Minimal Hepatic Encephalopathy in Indians: Psychometric Hepatic Encephalopathy Score and Inhibitory Control Test for Diagnosis and Rifaximin or Lactulose for Its Reversal.

Background and Aims: Psychometric hepatic encephalopathy score (PHES) is used widely for diagnosis of minimal hepatic encephalopathy (MHE). This prospective study aimed to determine the utility of the inhibitory control test (ICT) for the diagnosis of MHE. Additionally, the efficacy of rifaximin and lactulose for reversal of MHE was evaluated. Methods: A total of 180 eligible cirrhotic patients underwent testing for MHE. When PHES was ≤ -5 and ICT lures were ≥ 14, MHE was diagnosed. The 108 patients with MHE were randomized to three groups for treatment with either lactulose, rifaximin, or placebo. Treatment outcomes were measured at the end of 3 months. Results: The 108 patients with MHE diagnosed by PHES and/or ICT accounted for 60%. The diagnosis of MHE was made by both ICT and PHES positivity in 56 patients, by abnormal ICT and normal PHES in 37 patients, and by abnormal PHES and normal ICT in 15 patients. For diagnosis of MHE, ICT had sensitivity of 78.87%, specificity of 66.06% with 60.22% positive predictive value and 82.76% negative predictive value. An area under the curve value of 0.724 (95% CI: 0.653-0.788) was obtained for diagnosis of MHE. Reversal of MHE was seen in 71.42%, 70.27% and 11.11% of patients in the rifaximin, lactulose and placebo arms (p < 0.001). Rifaximin showed better tolerability compared to lactulose. Conclusions: For the diagnosis of MHE, ICT is a simple tool but has lower sensitivity and better specificity than PHES. Rifaximin is as efficacious as lactulose in the treatment of MHE and better tolerated.

Natural History and Treatment Outcomes of Severe Autoimmune Hepatitis.

GOALS: The aim of this study was to analyze the natural history and treatment outcomes of autoimmune hepatitis (AIH) variants presenting with severe-AIH. BACKGROUND: Severe acute presentation is an uncommon manifestation of AIH, and it remains poorly characterized. MATERIALS AND METHODS: We included 101 patients with AIH from January 2011 to December 2015. Patients were classified as seropositive-AIH and seronegative-AIH. Patients with acute liver failure, acute-on-chronic liver failure, and severe acute hepatitis were defined as severe-AIH patients. Patient characteristics and treatment outcomes with follow-up until 12 months were analyzed between the different groups. RESULTS: Out of 101 cases, 24 (23.76%) had severe AIH. Of them 9 (37.5%) had severe acute hepatitis, 3 (12.5%) had acute liver failure, and 12 (50%) had acute-on-chronic liver failure. Seronegative-AIH patients presented with severe-AIH significantly more frequently compared with seropositive-AIH patients (50% vs. 20.27%, P=0.022). Severe-AIH had 50% complete responders, 25% partial responders, and 25% treatment failures. Jaundice (88.88% vs. 68.7%, P=0.048), encephalopathy (55.55% vs. 6.66%, P=0.014), and higher international normalized ratio values (2.17±0.60 vs. 1.82±0.14, P=0.038) were factors associated with nonresponse rather than the presence or absence of autoantibodies in severe-AIH. The hazard ratio for predicting remission in the non-severe AIH group as compared with the severe-AIH group was 1.502, which was statistically not significant (95% CI, 0.799-2.827; P=0.205). CONCLUSION: Approximately 24% of patients with AIH have severe-AIH. Conventional autoantibodies are often absent in severe-AIH; however, it does not alter the outcome. Immunosuppressants should be given expediently in patients with severe-AIH.

A Child with Debilitating Pruritus.

We describe a case of two-year-old boy presenting with debilitating pruritus, patchy alopecia and jaundice since the age of 6 months. On evaluation he had intrahepatic cholestasis with persistently raised serum alkaline phosphatase, normal Gamma glutamyl transferase and raised serum bile acid levels. His liver biopsy showed bland cholestasis and electron microscopy showed granular bile suggestive of progressive familial intrahepatic cholestasis type I. Medical therapy with ursodeoxycholic acid, cholestyramine, rifampicin with nutritional modification was successful in alleviating the symptoms and correcting the nutritional status. To our knowledge this is only the sixth case of progressive familial intrahepatic cholestasis type I reported from India. Herein we discuss the diagnostic and therapeutic hurdles that one encounters in managing progressive familial intrahepatic cholestasis and also review the literature regarding this rare disorder.

