Lifestyle intervention for metabolic dysfunction-associated fatty liver disease: a 24-h integrated behavior perspective.

INTRODUCTION: The prevalence, health and socioeconomic burden of metabolic dysfunction-associated fatty liver disease (MAFLD) is growing, increasing the need for novel evidence-based lifestyle approaches. Lifestyle is the cornerstone for MAFLD management and co-existing cardiometabolic dysfunction. The aim of this review was to evaluate the evidence for lifestyle management of MAFLD, with a specific lens on 24-hour integrated behaviour and provide practical recommendations for implementation of the evidence. RESULTS: Weight loss ≥ 7-10% is central to lifestyle management; however, liver and cardiometabolic benefits are attainable with improved diet quality and exercise even without weight loss. Lifestyle intervention for MAFLD should consider an integrated '24-h' approach that is cognisant of diet, physical activity/exercise, sedentary behavior, smoking, alcohol intake and sleep. Dietary management emphasises energy deficit and improved diet quality, especially the Mediterranean diet, although sociocultural adaptations to meet preferences should be considered. Increasing physical activity and reducing sedentary behavior can prevent MAFLD, with strongest evidence in MAFLD supporting regular structured moderate-vigorous aerobic exercise for 150-240 min/week. Resistance training in addition to aerobic exercise should be considered and prioritised for those who are losing body mass via diet and/or pharmacological approaches and those with sarcopenia, to minimise bone and lean mass loss. Limited evidence suggests that sleep is important for MAFLD prevention. Emerging novel approaches to diet and exercise may address some of the key barriers to behaviour change (e.g. lack of time, access to resources and social support). FUTURE DIRECTIONS: Large-scale multidisciplinary trials in people with MAFLD with long-term follow-up, that can be scaled up into mainstream healthcare, are required. Future management guidelines should consider the heterogeneity of MAFLD and specialised models of care that coordinate the health workforce to manage the increased and growing MAFLD population.

Differences in the proteome within extracellular vesicles between premalignant and malignant plasma cell disorders.

BACKGROUND: Precursor plasma cell disorders such as monoclonal gammopathy of undetermined significance (MGUS) always precede the development of active malignancies such as multiple myeloma (MM). There is a need for novel biomarkers to identify those patients with such precursor plasma cell disorders who rapidly progress to MM. Plasma-derived extracellular vesicles (EVs) may serve as a reservoir of potential biomarkers that can shed light on the pathogenesis and disease biology of MM. METHODS: This study isolated small EVs (SEVs) and large EVs (LEVs) from the platelet-poor peripheral blood plasma of MGUS (n = 9) and MM (n = 12) patients using the size exclusion chromatography-based method and evaluated their proteome using a label-free proteomics workflow. RESULTS: In total, 2055 proteins were identified in SEVs, while 2794 proteins were identified in LEVs. The transferrin receptor (or CD71) protein was upregulated in both populations of EVs derived from MM patients compared to MGUS patients and was of prognostic significance. Similarly, three isoforms of serum amyloid A (SAA) protein, SAA1, SAA2, and SAA4, were also highly upregulated in SEVs within MM patients relative to MGUS patients. Finally, CD40 expression was also higher in the LEVs derived from MM patients than in MGUS patients. CONCLUSIONS: This study demonstrates the feasibility of successfully isolating both SEVs and LEVs from the peripheral blood of patients with plasma cell disorders and quantifying protein biomarkers within these EVs that could be of prognostic and diagnostic interest.

Expert consensus on the diagnosis and treatment of end-stage liver disease complicated by infections.

End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.

2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

A Study of Impact of Fixed-Dose Albumin Infusion on Outcome in Patients With Cirrhosis and Infection: A Randomized Open-label Clinical Trial.

