Haemophagocytic lymphohistiocytosis associated with liver injury in systemic sarcoidosis.

Hepatic involvement in sarcoidosis, though common, is usually asymptomatic. Hepatomegaly and deranged liver function tests are the usual manifestations. However, unexplained hepatomegaly in sarcoidosis not responding to immunosuppressive therapy could indicate an alternative pathology. Haemophagocytic lymphohistiocytosis (HLH), although seldom reported in sarcoidosis, can cause hepatosplenomegaly and cytopenias. HLH occurring concomitantly with hepatic sarcoidosis is extremely rare. We report a patient of systemic sarcoidosis who presented with fever, hepatosplenomegaly and jaundice despite being on steroid therapy. He was subsequently diagnosed with HLH. The clinical response to treatment with pulse steroid and oral cyclosporine was dramatic.

Gender Differences in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) has currently emerged as the most common liver disorder in both developed and developing countries. It has been observed that NAFLD exhibits sexual dimorphism, and there is limited understanding on the sex differences in adults with NAFLD. Nonalcoholic fatty liver disease shows marked differences in prevalence and severity with regards to gender. There are considerable biological disparities between males and females attributed to differences in the chromosomal makeup and sex hormone levels, distinct from the gender differences resulting from the sociocultural influences that lead to differences in lifestyle, which have a significant impact on the pathogenesis of this complex disorder. A multitude of factors contributes to the gender disparities seen and need to be researched in-depth to better understand the mechanisms behind them and the therapeutic measures that can be taken. In this article, we will review the gender disparities seen in NAFLD, as well as recent studies highlighting certain gender-specific factors contributing to its varying prevalence and severity. How to cite this article: Nagral A, Bangar M, Menezes S, et al. Gender Differences in Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S19-S25.

Association and functional significance of genetic variants present in regulatory elements of SERPINB5 gene in gallbladder cancer.

SERPINB5 is a mammary serine protease inhibitor, which is involved in various cellular functions. The aberrant expression of SERPINB5 is reported in many cancers along with GBC but limited information is available about its role in genetic predisposition for GBC. We carried out case-control study in 206 cases and 219 controls. Promoter SNPs were genotyped by Sanger's sequencing. In-silico promoter analysis and luciferase reporter assay were done to elucidate the role of promoter variants in regulation of SERPINB5 expression. Out of four SNPs, three SERPINB5 promoter variants showed association with GBC in different models. The 'C' allele of variant rs17071138 was found to be significantly associated with GBC (p = 0.017). The 'T' allele of rs3744940 significantly increased the risk for GBC in dominant (p = 0.035) and additive models (p = 0.005). Also, rs3744941 'T' allele increased the risk for GBC by dominant (p = 0.042) as well as additive models (p = 0.016). In-silico promoter analysis and luciferase reporter assay revealed the probable regulatory role of the SERPINB5 promoter variant rs17071138 on the expression. Overall, our study reveals the genetic association of SERPINB5 promoter variants with GBC and possible role of rs17071138 in the regulation of expression.

Oncogenic potential of ATAD2 in stomach cancer and insights into the protein-protein interactions at its AAA + ATPase domain and bromodomain.

ATAD2 has recently been shown to promote stomach cancer. However, nothing is known about the functional network of ATAD2 in stomach carcinogenesis. This study illustrates the oncogenic potential of ATAD2 and the participation of its ATPase and bromodomain in stomach malignancy. Expression of ATAD2 in stomach cancer is analyzed by in silico and in vitro techniques including western blot and immunofluorescence microscopy of stomach cancer cells (SCCs) and tissues. The oncogenic potential of ATAD2 is examined thoroughly using genetic alterations, driver gene prediction, survival analysis, identification of interacting partners, and analysis of canonical pathways. To understand the protein-protein interactions (PPI) at residue level, molecular docking and molecular dynamics simulations (1200 ns) are performed. Enhanced expression of ATAD2 is observed in H. pylori-infected SCCs, patient biopsy tissues, and all stages and grades of stomach cancer. High expression of ATAD2 is found to be negatively correlated with the survival of stomach cancer patients. ATAD2 is a cancer driver gene with 37 mutational sites and a predictable factor for stomach cancer prognosis with high accuracy. The top canonical pathways of ATAD2 indicate its participation in stomach malignancy. The ATAD2-PPI in stomach cancer identify top-ranked partners; ESR1, SUMO2, SPTN2, and MYC show preference for the bromodomain whereas NCOA3 and HDA11 have preference for the ATPase domain of ATAD2. The oncogenic characterization of ATAD2 provides strong evidence to consider ATAD2 as a stomach cancer biomarker. These studies offer an insight for the first time into the ATAD2-PPI interface presenting a novel target for cancer therapeutics. Communicated by Ramaswamy H. Sarma.

