Dengue hepatitis: Incidence, spectrum and outcome.

BACKGROUND AND AIMS: While dengue infection is common in India, there is scarce information on dengue hepatitis. The aim of this study was to analyze the incidence, spectrum and outcome of dengue hepatitis. METHODS: We retrospectively analyzed consecutive patients, who had hepatitis among those with dengue infection admitted to two tertiary care hospitals in western India from January 2016 to March 2021. Diagnosis of dengue infection was made by serology. Dengue hepatitis was diagnosed and the severity of dengue was categorized by standard criteria. RESULTS: Of 1664 patients admitted with dengue fever during the study period, 199 patients had hepatitis (i.e. incidence of dengue hepatitis was 11.9%). Of the 199 dengue hepatitis patients (age: 29 [13 - 80] years, median [range], 67% males), 100 patients (50%) had severe dengue, 73 (36%) had severe dengue hepatitis, 32 (16%) had dengue shock syndrome and eight (4%) had acute liver failure. Forty-five patients (23%) had acute lung injury and 32 (16%) had acute kidney injury. The dengue hepatitis patients were treated with standard medical care, including vital organ support, as needed-166 (83%) patients survived, while 33 patients (17%) died (cause of death: multi-organ failure: 24 patients, septic shock: nine patients). The presence of shock independently predicted mortality (odds ratio 6.4, 95% confidence interval: 1.2 - 34). Among patients with dengue hepatitis, mortality rate was higher in those with severe dengue (23%), dengue shock syndrome (47%), severe dengue hepatitis (24%) and acute liver failure (38%). CONCLUSION: In this large series of hospitalized patients with dengue infection, the incidence of dengue hepatitis was 11.9%. Among 199 dengue hepatitis, 17% died; multi-organ failure was the commonest cause for death and death rate was higher in patients with more severe disease. The presence of shock at presentation independently predicted mortality.

Positive white nipple sign on esophageal varices: Not a just bystander; our experience.

Background and study aims The goal of this study was to assess whether a white nipple sign on esophageal varices is of no prognostic significance or mandates more attention. Patients and methods We retrospectively analyzed data from 2601 patients undergoing upper gastrointestinal endoscopy for variceal bleed from January 2008 to January 2020. Intraprocedural events like onset of active spurt while performing endoscopy, active spurt while attempting to band the varix with a nipple, need for rescue glue therapy required to control bleed in cases of failed endoscopic variceal ligation (EVL), slipping of band and rebleed despite successful band application, need for emergency intubation, and pulmonary aspiration-related complications were noted. Results A total of 2601 patients underwent endoscopy for variceal bleeding. Of them, 631 had a positive white nipple sign. Of that subgroup, 137 (21.7 %) patients developed active spurt during endoscopy. In patients with the white nipple sign, 12.3 % required endotracheal intubation and 6.7 % developed aspiration pneumonia, which were significantly higher than in those without the sign. Rescue glue injection in esophageal varices was needed in 5.6 % as compared to 0.6 % in those without white nipple. Conclusions The white nipple sign is not only a predictor of recent bleed, but it carries statistically significant increased risk of intraoperative bleeding, need for endotracheal intubation, esophageal glue injections, and aspiration-related complications. Therefore, it is not just a bystander, but rather, a sign of increased danger and a need to be more vigilant with patient management.

Crush cytology: an expeditious diagnostic tool for gastrointestinal tract malignancy.

Background and study aims Crush cytology is a simple and rapid method used for diagnosis of central nervous system lesions. We have evaluated the diagnostic accuracy of crush cytology for gastrointestinal tract lesions. Patients and methods This was a prospective, cross-sectional, single center study, conducted on the patients who had suspected malignant lesions between August 2018 and March 2020. The crush cytologic diagnoses were correlated with histology to determine the diagnostic accuracy. Results During the period of interest, a total of 451 patients (26.4 % esophagus & GE junction, 16.6 % stomach, 5.9 % ampulla & duodenum, and 50.9 % colorectal) had a suspected malignant lesion on endoscopic examination. Histology confirmed 92.9 % cases as malignant lesions and 7.1 % as nonmalignant. On crush cytology, 84.5 % were positive for malignancy, 8.9 % were negative for malignancy and 6.6 % were reported as suspicious for malignancy. The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of crush cytology were 97.3 %, 90 %, 99.2 %, 72.5 % and 96.9 %, respectively. Conclusions Crush cytology is a highly sensitive, specific, rapid and cost effective technique to diagnose gastrointestinal malignancies in endoscopically suspected malignant lesions. However, it cannot entirely substitute histopathological examination for definite tumor typing, grading, confirming invasion and in cases in which cytology is suspicious. Crush cytology is an added asset to the histology to maximize diagnostic accuracy and accelerating decision making for the management of lesions.

