Novel predictors of response to therapy with terlipressin and albumin in hepatorenal syndrome-acute kidney injury.

Background: A combination of terlipressin and albumin is the first-line pharmacologic treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI). We assessed the response rates to terlipressin-albumin therapy in patients with HRS-AKI and determined early predictors of treatment response and survival. Methods: A total of 84 patients with HRS-AKI (International Club of Ascites definition 2015) treated with terlipressin-albumin were included. Predictors of HRS reversal were identified by logistic regression analysis. Survival analysis was performed using the Kaplan-Meier method, and Cox regression models were used to determine independent predictors of mortality. Results: Complete response to therapy was observed in 54.8%, partial response in 14.3%, and no response in 31% of patients. The factors associated with complete treatment response were the presence of systemic inflammatory response syndrome (SIRS), baseline serum creatinine, a rise in mean arterial pressure by day 3, and a reduction in the renal resistive index (ΔRRI) by day 3 of treatment. Independent predictors of HRS reversal were the presence of SIRS at baseline (P=0.022; odds ratio [OR] 15.74, 95% confidence interval [CI] 1.47-167.82) and ΔRRI ≥5% by day 3 of treatment (P=0.048; OR 6.67, 95%CI 1.021-43.62). Mean transplant-free survival at 6 months was significantly better in treatment responders (148 vs. 90 days, P<0.001). Independent predictors of 6-month mortality were response to treatment (P=0.004) and model for end-stage liver disease-sodium >23 (P=0.018). Conclusions: SIRS and ΔRRI are simple parameters to predict treatment response in HRS-AKI. Non-responders have higher mortality and should be identified early to expedite liver transplantation.

A case-cohort study of left ventricular diastolic dysfunction in patients with cirrhosis: the liver-heart axis.

Background: Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cirrhotic cardiomyopathy. Few studies have addressed its clinical significance in cirrhosis. We assessed the association of LVDD with the factors affecting cirrhosis patients' severity, complications, and survival. Methods: A total of 203 cirrhosis patients were enrolled and underwent investigations, including 2-dimensional echocardiography with tissue Doppler imaging, and 139 patients with LVDD (cases) were compared with 64 patients without LVDD (controls). Logistic regression and Kaplan-Meier analysis were applied. Results: Mean age was 52.76±10 years. Among LVDD patients, 56% had grade-1, and 44% had grade-2 LVDD. Cirrhosis related to NASH had a more significant association with LVDD (P<0.001) than other etiologies. LVDD was significantly associated with a greater incidence of Child-Turcotte-Pugh (CTP) class C (P<0.001), higher model for end-stage liver disease scores (P=0.001), duration of cirrhosis >2 years since diagnosis (P=0.028), ascites (P<0.001), hepatic encephalopathy (P<0.010), hepatorenal syndrome (P<0.001), and a history of obesity (P=0.004). Multivariate analysis showed that higher CTP score, ascitic fluid protein and prolonged QTc interval were independently associated with LVDD (P=0.009; P=0.018; P=0.016, respectively). Kaplan-Meier survival analysis showed significantly poorer survival status in patients with higher grades of LVDD (P<0.001). The area under the receiver operating characteristic curve (0.78) was greatest for ascitic fluid protein in predicting LVDD, with a cutoff of >1 g/dL. Conclusions: Higher CTP score, prolonged QTc, higher ascitic fluid protein levels, and poor survival are significantly associated with LVDD. Ascitic fluid protein >1 g/dL could be an indicator for evaluating LVDD.

Unusually high clarithromycin resistance in Mycobacterium abscessus subsp. abscessus isolated from human gastric epithelium.

