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.

Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of conditions, progressing from mild steatosis to advanced fibrosis. Sarcopenia, characterized by decreased muscle strength and mass, shares common pathophysiological traits with NAFLD. An association exists between sarcopenia and increased NAFLD prevalence. However, data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent. AIM: To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD. METHODS: We conducted a comprehensive search for relevant studies in MEDLINE, Embase, and Scopus from their inception to June 2023. We included studies that focused on patients with NAFLD, reported the prevalence of sarcopenia as the primary outcome, and examined secondary outcomes, such as liver fibrosis and other adverse events. We also used the Newcastle-Ottawa scale for quality assessment. RESULTS: Of the 29 studies included, the prevalence of sarcopenia in NAFLD varied widely (1.6% to 63.0%), with 20 studies reporting a prevalence of more than 10.0%. Substantial heterogeneity was noted in the measurement modalities for sarcopenia. Sarcopenia was associated with a higher risk of advanced fibrosis (odd ratio: 1.97, 95% confidence interval: 1.44-2.70). Increased odds were consistently observed in fibrosis assessment through biopsy, NAFLD fibrosis score/body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes (BARD) score, and transient elastography, whereas the fibrosis-4 score showed no such association. Sarcopenia in NAFLD was associated with a higher risk of steatohepatitis, insulin resistance, cardiovascular risks, and mortality. CONCLUSION: This systematic review highlights the critical need for standardized diagnostic criteria and measurement methods for sarcopenia in NAFLD patients. The variability in study designs and assessment methods for sarcopenia and liver fibrosis may account for the inconsistent findings. This review demonstrates the multidimensional impact of sarcopenia on NAFLD, indicating its importance beyond liver-related events to include cardiovascular risks, mortality, and metabolic complications.

Dengue-related acute liver failure-A scoping review.

Infection by dengue virus is common in tropical countries. Hepatic involvement in dengue can range from asymptomatic elevation of transaminases to life-threatening acute liver failure (ALF). Dengue-related ALF (DALF) is responsible for significant morbidity and mortality, especially in Southeast Asia. However, there is a scarcity of literature on DALF, necessitating a thorough examination of its clinical determinants and management strategies. All relevant studies related to DALF were reviewed until December 2023. Case reports, case series and studies reporting ALF in dengue infection were included. Demographics, clinical profiles, management and outcomes of DALF cases were analyzed, which revealed a predominance of DALF incidence in pediatric patients (1.1% to 15.8%) and an upward trend over the years, particularly in India. The proportion of ALF cases attributable to dengue was also higher among pediatric ALF patients (6.7% to 34.3%). Age ≤ 40 years, persistent nausea, vomiting and elevated serum bilirubin and alkaline phosphatase (ALP) with aspartate aminotransferase (AST) > 1000 IU/mL within the first five days of illness, more than 10% of atypical lymphocytes in peripheral blood, platelet count of < 50,000/cu·mm, severe hepatitis at presentation and baseline model for end-stage liver disease (MELD) > 15 were the risk factors for the development of DALF. Histopathological features of DALF included multi-lobular hepatic necrosis, steatosis and occasional cholestasis. Mortality in DALF ranged from 0% to 80%; admission pH and lactate strongly predicted mortality, while mortality was found to be significantly higher in patients with cirrhosis. N-Acetyl cysteine (NAC) has been used as a treatment modality with varying results. There is limited evidence regarding the use of extra-corporeal support systems, while candidate selection for liver transplantation (LT) in DALF remains poorly defined.

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.

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.