Narrative review of current and emerging pharmacological therapies for nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is the most common cause of chronic liver disease today, and it has now emerged as the leading etiology of end-stage liver disease requiring liver transplantation. It is a progressive form of non-alcoholic fatty liver disease which can not only progress to cirrhosis of liver and hepatocellular carcinoma (HCC), but is associated with increased cardiovascular risks too. Despite all the advances in the understanding of the risk factors and the pathogenetic pathways involved in the pathogenesis and progression of NASH, an effective therapy for NASH has not been developed yet. Although lifestyle modifications including dietary modifications and physical activity remain the mainstay of therapy, there is an unmet need to develop a drug or a combination of drugs which can not only reduce the fatty infiltration of the liver, but also arrest the development and progression of fibrosis and advancement to cirrhosis of liver and HCC. The pharmacologic therapies which are being developed target the various components believed to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)/NASH which includes insulin resistance, lipid metabolism oxidative stress, lipid peroxidation, inflammatory and cell death pathways, and fibrosis. In this review, we summarize the current state of knowledge on pharmacotherapy of NASH, and also highlight the recent developments in the field, for optimizing the management and treatment of NASH.

Management of Helicobacter pylori infection: The Bhubaneswar Consensus Report of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.

Genetic association of MMP14 promoter variants and their functional significance in gallbladder cancer pathogenesis.

Gallbladder cancer (GBC) is relatively rare but shows high frequency in certain geographical regions and ethnic groups, which include Northern and Eastern states of India. Previous studies in India have indicated the possible role of genetic predisposition in GBC pathogenesis. Although matrix metalloproteinase-14 (MMP14) is known modulator of tumour microenvironment and tumorigenesis and TCGA data also suggests its upregulation yet, its role in genetic predisposition for GBC is completely unknown. We explored MMP14 promoter genetic variants as risk factors and their implication in expression modulation and the pathogenesis of GBC. We genotyped all single nucleotide polymorphisms of MMP14 promoter by Sanger's sequencing in approximately 300 GBC and 300 control study subjects of Indian ethnicity and, in 26 GBC tissue samples. Protein expression of MMP14 in GBC tissue samples was checked by immunohistochemistry. In vitro luciferase reporter assay was carried out to elucidate role of promoter genetic variants on expression levels in two different cell lines. MMP14 promoter variants, rs1003349 (p value = 0.0008) and rs1004030 (p value = 0.0001) were significantly associated with GBC. Luciferase reporter assay showed high expression for risk alleles of both the SNPs. Genotype-phenotype correlation for rs1003349 and rs1004030, in patient sample, confirmed that risk allele carriers had higher expression levels of MMP14; moreover, the correlation pattern matched with genetic association models. Overall, this study unravels the association of MMP14 promoter SNPs with GBC which contribute to pathogenesis by increasing its expression.

SERPINB5 Genetic Variants rs2289519 and rs2289521 are Significantly Associated with Gallbladder Cancer Risk.

Serine protease inhibitor b5 (SERPINB5) is a tumor suppressor gene that plays a critical role in various cellular processes. In gallbladder cancer (GBC), SERPINB5's aberrant expression is reported but its role in genetic predisposition is not known. We enrolled 270 cases and 296 controls and genotyped them for single nucleotide polymorphisms (SNPs) using direct DNA sequencing, followed by genotype-phenotype analysis in GBC and other cancer cell lines. Luciferase assay was done to determine the role of rs2289521 SNP on expression regulation. We found that two SERPINB5 variants rs2289519 and rs2289521 are significantly associated with GBC and contribute to genetic predisposition. The TT genotype of variant rs2289519 was found to be significantly associated (p = 0.008) with GBC in a recessive model. C allele of rs2289521 increased the risk for GBC significantly at genotypic (CT, p = 0.026) and allelic (p = 0.04) levels. In silico analysis and luciferase assay uncovered the probable regulatory role of the rs2289521 variant on expression. Genotype-phenotype correlation in GBC and breast cancer cell lines showed reduced expression of SERPINB5 in the presence of C allele that was consistent with the result of luciferase assay. Overall, our study reveals the genetic association of two SERPINB5 variants with GBC and rs2289521's possible role in the regulation of expression.

