Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status.

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and has a high mortality rate. The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage. The recent description of the tumor microenvironment (TME) in HCC has provided a new concept of immunogenicity within the HCC. Virus-related HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells. This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors (ICIs). In addition, the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity. Therefore, data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

Non-invasive assessment of esophageal varices: Status of today.

With increasing burden of compensated cirrhosis, we desperately need non-invasive methods for assessment of clinically significant portal hypertension. The use of liver and spleen stiffness measurement helps in deferring unnecessary endoscopies for low risk esophageal varices. This would reduce cost and patient discomfort. However, these special techniques may not be feasible at remote areas where still we need only biochemical parameters. More prospective studies validating the non-invasive risk prediction models are definitely needed.

Nonsmoker COPD represents a clinically Distinct Phenotype: A Prospective Observational Study.

BACKGROUND: Chronic obstructive lung disease (COPD) has been characterized as a smoker's disease, which has resulted in the usual exclusion of never-smokers from COPD studies. It is now recognized that never-smokers account for nearly one-fourth of all COPD cases, and thus airflow limitation in never-smokers needs further evaluation. Our study aims to elucidate the clinical and physiological aspects of COPD in nonsmokers and to compare smokers and nonsmokers with COPD. MATERIALS AND METHODS: A total of 200 naïve sequential patients with COPD were recruited. The severity of airflow limitation in COPD patients was defined as per Global Initiative for COPD (GOLD) 2019 criteria, and the severity of breathlessness was assessed by the modified Medical Research Council (MRC) dyspnea scale. Data was collected using a patient pro forma, including risk factors for COPD and detailed clinical history. Phenotypic differences along with biomass exposure between never-smokers and smokers were analyzed. RESULTS: Compared to smokers, never-smokers presented at a younger age (55.69 ± 11.5 years; p < 0.001), with a longer duration of dyspnea (5.05 ± 4.96 vs 7.35 ± 6.98 years, p < 0.01). Chest radiographs revealed hyperinflation in a higher number of smokers as compared to never-smokers (82.9 vs 64.6%, p < 0.05). On spirometry evaluation, smokers were found to have significantly poorer lung function [forced expiratory volume in first second (FEV1) 40.36 ± 17.76%; forced vital capacity (FVC): 58.16 ± 17.02%] as compared to never-smokers (FEV1: 47.1 ± 16.47%; FVC: 67.38 ± 17.02%) with p < 0.05. With respect to severity at presentation, most (45.8%) never-smokers presented with stage 2 COPD as compared to the majority of smokers (46.7%) who presented with stage 3 COPD (p-value of <0.05). Absolute eosinophil count (AEC) and eosinophil proportion in total leucocyte count (TLC) was significantly higher in never-smokers as compared to the smokers (232 ± 204.2 vs 309 ± 238.8, p < 0.05). Risk factor analysis showed mean biomass exposure index was significantly higher in never-smokers as compared to smokers (56.02 vs 6.28; p-value of <0.001). CONCLUSION: Compared to smokers, COPD in never-smokers presents at a younger age, with a longer duration of dyspnea and higher eosinophil count. Biomass exposure is one of the major contributors to etiologies for COPD in nonsmokers.

Acute Hepatitis in an Immunosuppressed Patient: A Dilemma.

Acute hepatitis in patients on chemotherapy has always been challenging. Demystifying the truth becomes essential to continue chemotherapy. Wepresent a case of carcinoma buccal mucosa who developed acute hepatitis following a single dose of cisplatin and radiotherapy. In the background of a history of chronic alcoholism, and alcohol abstinence of more than 3 months, acute alcoholic hepatitis was unlikely. Though he had occult hepatitis B with HBsAg negative and positive IgG anti-HBc antibody status, however, with undetectable HBV DNA PCR quantitative, hepatitis B was unlikely to be the cause of acute hepatitis. With all viral markers including atypical viruses and autoimmune work-up being negative, it was a real-time challenge to find the exact cause. How to cite this article: Gupta T. Acute Hepatitis in an Immunosuppressed Patient: A Dilemma. Euroasian J Hepato-Gastroenterol 2023;13(1):26-27.