Symptomatic improvement with gluten restriction in irritable bowel syndrome: a prospective, randomized, double blinded placebo controlled trial.

BACKGROUND/AIMS: The existence of non-celiac gluten sensitivity has been debated. Indeed, the intestinal and extra-intestinal symptoms of many patients with irritable bowel syndrome (IBS) but without celiac disease or wheat allergy have been shown to improve on a gluten-free diet. Therefore, this study set out to evaluate the effects of gluten on IBS symptoms. METHODS: We performed a double-blind randomized placebo-controlled rechallenge trial in a tertiary care hospital with IBS patients who fulfilled the Rome III criteria. Patients with celiac disease and wheat allergy were appropriately excluded. The participants were administered a gluten-free diet for 4 weeks and were asked to complete a symptom-based questionnaire to assess their overall symptoms, abdominal pain, bloating, wind, and tiredness on the visual analog scale (0-100) at the baseline and every week thereafter. The participants who showed improvement were randomly assigned to one of two groups to receive either a placebo (gluten-free breads) or gluten (whole cereal breads) as a rechallenge for the next 4 weeks. RESULTS: In line with the protocol analysis, 60 patients completed the study. The overall symptom score on the visual analog scale was significantly different between the two groups (P<0.05). Moreover, the patients in the gluten intervention group scored significantly higher in terms of abdominal pain, bloating, and tiredness (P<0.05), and their symptoms worsened within 1 week of the rechallenge. CONCLUSIONS: A gluten diet may worsen the symptoms of IBS patients. Therefore, some form of gluten sensitivity other than celiac disease exists in some of them, and patients with IBS may benefit from gluten restrictions.

Most overweight and obese Indian children have nonalcoholic fatty liver disease.

 Background and rationale. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of pediatric liver disease in western countries. Its prevalence in Indian subcontinent is not well studied. MATERIAL AND METHODS: In a school based cross sectional study we have screened overweight and obese children in the age group of 11 to 15 years for NAFLD. Ultrasonography, elevated serum transaminases, fibroscan were used for defining NAFLD. Dietary habits, blood pressure, serum lipid profile, blood counts and insulin resistance were recorded. The relation of fibrosis 4 score, pediatric NAFLD fibrosis index, aspartate transaminases to platelet ratio index (APRI) with fibroscan was evaluated. RESULTS: Out of 616 students screened 198 were overweight and obese. Hundred students and their parents gave informed consent for the further evaluation. The prevalence of NAFLD was 62% in overweight and obese children. Fatty liver was found in 50 % students on ultrasonography, liver stiffness (≥ 6.1 Kilopascals) in 23% and raised alanine transaminase in 30%. Hypertension, dyslipidemia, diabetes mellitus and insulin resistance were seen in 6%, 18%, 2% and 66% students respectively. Systolic hypertension, serum triglyceride, aspartate transaminase, APRI was significantly higher in the NAFLD group. On binary logistic regression only systolic hypertension was an independent risk factor for NAFLD. CONCLUSION: In conclusion NAFLD is common in asymptomatic overweight and obese Indian children. Systolic hypertension is the only independent factor associated with NAFLD. Fibroscan has limited role for screening. We recommend screening for NAFLD in this high risk group with alanine transaminases and ultrasonography.

Congenital Esophageal Duplication Cyst: A Rare Cause of Dysphagia in an Adult.