HIF1α-dependent upregulation of ATAD2 promotes proliferation and migration of stomach cancer cells in response to hypoxia.

Stomach cancer is a difficult-to-treat disease. Lack of detection markers and limited understanding of the disease mechanisms contribute to the aggressive nature of stomach cancer cells (SCCs). Recently, an ATPase, ATAD2 has been found to be highly expressed in stomach cancer contributing to increased malignancy. However, nothing is known about the mechanism of ATAD2 upregulation and its involvement in stomach carcinogenesis. Since hypoxic microenvironment plays a crucial role in the progression of solid tumors like stomach cancer; we have examined the regulation and function of ATAD2 expression in hypoxic SCCs. ATAD2 is induced in hypoxia-treated SCCs. Stomach adenocarcinoma and metastatic tissues with high HIF1α level also show enhanced ATAD2 expression. In the absence of hypoxia-inducible factor HIF1α, ATAD2 protein level is found to be less indicating towards a potential correlation between them. We identify the presence of HIF1α-binding site (HBS) and HIF1α ancillary site (HAS) in the ATAD2 promoter. Using both in vitro and in vivo binding studies, we confirm that HIF1α binds with the ATAD2 promoter in hypoxic condition. ATAD2 upregulation promotes proliferation and migration of SCCs exposed to hypoxia. Thus, we identify ATAD2 as a hypoxia-responsive and HIF1α-regulated gene and elucidate that upregulated expression of ATAD2 enhances tumor-promoting functions in hypoxic SCCs. Therefore, we propose ATAD2 as a promising therapeutic target for stomach cancer.

Testin and filamin-C downregulation by acetylated Siah2 increases invasiveness of Helicobacter pylori-infected gastric cancer cells.

Helicobacter pylori is the strongest known risk-factor for gastric cancer. However, its role in gastric cancer metastasis remains unclear. Previously we have reported that H. pylori promotes gastric cancer invasiveness by stabilizing the E3 ubiquitin ligase Siah2 which is mediated by Siah2 acetylation at Lys 139 (K139) residue. Here we identify that cell adhesion-related proteins testin (TES) and filamin-C (FLN-C) interact with Siah2 and get proteasomally degraded. The efficiency of TES and FLN-C degradation is significantly potentiated by K139-acetylated Siah2 (ac-K139 Siah2) in infected gastric cancer cells (GCCs). ac-Siah2-mediated downregulation of TES and FLN-C disrupts filopodia structures but promotes lamellipodia formation and enhances invasiveness and migration of infected GCCs. Since H. felis-infected mice as well as human gastric cancer biopsy samples also show high level of ac-K139 Siah2 and downregulated TES and FLN-C, we believe that acetylation of Siah2 is an important checkpoint that can be useful for therapeutic intervention.

Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori-infected gastric epithelial cancer cells.

Gastric epithelial cells infected with Helicobacter pylori acquire highly invasive and metastatic characteristics. The seven in absentia homolog (Siah)2, an E3 ubiquitin ligase, is one of the major proteins that induces invasiveness of infected gastric epithelial cells. We find that p300-driven acetylation of Siah2 at lysine 139 residue stabilizes the molecule in infected cells, thereby substantially increasing its efficiency to degrade prolyl hydroxylase (PHD)3 in the gastric epithelium. This enhances the accumulation of an oncogenic transcription factor hypoxia-inducible factor 1α (Hif1α) in H. pylori-infected gastric cancer cells in normoxic condition and promotes invasiveness of infected cells. Increased acetylation of Siah2, Hif1α accumulation, and the absence of PHD3 in the infected human gastric metastatic cancer biopsy samples and in invasive murine gastric cancer tissues further confirm that the acetylated Siah2 (ac-Siah2)-Hif1α axis is crucial in promoting gastric cancer invasiveness. This study establishes the importance of a previously unrecognized function of ac-Siah2 in regulating invasiveness of H. pylori-infected gastric epithelial cells.-Kokate, S. B., Dixit, P., Das, L., Rath, S., Roy, A. D., Poirah, I., Chakraborty, D., Rout, N., Singh, S. P., Bhattacharyya, A. Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori-infected gastric epithelial cancer cells.