Background and aim: Antibiotics and albumin infusion constitute the standard of treatment in patients with decompensated cirrhosis who have spontaneous bacterial peritonitis (SBP). Recent studies have also shown that the use of albumin in patients with advanced liver disease who have infections other than SBP leads to the resolution of acute and chronic liver failure and prevents the development of nosocomial infections. The recommended dose of albumin for these patients is out of reach for many in resource-limited settings like India. The evidence for this recommendation is also scarce. This study aimed to assess the efficacy of a lower dose of albumin infusion in addition to antibiotics on short-term mortality and morbidity in patients with cirrhosis and infections. Patients and methods: A prospective, open-label, randomized control study was performed. Consecutive patients with cirrhosis and infections were randomized in a 2:1 ratio into two groups: group A (116) and group B (58) patients. In addition to antibiotics and standard medical therapy, group A was given albumin in a dose of 20 g/day for five days, and group B was given the recommended dose (1.5 g/kg/body weight and 1 g/kg body weight on days one and three, respectively). The primary outcome was in-hospital mortality. Secondary outcomes were improvements in clinical and laboratory parameters. Results: Except for etiology, all the baseline clinical and laboratory variables in both groups were comparable. The in-hospital mortality in groups A and B was (11 [10.67%] vs. 6 [10.09%], (P = 0.965). The duration of hospitalization, 30-day mortality, improvement in shock and sensorium, and absolute improvements in serum creatinine, international normalized ratio (INR), and serum bilirubin were also comparable in both groups. Conclusion: Low-dose albumin infusion in patients with cirrhosis and infections can have the same results as standard-dose albumin and can be used in resource-limited situations. Clinical trial registration number: CTRI/2020/03/023794.

Role of Computed Tomography Perfusion in Patients with Liver Cirrhosis and Hepatocellular Carcinoma.

Background: There is a lack of data on computed tomography (CT) perfusion parameters in patients with cirrhosis and the vascular changes that occur with increasing severity of cirrhosis, as well as changes that can occur in the remote/background liver parenchyma when hepatocellular carcinoma (HCC) develops. This study aimed to evaluate the association between CT perfusion parameters in the background liver parenchyma in cirrhotic patients with and without HCC. Methods: This prospective study comprised consecutive patients with cirrhosis with or without HCC. A CT perfusion scan of the whole liver was done on a 128-detector row CT scanner in the four-dimensional spiral mode. Arterial liver perfusion (ALP), portal venous perfusion (PVP), hepatic perfusion index (HPI), blood flow (BF), blood volume (BV), and time to peak (TTP) were assessed. The perfusion parameters of the background liver parenchyma (bALP, bPVP, bHPI, bBF, bBV, and bTTP) were compared between the patients with cirrhosis (group I) and cirrhosis with HCC (group II). Perfusion parameters were also compared between the background liver parenchyma and the HCC in group II. Results: Of the 93 patients evaluated during the study period, 60 patients (30 in group I and 30 in group II, mean age, 54.5 years, 53 men) were included in the analysis. Among the perfusion parameters in the background parenchyma, bPVP was lower and bHPI was higher in group II, suggesting increased hepatic arterial perfusion of even the remote background liver parenchyma in patients with HCC (P = 0.001 and P = 0.01, respectively). Perfusion parameters were significantly altered with increasing severity of cirrhosis (based on Child-Pugh class) both within and between groups. Additionally, there were significant differences in all the perfusion parameters between HCC and the background cirrhotic liver. Conclusion: HPI and PVP of background liver parenchyma were significantly different in cirrhosis with and without HCC and also showed a worsening trend with increasing grades of cirrhosis.

Preventive hepatology: An ounce of prevention or pounds of cure to curb liver diseases.

Liver diseases are now the leading cause of both morbidity and mortality profile globally with rising trends due to unhealthy lifestyle. Most of the liver diseases are preventable. Scientific evidences have well supported and documented that almost 90 percent of all major liver diseases are either the manifestations of asymptomatic hepatitis virus infections or poor lifestyle choices leading to accumulation of fat in liver that could be detected even before they present themselves as chronic liver diseases. Understanding liver diseases as a preventable disease and practising necessary preventive measures will help in lowering the risks of various types of liver diseases as well as liver cancer.

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.

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.

Effect of Nonalcoholic Fatty Liver Disease (NAFLD) on COVID-19: A Single-Center Study of 3983 Patients With Review of Literature.