Esophageal duplication cyst is a rare congenital embryonal gastrointestinal (GI) malformation which is diagnosed most commonly in childhood. In adults, they can present with a variety of symptoms ranging from dysphagia, chest pain, epigastric discomfort, and vomiting to more serious complications including infections, hemorrhage, and ulcerations. A 30-year-old male presented with gradually progressive dysphagia to solids for 4 months without significant weight loss. Clinical examination and routine laboratory examination were unrevealing. Upper GI endoscopy revealed a well-defined submucosal lesion bulging into the esophageal lumen involving the right antero-lateral wall of the distal esophagus. The overlying mucosa was normal with mild luminal narrowing but gastroscope could be negotiated across this narrowing. Differential diagnosis included lipoma, leiomyoma or GI stromal tumors. Contrast-enhanced computed tomography of thorax revealed a 3.5 × 2.3 × 3 cm well-defined homogenous hypodense lesion involving the right antero-lateral wall of the distal thoracic esophagus with likely possibility of submucosal or intramural lesion. Subsequently, endoscopic ultrasonography (EUS) revealed a 3.3 × 2.8 cm homogenous hypoechoic lesion without any vascularity involving the distal esophagus wall suggestive of duplication cyst. The lesion was intramural in location as muscularis propria was seen to go around the lesion. Bronchogenic cyst was excluded due to absence of cartilage and close proximity of the cyst to lumen. Fine-needle aspiration was not attempted in view of high risk of introducing infection. Being symptomatic, the patient underwent complete surgical excision of the cyst with exteriorization of the base which on histopathology confirmed duplication cyst. Esophageal duplication cysts are exceedingly rare congenital embryonal malformations with estimated prevalence of 0.0122% arising from aberration of posterior division of embryonic foregut at 3 - 4 weeks of gestation. This case shows that duplication cysts can rarely masquerade as submucosal tumor in adults and EUS is highly accurate in pre-operative diagnosis and therapeutic decision making. Literature search revealed only a handful of cases of EUS-guided diagnosis of esophageal duplication cyst reported in the literature.

Primary Esophageal Intramural Squamous Cell Carcinoma Masquerading as a Submucosal Tumor: A Rare Presentation of a Common Disease.

Esophageal squamous cell carcinoma (ESCC) is the commonest primary malignant esophageal tumor, which typically presents as endoscopically visible surface mucosal ulcerations, irregularities, or polyploidal masses. We here report a rare case of primary ESCC with completely intramural growth under a normal looking intact nondysplastic surface squamous epithelium disguising as a submucosal tumor. Upper gastrointestinal endoscopy-guided mucosal biopsy was negative for malignancy. Endoscopic ultrasound (EUS) revealed a heteroechoic solid mass originating from the muscularis propria of the distal esophagus. Cytological study of EUS-guided fine needle aspiration from the mass was suggestive of squamous cell carcinoma, which was confirmed on immunohistochemistry. There was no evidence of metastatic origin of this tumor or continuous cancer involvement from the surrounding structures, including the head, neck, and lungs on bronchoscopy, computed tomography scan, and positron emission tomography scan. Exclusive intramural squamous cell carcinoma with normal overlying mucosa is an exceedingly rare presentation of primary ESCC with only four cases reported in the literature so far. A high index of suspicion is required by the gastroenterologists and pathologists in diagnosing these cases as these tumors closely mimic the mesenchymal submucosal tumors such as lipoma, leiomyoma, and gastrointestinal stromal tumors. EUS is an indispensable tool in making a preoperative diagnosis and therapeutic decision making.

Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

BACKGROUND: Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. CASE REPORT: We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them.

Prevalence of Overweight and Obesity in 4 Schools of South Mumbai.

INTRODUCTION: The paediatric obesity is on the rise so as the complications of obesity like cardiovascular diseases, liver diseases, dyslipidaemia are increasing. The changing dietary habits and less of outdoor activities are risk factors for obesity. AIM: The study was conducted to find out prevalence of overweight and obesity among students in four schools of the Mumbai and compare with studies from rest of the country. MATERIALS AND METHODS: It is school based, cross-sectional study conducted in four Schools from class of 5(th) to 10(th). The anthropometric measurements of height, weight were taken of each student. The body mass index was calculated based on the age based Cole et al., criteria (International) as well as Khadilkar et al., criteria which are specially develop for Indian children. The data was analysed with chi-square test. RESULTS: Total 1828 students were screened from 4 schools. Out of which 590 were girls and 1238 were boys. The prevalence of overweight and obesity by Cole et al., criteria were 11.3% and 3.3% and by Khadilkar et al., criteria were 17.5% and 7.8 % respectively. CONCLUSION: It shows significant difference in obesity between boys and girls and also between government and private schools. There is overall decrease in prevalence of overweight and obesity as age increases. The overweight and obesity among these schools in Mumbai is comparable with the rest of the studies from India.