p=0.002; OR 2.89, 95% CI 1.01-8.25, p=0.04 and OR 8.43, 95% CI 2.38-29.84, p=0.001, respectively) were associated with clinical remission on multivariate logistic regression. A mathematical model (nomogram) was developed for estimating the probability of remission with FMT protocol. CONCLUSION: Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.

Incidental benefits after fecal microbiota transplant for ulcerative colitis.

Gut dysbiosis can result in several diseases, including infections (Clostridium difficile infection and infectious gastroenteritis), autoimmune diseases (inflammatory bowel disease, diabetes, and allergic disorders), behavioral disorders and other conditions like metabolic syndrome and functional gastrointestinal disorders. Amongst various therapies targeting gut microbiome, fecal microbiota transplantation (FMT) is becoming a focus in the public media and peer reviewed literature. We have been using FMT for induction of remission in patients with moderate to severe active ulcerative colitis (UC) and also for subsequent maintenance of remission. Four cases reported incidental benefits while being treated with FMT for UC. These included weight loss (n=1), improvement in hair loss (n=1), amelioration of axial arthritis (n=1) and improvement in allergic rhinitis (n=1), thereby suggesting potential clinical applications of FMT in treating extraintestinal diseases associated with gut dysbiosis.

Impact of "Sambhav" Program (Financial Assistance and Counselor Services) on Hepatitis C Pegylated Interferon Alpha Treatment Initiation in India.

BACKGROUND: Financial constraints, social taboos and beliefs in alternative medicine are common reasons for delaying or not considering treatment for hepatitis C in India. The present study was planned to analyze the impact of non-banking interest free loan facility in patients affected with hepatitis C virus (HCV) in North India. METHODS: This one year observational, retrospective study was conducted in Department of Gastroenterology (January 2012-December 2013), Dayanand Medical College and Hospital Ludhiana, to evaluate the impact of program titled "Sambhav" (which provided non-banking financial assistance and counselor services) on treatment initiation and therapeutic compliance in HCV patients. Data of fully evaluated patients with chronic hepatitis, and/or cirrhosis due to HCV infection who were treated with Peginterferon alfa and ribavirin (RBV) combination during this duration (2012-2013) was collected from patient medical records and analyzed. In the year 2012, eligible patients who were offered antiviral treatment paid for treatment themselves, while in 2013, 'Sambhav' program was launched and this provided interest free financing by non-banking financial company (NBFC) for the treatment of HCV in addition to free counselor services for disease management. The treatment initiation and compliance rates were compared between the patients (n = 585) enrolled in 2013 who were offered 'Sambhav' assistance and those enrolled in 2012 (n = 628) when 'Sambhav' was not available. RESULTS: Introduction of Sambhav program improved the rates of treatment initiation (59% in 2013 vs. 51% in 2012, P=.004). Of the 585 eligible patients offered 'Sambhav' assistance in 2013, 233 patients (39.8%) applied but 106/233 (45.4%) received assistance. Antiviral therapy was started in 93/106 (87.7%) of these patients, while only 52 (42.5%) of 127 patients whose applications were rejected underwent treatment. Compliance to antiviral therapy also improved with the introduction of 'Sambhav' program (87.7% vs. 74.1%, P=.001). CONCLUSION: 'Sambhav' program had significant impact on the initiation of antiviral therapy by overcoming the financial hurdles. The free counselor services helped to mitigate social taboos and imparted adequate awareness about the disease to the patients. Initiatives like 'Sambhav' can be utilized for improving healthcare services in developing countries, especially for chronic diseases.

Clinical profile of hepatitis C virus infection in a developing country: India.

BACKGROUND AND AIM: The epidemiology and clinical profile of hepatitis C virus (HCV) varies worldwide, and data from developing countries are sparse. The aim of the present study was to assess the clinical profile of HCV infection in a developing country in South-East Asia (India). METHODS: This observational study assessed patient demographics, viral characteristics, risk factors for virus acquisition, and disease characteristics in HCV patients diagnosed between January 2004 and December 2015. RESULTS: Of 8035 patients who were diagnosed with HCV infection, a majority were men (68.3%), middle aged (52.2%), and from low (34%) to middle (46%) socioeconomic status and rural population (69.8%). Eighty-two percent had identifiable risk factors, the most common being history of dental treatment (52%) and therapeutic injections with reusable syringes/needles (45%). Household contacts of index patients had high prevalence of HCV (15.3%). Common genotypes were genotype 3 (70.4%) and genotype 1 (19.3%). Although a majority of patients were either asymptomatic (54.8%) or had non-specific symptoms (6.7%) at presentation, a significant proportion (9.3%) had advanced liver disease. Presentation with cirrhosis (38.8%) was associated with male gender, higher age at time of virus detection, rural residence, alcohol or opium intake, and coinfections with hepatitis B virus or human immunodeficiency virus. CONCLUSIONS: Hepatitis C virus infection in northern India is seen more commonly in men, the middle aged and people from rural background and low to middle socioeconomic status. The common possible risk factors are dental treatment and exposure to reused syringes and needles. Although the most common presentation is incidental detection, a large number of patients present with advanced liver disease.

Results of sofosbuvir-based combination therapy for chronic hepatitis C cohort of Indian patients in real-life clinical practice.

BACKGROUND AND AIM: The introduction of sofosbuvir has revolutionized the treatment of chronic hepatitis C. This study was planned to observe whether the efficacy and tolerability of sofosbuvir-based regimens demonstrated in phase 3 clinical trial results translate into real-life clinical practice. METHODS: This prospective, non-randomized observational study conducted in Dayanand Medical College and Hospital, Punjab, included all consecutive treatment-naïve patients with chronic hepatitis C (genotypes 1-5) who were treated with sofosbuvir-based regimens. Response to therapy was assessed at week 4 (rapid virological response), week 12 or 24 (end of treatment response), and 12 weeks after cessation of therapy (sustained virological response [SVR]). RESULTS: Of 947 patients diagnosed with chronic hepatitis C virus and considered for treatment with direct-acting antivirals, 736 patients (77.1%) opted for treatment (age 45.1 ± 10.1 years, 64% men, genotype 3 [80%], genotype 1 [14.7%], and genotype 4 [4.9%]). Viral load was high (>600 000 IU/mL) in 361/736 (49%); 330 patients (44.8%) had cirrhosis (80 [14.3%] were decompensated). Patients with genotypes 1, 4, and 5 (n = 135) were treated with triple drug regime (pegylated interferon, ribavirin, and sofosbuvir) for 12 weeks. Patients with genotype 3 (n = 589) were treated either with dual therapy (sofosbuvir and ribavirin) for 24 weeks (n = 405) or triple therapy for 12 weeks (n = 184). SVR was achieved in 453/473 (95.8%). SVR rates did not differ among different genotypes but were higher in non-cirrhotics. CONCLUSION: Sofosbuvir-based treatment regimens achieve high SVR rates in real-life cohort of Indian patients with chronic hepatitis C infection (including those with cirrhosis).