Host transcription factor Speckled 110 kDa (Sp110), a nuclear body protein, is hijacked by hepatitis B virus protein X for viral persistence.

Promyelocytic leukemia nuclear bodies (PML-NB) are sub-nuclear organelles that are the hub of numerous proteins. DNA/RNA viruses often hijack the cellular factors resident in PML-NBs to promote their proliferation in host cells. Hepatitis B virus (HBV), belonging to Hepadnaviridae family, remains undetected in early infection as it does not induce the innate immune response and is known to be the cause of several hepatic diseases leading to cirrhosis and hepatocellular carcinoma. The association of PML-NB proteins and HBV is being addressed in a number of recent studies. Here, we report that the PML-NB protein Speckled 110 kDa (Sp110) is SUMO1-modified and undergoes a deSUMOylation-driven release from the PML-NB in the presence of HBV. Intriguingly, Sp110 knockdown significantly reduced viral DNA load in the culture supernatant by activation of the type I interferon-response pathway. Furthermore, we found that Sp110 differentially regulates several direct target genes of hepatitis B virus protein X (HBx), a viral co-factor. Subsequently, we identified Sp110 as a novel interactor of HBx and found this association to be essential for the exit of Sp110 from the PML-NB during HBV infection and HBx recruitment on the promoter of these genes. HBx, in turn, modulates the recruitment of its associated transcription cofactors p300/HDAC1 to these co-regulated genes, thereby altering the host gene expression program in favor of viral persistence. Thus, we report a mechanism by which HBV can evade host immune response by hijacking the PML-NB protein Sp110, and therefore, we propose it to be a novel target for antiviral therapy.

Anti-hepatitis B virus (HBV) response of imiquimod based toll like receptor 7 ligand in hbv-positive human hepatocelluar carcinoma cell line.

BACKGROUND: Toll like receptors (TLRs) play an important role in innate immunity and various studies suggest that TLRs play a crucial role in pathogenesis of hepatitis B virus (HBV) infection. The present study aims in looking into the status of crucial host and viral gene expression on inciting TLR7. METHODS: The transcription of TLR7 pathway signaling molecules and HBV DNA viral load were quantified by Real Time-PCR after stimulation of TLR7 with its imiquimod based ligand, R837. Cell cycle analysis was performed using flow-cytometry. Expression of TLR7 and chief cell cycle regulator governing G1/S transition, p53 was also seen in liver biopsysss samples of CHB patients. HBV induced alteration in histone modifications in HepG2 cells and its restoration on TLR7 activation was determined using western blot. RESULTS: The TLR7 expression remains downregulated in HepG2.2.15 cells and in liver biopsy samples from CHB patients. Interestingly HBV DNA viral load showed an inverse relationship with the TLR7 expression in the biopsy samples. We also evaluated the anti-viral activity of R837, an agonist of TLR7. It was observed that there was a suppression of HBV replication and viral protein production upon TLR7 stimulation. R837 triggers the anti-viral action probably through the Jun N-terminal Kinase (JNK) pathway. We also observed a downregulation of histone H3K9Me3 repression mark upon R837 treatment in HBV replicating HepG2.2.15 cells, mimicking that of un-infected HepG2 cells. Additionally, the G1/S cell cycle arrest introduced by HBV in HepG2.2.15 cells was released upon ligand treatment. CONCLUSION: The study thus holds a close insight into the changes in hepatocyte micro-environment on TLR7 stimulation in HBV infection.

A 10-year-old child presenting with syndromic paucity of bile ducts (Alagille syndrome): a case report.

