Cirrhotics with Monocyte Chemotactic Protein 1 Polymorphism are at Higher Risk for Developing Spontaneous Bacterial Peritonitis - A Cohort Study.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a complication of liver cirrhosis and its occurrence portends poor patient survival. There is emerging evidence that genetic predisposition could significantly alter the occurrence and course of SBP. Monocyte chemotactic protein 1 (MCP1) is a potent chemokine that perpetuates the pro-inflammatory milieu in SBP. AIM: This study aimed at investigating MCP1 genotype polymorphism and its survival impact in patients with decompensated liver cirrhosis. METHODS: We recruited 107 individuals with decompensated liver cirrhosis and categorized them into two groups. Patients having SBP formed the cases (Group 1) and controls were patients without SBP (Group 2). MCP1 polymorphism (-2518A/G) was assessed in both groups by restriction fragment length polymorphism method. The Chi-square test was used to assess the differences in categorical variables and Kaplan-Meier analyses were used to assess the survival. RESULTS: Patients with SBP (36.5%) had higher frequency of G allele than patients without SBP (23%) (P=0.031; odds ratio=1.955, 95% confidence interval: 1.0553-3.6216). Kaplan-Meir analysis revealed that presence of SBP (P=0.030) and G allele (P=0.021) had significantly reduced the likelihood of survival among cirrhotics. CONCLUSIONS: Cirrhotic patients with MCP1 G allele have a higher risk for developing SBP. In general, the presence of the MCP1 polymorphic G allele (AG/GG genotype) reduced the likelihood of survival among patients with cirrhosis. RELEVANCE FOR PATIENTS: This study identifies a critical subgroup of patients with SBP and also predicts prognosis in these individuals. The presence of this genetic polymorphism in addition to the underlying clinical condition may prompt aggressive monitoring, treatment, and follow-up.

Rodenticide ingestion is an important cause of acute hepatotoxicity in Tamil Nadu, southern India.

BACKGROUND AND AIM: Though rodenticidal hepatotoxicity is reported from India, there is no systematic study to assess its magnitude. This study aimed to assess exposure to rodenticide as a risk factor for acute hepatotoxicity in Tamil Nadu, India. METHODS: We retrospectively analyzed acute hepatotoxicity caused by ingestion of hepatotoxin or potentially hepatotoxic drug overdose across 15 hospitals in 6 districts of Tamil Nadu from 1 January 2019 to 30 June 2019. Study exclusion criteria were idiosyncratic drug-induced liver injury and chronic liver diseases. RESULTS: Of the 702 patients, 685 gave history of consuming rodenticide; hepatotoxicity in the other patients resulted from paracetamol overdose (n=10) and due to other drugs (n=7); 97% patients had a suicidal intent. Of 671 patients with complete data, ratio of number of patients with hepatotoxicity due to rodenticide to paracetamol overdose was 450:6 (i.e. 75:1). The 451 rodenticidal hepatotoxicity patients (255 males, 75% were 15-34 years old) underwent conservative management (n=396), plasma exchange (n=54) and plasma exchange followed by liver transplant (n=1); 159 patients (35%) had poor outcome (131 died, 28 discharged in moribund state). Based on our observations, we estimate a case burden of 1584 rodenticidal hepatotoxicity patients (95% CI: 265-6119) with poor outcome in 554 patients in Tamil Nadu from January 2019 to June 2019. Population attributable risk for rodenticide as cause of hepatotoxicity was 22.7%. CONCLUSION: Rodenticide ingestion was an important cause of acute hepatotoxicity in Tamil Nadu. Most patients were young and one-third had poor outcome. Public health interventions are needed to address this.

The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients.

BACKGROUND: Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality. METHODS: We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival. RESULTS: Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. Combination anti-TB drugs (ATD) 46.4%, complementary and alternative medicines (CAM) 13.9%, anti-epileptic drugs (AED) 8.1%, non-ATD antimicrobials 6.5%, anti-metabolites 3.8%, anti-retroviral drugs (ART)3.5%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics. CONCLUSION: In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.

Hereditary hemorrhagic telangiectasia of liver: Pathophysiology with role of radiology in diagnosis and treatment.

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is a rare condition which can result in significant systemic and hepatobiliary abnormalities. Liver involvement in HHT consists primarily of the consequence of various intrahepatic shunts. Even though these vascular shunts are present in the majority of patients with HHT, symptoms occur only in minority with clear predilection to female gender. The symptoms and imaging findings of liver vascular malformations can be easily overlooked or misdiagnosed which can result in delay in treatment or potentially harmful vascular interventions. In this case report, we discuss the pathophysiology of HHT in liver involvement, role of imaging in diagnosis, and the possible role of interventional radiologist in the treatment.