Sofosbuvir-velpatasvir single-tablet regimen administered for 12 weeks in a phase 3 study with minimal monitoring in India.

BACKGROUND AND AIMS: In clinical studies, sofosbuvir-velpatasvir has demonstrated high cure rates and favorable tolerability in patients chronically infected with chronic hepatitis C virus (HCV) of any genotype. We evaluated the effectiveness and safety of sofosbuvir-velpatasvir administered with minimal medical monitoring to patients in India. METHODS: At 16 sites in India, 129 adult patients with chronic HCV infection of any genotype initiated 12 weeks of once-daily sofosbuvir-velpatasvir (400-100 mg). Patients with compensated cirrhosis or prior treatment experience could be included in the study. Study drug was dispensed monthly, but there were no on-treatment study assessments. The primary efficacy endpoint was rate of sustained virologic response (HCV RNA < 15 IU/mL) 12 weeks after treatment (SVR12), which was compared to a pre-specified performance goal of 85%. RESULTS: The majority of patients had HCV genotype 3 infection (70%), followed by HCV genotype 1 (22%). The SVR12 rate was 93% (120/129; 95% CI, 87% to 97%) (p = 0.009 compared with the 85% performance goal). Of the nine patients who did not achieve SVR12, 1 experienced virologic failure, 2 relapsed after treatment, 1 withdrew consent after treatment, and 5 were lost to follow-up (1 during and 4 after treatment). Sofosbuvir-velpatasvir was well-tolerated, and no patients discontinued treatment because of an adverse event. The most frequently reported adverse events were headache (3% of patients), upper abdominal pain (2%), and pyrexia (2%). CONCLUSIONS: In this study conducted at multiple sites in India, sofosbuvir-velpatasvir administered without genotype restriction or on-treatment safety assessments was well-tolerated and highly effective.

Preliminary experience with single fecal microbiota transplant for treatment of recurrent overt hepatic encephalopathy-A case series.

Experimental studies demonstrated that fecal microbiota transplant (FMT) may reverse intestinal microbial dysbiosis. In this retrospective case series, we share our experience of treating recurrent overt hepatic encephalopathy (HE) with single FMT treatment. A total of 10 patients, age ranged from 25 to 65 years, were treated with single FMT through colonoscopy using fecal material received from rigorously screened patient-identified donors. There was sustained clinical response with single FMT treatment in 6 patients at post-treatment week 20. Arterial ammonia concentration decreased considerably (96 [87.25-117.75] vs. 74 [70-82]; p = 0.024) at post-treatment week 20. Moreover, there was statistically significant decrease in Child-Turcotte-Pugh (CTP) score (9.5 [9-10.75] vs. 8 [7-8]; p = 0.005) and model for end-stage liver disease (MELD) score (18 [16.25-19] vs. 15 [14-16]; p = 0.008). Four patients experienced six adverse-events. Overt HE and re-hospitalization were observed in 3 and 2 patients, respectively. One patient (who also experienced overt HE) died within 2 months of the index procedure.

Safety and Efficacy of Sofosbuvir and Daclatasvir for Hepatitis C Virus Infection in Patients with ß-Thalassemia Major.