BACKGROUND: Alagille syndrome, a rare genetic disorder with autosomal dominant transmission, manifests with five major features: paucity of interlobular bile ducts, characteristic facies, posterior embryotoxon, vertebral defects, and peripheral pulmonary stenosis. Globally, only 500 cases have so far been reported, with only five cases reported in the Indian subcontinent. Rarely, Alagille syndrome also presents with skin manifestations and early-onset chronic liver disease, which was found in our case. We believe that we report what could be the first case of Alagille syndrome presenting with café au lait spots, as no such published case report could be found in the literature. CASE PRESENTATION: We report an unusual case of childhood cholestatic jaundice with neonatal onset of jaundice. A 10-year-old boy from the Indian subcontinent presented with obstructive jaundice from early infancy. He also had recurrent fractures of his upper limb bones, intermittent bleeding from his nose, productive cough, decreased night vision, hyperpigmented spots over his skin, and progressive enlargement of his abdomen. Histological examination of a liver biopsy specimen revealed a paucity of bile ducts and changes suggestive of chronic liver disease. Our patient was diagnosed with Alagille syndrome and managed conservatively but died 1 year after the final diagnosis. CONCLUSIONS: This particular syndromic form of paucity of bile duct disorder has been rarely reported in the Indian literature so far. Our case is notable because the child had café au lait spots and very early onset of chronic liver disease, which is quite rare in Alagille syndrome. We believe this to be the first case report on Alagille syndrome manifesting with café au lait syndrome and such early onset of chronic liver disease.

Socioeconomic impact of alcohol in patients with alcoholic liver disease in eastern India.

AIM: The aim of this study is to estimate the socioeconomic impact of alcohol use on patients with alcoholic liver disease (ALD) and their families. METHODS: The demographic and socioeconomic data were collected from hospitalized ALD patients and attendants using a self designed non validated questionnaire and analyzed. RESULTS: Study subjects included 100 consecutive ALD patients (all males). Sixty percent were between 30 and 50 years. Most were married (96 %), literate (63 %), either businessmen (37 %) or employed (30 %) and belonged to middle socioeconomic class. Ninety percent started alcohol use before age 30 years and half during teenage. Mean alcohol intake was 190 mL/day (mean duration 23 years); 60 % consumed alcohol daily. Concomitant tobacco abuse was noted in 79 %. Average expenditure on alcohol was Rs 3800/month. Average hospitalizations for ALD related problems was 2.6 times/year with average expenditure of INR 30,000 (~440 US$) during each hospitalization. For treatment expenses, 86 % of patients borrowed money from friends/relatives, 36 % used saving deposits, and 4 % sold personal belongings. Eleven percent lost their job, and 7 % sold immovable property. In 43 % of cases, children were deprived of education. Besides, 52 % had disturbed social and family life, 34 % abused their spouse, 20 % suffered accidents, and 37 % indulged in physical violence. CONCLUSION: Majority of ALD patients and their families had disturbed social and family life and incurred severe financial loss arising of alcohol use.

ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.

Helicobacter pylori infection is one of the most potent factors leading to gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3 ubiquitin ligase which has been implicated in various cancers but its role in H. pylori-mediated gastric carcinogenesis has not been established. We investigated the involvement of Siah2 in gastric cancer metastasis which was assessed by invasiveness and migration of H. pylori-infected gastric epithelial cancer cells. Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly induced expression of Siah2, increased invasiveness and migration after being challenged with the pathogen. Siah2-expressing stable cells showed increased invasiveness and migration after H. pylori infection. Siah2 was transcriptionally activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These transcription factors dose-dependently enhanced the aggressiveness of infected GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and invasiveness through Siah2 induction. As gastric cancer biopsy samples also showed highly induced expression of ETS2, Twist1 and Siah2 compared with noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up-regulation has potential diagnostic and prognostic significance and could be targeted for therapeutic purpose.

Association Analysis of PRSS1-PRSS2 and CLDN2-MORC4 Variants in Nonalcoholic Chronic Pancreatitis Using Tropical Calcific Pancreatitis as Model.

