Changing Etiological Spectrum of Hepatocellular Carcinoma in India-A Systematic Review and Meta-analysis.

Background: Recent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis. Methods: Electronic databases of PubMed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics. Results: A total of 60 studies (n = 12,327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5-62.6) and 43.1% (36.5-49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8-46.1), while those with positive markers for hepatitis C virus were 20.3 (17.0-23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6-22.4), and those related to nonalcoholic fatty liver disease (NAFLD) were 16.9% (12.1-21.7). Around 7.9% (5.8-10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with hepatitis C virus and alcohol did not change significantly. Conclusion: Viral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining.

Impact of nutritional status on the outcome of transjugular intrahepatic portosystemic shunt in patients with cirrhosis: a systematic review.

OBJECTIVES: Malnutrition and sarcopenia have been reported to adversely affect the outcome of patients with cirrhosis of the liver. There is an emerging body of evidence suggesting malnutrition and sarcopenia increase the risk of hepatic encephalopathy (HE) and mortality after transjugular intrahepatic portosystemic shunt (TIPS). The current systematic review aims to determine whether the body of evidence supports an association between nutritional status and post-TIPS outcomes in patients with cirrhosis. METHODS: Electronic databases of PubMed, Embase, and Scopus were searched from inception to June 3, 2023, for studies analysing the effect of nutritional status on post-TIPS outcomes in patients with cirrhosis. RESULTS: A total of 22 studies were included in the systemic review. Assessment of sarcopenia was done by skeletal muscle index (SMI) at the L3 level, transversal psoas muscle thickness, psoas muscle density, malnutrition as per ICD, relative sarcopenia with excess adiposity, lipid profile, controlling nutritional status score, body composition analysis, hospital frailty risk score, and visceral and subcutaneous fat area index. Ten out of 12 studies in this systematic review showed a significant association with the incidence of post-TIPS HE. Thirteen out of 14 studies reported that the presence of malnutrition was associated with increased odds of mortality following TIPS. One study reported sarcopenia as an independent predictor of liver failure, and another study reported that Pre-TIPS SMI was an independent predictor of substantial improvement in post-TIPS SMI. CONCLUSIONS: The current systematic review shows that the presence of pre-TIPS malnutrition or sarcopenia is an independent predictor of adverse outcomes after TIPS. Incorporating these parameters into present prediction models can provide additional prognostic information. ADVANCES IN KNOWLEDGE: Nutritional assessment should be part of the evaluation of patients planned for TIPS for prediction of adverse events after the procedure.

Effectiveness and safety of Shankhaprakshalana-a yogic technique-in bowel preparation for colonoscopy: A retrospective study.

INTRODUCTION: Shankhaprakshalana (SP) is a yogic method aiming to cleanse the bowel. It involves the use of warm saline water and a combination of five asanas. This study was designed to assess the effectiveness and safety of bowel preparation by SP. METHODS: This is a retrospective observational study of prospectively collected data. Patients planned for colonoscopy were screened and enrolled to undergo bowel preparation by SP on the day of the colonoscopy. Patients having comorbid conditions, poor performance status, suspected or previously diagnosed intestinal stricture and past history of major abdominal surgery and those unable to perform asanas of SP were excluded. A low-fiber diet was advised for one day before the colonoscopy. Patients were advised to drink 400 mL of lukewarm saline water followed by five asanas (exercises) of SP, each done eight times dynamically and sequentially. After completing six such cycles, patients underwent colonoscopy. Boston Bowel Preparation Scale (BBPS) score was used to assess the quality of bowel preparation. RESULTS: Total 238 patients were included. The major indications for colonoscopy were abdominal pain (35.3%), hematochezia (23.9%), diarrhea (20.2%), constipation (10.9%) and anemia (9.7%). The mean age was 37.7 (± 12) years. The mean BBPS was 8 (± 1.2). Bowel preparation was inadequate (BBPS < 6) in only two patients. Mean segmental BBPS for the three segments of the colon (right, transverse and left) was 2.6 (± 0.5), 2.7 (± 0.4) and 2.6 (± 0.7), respectively. Minor adverse events (nausea, abdominal pain, vomiting, giddiness and bloating) were noted in 10 participants (4.2%), which did not require hospitalization. Bowel preparation was completed in 133 (± 35) minutes. CONCLUSION: Shankhaprakshalana is an effective and safe method to achieve adequate bowel preparation before colonoscopy. Since this is a single-center and retrospective study, future multi-centric, prospective studies comparing it with the standard bowel preparation regimens are warranted.

Poor Performance of Non-invasive Tests for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: A Multicentric Asian Study.