COVID-19 and the liver: Are footprints still there?

The coronavirus disease 2019 (COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionally, liver function abnormalities were noted in patients with severe COVID-19. Profound cytokine storm, direct viral infection, drugs and reactivation of viral infections were causes of deranged liver functions. Here, we discuss the relation between COVID-19 and chronic liver disease, specifically cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease (NAFLD), as well as the liver manifestations of COVID-19. The metabolic syndrome, obesity, diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide. Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19. Recently, COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis. The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.

Linguistic adaptation and validation of All Aspects of Health Literacy Scale (AAHLS): A health literacy assessment tool for use in Hindi-speaking population.

Background Health literacy plays an important role in determining healthcare and medication outcomes. There is a lack of an appropriate, validated scale to assess health literacy status among the Hindi-speaking population. We translated and validated the English version of the All Aspects of Health Literacy Scale (AAHLS) into Hindi. Methods We translated the scale as per WHO guidelines on translation and adaptation of instruments. We did preliminary pilot testing in 30 bilingual subjects and evaluated cross-language concordance of the scale. The final translated scale so obtained after cross-cultural adaptation was tested in a validation study on 130 subjects from the outpatient department of internal medicine in which test-retest repeatability, construct validity, discriminant validity and internal consistency were assessed. Analysis was done using paired t-test, one-way ANOVA, Cronbach α and intra-class correlation coefficient. Results An excellent correlation between Hindi and English versions of the scale for various factors ensured cross-language concordance. Hundred percentage response rate was observed in the validation study. The scale showed good internal consistency (Cronbach α=0.99). The difference in total mean AAHLS score was not statistically significant across different age groups, genders and educational levels. Factor analysis showed a positive correlation among four factors/components of health literacy. For test-retest reliability, the intra-class correlation coefficient for all the items in different factors was significant (range 0.88-1.00; p<0.0001). Significant association of critical literacy sub-scores with functional (r=0.274, p=0.002) and communicative (r=0.283, p=0.001) sub-scores revealed a good construct validity. Conclusion The Hindi translated version of the AAHLS scale is a valid and reliable tool to assess health literacy in the Hindi-speaking population.

Comparison of intravenous terlipressin infusion versus bolus in patients with acute-on-chronic liver failure-acute kidney injury - an open label RCT.

Aim of the study: Despite having ample literature in hepatorenal syndrome-acute kidney injury (HRS-AKI) in decompensated cirrhosis patients, there is a scarcity of data on acute-on-chronic liver failure-acute kidney injury (ACLF-AKI). We compared terlipressin infusion with bolus in ACLF-AKI patients. Material and methods: Patients with ACLF (as per the CANONIC study) were screened for AKI as per the 2015 ICA-AKI criteria. If after 48 h of volume expansion with albumin, serum creatinine (sCr) did not improve, patients were randomized into two groups: Terli-infusion (Terli-I) 2 mg/day and Terli-bolus (Terli-B) 1 mg q6h. If sCr did not decrease < 25% of pretreatment value after 48 h, the terlipressin dose was increased to a maximum of 12 mg/day. The primary outcome was taken as regression (full or partial response), stable/no response and progression of AKI to higher stages and secondary outcomes were taken as 28-day and 90-day mortality. Results: After screening 136 patients with ACLF-AKI, Terli-I (n = 50) and Terli-B (n = 50) with mean sCr 2.4 and 2.1 mg/dl respectively were enrolled. The regression of AKI (full response 37 vs. 27, partial response 3 vs. 9, p = 0.5), stable (2 vs. 5, p = 0.6), progression of AKI (8 vs. 7, p = 0.2) were present in Terli-I and Terli-B respectively. No significant difference was found in 28-and 90-day mortality. In Terli-B, mean terlipressin dose was 8 vs. 4 mg, p < 0.008 with more side effects, 15 vs. 0, p < 0.01 than Terli-I respectively. Conclusions: Terlipressin infusion is more effective than bolus doses in regression of acute kidney injury and better tolerated in acute-on-chronic liver failure-AKI patients.

Nonalcoholic steatohepatitis and hepatocellular carcinoma: Beyond the boundaries of the liver.

The burden of non-alcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) is drawing attention due to the emerging epidemic of obesity and metabolic syndrome and is expected to increase in the near future. Antidiabetic medications, air pollutants, and newer genetic mutations are latest concerns as risk factors for HCC development in patients with NASH. Although molecular signatures are very accurate, they are not cost-effective and cannot be applied in larger population due to logistic issues. We need multicentric longitudinal studies including diverse geographical areas to evaluate the complex interplay of different risk factors and genetics in these patients.

CYANOACRYLATE GLUE FOR GASTROESOPHAGEAL VARICES: A SINGLE CENTRE EXPERIENCE FROM NORTH INDIA.

BACKGROUND: In natural history of cirrhosis, variceal bleeding is one of the earliest decompensations to happen, and, if adequately managed, survival is improved. Gastric varices have challenges in management due to their location, size and propensity to bleed. The N-butyl 2-cyanoacrylate (NBC) glue application has emerged as definitive therapy in bleeding gastric varices. Here we present our experience with use of NBC in management of gastric and difficult cases of esophageal varices. METHODS: A total of 75 patients underwent NBC glue application for varices which included 69 patients with gastric varices and six patients with esophageal varices. All the procedures were done with flexible endoscope and sclerotherapy needle after due precautionary measures. RESULTS: Hemostasis was varices in all patients after endotherapy. The average quantity of glue used was 2.75±0.95 mL. Complete obliteration with single session of NBC application was achieved in 55 patients. Re-bleeding occurred in five patients within 5 days of index event. 20 patients had in-hospital mortality but none was related to gastrointestinal bleeding. 6-week all-cause mortality was 26 (35%). CONCLUSION: Glue therapy with NBC is a life saving therapy in patients with bleeding gastric varices and esophageal varices not amenable to endoscopic variceal ligation or sclerotherapy.

Hepatitis B core-related antigen: Are we near a treatment endpoint?

Different serological and virological markers in chronic hepatitis B patients guide staging of viral infection, and initiation and response to therapy. Due to the persistence of intrahepatic covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, hepatitis B is not curable. Even after undetectable hepatitis B virus DNA levels, the persistence of hepatitis B surface antigen and novel markers such as hepatitis B core-related antigen (HBcrAg) indicate the persistence of intrahepatic cccDNA. In this study, HBcrAg levels at baseline and after 24 and 48 wk of antiviral therapy predicted hepatitis B e antigen seroconversion. Due to the poor sensitivity of assays and detectable levels in HBsAg-negative patients, the long-term utility of HBcrAg needs future research.

Cola de cianoacrilato para varizes gastroesofágicas: uma única experiência central no norte da Índia / Cyanoacrylate glue for gastroesophageal varices: a single centre experience from north india

ABSTRACT Background: In natural history of cirrhosis, variceal bleeding is one of the earliest decompensations to happen, and, if adequately managed, survival is improved. Gastric varices have challenges in management due to their location, size and propensity to bleed. The N-butyl 2-cyanoacrylate (NBC) glue application has emerged as definitive therapy in bleeding gastric varices. Here we present our experience with use of NBC in management of gastric and difficult cases of esophageal varices. Methods: A total of 75 patients underwent NBC glue application for varices which included 69 patients with gastric varices and six patients with esophageal varices. All the procedures were done with flexible endoscope and sclerotherapy needle after due precautionary measures. Results: Hemostasis was varices in all patients after endotherapy. The average quantity of glue used was 2.75±0.95 mL. Complete obliteration with single session of NBC application was achieved in 55 patients. Re-bleeding occurred in five patients within 5 days of index event. 20 patients had in-hospital mortality but none was related to gastrointestinal bleeding. 6-week all-cause mortality was 26 (35%). Conclusion: Glue therapy with NBC is a life saving therapy in patients with bleeding gastric varices and esophageal varices not amenable to endoscopic variceal ligation or sclerotherapy.