Mycobacterium abscessus subsp. abscessus is a rapidly growing facultative intracellular pathogen that usually infects human lung and skin epithelium. Recently, we and another group have shown that it also has the potential to colonize human gastric epithelium, but its significance with respect to gastric diseases remains unclear. Although Helicobacter pylori still remains the only definite gastric pathogen, recent studies have shown that M. abscessus subsp. abscessus also has the potential to colonize human gastric epithelium. M. abscessus subsp. abscessus is known to exhibit multidrug resistance and clarithromycin has been used as the drug of choice. We aimed to determine the clarithromycin resistance profile of 117 (74 rough and 43 smooth) gastric M. abscessus subsp. abscessus strains and to detect the point mutations in rrl and erm (41) genes conferring the resistance. Our data showed 79.48% (19 smooth and 74 rough) of M. abscessus subsp. abscessus strains were resistant to clarithromycin (MIC90 ≤ 512 µg/mL), while 20.51% (24 smooth) were susceptible (MIC90 ≤ 8 µg/mL). Nucleotide sequence analysis of the rrl gene with reference strains of M. abscessus subsp. abscessus did not show any mutation that is relevant to the clarithromycin resistance. However, analysis of erm (41) gene showed that M. abscessus subsp. abscessus strains, which were susceptible to clarithromycin had C, C, G, and C at their nucleotide positions 28, 159, 238, and 330, respectively, while the resistant strains showed T, T, A, and A at the same positions. Based on antibiogram and sequence analysis data we recommend further studies involving genomic analysis to identify the other genes involved in high clarithromycin resistance in gastric M. abscessus subsp. abscessus along with the mechanisms involved.

Multi-center prospective survey of hepatocellular carcinoma in Kerala: More than 1,200 cases.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered uncommon in India. The aim of this study was to document the demographic characteristics and clinical aspects of HCC in Kerala, India. METHODS: A survey of HCC in Kerala was performed. All gastroenterologists in the region were invited. From May 2018 to April 2020, data was collected in a standardized questionnaire. RESULTS: Forty-three doctors from 15 centers contributed the data. Total 1217 patients were analyzed. This is the largest state-wide survey of HCC in India. HCC was more common in men (90%) than in women (p < 0.01). The etiology of liver disease was hepatitis B virus (7%), hepatitis C virus (4%) and alcohol (40%). Diabetes mellitus was present in 64%, hypercholesterolemia in 17% and hypertension in 38%. Obesity was present in 33% and 15% were overweight. Non-alcoholic fatty liver disease (NAFLD) with or without metabolic syndrome was present in 44%. Serum alpha-fetoprotein was > 400 ng/mL in 24%, total tumor diameter was > 5 cm in 59%, portal vein invasion was seen in 35% and distant metastasis was seen in 15%. Specific therapy was given to 52%. Treatments given included liver transplantation (n = 24), liver resection (n = 39) and transarterial chemoembolization (TACE, n = 184). Although the study was not designed to compare survival, patients who had liver transplantation had longer survival (median 69 months) compared to matched patients given only TACE (median 18 months) (p = 0.03). CONCLUSION: HCC is common in Kerala, India. NAFLD has a predominant association with HCC in Kerala. Most of the patients report late when curative treatment is not possible.

CRAB score for prediction of colectomy within 2 years following admission for acute severe ulcerative colitis.

Background: The Oxford and Swedish indexes were developed to predict in-hospital colectomy in acute severe ulcerative colitis (ASUC), but not long-term prediction, and all these indexes were based on Western data. Our study aimed to analyze the predictors of colectomy within 3 years of ASUC in an Indian cohort and derive a simple predictive score. Methods: A prospective observational study was conducted in a tertiary health care center in South India over a period of 5 years. All patients admitted with ASUC were followed up for a period of 24 months after the index admission, to look for progression to colectomy. Results: A total of 81 (47 male) patients were included in the derivation cohort. Fifteen (18.5%) patients required colectomy during a follow-up period of 24 months. On regression analysis, C-reactive protein (CRP) and serum albumin were independent predictors of 24-month colectomy. The CRAB (CRP + AlBumin) score was obtained by multiplying coefficient of beta to albumin and CRP (CRAB score = CRP x 0.2 - Albumin x 0.26). The CRAB score demonstrated an AUROC of 0.923 and a score of >0.4 with a sensitivity of 82% and specificity of 92% for the prediction of 2-year colectomy following ASUC. The score was validated in a validation cohort of 31 patients, and at >0.4, the score had a sensitivity of 83% and a specificity of 96% in predicting colectomy. Conclusion: CRAB score is a simple prognostic score that can predict 2-year colectomy in ASUC patients with high sensitivity and specificity.

Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

Assessment of Visceral Fat Volume and Its Correlation with the Severity of Hepatic Fibrosis in Patients with NAFLD.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease. The spectrum of NAFLD includes simple steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. Our study aimed to calculate visceral fat volume at the L3-L4 vertebral level and its association with hepatic fibrosis assessed by transient elastography. METHODS: All patients above 18 years undergoing computed tomography (CT) abdomen in the Department of Radiodiagnosis of Medical College Thiruvananthapuram during the study period with NAFLD were included. Transient elastography was done. Patients were categorized to advanced fibrosis (>10 kPa) and without advanced fibrosis (<10 kPa). The area under the receiver operating characteristic (AUROC) curve was plotted. RESULTS: Sixty-four patients comprised 36 males and 28 females. Thirty-one (46%) were having advanced fibrosis (transient elastography>10 kPa) and 34 (54%) patients were without advanced fibrosis. About 0.733 was the AUROC for visceral fat in predicting advanced fibrosis. The cutoff was 167.5cm3 (sensitivity was 77.4% and specificity was 51.5% in predicting advanced fibrosis). CONCLUSION: About 0.733 was the AUROC for visceral fat in predicting advanced fibrosis. The cutoff was 167.5cm3 (sensitivity was 77.4% and specificity was 51.5% in predicting advanced fibrosis).

Clinicopathological Profile and Outcome of a Large Cohort of Patients with Nonalcoholic Fatty Liver Disease from South Asia: Interim Results of the Indian Consortium on Nonalcoholic Fatty Liver Disease.

Background: Previous data from South Asia and India had shown that patients with nonalcoholic fatty liver disease (NAFLD) have mild liver disease severity. There are no data regarding long-term clinical outcomes in patients with NAFLD from South Asia. The aim of the study was to evaluate the clinicopathological profile, severity of NAFLD, and clinical outcomes in a large cohort of patients with NAFLD from South Asia. Methods: In an ongoing real-life study [Indian Consortium on nonalcoholic fatty liver disease (ICON-D)], interim data captured across 23 centers in India over 18 months was analyzed for clinicopathological profile, severity of NAFLD, and hepatic/extrahepatic events on follow-up. Results: Of 4313 patients (mean age 45 ± 12.2 years, males 52%), data on metabolic risk factors in 3553 (82.3%) patients revealed that 378 (10.6%) were lean, 575 (16.2%) overweight, 2584 (72.7%) obese; metabolic syndrome in 1518 (42.7%) and at least one metabolic risk factor in 3292 (92.6%) patients. Evidence of significant or advanced fibrosis assessed with [aspartate transaminase to platelet ratio index (APRI), n = 3196 (74%)], [fibrosis-4 (FIB-4), n = 3554 (82.4%)], [NAFLD fibrosis score (NFS), n = 1924 (44.6%)], [Fibroscan, n = 2475, (57.3%)], and histology [n = 267 (6.2%)] was present in 682 (21.3%), 676 (19%), 397 (20.6%), 715 (29%), and 41 (15.4%) patients, respectively; 246 (10%) patients on Fibroscan and 22 (8.2%) on histology had evidence of cirrhosis. On a mean follow-up 43.5 months, hepatic and extrahepatic events recorded in 1353 (31.3%) patients showed that patients with compensated cirrhosis [71 (5.2%)] had more hepatic [26 (36.7%)] and extrahepatic events [8 (11.3%)] in comparison with those without cirrhosis (P < 0.0001). Conclusion: Around one fifth of patients with NAFLD in South Asia have significant liver disease. Both hepatic and extrahepatic events on follow-up are observed more commonly in patients with nonalcoholic steatohepatitis-related compensated cirrhosis.