BACKGROUND: Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. METHODS: Biopsy-proven 641 NAFLD patients (55.2% males, median age 42 years) were included from three different centers of Asia. AF (≥ F3) was identified as per histological staging (24.8%). RESULTS: TE had the highest area under the receiver operating characteristic curve (AUROC) 0.82 (0.79-0.86), and all other biomarker-based NITs had low AUROC (< 0.7). NITs performed poorly at established thresholds. The combination of NITs utilizing liver stiffness measurement (LSM) and biomarkers, Agile 3+ and FAST, demonstrated acceptable diagnostic accuracy (AUROC 0.82 and 0.78, respectively), but none were superior to LSM alone. LSM measured using appropriate M and XL probes remained accurate regardless of body mass index (BMI); NFS and APRI scores were less accurate at higher BMI ranges. A two-step approach using NFS rule-out criteria (< - 2.97 to rule out) followed by LSM (< 7.3 kPa to rule out and ≥ 12.7 kPa to rule in) correctly classified 62.4% of patients, with only 10.2% of patients incorrectly classified. CONCLUSION: NITs have not been validated to identify AF in the Asian NAFLD population, and internationally accepted thresholds yield high false-negative rates. LSM and LSM-based combination tests remain the most accurate.

INASL-SAASL Consensus Statements on NAFLD Name Change to MAFLD.

There is an ongoing debate on the change of terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). Experts from the Indian National Association for Study of the Liver (INASL) and the South Asian Association for Study of the Liver (SAASL) involved in diagnosing, managing, and preventing NAFLD met in March 2022 to deliberate if the name change from NAFLD to MAFLD is appropriate, as proposed by a group of experts who published a "consensus" statement in 2020. Proponents of name change to MAFLD opined that NAFLD does not reflect current knowledge, and the term MAFLD was suggested as a more appropriate overarching term. However, this "consensus" group which proposed the name change to MAFLD did not represent the views and opinions of gastroenterologists and hepatologists, as well as perceptions of patients across the globe, given the fact that change of nomenclature for any disease entity is bound to have multidimensional impact on all aspects of patient care. This statement is the culmination of the participants' combined efforts who presented recommendations on specific issues concerning the proposed name change. The recommendations were then circulated to all the core group members and updated based on a systematic literature search. Finally, all the members voted on them using the nominal voting technique as per the standard guidelines. The quality of evidence was adapted from the Grades of Recommendation, Assessment, Development and Evaluation system.

Acute Kidney Injury (AKI) at Admission Predicts Mortality in Patients With Severe Alcoholic Hepatitis (SAH).

Background & aims: Severe alcoholic hepatitis (SAH) is a grave condition, and the presence of acute kidney injury (AKI) further jeopardizes patient survival. However, the impact of AKI on survival in SAH has not been assessed from this region of Asia. Materials and methods: This study was conducted on consecutive alcohol-associated liver disease (ALD) patients hospitalized in Gastroenterology Department, SCB Medical College, Cuttack, India, between October 2016 and December 2018. On diagnosis of SAH (mDF score ≥32), demographic, clinical, and laboratory parameters were recorded, and survival was compared between patients with and without AKI (AKIN criteria). In addition, survival was compared among SAH patients defined by other criteria and prognostic models in the presence and absence of AKI. Results: 309 (70.71%) of ALD patients had SAH, and 201 (65%) of them had AKI. SAH patients with AKI had higher total leucocyte count, total bilirubin, serum creatinine, serum urea, INR, MELD (UNOS), MELD (Na+), CTP score, mDF score, Glasgow score, ABIC score, and increased prevalence of acute on chronic liver failure (ACLF) as per EASL-CLIF Consortium criteria (P < 0.001). Further, they had prolonged hospital stay, and increased death during hospitalization, at 28 days as well as 90 days (P < 0.001). Significant differences in survival were also seen in SAH (as per MELD, ABIC, and GAHS criteria) patients above the marked cut offs in respect to AKI. Conclusions: Over two-thirds of ALD patients had SAH, and about two-thirds had AKI. Patients with SAH and AKI had an increased prevalence of ACLF, longer hospital stay, and increased mortality during hospitalization at 28 days and 90 days. Lay summary: SAH is a critical condition, and the presence of AKI negatively affects their survival. Hence, early identification of SAH and AKI, as well as early initiation of treatment, is crucial for better survival. Our study from the coastal part of eastern India is the first to demonstrate the prevalence of SAH among patients with ALD along with the prevalence of AKI among SAH patients in this region. This knowledge will be helpful in managing these patients from this region of world.