BACKGROUND AND AIMS: ß-thalassemia major patients are susceptible to Hepatitis C Virus (HCV) infection owing to life-long dependency for blood-transfusion. Moreover, this patient population is at risk of progression of liver fibrosis or development of cirrhosis as a consequence of both iron overload and HCV infection. Hence, this study was carried out to evaluate efficacy and safety of the combination regimen of sofosbuvir and daclatasvir for HCV infection in ß-thalassemia major patients. METHODS: The present study was a prospective observational study which enrolled multi-transfused ß-thalassemia major patients treated with a combination regimen of sofosbuvir (400 mg) and daclatasvir (60 mg) daily for 12 weeks for HCV infection during May 2016 and November 2016 depending upon inclusion and exclusion criteria of the study. Sustained virological response at post-treatment week-12 (SVR-12) was defined as negative HCV-RNA at week-12 after completion of antiviral treatment. RESULTS: A total of 10 multi-transfused patients with ß-thalassemia major were included in the study. Average age of the patient was 13.60 ± 4.38 years. All the included patients were treatment-naïve, non-cirrhotic and infected with HCV genotype-3. All the patients achieved SVR-12. There was significant reduction in aspartate aminotransferase (p = 0.005) and alanine aminotransferase level (p = 0.005) and serum ferritin level (p = 0.028) after completion of the antiviral treatment. The reported adverse events include nausea, vomiting and anorexia which were managed conservatively. None of the patient required dose reduction or termination of antiviral treatment. CONCLUSION: The study reports safety and efficacy of sofosbuvir-based treatment in non-cirrhotic, treatment-naive ß-thalassemia major patients infected with HCV genotype-3. However, further studies with larger patient populations are needed to build up stronger evidence of safety and efficacy of this treatment approach for HCV infection in thalassemic patients.

Early Experience of Sofosbuvir based Combination Therapy in "Real-Life" Cohort with Chronic Hepatitis-C Infection.

INTRODUCTION: There is scarcity of data in literature regarding the treatment response with Sofosbuvir (SOF) based therapy in Indian patients with chronic Hepatitis-C Virus (HCV) infection. AIM: This study was designed to observe initial treatment response to SOF based therapy in a "real-life" cohort of Indian patients with HCV infection. MATERIALS AND METHODS: This is a prospective, observational and single center study. A total of 107 patients who were diagnosed with chronic HCV infection and received SOF based treatment between March 2015 and December 2015 were included. The patients were treated with either triple drug regimen [SOF, Ribavirin (RBV) and Pegylated Interferon-α (Peg IFN-α)] or dual drug regimen (SOF and RBV) for either 12 or 24 weeks. The virological responses were obtained at baseline and thereafter weekly (up to four weeks) till viral load became undetected during treatment. RESULTS: A total of 107 patients who received SOF based therapy for chronic HCV infection were included in the study. Mean age of the patients was 48.7±10.7 years. Among included patients, 24 (22.4%) patients were treatment-experienced. Majority of the patients (n=69; 64.5%) were infected with HCV genotype-3. Except one patient, all the included patients achieved virological response up to week-4 of the treatment. There was statistically insignificant association between virological response (up to four week of the treatment) and severity of the disease (cirrhosis and non-cirrhosis) or treatment status (treatment-naïve and treatment-experienced), or HCV genotype (genotype-1 and 3). CONCLUSION: The results of this observational study demonstrated rapid initial virological response of SOF based therapy in "real-life" cohort of Indian patients with chronic HCV infection. However, long-term follow-up data are needed to ensure the sustained antiviral efficacy of SOF based therapy.

Efficacy and safety of sofosbuvir-based therapy for chronic hepatitis C infection in "real-life" cohort.

BACKGROUND: The safety and efficacy of sofosbuvir-based treatment (sofosbuvir and ribavirin with or without pegylated interferon-α) for hepatitis C virus (HCV) infection has been established in clinical trials. However, there is limited data regarding safety and efficacy of sofosbuvir-based treatment for HCV infection in a "real-life" cohort. We describe our experience with sofosbuvir-based treatment for HCV infection in a real-life cohort. METHODS: This was a prospective, nonrandomized and observational study at a tertiary care centre in Surat, India. The primary end-point was proportion of the study patients who achieved a sustained virological response 12 weeks after cessation of treatment (SVR 12). Secondary end-points of the study include SVR 4, virological relapse and appearance of adverse events. RESULTS: A total of 107 patients with chronic HCV who received sofosbuvir-based treatment were included in the study. During study period, two patients died due to severity of liver complications. Hence, overall rate of SVR 4 and SVR 12 was 98.1 % (n = 103/105) and 94.3 % (n = 99/105), respectively. Among 67 patients with HCV genotype-3 infection, the SVR 12 rate was 92.5 % (n = 62/67), and among 38 patients with HCV genotype-1 infection, the rate of SVR 12 was 97.4 % (n=37/38). A total of 32 (29.9 %) patients reported adverse events during the course of sofosbuvir-based treatment. None of the patient discontinued treatment due to adverse event. CONCLUSIONS: Sofosbuvir-based treatment is safe and efficacious in clinical practice in Indian patients with HCV genotype-1 and genotype-3 infection.