Barrett's Esophagus: A Comparison Study between Two Cohorts of Gastroesophageal Reflux Disease.

INTRODUCTION: Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease (GERD). It is seen among 15% of GERD patients as per a population-based study by Ronkainen et  al. Barrett's has malignant potential and annual progression to carcinoma depends on the presence or absence of dysplasia. There are various risk factors for the development of BE. We compared two symptomatic cohorts of GERD patients from the same geographical area who were evaluated for the presence of Barrett's and various factors that can contribute to Barrett's Materials and methods: Cross-sectional study. Two GERD cohorts, one from Kottayam and the other from Trivandrum were taken. The presence of Barrett's and the factors contributing to the development of Barrett's were analyzed between the two groups. Since biopsy data of all patients were not available, endoscopically suspected esophageal metaplasia (ESEM) was taken as Barrett's Results: 415 patients were enrolled for the study (203 from Trivandrum and 212 from Kottayam). 192 females (99 from Trivandrum and 93 from Kottayam), and 223 males (104 from Trivandrum and 119 from Kottayam). Barrett's esophagus and especially long-segment Barrett's were significantly more common in Kottayam than Trivandrum (68 vs 22 and 36 vs 9) (p-value <0.001). Among the factors that were traditionally thought to contribute to the development of Barrett's esophagus, age (>50 years) was not statistically significant among the two cohorts (mean age of Trivandrum was 48 years and Kottayam was 49 years). Duration of GERD symptoms was significantly more in the Trivandrum cohort compared to Kottayam (p-value <0.001). Hiatus hernia and body mass index (BMI) were more common in Kottayam. There were no statistically significant differences in erosive esophagitis and antral gastritis (%age?) between the two cohorts. CONCLUSION: Both Trivandrum and Kottayam belong to the same geographical area and are separated by a distance of only 150 km. The Kottayam cohort is more prone to develop distal esophageal carcinoma as the BE is more in Kottayam. This data also suggests the need for GERD registries so that high-risk population can be targeted and early intervention can lead to a decrease in the incidence of distal esophageal carcinomas.

Validation of Spleen Shear Wave Elastography for the Screening of High-risk Varices in Patients with Compensated Advanced Chronic Liver Disease.

OBJECTIVES: Total number of avoided endoscopies using Baveno VI criteria is relatively low. Spleen elastography is an attractive tool and when compared with liver stiffness, it better represents the dynamic changes occurring in portal hypertension. The aim of the study was to evaluate spleen shear wave elastography (SWE) in compensated advanced chronic liver disease (cACLD) patients for ruling out the presence of esophageal high-risk varices (HRV). METHODS: A total of 401 patients with cACLD were included in this cross-sectional study. The total sample was split into training set (200 patients) and validation set (201 patients). Spleen stiffness was measured with two-dimensional shear wave elastography (2D SWE). Esophageal HRV were defined as large varices (diameter >5 mm) or small varices with red color signs. In the training set, the receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) of spleen SWE was assessed. A cutoff value was chosen (highest sensitivity and negative predictive value). In the validation set, the spleen SWE cutoff score and Baveno VI criteria were validated. RESULTS: The prevalence of HRV was 12% in the training set and 13% in the validation set. Spleen SWE had an AUC of 0.89 in ruling out the presence of high-risk esophageal varices (cutoff value of 48.7 kPa, sensitivity of 100%, and specificity of 53%). Validating spleen SWE ≤48.7 kPa in a different cohort of 201 cACLD patients, 55% of screening endoscopies could be avoided without missing any HRV, whereas using Baveno VI criteria only 30% of screening endoscopies could be spared. CONCLUSION: Spleen SWE ≤48.7 kPa was able to identify cACLD patients who could safely avoid screening endoscopy with good accuracy. Spleen SWE could avoid an additional 25% of screening endoscopies compared to the Baveno VI criteria and no HRV were missed.