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.

International Survey of Physicians' Perspectives on Percutaneous Endoscopic Gastrostomy Tube Feeding in Patients with Dementia and Review of Literature.

Percutaneous endoscopic gastrostomy (PEG) tube often remains to be used as a primary modality for feeding in patients with advanced dementia, perhaps due to misconceptions regarding the outcomes. Physicians' perceptions regarding the PEG tubes could be a significant contributing factor globally. A multidisciplinary approach involving the ethics committee can help address the issue. Our survey is focused on gauging physicians' perceptions regarding PEG tube utilization and its global impact on outcomes in dementia.

CagA and VacA genes of Helicobacter pylori and their clinical relevance.

CONTEXT: : Helicobacter pylori is associated with the development of a variety of gastroduodenal diseases which varies with ethnicity and the type of strains that infect the population. AIMS: This study aims to evaluate the prevalence of H. pylori cagA and vacA genotypes in our region and to determine their relationship to the severity of the lesions that they cause. SETTINGS AND DESIGN: : This study was an observational cross-sectional study. SUBJECTS AND METHODS: DNA was extracted from 165 gastric biopsies from patients evaluated for dyspepsia. PCR was used to detect cagA and vacA (s1, s2, m1, m2) genes of H. pylori. Statistical analysis of associations was performed between endoscopy findings and virulence genes. STATISTICAL ANALYSIS USED: Pearson Chi-square test and Fischer's exact test. RESULTS: The prevalence of H. pylori infection was 37% and the dominant genotypes was vacA s1 cagA-positive strain (54.1%) in this study. The vacAs1 subtype was found in all patients with peptic ulcer disease (PUD). The entire normal study group had VacA s2 variant only. This clearly shows that vacA s1 is a significant virulence marker and patients harboring s1 strains are more prone to develop ulcers (P = 0.007). There was a significant association of cagA with s1 strain rather than s2. Variation in VacA m genotype did not seem to have any association with disease status. There was a statistically significant association between the presence of cagA gene and PUD rather than the nonulcer dyspepsia (P = 0.027). CONCLUSION: The predominant genotype in our population was cagA positive vacA s1, which was found to be significantly associated with patients with gastric diseases, especially PUD. VacA s1 can serve as a single best virulence marker of the disease manifestation.

Fibrolamellar variant of hepatocellular carcinoma presenting during pregnancy: management dilemmas.

The Fibrolamellar variant of Hepatocellular Carcinoma (FLHCC) is a rare form of liver cancer that presents in the 3rd decade of life, is rarely associated with cirrhosis or chronic Hepatitis B/C virus infection, and usually presents with normal serum alpha-fetoprotein (AFP) levels. FLHCC presenting during pregnancy is extremely rare, with only 4 cases reported. We present a case of FLHCC in pregnancy and discuss the dilemmas in management. A 26 year-old primigravida, 26 weeks of gestation presented with a month's history of obstructive jaundice secondary. Investigations revealed a mass in the left lateral segment of the liver with extension down the left hepatic duct into the common bile duct. Following an emergency caesarean section at 31 weeks, she underwent a left hepatectomy with extrahepatic bile duct excision. The postoperative course was uneventful. Histopathology showed FLHCC. In conclusion, liver tumors presenting during pregnancy should be managed in a multidisciplinary setup with facilities for neonatal intensive care. Management depends on the presumed pathology, period of gestation and family preferences.

Persistent Systemic Inflammatory Response Syndrome predicts the need for tertiary care in Acute Pancreatitis.