Background The presence of metabolic syndrome (MS) is associated with increased disease severity in patients with coronavirus disease 2019 (COVID-19). Non-alcoholic fatty liver disease (NAFLD) associated with or without MS may be related to increased morbidity and mortality in COVID-19, but large Indian studies are lacking. The present study was carried out to assess the impact of NAFLD on the clinical outcomes in patients with COVID-19 infection. Methods All patients with COVID-19 hospitalized at a tertiary care hospital in eastern India from April 4 to December 31, 2020, were included in the study. Patients who underwent non-contrast CT (NCCT) chest were evaluated for the presence of hepatic steatosis based on a validated criterion liver attenuation (HU) value lower than the spleen, absolute liver attenuation lower than 40 HU, and liver to spleen attenuation ratio less than 1. Patients were divided into two groups, those with or without fatty liver. Baseline characteristics including age, sex, liver function tests, and outcomes including duration of hospital stay and mortality were compared. Results A total of 6003 COVID-19-positive patients were admitted during the study period. Of these patients, 214 children (<18 years) with COVID-19 infection were excluded. One hundred and eight patients with a history of significant ethanol abuse were excluded from the analysis. NCCT scan was not done in 1698 patients. Finally, 3983 patients were included in the study. They were divided into two groups depending on the presence or absence of NAFLD. Of the 3983 patients, 814 (20.4%) had NAFLD. Overall in-hospital mortality among the study group was 6.4%. The mortality rate among patients with NAFLD was 6.7% while that in patients without fatty liver was 6% (P=0.381). Similarly, the mean duration of hospital stay was also comparable between both the groups (10.63±7.2days vs 10.65±6.6 days;P=0.66). Prevalence of NAFLD was similar in survivors and non-survivors; 759 of 2981 patients (25.4%) and 55 of 188 patients 29.2% (P=0.381), respectively. On univariate analysis, male sex, older age, elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) along with low serum albumin and low absolute eosinophil counts (AEC) were associated with higher mortality. However, on multivariate analysis, only older age, male sex, and low albumin levels were associated with higher mortality. Surprisingly, a sub-group analysis showed that females without NAFLD were at a higher risk of mortality than those with fatty liver (4.9% vs 12.3%; P=0.006). Similarly, patients with lower AST levels had higher mortality compared to patients with significantly elevated AST levels (more than two times the upper limit of normal (ULN)), irrespective of the presence of fatty liver. Conclusions The prevalence of fatty liver in severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infected patients is similar to the general population in India, the presence of which is not a predictor of severe disease. However, mortality is higher in males and elderly patients.

Association of Obesity With COVID-19 Severity and Mortality: An Updated Systemic Review, Meta-Analysis, and Meta-Regression.

Background: Obesity affects the course of critical illnesses. We aimed to estimate the association of obesity with the severity and mortality in coronavirus disease 2019 (COVID-19) patients. Data Sources: A systematic search was conducted from the inception of the COVID-19 pandemic through to 13 October 2021, on databases including Medline (PubMed), Embase, Science Web, and Cochrane Central Controlled Trials Registry. Preprint servers such as BioRxiv, MedRxiv, ChemRxiv, and SSRN were also scanned. Study Selection and Data Extraction: Full-length articles focusing on the association of obesity and outcome in COVID-19 patients were included. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used for study selection and data extraction. Our Population of interest were COVID-19 positive patients, obesity is our Intervention/Exposure point, Comparators are Non-obese vs obese patients The chief outcome of the study was the severity of the confirmed COVID-19 positive hospitalized patients in terms of admission to the intensive care unit (ICU) or the requirement of invasive mechanical ventilation/intubation with obesity. All-cause mortality in COVID-19 positive hospitalized patients with obesity was the secondary outcome of the study. Results: In total, 3,140,413 patients from 167 studies were included in the study. Obesity was associated with an increased risk of severe disease (RR=1.52, 95% CI 1.41-1.63, p<0.001, I2 = 97%). Similarly, high mortality was observed in obese patients (RR=1.09, 95% CI 1.02-1.16, p=0.006, I2 = 97%). In multivariate meta-regression on severity, the covariate of the female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2 = 40% of the between-study heterogeneity for severity. The aforementioned covariates were found to be significant for mortality as well, and these covariates collectively explained R2 = 50% of the between-study variability for mortality. Conclusions: Our findings suggest that obesity is significantly associated with increased severity and higher mortality among COVID-19 patients. Therefore, the inclusion of obesity or its surrogate body mass index in prognostic scores and improvement of guidelines for patient care management is recommended.

Erratum to 'Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure' [J Clin Exp Hepatol 10 (2020) 477-517].

[This corrects the article DOI: 10.1016/j.jceh.2020.04.011.].

NLRP3 Inflammasome Activation is a Prognostic Marker of Recovery in HEV-Infected Patients.