Association of Sarcopenia with Health Related Quality of Life in Cirrhotics.

BACKGROUND & OBJECTIVES: Sarcopenia is one of the most common complication associated with mortality in cirrhotic patients. However, the lack of an objective and reliable method to quantify muscle mass has limited the general incorporation of sarcopenia into cirrhosis prognostic scores. In this article, we highlight crosssectional imaging-based estimation of skeletal muscle mass for diagnosing sarcopenia in cirrhotic patients and its effect on health related quality of life. METHODS: After getting ethical clearance and informed consent, all patients with cirrhosis were taken and assessed for sarcopenia using thigh muscle based index The average feather index was used in conjunction with BMI in determining the probability of sarcopenia. The CLDQ was used to assess the health related quality of life. The chi-square and Pearsons coefficient were used for analyzing correlation between sarcopenia and other variables. RESULTS & DISCUSSION: In our study, out of the 288 patients, sarcopenia was present in 132 patients (45.83%). Sarcopenia was present in 18.2% in CHILD A,42.4 % in CHID B and 90.5 % in CHILD C cirrhotics. Sarcopenia was highest in autoimmune hepatitis related cirrhosis (80%), followed by NASH (61.9%),followed by ethanol (42.4%), followed by HCV (28.5%) and HBV (16.6%). Sarcopenia had a moderate negative correlation with health related Quality of life as assessed by CLD Q particularly in relation with systemic symptoms and activity. CONCLUSION: The factors like high MELD, CHILD C cirrhosis, NASH as etiology, were associated with higher prevalence of sarcopenia.NASH related cirrhotics have high prevalance of sarcopenia even in CHILD A patients. The patients with sarcopenia were having a low overall quality of life as per CLDQ,especially in specific aspects related to systemic symptoms and activity.

Antimicrobial resistance and virulence in Helicobacter pylori: Genomic insights.

Microbes evolve rapidly by modifying their genome through mutations or acquisition of genetic elements. Antimicrobial resistance in Helicobacter pylori is increasingly prevalent in India. However, limited information is available about the genome of resistant H. pylori isolated from India. Our pan- and core-genome based analyses of 54 Indian H. pylori strains revealed plasticity of its genome. H. pylori is highly heterogenous both in terms of the genomic content and DNA sequence homology of ARGs and virulence factors. We observed that the H. pylori strains are clustered according to their geographical locations. The presence of point mutations in the ARGs and absence of acquired genetic elements linked with ARGs suggest target modifications are the primary mechanism of its antibiotic resistance. The findings of the present study would help in better understanding the emergence of drug-resistant H. pylori and controlling gastric disorders by advancing clinical guidance on selected treatment regimens.

Helicobacter pylori in Human Stomach: The Inconsistencies in Clinical Outcomes and the Probable Causes.

Pathogenic potentials of the gastric pathogen, Helicobacter pylori, have been proposed, evaluated, and confirmed by many laboratories for nearly 4 decades since its serendipitous discovery in 1983 by Barry James Marshall and John Robin Warren. Helicobacter pylori is the first bacterium to be categorized as a definite carcinogen by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO). Half of the world's population carries H. pylori, which may be responsible for severe gastric diseases like peptic ulcer and gastric cancer. These two gastric diseases take more than a million lives every year. However, the role of H. pylori as sole pathogen in gastric diseases is heavily debated and remained controversial. It is still not convincingly understood, why most (80-90%) H. pylori infected individuals remain asymptomatic, while some (10-20%) develop such severe gastric diseases. Moreover, several reports indicated that colonization of H. pylori has positive and negative associations with several other gastrointestinal (GI) and non-GI diseases. In this review, we have discussed the state of the art knowledge on "H. pylori factors" and several "other factors," which have been claimed to have links with severe gastric and duodenal diseases. We conclude that H. pylori infection alone does not satisfy the "necessary and sufficient" condition for developing aggressive clinical outcomes. Rather, the cumulative effect of a number of factors like the virulence proteins of H. pylori, local geography and climate, genetic background and immunity of the host, gastric and intestinal microbiota, and dietary habit and history of medicine usage together determine whether the H. pylori infected person will remain asymptomatic or will develop one of the severe gastric diseases.

Low Bifidobacterium Abundance in the Lower Gut Microbiota Is Associated With Helicobacter pylori-Related Gastric Ulcer and Gastric Cancer.

Helicobacter pylori infection in stomach leads to gastric cancer, gastric ulcer, and duodenal ulcer. More than 1 million people die each year due to these diseases, but why most H. pylori-infected individuals remain asymptomatic while a certain proportion develops such severe gastric diseases remained an enigma. Several studies indicated that gastric and intestinal microbiota may play a critical role in the development of the H. pylori-associated diseases. However, no specific microbe in the gastric or intestinal microbiota has been clearly linked to H. pylori infection and related gastric diseases. Here, we studied H. pylori infection, its virulence genes, the intestinal microbiota, and the clinical status of Trivandrum residents (N = 375) in southwestern India by standard H. pylori culture, PCR genotype, Sanger sequencing, and microbiome analyses using Illumina Miseq and Nanopore GridION. Our analyses revealed that gastric colonization by virulent H. pylori strains (vacAs1i1m1cagA+) is necessary but not sufficient for developing these diseases. Conversely, distinct microbial pools exist in the lower gut of the H. pylori-infected vs. H. pylori-non-infected individuals. Bifidobacterium (belonging to the phylum Actinobacteria) and Bacteroides (belonging to the phylum Bacteroidetes) were present in lower relative abundance for the H. pylori+ group than the H. pylori- group (p < 0.05). On the contrary, for the H. pylori+ group, genus Dialister (bacteria belonging to the phylum Firmicutes) and genus Prevotella (bacteria belonging to the phylum Bacteroidetes) were present in higher abundance compared to the H. pylori- group (p < 0.05). Notably, those who carried H. pylori in the stomach and had developed aggressive gastric diseases also had extremely low relative abundance (p < 0.05) of several Bifidobacterium species (e.g., B. adolescentis, B. longum) in the lower gut suggesting a protective role of Bifidobacterium. Our results show the link between lower gastrointestinal microbes and upper gastrointestinal diseases. Moreover, the results are important for developing effective probiotic and early prognosis of severe gastric diseases.

Comparison of conventional scoring systems versus MAGIC score to predict short-term mortality in patients hospitalized for alcoholic hepatitis.

BACKGROUND: Multiple prognostic models are available to predict mortality in alcoholic hepatitis (AH) which are of modest benefit, but the best model remains unexplored. METHODS: This is a retrospective analysis (2012-2015) of AH patients. Conventional prognostic scoring systems viz. Maddrey's Discriminant Function (mDF), Age Bilirubin International Normalized Ratio and Creatinine (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), and the Model for End-stage Liver Disease score (MELD), were compared with Model for AH to Grade the Severity in an Asian patient cohort (MAGIC) score, using area under the ROC curves for ascertaining 30/90-day mortality. RESULTS: Eighty-eight patients (100% male); mean (SD) age of 45.6 (7.6) years with a follow-up of 80.7 (45.1) days were included. The 30 and 90-day mortality were 21 (23.9%) and 42 (47.7%), respectively; the commonest cause being sepsis in 22 (48.9%) patients. Survival probabilities for mDF < 32 and mDF > 32 were 100% and 42.25% ± 4.46%, respectively (p = .001). The mean (SD) scores of mDF, MELD and GAHS were significantly higher in deceased patients 70.8 (26.5), 23.4 (5.2), 8.1 (1.01), respectively, as compared to those who survived 40.8 (23.1), 18.9 (5.1), 7.3 (0.9), respectively; p = .001. ABIC and MAGIC scores were higher among the deceased, but were not significant. mDF had the best predictive AUROC value 0.872, followed by MELD 0.772, and MAGIC 0.626, respectively. mDF was significantly superior in comparison to MAGIC score (p < .001). CONCLUSION: This study showed that mDF had a better predictive performance than other scoring systems in patients with AH.