OBJECTIVE: Association of PRSS1-PRSS2 (rs10273639) and CLDN2-MORC4 (rs12688220 and rs7057398) variants with alcohol-related chronic pancreatitis (CP) is established but with nonalcoholic CP is unclear. We addressed this inconsistency using tropical calcific pancreatitis (TCP) as model. METHODS: We sequenced 5'-UTR of PRSS1 and genotyped CLDN2-MORC4 variants in 555 patients with TCP and 801 controls and performed association analysis. Gene-gene interaction between PRSS1 and CLDN2-MORC4 variants and with p.Asn34Ser SPINK1 and p.Leu26Val CTSB was also evaluated. RESULTS: We observed significant association of rs10273639/rs4726576 in PRSS1-PRSS2 (odds ratio [OR] = 0.72; P = 3.50 × 10) and CLDN2-MORC4 variants, rs12688220 (OR = 1.54; P = 1.22 × 10) and rs7057398 (OR = 1.50; P = 1.22 × 10) with TCP. Patients carrying p.Asn34Ser SPINK1 were significantly younger than those with rs4726576 risk genotype (30.0 vs 38.0 years; P = 0.015) and those carrying both were even younger (22.0 years; P = 0.001). Presence of risk allele at rs12688220 in patients carrying p.Asn34Ser SPINK1 delayed the age of onset (32.0 vs 24.0 years; P = 0.013). CONCLUSIONS: Our study establishes strong association of PRSS1-PRSS2 and CLDN2-MORC4 variants with TCP and thus with nonalcoholic CP. These variants independently interact with p.Asn34Ser SPINK1 and influence the age of onset in TCP. However, latter results need to be replicated in other cohorts.

Ultrasonographic demonstration of inner tube sign: a tropical dilemma.

INTRODUCTION: Ultrasonographic demonstration of intra biliary parallel lines or "inner tube sign" is considered diagnostic for biliary ascariasis in regions where ascariasis is endemic. PATIENTS & METHODS: 148 patients with inner tube sign on ultrasonography were evaluated. In most, diagnosis was confirmed by ultrasonographic demonstration of restitution of normal appearance of bile duct with passage of round worms in vomitus or faeces. RESULTS: Diagnosis was confirmed in 122 of 148 patients. 26 patients were lost to follow-up. Biliary ascariasis was responsible for the sign "parallel lines" in 113 patients. Of the remaining, intrabiliary stents were responsible for the "inner tube sign" in six whereas in three it was due to hydatid membranes following intrabiliary rupture of hydatid cyst. CONCLUSION: Biliary ascariasis is the commonest cause of inner tube sign in the tropics. However, this sign can also be produced by biliary stents and hydatid membranes. Awareness of these possibilities is essential for sonologists in the tropics.

Spectrum of upper gastrointestinal hemorrhage in coastal Odisha.

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is one of the commonest gastrointestinal emergencies encountered by physicians and surgeons. The spectrum of upper gastrointestinal bleeding varies from region to region and depends on the status of the center in healthcare hierarchy. AIM: To determine the etiology of UGIB at a gastroenterology clinic in coastal Orissa and to compare it with other regions of India. METHODS: Six hundred and eight consecutive patients with UGIB reporting to a gastroenterology outpatient clinic were subjected to upper gastrointestinal endoscopy (UGIE) to find out the etiology. The clinical profile and endoscopic findings were analyzed and compared with the data on UGIB from other regions of the country. RESULTS: The mean age of patients was 42+/-18.2 years. Majority of them were males (85.53%) and male: female ratio was 6:1. The commonest cause of UGIB was duodenal ulcer (DU) which accounted for 57.57% cases. Portal hypertension was responsible for bleed in only 12.83%. Benign prepyloric ulcer accounted for 6.41% cases and concomitant duodenal ulcer and benign pyloric ulcer were seen in 3.61%. Gastric ulcer was responsible for 1.8% only. Neoplasm accounted for 7.73% of cases. Other less common causes were erosive gastritis (1.8%), Mallory Weiss tear (1.8%), and retch gastropathy (1.1%). Non steroidal anti inflammatory (NSAID) ingestion was reported in 7.56% of cases. Melena was the commonest mode of presentation. Surprisingly, over two third cases of DU bleeds were not associated with abdominal pain. CONCLUSIONS: Bleeding duodenal ulcer was the commonest cause of UGIB in coastal Odisha. This is in contrast to reports from other parts of India, where variceal bleeding is the predominant etiology. The differences could be due to the reason that the studies which have portrayed variceal bleeding as the commonest cause of UGIB reflect the etiology of bleed of only severe cases which were referred to these centers - all of whom needed urgent hospitalization. The figures from our study are true reflection of the real etiological spectrum of UGIB in this region.