Risk of Bleeding with Endoscopic Ultrasound-Guided Tissue Acquisition in Patients on Antithrombotic Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: The present guidelines stratify endoscopic ultrasound-guided tissue acquisition (EUS-TA) as a high-bleeding risk procedure in patients on antithrombotics. However, the data regarding the same are conflicting. Therefore, this meta-analysis aimed to analyze the bleeding event rates associated with EUS-TA in patients receiving antithrombotic therapy. METHODS: A literature search from January 2000 to August 2022 was done for studies on EUS-guided TA in patients receiving antithrombotics. The primary outcome was incidence of overall and major bleeding. Pooled event rates across studies were expressed with summative statistics. RESULTS: A total of 12 studies were included in the meta-analysis. The pooled risk of overall bleeding and major bleeding in patients on antithrombotics was 2.0% (0.6-3.4) and 0.8% (0.0-1.6), respectively. In patients taking thienopyridine or anticoagulants, the pooled risk of overall bleeding and major bleeding was 2.4% (0.9-3.9) and 1.7% (0.4-3.1), respectively. Patients on antithrombotics had a higher odd of overall bleeding (OR 2.12, 1.20-3.83) and major bleeding (OR 3.58, 1.11-11.52) compared to controls. The odds of overall bleeding (OR 0.95, 95%CI 0.38-2.42) and major bleeding (OR 1.57, 95%CI 0.45-5.54) were comparable between patients on antithrombotics who continued and those who discontinued it preprocedural. CONCLUSION: Despite an increase risk of bleeding with EUS-TA in patients on antithrombotics, the pooled incidence remains low. Compared to the previous guidelines stating thienopyridine use as high risk for bleeding, the present analysis showed a bleeding rate of less than 1%. Discontinuing antithrombotics prior to EUS-TA does not reduce the bleeding risk significantly, requiring strict monitoring.

NAFLD vs MAFLD: South Asian NAFLD Patients don't Favor Name Change.

Aim: There have been vociferous attempts to change the name of Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Associated Fatty Liver Disease (MAFLD). Of the many arguments put forth in support of this, an important one is the presumed demand by patient groups insisting on the change. However, this claim does not have credible evidence to support it. Therefore, we decided to conduct a survey among South Asian NAFLD patients to understand their perspectives with regard to the change in nomenclature. Materials and Methods: The study was conducted at multiple centers across South Asia from January 2021 to June 2021. Patients were surveyed using an 8-question survey questionnaire and responses were categorized by multiple-choice format. Results: Of 218 patients surveyed, 80.3% of the patients were not aware of the entity "NAFLD" before they were first diagnosed. Although 74.3% of patients admitted to being questioned about alcohol intake at the time of the first diagnosis, 75.9% of female patients were not questioned regarding this. After being labelled NAFLD, 92.1% of patients were never questioned again about alcohol intake. While 86.3% of patients found the term "NAFLD" consoling, 83% did not feel that "Non" in NAFLD trivialized their problem. In addition, only 6.9% of patients were scared of developing cardiovascular disease. Conclusion: The term "NAFLD" destigmatizes patients of the taboo associated with alcohol use. It was found to be consoling to most patients and they did not feel it trivialized their problem. A change of name without considering patients' perspectives and peculiarities specific to different populations will have enormous ramifications for both patients and physicians. Clinical significance: Our survey clearly shows that patients are happy with the term "NAFLD" and it effectively destigmatizes them from the taboo of alcohol. This would lead to higher compliance with management and greater patient participation in future studies and trials. How to cite this article: Singh SP, Anirvan P, Butt AS, et al. NAFLD vs MAFLD: South Asian NAFLD Patients don't Favor Name Change. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S1-S4.

Nonalcoholic Fatty Liver Disease (NAFLD) Name Change: Requiem or Reveille?

Nonalcoholic fatty liver disease (NAFLD) affects about a quarter of the world's population and poses a major health and economic burden globally. Recently, there have been hasty attempts to rename NAFLD to metabolic-associated fatty liver disease (MAFLD) despite the fact that there is no scientific rationale for this. Quest for a "positive criterion" to diagnose the disease and destigmatizing the disease have been the main reasons put forth for the name change. A close scrutiny of the pathogenesis of NAFLD would make it clear that NAFLD is a heterogeneous disorder, involving different pathogenic mechanisms of which metabolic dysfunction-driven hepatic steatosis is only one. Replacing NAFLD with MAFLD would neither enhance the legitimacy of clinical practice and clinical trials, nor improve clinical care or move NAFLD research forward. Rather than changing the nomenclature without a strong scientific backing to support such a change, efforts should be directed at understanding NAFLD pathogenesis across diverse populations and ethnicities which could potentially help develop newer therapeutic options.

Association of non-alcoholic fatty liver disease and COVID-19: A literature review of current evidence.

The coronavirus disease 2019 (COVID-19) pandemic has swept through nations, crippled economies and caused millions of deaths worldwide. Many people diagnosed with COVID-19 infections are often found to develop liver injury, which, in a small portion of patients, progresses to severe liver disease. Liver injury in the form of elevated transaminases, hyperbilirubinemia and alterations in serum albumin has been observed to be higher in patients with severe forms of the disease. Those who already have insult to the liver from chronic disease, such as nonalcoholic fatty liver disease (NAFLD) may be at the greatest disadvantage. The severity of COVID-19 also seems to be driven by the presence of NAFLD and other co-morbidities. About 25% of the global population has NAFLD. With such a widespread prevalence of NAFLD, understanding the disease progression of COVID-19 and the occurrence of liver injury in this vulnerable population assumes great significance. In this review, we present an overview of COVID-19 infection in patients with NAFLD.