Hepatitis E contributes to 3.3 million acute hepatitis cases worldwide with 30% mortality in pregnant women. Pathogenesis of Hepatitis E is complex; thus, the present study was aimed at inflammasomes and associated cytokines in the immunopathogenesis of viral hepatitis E. PBMCs were isolated from 45 HEV IgM/HEV RNA-positive AVH/ALF and 19 healthy individuals and processed for mRNA expressions of NLRs, RLRs, and cytokines. PBMCs were cultured and stimulated with HEV-pORF-2 peptide in vitro for mRNA expression by RT-PCR and cytokines levels in serum/culture supernatant by ELISA. siRNA transfection and post-silencing effect in AVH PBMCs were also assessed by NLRP3 gene expression and IL-1ß and IL-18 levels by ELISA. The results demonstrated high viral load in ALF than AVH cases. mRNA expression of NLRP3 in AVH patients was found to be positively correlated with IL-18 (r = 0.74) and IL-1ß (r = 0.68); P < 0.0001***. Significant levels of serum IL-1ß and IL-18 cytokines were observed in AVH as compared to ALF patients. The levels of IL-1ß in the culture supernatant in mock and stimulated conditions were significantly higher in AVH than in ALF patients. Significant downregulation in NLRP3 gene expression was correlated with the reduced levels of IL-1ß and IL-18 cytokines in NLRP3-siRNA-transfected PBMCs. This study highlighted the significance of upregulated NLRP3 inflammasome leading to increased production of IL-18 and IL-1ß cytokines in sera of AVH patients. Thus, it indicated the role of Th1 response acting through the NLRP3 pathway which might have been helpful in the recovery of AVH patients. These promising results open multiple treatment avenues where specific inhibitors can be designed to modulate the progress of disease and its pathogenicity.

Should We Treat Immune Tolerant Chronic Hepatitis B? Lessons from Asia.

BACKGROUND: Chronic hepatitis B (CHB) remains a public health burden, with more than 257 million persons living with hepatitis B virus globally. Despite the availability of a safe and efficacious vaccine, access to immunization remains poor. As per current estimates, if Asian countries rely only on immunization to reduce the burden of disease, the timelines for HBV elimination will be extended to 2060-2090, a far cry from the World Health Organization's clarion call for viral hepatitis elimination by 2030. METHODS: Currently, all practice guidelines lay stress on immunization, prevention of mother-to-child transmission and treatment of immune active disease or cirrhosis. In this review, we critically examine the data from the Asian cohorts, clinical and public health rationale of early treatment, risk of HCC, and assess the need for revision of guidelines. DISCUSSION: Patients in the immune tolerant phase (IT) remain untreated till they meet variable age, transaminase, or fibrosis criteria, are often lost to follow up and continue transmitting the infection. With global migration patterns, immunization programmes alone cannot prevent the complications of HBV like cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC). In addition, data from Asian cohorts from Taiwan and Korea suggest that HBV DNA levels are directly associated with increased risk of HCC. Histological evidence of advanced fibrosis or immune reactive T cell subsets in the IT phase also raises doubts about the viability of current guidelines that focus on age, alanine transaminase levels, and liver stiffness as markers of risk of inflammation and fibrosis. Current practice does not take into account the histological subsets with minimal inflammation, HBV genome integration or risk of HCC with high viral loads. CONCLUSION: New data from Asian cohorts argue the case of expanding access to care to IT-CHB from public health and clinical perspective.

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. METHODS: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. RESULTS: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. CONCLUSIONS: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

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.

Association of interleukin-18 genotypes (-607C > A) and (-137 G > C) with the hepatitis B virus disease progression to hepatocellular carcinoma.

Chronic infection with HBV has been reported to be associated with the development of HCC. The inflammation mounted by cytokine-mediated immune system plays an important role in the pathogenesis of HBV-associated HCC. IL-18 is a pro-inflammatory cytokine whose role in the development of HBV-associated chronic to malignant disease state has not been much studied. The present study was conceived to determine the role of genetic polymorphisms in IL-18, serum levels of IL-18, and expression level of its signal transducers in the HBV disease progression. A total of 403 subjects were enrolled for this study including 102 healthy subjects and 301 patients with HBV infection in different diseased categories. Polymorphism was determined using PCR-RFLP. Genotypic distributions between the groups were compared using odd's ratio and 95% CI were calculated to express the relative risk. Circulating IL-18 levels were determined by ELISA. Expression levels of pSTAT-1 and pNFƙB was determined by western blotting. In case of IL-18(- 607C > A), the heterozygous genotype (CA) was found to be a protective factor while in case of IL-18(- 137G > C) the heterozygous genotype (GC) acted as a risk factor for disease progression from HBV to HCC. Moreover, serum IL-18 levels were significantly increased during HBV disease progression to HCC as compared to controls. Also the levels of activated signal transducers (pSTAT-1 and pNF-κB) of IL-18 in stimulated PBMCs were significantly increased during HBV to HCC disease progression. These findings suggest that IL-18 has the potential to act as a biomarker of HBV-related disease progression to HCC.

INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

Chronic Hepatitis E With Genotype 1-Masquerading as Allograft Rejection After LiverTransplantation.

Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting.