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.

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.

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.

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.

Doppler assessment of hepatic venous waves for predicting large varices in cirrhotic patients.

BACKGROUND/AIM: Color Doppler examination of changes in hepatic venous waveforms is being evaluated as a means of prediction of severity of portal hypertension and presence of esophageal varices. Normal hepatic venous waveform shows a triphasic pattern. In cirrhosis, this pattern changes to a biphasic or monophasic pattern. We aimed to study the sensitivity of loss of normal hepatic venous waveforms in predicting large varices in a cross-sectional analysis. MATERIALS AND METHODS: All patients, admitted or attending the outpatient department, with a diagnosis of cirrhosis were included in the study. All patients were subjected to oesophagogastroduodenoscopy and Color Doppler examination, and waveform patterns in hepatic vein were recorded. The sensitivity and specificity of changes in waveform in detecting large varices were studied. RESULTS: A total of 51 cases were examined. Triphasic waves were seen in 4 (7.8%) cases, biphasic in 26 (51%) cases, and monophasic in 21 (41.2%) cases. Small varices were seen in 30 (58.8%) cases and large varices in 21 (41.2%) cases. The sensitivity of loss of the triphasic wave pattern in detecting significant varices (Grade 3 or 4) was very high (95.23%) and negative predictive value was also high (75%). Severity of liver disease as indicated by Child-Pugh and MELD scores did not correlate with changes in hepatic venous waveforms. CONCLUSION: Loss of triphasic hepatic venous waveform is highly sensitive in predicting significant varices in patients with cirrhosis.