INTRODUCTION: Patients with Acute Pancreatitis (AP) presenting with Systemic Inflammatory Response syndrome (SIRS) are more likely to have severe acute pancreatitis and are at increased risk of complications. Additionally, persistence of SIRS at 48 hrs after admission is associated with persistent organ failure and a worse outcome. We investigated the usefulness of SIRS as a criterion for referring patients to a tertiary pancreatic care centre. MATERIAL AND METHODS: Retrospective analyses of patients admitted with AP over a one year period. Patients were classified into 2 severity groups - 1) Mild AP, 2) Moderate and Severe AP (MASP) as per the Revised Atlanta Classification. SIRS was determined at presentation and following 48 hours of best medical management. Outcomes were compared between patients who had no SIRS at presentation, transient SIRS(SIRS≤48hrs) and persistent SIRS(>48hrs). RESULTS: 134 patients were included in the study. SIRS at presentation had a sensitivity of 88%(95% CI 75-96) and a specificity of 66%(95% CI 55-75) in predicting MASP. However, persistent SIRS and recovery from SIRS within 48hrs were poor predictors of MASP. Only 23/43 (53.5%) patients with MASP had persistent SIRS. Interestingly, MASP patients with persistant SIRS had a significant higher risk of complications, readmission, intervention, culture positivity and hospital stay as compared to those with transient SIRS. CONCLUSION: Persistent SIRS could be used to identify patients with MASP requiring tertiary care. This could be used as an effective tool by community hospitals with limited facilities. Further, prospective studies are required to validate our findings.

Giant-cell Hepatitis-Rare Entity in Adults.

Giant-cell hepatitis (GCH) is characterized by parenchymal inflammation with formation of large multinucleated hepatocytes in response to a variety of insults to the liver. Although it is commonly described in neonates, it rarely occurs in adults. Here we report a case of GCH because of herbal medicine intake.

High-grade non-Hodgkin's lymphoma of ovary presenting as peritonitis.

Primary ovarian lymphoma is rare, with ovary more commonly involved secondarily in generalized disease. Primary ovarian lymphoma presents as mass in the ovary with chronic symptoms; an acute presentation has not been described previously. A 75-year-old female presented with acute abdomen and features of peritonism. Computed tomography and magnetic resonance imaging demonstrated large mass in left ovary along with infiltration of adjacent sigmoid colon causing perforation and pneumoperitoneum. Few jejunal loops were also involved. Intraoperatively, there was left ovarian mass infiltrating the sigmoid colon with perforation and fecal peritonitis. Distal jejunal loops were adherent to the tumor. The involved sigmoid colon was resected with total abdominal hysterectomy, bilateral salpingo-oophorectomy and resection of adherent jejunal loops. Histopathology revealed ovarian tissue with necrotic neoplasm composed of small-to medium-sized round cells exhibiting nuclear irregularity and scanty cytoplasm, forming discohesive sheets with the neoplasm infiltrating the retroperitoneal remnant tissue and resected bowel. This case highlights an unusual presentation of primary ovarian lymphoma.

Jejunal diverticulosis - rare cause of gastrointestinal bleed.

Jejunal diverticulosis was first described by Somerling in 1794 and by Sir Astley Cooper in 1807. Jejunal diverticula are rare. Hemorrhage from jejunal diverticula usually presents as gastrointestinal bleeding. Here, we present a case of severe gastrointestinal bleeding presenting as malena due to jejunal diverticulosis.

Runt-related transcription factor 3: single nucleotide polymorphism rs760805, gene expression, and methylation status in Helicobacter pylori -infected patients for determination of gastric cancer risk.

PURPOSE: Repression of Runt-related transcription factor 3 (Runx3) gene, a tumor suppressor, has been known to be involved in Helicobacter pylori (H. pylori)-associated gastric carcinogenesis and cancer development. The present study was undertaken to study the Runx3 intronic T/A polymorphism (rs760805) in H. pylori-infected patients and uninfected controls of Tamil Nadu region, South India. Also, Runx3 gene expression, HK alpha (H,K-ATPase) gene expression and the methylation status of the Runx3 CpG island was determined. METHODS: In a prospective study, tissue biopsies were collected from 40 H. pylori-infected patients and 40 infection negative controls. Single nucleotide polymorphism analysis was carried out by polymerase chain reaction (PCR)-single-strand conformational polymorphism, and DNA sequencing. Gene expression analysis of Runx3 and HK alpha was carried out using semiquantitative reverse transcriptase-PCR. Methylation analysis of Runx3 CpG island was undertaken using methylationspecific restriction digestion-PCR. RESULTS: The homozygous TT genotype was found to be the predominant genotype in positive samples and negative controls. No significant variation in gene expression was observed in positive samples and controls with respect to Runx3 and Hk alpha genes. Methylation analysis suggested that there was a lack of methylation except in a few subjects studied. CONCLUSION: The present study, first from this region, could neither detect significant repression of the Runx3 and HK alpha genes nor methylation in positive patients studied suggesting a lack of involvement of this tumor suppressor as a risk factor in the H. pylori-associated gastric carcinogenesis in the South Indian population studied.