Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial.

Background: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24 h, day 3, and day 7. The primary outcome was an improvement in encephalopathy by ≥ 1 grade at 72 h. Patients and methods: European association for study of liver (EASL) defined ACLF patients with overt HE were assessed and randomized into the experimental arm (IV-BCAA - 500 mL/day for 3 days + Lactulose; n = 39) and the comparator arm (Lactulose alone; n = 37). Six patients developed COVID-19 after randomization and were excluded (4-experimental arm and 2-comparator arm). Results: Of 222 screened patients, 70 (35 in each arm) were included in the analysis. Baseline characteristics, including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7; P = 0.86) and (chronic liver failure) CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7; P = 0.65), were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%; P = 0.14). Improvement in hepatic encephalopathy scoring algorithm (HESA) by ≥ 1 grade at 24 h occurred in 14 patients (40%) in the BCAA arm and 6 patients (17.1%) in the control group (P = 0.03) which translated to a shorter intensive care unit (ICU) stay. The median change in HESA at 24 h was greater in the BCAA arm than the control arm (P = 0.006), which was not sustained at days 3 or 7. Ammonia levels did not correlate with the grade of HE (Spearman's correlation coefficient (ρ) = - 0.0843; P = 0.29). Conclusion: Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. Trial registration no: NCT04238416 (clinicaltrials.gov).

Spectrum of Autoimmune Liver Disease and Real-World Treatment Experience from a Tertiary Care Hospital.

Background and aims: Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. Methods: A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Results: Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P = 0.034), high albumin (OR 1.91 [1.05-3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P = 0.020) predicted complete response. Conclusion: AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.

Bacterial metabolite butyrate in modulating sorafenib-targeted microRNAs to curtail its resistance in hepatocellular carcinoma.

BACKGROUND AND AIM: The host dietary fibre is fermented into short-chain fatty acids (SCFA) by intestinal microbiota as bacterial metabolites like propionate, acetate and butyrate. Among these metabolites, the role of butyrate is well documented to provide energy to intestinal epithelial cells. Also, butyrate has anti-inflammatory and anti-tumour properties and decrease in its level by unbalanced diet can develops cancer. Lately, some research has suggested that sodium butyrate as an inhibitor of histone deacetylase (HDAC) may have anticancer potential for hepatocellular carcinoma (HCC), the most common type of liver cancer. Since, HCC is asymptomatic it is usually diagnosed at its advanced stage. Sorafenib with antiproliferative and antiangiogenic effects is the first line of treatment in advanced HCC. However, prolonged drug treatment to HCC patients develops adaptive resistance towards the sorafenib. Sorafenib resistance can also be enhanced by differentially expressed microRNAs. However, the significance of butyrate in HCC sorafenib resistance and its association with sorafenib-targeted microRNAs is yet to be unfurled. Here, an attempt has been made to explore the role of bacterial metabolite butyrate on sorafenib resistant HCC as well as on sorafenib-targeted microRNAs (miR-7641 and miR-199) to curtail sorafenib resistance in HCC. METHODS: Initially, in-silico analysis was performed using Human Metabolome Database (HMDB) so to identify specific butyrate producing faecal bacteria. Then, their specific 16s rRNA expression was compared between HCC patients and healthy individuals using qRT-PCR. Additionally, the cell viability (MTT) and apoptosis assays were performed in both parental and sorafenib resistant HepG2 cells to evaluate the role of sodium butyrate in sorafenib resistant HCC. Moreover, the association of sodium butyrate with sorafenib-targeted miR-7641 and miR-199 was also assessed using real time PCR, cell viability, cell apoptosis and transfection assays. RESULTS: In silico analysis demonstrated Roseburia cecical, Roseburia intestinalis, Eubacterium rectal, Faecalibacterium prausnitzii as specific butyrate producing faecal bacteria and their 16s rRNA expression was downregulated in HCC patients. In vitro study revealed the presence of sodium butyrate also decreased the cell viability as well as enhanced cell apoptosis of both parental and resistant HepG2 cells. Interestingly, sodium butyrate also decreased the expression of both sorafenib-targeted miR-7641 and miR-199. Further, combination of both sodium butyrate and antimiR-7641 or antimiR-199 also increased apoptosis and decreased viability of resistant cells. CONCLUSION: This is first study to unravel the association of butyrate producing bacteria with HCC patients and the significance of bacterial metabolite butyrate as anti-tumour in sorafenib resistant hepatocellular carcinoma. The study also demonstrated the plausible new aspects of bacterial metabolite butyrate association with sorafenib-targeted miRNAs (miR-7641 and miR-199). Hence, the study highlighted the therapeutic potential of bacterial metabolite butyrate that might improve the clinical management of hepatocellular carcinoma.

miR-23b-3p Modulating Cytoprotective Autophagy and Glutamine Addiction in Sorafenib Resistant HepG2, a Hepatocellular Carcinoma Cell Line.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common malignancy with increasing cancer deaths worldwide. HCC is mainly diagnosed at its advanced stage, and treatment with FDA-approved sorafenib, the multikinase inhibitor drug, is advised. Acquired resistance against sorafenib develops through several pathways involving hypoxia, autophagy, high glycolysis, or glutaminolysis. Small non-coding RNAs, similar to microRNAs (miRNAs), are also known to affect sorafenib resistance in HCC. However, there is a lack of information regarding the significance of differentially expressed miRNA (if any) on autophagy and glutamine regulation in sorafenib-resistant HCC. METHODS: The expression of autophagy and glutaminolysis genes was checked in both parental and sorafenib resistant HepG2 cell lines by real-time PCR. MTT and Annexin/PI assays were also performed in the presence of inhibitors such as chloroquine (autophagy inhibitor) and BPTES (glutaminolysis inhibitor). Next generation sequencing and in silico analysis were performed to select autophagy and glutamine addiction-specific microRNA. Selected miRNA were transfected into both HepG2 cells to examine its effect on autophagy and glutamine addiction in regulating sorafenib-resistant HCC. RESULTS: Our in vitro study depicted a higher expression of genes encoding autophagy and glutaminolysis in sorafenib-resistant HepG2 cells. Moreover, inhibitors for autophagy (chloroquine) and glutaminolysis (BPTES) showed a diminished level of cell viability and augmentation in cell apoptosis of sorafenib-resistant HepG2 cells. NGS and real-time PCR demonstrated the downregulated expression of miR-23b-3p in sorafenib-resistant cells compared to parental cells. In silico analysis showed that miR-23b-3p specifically targeted autophagy through ATG12 and glutaminolysis through GLS1. In transfection assays, mimics of miR-23b-3p demonstrated reduced gene expression for both ATG12 and GLS1, decreased cell viability, and increased cell apoptosis of sorafenib-resistant HepG2 cells, whereas the antimiRs of miR-23b-3p demonstrated contrasting results. CONCLUSION: Our study highlights the cytoprotective role of autophagy and glutamine addiction modulated by miR-23b-3p (tumor suppressor), suggesting new approaches to curb sorafenib resistance in HCC.

A Comparison of Different Frailty Scores and Impact of Frailty on Outcome in Patients With Cirrhosis.

Background & aims: There is no "gold standard" tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis. Methods: 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period. Results: 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4-51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) (P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4-54.2)], alcohol-related cirrhosis [OR 4.2 (1.1-16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4-2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1-0.4)] scores. Conclusions: LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application.

Experience With Changing Etiology and Nontransplant Curative Treatment Modalities for Hepatocellular Carcinoma in a Real-Life Setting-A Retrospective Descriptive Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) has variable etiological risk factors. Radiofrequency ablation (RFA) and surgical resection (SR) are frequently used as curative treatment options. In the present study, we assessed the etiological factors and efficacy of RFA and SR in patients with unifocal HCC in a real-life setting. METHODS: Of 870 patients with HCC seen over a period of nine years, 785 patients were assessed for stage and etiological risk factors. Of these, 110 (14%) patients with single HCC who were either treated with RFA (n = 72) or SR (n = 38) were evaluated for their outcomes in terms of overall survival (OS) and disease-free survival (DFS) over 3 years. RESULTS: Of 785 patients [median age 60 (range 51-65) years, males (n = 685, 87.3%)] with HCC, viral hepatitis [HBV and HCV with or without alcohol = 502 (63.9%)] was the most common etiology; nonalcoholic steatohepatitis (NASH) and alcohol as an etiology showed increase over the years. About 677 (86.2%) patients had evidence of cirrhosis; NASH and HBV were predominant causes in noncirrhotic patients. Even though the groups were not matched, in 110 patients subjected to either RFA [mean tumor size, 2.2 (1.9-2.8) cm] or SR [mean tumor size, 7.1 (4.8-9.7) cm], tumor progression was observed in 49 (68%) and 16 (42%) patients in RFA and SR groups, respectively, with superior DFS in the SR group (P < 0.01). Of total 31 deaths, 20 (27.8%) deaths were in the RFA group and 11 (28.9%) in the SR group with no difference in OS at 3 years. CONCLUSION: Viral hepatitis with or without alcohol is the commonest etiological factor for HCC in Northern India; NASH and alcohol are increasing over the years. In a real-life setting, in patients with unifocal HCC, there is no difference in overall 3-year survival subjected to SR or RFA with better DFS in the SR group.

Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model.

BACKGROUND: The prevalence of chronic hepatitis C (CHC) in People Who Inject Drugs (PWID) is 8-10% as compared to 3·6% in the general population in Punjab, India. We assessed the real-world efficacy and safety of free-of-charge generic direct-acting antivirals (DAAs), sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir)±ribavirin in the microelimination of CHC in PWID in a public health setting. METHODS: An integrated care team at 25 sites provided algorithm based DAAs treatment to PWID supervised by telemedicine clinics between 18th June 2016 and 31st July 2019. The primary endpoint was sustained virological response at 12 weeks (SVR-12); the secondary endpoints were treatment completion, adherence, safety, and adverse events. ClinicalTrials.gov number: NCT01110447. FINDINGS: We enrolled 3477 PWID (87·2% men; mean age 33·6±12·5 years; 83·8% rural; 6·8% compensated cirrhosis). While 2280 (65·5%) patients completed treatment, 1978 patients completed 12 weeks of follow up for SVR-12. SVR-12 was achieved in 91·1% of patients per protocol, 49.5% as per intention to treat (ITT) and 90·1% in a modified ITT analysis. Of 546 (15·7%) patients with treatment interruptions, 99 (19·7%) could be traced to test for SVR-12 with a cure rate of 77·8%. There were no major adverse events or consequent treatment discontinuation. INTERPRETATION: Integrated care of PWID with CHC with DAAs is safe and effective. Measures for reducing treatment interruptions will further improve outcomes. FUNDING: The Government of the state of Punjab, India under the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) project, funds the project.

Percutaneous Cryoablation of Liver Tumors: Initial Experience from a Tertiary Care Center in India.

BACKGROUND: Percutaneous ablation is an important part of management strategy for liver tumors. While radiofrequency ablation and microwave ablation are the most widely used ablative techniques, cryoablation (CA) has several technical advantages but has been underused till recently. In this study, we report the initial experience with percutaneous CA of liver tumors. METHODS: This was a retrospective evaluation of consecutive patients with liver tumors who underwent percutaneous CA between October 2018 and August 2019. The ablation procedures were performed under combined ultrasound and computed tomography guidance using argon-helium-based CA systems. The baseline tumor characteristics (including size and location), Barcelona Clinic Liver Cancer stage, and Child-Pugh score were recorded. Each patient underwent a follow-up after 1 month and at 3 months subsequently. Technical success, complete response, local tumor progression, and overall survival were evaluated. RESULTS: Nine patients (mean age, 62.4 years, median age, 66 years, five men and four women) with 10 liver tumors (mean size, 2.22 cm) underwent CA. Seven (77.8%) patients had hepatocellular carcinoma (HCC), and 2 patients had solitary liver metastasis. One patient with HCC had two lesions, while the rest had only one lesion. Of the two metastatic lesions, one was from carcinoma of the cervix and the other was from jejunal neuroendocrine tumor. Five tumors were located adjacent to the gallbladder, two lesions were adjacent to the right portal vein, two lesions were subcapsular, and one lesion was adjacent to the stomach. Technical success was achieved in all the patients. Complete response was achieved in 7 (77.8%) patients. The median follow-up period was 7 months (range, 3-12 months). There was no local tumor progression and no death during the follow-up period. No procedure-related complication was seen. CONCLUSION: Percutaneous CA of hepatic tumors is technically feasible and is a safe and effective ablative technique.

Idiopathic Hypercalcemia in Decompensated Cirrhosis: Reexploring an Entity in Oblivion.

Hypercalcemia is a rare metabolic abnormality seen in patients with cirrhosis and is usually considered a paraneoplastic manifestation of hepatocellular carcinoma. Idiopathic hypercalcemia in cirrhosis is a diagnosis of exclusion, which is considered when all the causes of hypercalcemia have been ruled out. Here, we report a rare case of idiopathic hypercalcemia presenting as acute kidney injury in a case of decompensated cirrhosis, managed with adequate hydration and injection of ibandronate and intranasal calcitonin, leading to the normalization of serum calcium and resolution of acute kidney injury.

Comparison of Elastography Point Quantification with Transient Elastography in Patients with Chronic Viral Hepatitis and Nonalcoholic Fatty Liver Disease: A Pilot Study.

AIMS: The objective of this study was to compare diagnostic accuracy of elastography point quantification (ElastPQ) with transient elastography (TE) and liver histology for measuring liver stiffness in patients with chronic viral hepatitis (CVH) and nonalcoholic fatty liver disease (NAFLD). METHODS: Thirty-two patients with chronic liver disease (CVH and NAFLD) were evaluated by ElastPQ and TE within 7 days of liver biopsy. Within the CVH group, subgroup analysis was carried out in patients with end-stage renal disease (ESRD) and without ESRD. Area under the receiver operating characteristic (AUROC) curves were calculated for ElastPQ and TE. RESULTS: There were 15 patients with CVH and 17 patients with NAFLD. In the CVH group, there were 8 patients with ESRD and 7 patients without ESRD. Taking liver histopathology as the gold standard, liver stiffness measurement by ElastPQ (ρ = 0.826;P < 0.0001) and TE (ρ = 0.649; P < 0.0001) correlated significantly with the stage of fibrosis. AUROCs of ElastPQ and TE for the diagnosis of any fibrosis (F ≥ 1), significant fibrosis (F ≥ 2), and advanced fibrosis (F ≥ 3) were 0.907, 0.959, 0.926 and 0.870, 0.770, 0.881, respectively, in both CVH and NAFLD groups. However, the accuracy of both these techniques was poor in patients with CVH and ESRD (AUROCs for ElastPQ and TE of 0.667 and 0.167 for the diagnosis of significant fibrosis, respectively, and 0.429 and 0.143 for the diagnosis of advanced fibrosis, respectively). The diagnostic accuracy of both ElastPQ and TE for detecting significant fibrosis was excellent in patients with NAFLD (AUROC of 1.000 and 0.936, respectively). ElastPQ was superior to TE in the diagnosis of significant fibrosis in the combined analysis (P = 0.0149) and in the CVH group (P = 0.0391), while both modalities were comparable in patients of the NAFLD group (P = 0.2539). CONCLUSION: ElastPQ may be equally accurate as Fibroscan, and large prospective studies are required to validate the same.

Cost-effectiveness and budget impact analysis of facility-based screening and treatment of hepatitis C in Punjab state of India.

OBJECTIVE: Despite treatment availability, chronic hepatitis C virus (HCV) public health burden is rising in India due to lack of timely diagnosis. Therefore, we aim to assess incremental cost per quality-adjusted life year (QALY) for one-time universal screening followed by treatment of people infected with HCV as compared with a no screening policy in Punjab, India. STUDY DESIGN: Decision tree integrated with Markov model was developed to simulate disease progression. A societal perspective and a 3% annual discount rate were considered to assess incremental cost per QALY gained. In addition, budgetary impact was also assessed with a payer's perspective and time horizon of 5 years. STUDY SETTING: Screening services were assumed to be delivered as a facility-based intervention where active screening for HCV cases would be performed at 22 district hospitals in the state of Punjab, which will act as integrated testing as well as treatment sites for HCV. INTERVENTION: Two intervention scenarios were compared with no universal screening and treatment (routine care). Scenario I-screening with ELISA followed by confirmatory HCV-RNA quantification and treatment. Scenario II-screening with rapid diagnostic test (RDT) kit followed by confirmatory HCV-RNA quantification and treatment. PRIMARY AND SECONDARY OUTCOME MEASURES: Lifetime costs; life years and QALY gained; and incremental cost-effectiveness ratio for each of the above-mentioned intervention scenario as compared with the routine care. RESULTS: Screening with ELISA and RDT, respectively, results in a gain of 0.028 (0.008 to 0.06) and 0.027 (0.008 to 0.061) QALY per person with costs decreased by -1810 Indian rupees (-3376 to -867) and -1812 Indian rupees (-3468 to -850) when compared with no screening. One-time universal screening of all those ≥18 years at a base coverage of 30%, with ELISA and RDT, would cost 8.5 and 8.3 times more, respectively, when compared with screening the age group of the cohort 40-45 years old. CONCLUSION: One-time universal screening followed by HCV treatment is a dominant strategy as compared with no screening. However, budget impact of screening of all ≥18-year-old people seems unsustainable. Thus, in view of findings from both cost-effectiveness and budget impact, we recommend beginning with screening the age cohort with RDT around mean age of disease presentation, that is, 40-45 years, instead of all ≥18-year-old people.

Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure.

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors.

Cost-Effectiveness Analysis and Decision Modelling: A Tutorial for Clinicians.

Cost-effectiveness analysis (CEA) provides information on how much extra do we need to spend per unit gain in health outcomes with introduction of any new healthcare intervention or treatment as compared to the alternative. This information is crucial to make decision regarding funding any new drug, diagnostic test or determining standard treatment protocol. It becomes even more important to consider this evidence in resource constrained low-income and middle-income country settings. Generating evidence on costs and consequences of a treatment or intervention could be performed in the setting of a randomized controlled trial, which is the perfect platform to evaluate efficacy or effectiveness. However, we argue that randomized controlled trial (RCT) offers an incomplete setting to generate comprehensive data on all costs and consequences for the purpose of a CEA. Hence, it is needed to use a decision model, either in combination with the evidence from RCT or alone. In this article, we demonstrate the application of decision model-based economic evaluation using 2 separate techniques - a decision tree and a Markov model. We argue that application of a decision model allows computation of health benefits in terms of utility-based measure such as a quality-adjusted life year or disability-adjusted life year which is preferred for a CEA, measure distal costs and consequences which are much more downstream to the application of intervention, allows comparison with multiple intervention and comparators, and provides opportunity of making use of evidence from multiple sources rather than a single RCT which may have limited generalizability. This makes the use of such evidence much more acceptable for clinical use and policy relevant.

Corrigendum to "Joint Consensus Statement of the Indian National Association for Study of the Liver and Indian Radiological and Imaging Association for the Diagnosis and Imaging of Hepatocellular Carcinoma Incorporating Liver Imaging Reporting and Data System" [J Clin Expt Hepatol 9 (2019) 625-651].

[This corrects the article DOI: 10.1016/j.jceh.2019.07.005.].

2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.

Fusion Image-Guided and Ultrasound-Guided Fine Needle Aspiration in Patients With Suspected Hepatic Metastases.

AIM: The aim of this study was to compare the diagnostic adequacy of computed tomography (CT)-ultrasound (US) fusion image-guided fine needle aspiration (FNA) and US-guided FNA in patients with suspected hepatic metastases. METHODS: Thirty consecutive patients of either sex with known or unknown primary malignancy suspected of having liver metastases on both US and CT, whose multiphasic contrast-enhanced computed tomography was performed using a 64-slice or a higher slice CT scanner, and who were referred for percutaneous FNA were included in this prospective study approved by the institutional review board of the study institute. CT-ultrasound fusion image-guided FNA of the largest lesion using electromagnetic tracking and with freehand ultrasound-guided FNA were performed in the same sitting. Value of fitness, which is a rough estimate of how well the fusion has been achieved, was recorded. Diagnostic adequacy of smears was assessed by a scoring system based on cellular material, background blood/clot, degree of cellular degeneration or trauma, and retention of architecture. RESULTS: The size of the lesions ranged from 1 to 10 cm, and the depth of location of the lesions ranged from 1.4 to 9.3 cm. The fusion fitness values ranged from 1.2 to 10 mm. The scores of the smears did not correlate with lesion size, depth of location, and fusion fitness value. Diagnostic adequacy was seen in 90% and 93.3% of lesions sampled by fusion image guidance and ultrasound guidance, respectively (p = 0.655). All the lesions that yielded inadequate smears by fusion guidance were deep-seated lesions (>5 cm). All the lesions that yielded inadequate smears by ultrasound guidance were small lesions (<3 cm). No complications were encountered in any of the patients. CONCLUSION: Fusion image-guided FNA is a safe procedure with a high diagnostic adequacy rate. Fusion image-guided FNA is not better than US-guided FNA for conspicuous hepatic lesions; however, it may be useful in inconspicuous lesions.

Joint Consensus Statement of the Indian National Association for Study of the Liver and Indian Radiological and Imaging Association for the Diagnosis and Imaging of Hepatocellular Carcinoma Incorporating Liver Imaging Reporting and Data System.

Hepatocellular carcinoma (HCC) is the 6th most common cancer and the second most common cause of cancer-related mortality worldwide. There are currently no universally accepted practice guidelines for the diagnosis of HCC on imaging owing to the regional differences in epidemiology, target population, diagnostic imaging modalities, and staging and transplant eligibility. Currently available regional and national guidelines include those from the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver, the Japan Society of Hepatology, the Korean Liver Cancer Study Group, Hong Kong, and the National Comprehensive Cancer Network in the United States. India with its large population and a diverse health infrastructure faces challenges unique to its population in diagnosing HCC. Recently, American Association have introduced a Liver Imaging Reporting and Data System (LIRADS, version 2017, 2018) as an attempt to standardize the acquisition, interpretation, and reporting of liver lesions on imaging and hence improve the coherence between radiologists and clinicians and provide guidance for the management of HCC. The aim of the present consensus was to find a common ground in reporting and interpreting liver lesions pertaining to HCC on imaging keeping LIRADSv2018 in mind.

Cost-effectiveness of Sorafenib for Treatment of Advanced Hepatocellular Carcinoma in India.

BACKGROUND: Majority of patients of hepatocellular carcinoma (HCC) in India present in advanced stages, when curative treatment options are limited. We undertook this study to assess the cost-effectiveness of treating advanced HCC patients with sorafenib compared with best supportive care (BSC). METHODS: A Markov model was parameterized to model the lifetime costs and consequences of treating advanced HCC patients with sorafenib versus BSC using a societal perspective. Cost of routine care, diagnostics, management of complications in both the arms and management of adverse effects of sorafenib treatment were considered. A probabilistic sensitivity analysis was undertaken to assess the effect of parameter uncertainty. RESULTS: The incremental cost and benefit gained by treating HCC using sorafenib was Indian rupees 94,182 ($1459) and 0.19 quality adjusted life years (QALYs) per patient, implying an incremental cost of Indian rupees 507,520 ($7861) per QALY gained. CONCLUSIONS: Sorafenib is not cost-effective for use in advanced hepatocellular carcinoma treatment in India.

Prevalence of Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Cross-Sectional, Clinicoepidemiological, Multicenter, Nationwide Study in India: The PREDICT Study.

BACKGROUND: The study aimed at assessing the prevalence and clinical profile of minimal hepatic encephalopathy (MHE) in patients with cirrhosis using neuropsychological assessment and at understanding the management practices of MHE in the Indian clinical setting. METHODS: This cross-sectional, clinicoepidemiological study conducted at 20 sites enrolled liver cirrhosis patients with Grade 0 hepatic encephalopathy according to West-Haven Criteria. Patients were subjected to mini-mental state examination and those with a score of ≥24 were assessed using psychometric hepatic encephalopathy score. Short Form-36 questionnaire was administered to assess the impact on health-related quality of life. RESULTS: Of the 1260 enrolled patients, 1114 were included in the analysis. The mean age was 49.5 years and majority were males (901 [81%]). The prevalence of MHE was found to be 59.7% (665/1114) based on the psychometric hepatic encephalopathy score of ≤-5. Alcohol-related liver disease was the most common etiology (482 [43.27%]) followed by viral infection (239 [21.45%]). Past smokers as well as those currently smoking were more likely to have MHE than nonsmokers. A significant association was found between tobacco chewing, smoking, alcohol consumption, diabetes, and the presence of MHE. Multivariable analysis revealed smoking as the only parameter associated with MHE. A total of 300 (26.9%) patients were on prophylaxis with lactulose/lactitol or rifaximin. These patients were less likely to have MHE as compared to those not on prophylaxis (odds ratio, 0.67; 95% confidence interval, 0.50-0.88; P = 0.005). CONCLUSION: The disease burden of MHE is quite substantial in patients with cirrhosis with no apparent cognitive defect. Smoking, whether past or current, has significant association with the presence of MHE. Although MHE has been shown to adversely affect quality of life, prophylaxis for MHE is not routinely practiced in the Indian setting.The study has been registered under clinical trials registry of India (CTRI/2014/01/004306).