Validation of Baveno VI Criteria for Screening of Esophageal Varices in a Cohort of South Asian Patients with Compensated Chronic Liver Disease.

OBJECTIVES: A patient with liver stiffness by Vibration controlled Transient elastography(TE) <20 kPa and a platelet count >150,000/mm3 does not require screening endoscopy according to Baveno VI consensus. The Baveno consensus statement on esophageal varices screening has not been validated in the South Asian population. TE may not be widely available in resource limited areas. We tried to see whether easily available parameters could be used to predict high risk varices(HRV). METHOD: A cross-sectional study evaluating patients with liver stiffness >10 kPa who had endoscopy within 6 months of TE evaluation. RESULTS: 375 patients who underwent TE and upper GI endoscopy over one year were included. Commonest etiology was HBV(42 %) followed by Hepatitis C(39%), NAFLD(9.1%) and alcohol(9%). 262 of the 266 patients satisfying Baveno VI consensus criteria for avoiding screening endoscopy did not have HRV. Sensitivity, specificity, positive predictive value(PPV) and negative predictive value(NPV) was 96 %, 90 %, 74% and 99 % respectively and (AUC = 0.91). By using MELD 6 or MELD < 8 and platelet >150000/mm3 criteria, 67% endoscopies could have been circumvented. Using Baveno VI criteria, 70% endoscopies could have been circumvented. CONCLUSION: This study validates the Baveno VI consensus statement on esophageal variceal screening in cirrhosis, in a South Asian population. It also describes a new strategy using MELD 6 or MELD < 8 and platelet > 150000/mm3 in areas with limited resources where TE is not widely available.

Quality of life, caregiver burden and mental health disorders in primary caregivers of patients with Cirrhosis.

BACKGROUND AND AIMS: Caregivers are needed for cirrhotic patients as there is progressive decline in cognition and self-care. We intend to study the quality of life (QOL), psychosocial burden and prevalence of mental health disorders among caregivers. METHODS: Cross-sectional study where caregivers, defined as person who takes responsibility of providing care to patient, of cirrhotic patients were included. Short form 36 health survey (SF-36) to assess QOL, Zarit Burdern Index12 (ZBI) for caregiver burden (CB). Patient Health Questionnaire (PHQ) identified depression and Generalized Anxiety Disorder (GAD-7) questionnaires, anxiety. RESULTS: Of 132 caregivers, mean age of caregiver was 41.2 ± 10.3 years, with female preponderance. Mean MELD was 21.4 ± 7, majority belonged to CHILD C. Comparing the SF36 score of caregivers to normal population showed lower level of QOL for caregivers. Mean ZBI score - 14 ± 5.8. Mean GAD score - 8.1 ± 5.1, 54 (41%) had anxiety. Mean PHQ score - 7.8 ± 5.2, 45 (34%) had depression. REGRESSION ANALYSIS: Alcoholic cirrhosis, history of hepatic encephalopathy (HE), Anxiety, Depression and recidivism predicted CB. Treatment costs (ODDS-1.15), alcoholic cirrhosis (ODDS -8.9), history of HE (ODDS-7.5) and caregiver duration (ODDS-0.25) predicted anxiety. Treatment costs (ODDS-1.5), caregiver age (ODDS-0.87), spouse as caregiver (ODDS-10.9) and higher education (ODDS-0.79) predicted depression. CONCLUSIONS: Caregivers of cirrhotic patients have high prevalence of CB with low QOL and high incidence of anxiety and depression, compared with the general population. Alcoholism in patients precipitates while higher education helps cope up with these disorders.

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.

Mycobacterium abscessus infection in the stomach of patients with various gastric symptoms.

Development of gastric diseases such as gastritis, peptic ulcer and gastric cancer is often associated with several biotic and abiotic factors. Helicobacter pylori infection is such a well-known biotic factor. However, not all H. pylori-infected individuals develop gastric diseases and not all individuals with gastric diseases are infected with H. pylori. Therefore, it is possible that other gastric bacteria may contribute to the formation and progression of gastric disease. The aim of this study was to isolate prevalent gastric bacteria under microaerobic condition and identify them by 16S rRNA gene sequence analysis. Analysis of gastric biopsies showed infection of Mycobacterium abscessus (phylum Actinobacteria) to be highly prevalent in the stomachs of subjects included. Our data show that of 129 (67 male and 62 female) patients with gastric symptoms, 96 (51 male and 45 female) showed the presence of M. abscessus in stomach tissues. Infection of M. abscessus in gastric epithelium was further confirmed by imaging with acid fast staining, immunohistochemistry and immunofluorescence. Our imaging data strongly suggested that M. abscessus is an intracellular colonizer residing inside the gastric epithelial cells rather than in macrophages. Additionally, phylogenetic analysis of the mycobacterial hsp65 gene showed that the nearest match to the M. abscessus strains isolated from our study subjects is the M. abscessus strain ATCC 19977. Surprisingly, the subjects studied, the prevalence of M. abscessus infection in stomach is even higher than the prevalence of H. pylori infection. This, to the best of our knowledge, is the first study showing the colonization of M. abscessus in human gastric mucosa among patients with various gastric symptoms. This study could provide usher in a new opportunity to understand the role of less studied gastric bacteria in the development of gastric diseases.

Hepatic artery duplex Doppler ultrasound in severe alcoholic hepatitis and correlation with Maddrey's discriminant function.

BACKGROUND: Alcoholic hepatitis is associated with altered hepatic artery hemodynamics. Maddrey's discriminant function (MDF) can identify patients with poor prognosis (DF >32). We studied hepatic artery hemodynamic parameters of hepatic artery diameter (HAD), resistive index (RI) and pulsatility index (PI) in severe acute alcoholic hepatitis (SAAH) and for the presence of correlation of parameters with severity factor MDF. METHODS: A total of 20 consecutive SAAH patients defined as MDF >32 and a group of 20 alcoholic cirrhosis patients without alcoholic hepatitis formed the two study groups. Hepatic artery Doppler parameters HAD, RI, PI were determined after admission in the Gastroenterology Department, Government Medical College, Thiruvananthapuram, India. MDF score of SAAH was calculated at the time of admission to the hospital. RESULTS: The mean HAD showed statistically significant increase in SAAH compared with cirrhosis (3.96±0.51 vs. 2.86±0.41, P<0.001). There was statistically significant decrease in mean RI (0.49±0.08 vs. 0.81±0.09, P<0.001) and mean PI (1.67±0.13 vs. 1.80±0.13, P<0.001) in SAAH compared with alcoholic cirrhosis. Statistically significant correlation between MDF and HAD (r=0.63, P<0.003) was found in SAAH. On linear regression, 36% of the variability in MDF could be independently predicted by HAD. CONCLUSION: Hepatic artery parameters of HAD, RI, PI had a significant difference in SAAH compared with alcoholic cirrhosis patients thereby being useful as a diagnostic tool. HAD showed correlation with MDF score assessing the severity of alcoholic hepatitis and may be a useful non-invasive prognostic tool.