RESUMO Contexto: Na história natural da cirrose, o sangramento de varizes é uma das primeiras descompensações a acontecer e, se adequadamente controlada, a sobrevivência é melhorada. Varizes gástricas têm desafios na sua gestão devido à sua localização, tamanho e propensão a sangrar. A aplicação de cola N butil 2-cianoacrilato (NBC) surgiu como terapia definitiva em varizes gástricas sangrantes. Apresentamos nossa experiência com o uso da NBC na gestão de casos gástricos e difíceis de varizes esofágicas. Métodos: Um total de 75 pacientes foram submetidos à aplicação de cola NBC para varizes que incluiu 69 pacientes com varizes gástricas e seis pacientes com varizes de esôfago. Todos os procedimentos foram feitos com endoscópio flexível e agulha de escleroterapia após as devidas medidas de precaução. Resultados: A hemostasia foi alcançada em todos os pacientes após a endoterapia. A quantidade média de cola utilizada foi de 2,75+0,95 mL. A obliteração completa com sessão única de aplicação da NBC foi alcançada em 55 pacientes. O reexame ocorreu em cinco pacientes dentro de 5 dias após o evento de índice. 20 pacientes tiveram mortalidade hospitalar, mas nenhum foi relacionado com o sangramento gastrointestinal. A mortalidade após 6 semanas foi de 26 (35%). Conclusão: A terapia de cola com a NBC é uma terapia que salva vidas em pacientes com varizes gástricas hemorrágicas e varizes esofágicas não condizíveis à ligadura endoscópica ou escleroterapia.

Predictors of mortality at 28-days in infection associated acute kidney injury in cirrhosis.

BACKGROUND: Acute kidney injury (AKI) in cirrhosis is important complication with poor outcomes. And infections are common cause for acute decompensation. Infections in cirrhosis lead to acute deterioration of hemodynamics leading to precipitation of AKI. AIM: To study predictors of mortality in patients with infection-associated AKI in cirrhosis. METHODS: This was a prospective, observational study conducted at tertiary care centre from January 2018 till April 2019. Total 119 participants with cirrhosis of liver presenting with AKI were included into the study. AKI was defined as per international club of Ascites-AKI criteria 2015. Patients were grouped into infection AKI and non-infection AKI. Non-infection AKI included patients with diuretic induced AKI and pre-renal AKI. Logistic regression analysis was used to determine predictors of mortality at 28-d. RESULTS: Out of 119 patients, alcohol (n = 104) was most common etiology of cirrhosis. The infection AKI included 67 (56%) patients and non-infection AKI (n = 52) included pre-renal AKI in 36 (30%) and diuretic-induced AKI in 16 (14%) patients. Infection AKI had significantly higher bilirubin, higher international normalized ratio (INR), low serum sodium, higher total leukocyte count (TLC) and higher prevalence of hepatic encephalopathy (HE) as compared to non-infection AKI. Infection AKI had higher progression of AKI (19/67 vs 2/52; P = 0.01) and 28-d mortality (38/67 vs 4/5; P ≤ 0.01) as compared to non-infection AKI. At 28-d, non-survivors (n = 42) had significantly higher bilirubin, higher INR, low serum sodium, higher TLC and higher prevalence of HE as compared to survivors (n = 77). On subgroup analysis of Infection AKI group, on multivariate analysis, serum bilirubin as well as presence of HE were independent predictors of 28-d mortality. There was no significant difference of mortality at 90-d between two groups. CONCLUSION: Infection AKI in cirrhosis has a dismal prognosis with higher 28-d mortality as compared to non-infection AKI. Serum bilirubin and presence of HE predict 28-d mortality in infection AKI.

COVID-19 and liver disease: Are we missing something?

Since the coronavirus disease 2019 (COVID-19) has hit the world as a pandemic, researchers all over the world have worked on its diagnostics, prognosticating factors, etc. The present study showed liver enzymes, especially aspartate aminotransferase (AST) levels, to be high in non-survivors with raised AST/alanine aminotransferase ratio. Considering the non-specific nature of AST with its presence in organs other than liver such as muscle, heart, kidney and brain makes it difficult to interpret. Even pre-existing metabolic syndrome and non-alcoholic fatty liver disease are confounding factors for deranged liver functions detected during COVID-19 disease. Therefore, the results of the study should be taken with caution.

Prediction of Cirrhosis in Patients with Chronic Hepatitis C by Genotype 3.

BACKGROUND: Genotype 3 increases fibrosis in chronic hepatitis C (CHC). AIM: To evaluate the effect of the hepatitis C virus (HCV) genotype on prevalence and severity of liver disease in CHC. MATERIALS AND METHODS: Nine hundred and forty-nine individuals with positive anti-HCV from June 2016 to May 2017 were enrolled in the study. We compared biochemical and hematological parameters, HCV RNA load, transient elastography, and ultrasound, in genotype 3 and nongenotype 3 patients. Cirrhosis was diagnosed in patients with liver stiffness measurement (LSM) ≥13 kPa. RESULTS: Out of 835 CHC patients, overall, genotype 3 had higher LSM (11.3 vs 7.62, p = 0.01), higher aspartate aminotransferase (AST) (88.4 vs 68.6, p = 0.02), and low platelets (228.4 vs 261, p = 0.03) with higher prevalence of cirrhosis (115/415 vs 25/245, p = 0.01) than nongenotype 3. However, decompensation rates were not significantly different between two groups (32/115 vs 7/25, p = 0.98). The subgroup analysis revealed that cirrhotic genotype 3 had advanced age (50 vs 35, p < 0.01), male predominance, and higher AST (74.4 vs 57, p = 0.01) as compared to noncirrhotic genotype 3 patients. On multivariate analysis, age and AST values were higher in cirrhotic than noncirrhotic genotype 3 patients. CONCLUSION: Genotype 3 patients have higher prevalence of cirrhosis and fibrosis compared to nongenotype 3 patients; however, decompensation was not different between two groups. HOW TO CITE THIS ARTICLE: Gupta T, Aggarwal HK, Goyal S, et al. Prediction of Cirrhosis in Patients with Chronic Hepatitis C by Genotype 3. Euroasian J Hepato-Gastroenterol 2020;10(1):7-10.

Prediction of 28-day mortality in acute decompensation of cirrhosis through the presence of multidrug-resistant infections at admission.

BACKGROUND AND AIM: The aim of this study is to evaluate the epidemiology and impact of bacterial infections at admission in patients with acute decompensation (AD) of cirrhosis. METHODS: A cohort with AD of cirrhosis (European Association for the Study of the Liver criteria) admitted at a tertiary center was evaluated between 2013 and 2014 for the presence of bacterial infections at admission. Clinical, demographic, and microbiological data were collected prospectively till death, transplant, or 90 days. RESULTS: Of 179 patients with AD, 102 (56.9%) had bacterial infections at admission. The commonest infections were spontaneous bacterial peritonitis (SBP) (n = 65; 63.7%), spontaneous bacteremia (n = 10; 9.8%), pneumonia (n = 9; 8.8%), urinary tract infection (n = 8; 7.8%), spontaneous bacterial empyema (n = 4; 3.9%), and cellulitis (n = 2; 1.9%). The commonest source was community acquired (n = 85; 83.3%). Serum albumin and sodium levels were lower in infected as compared with non-infected cohort (P = 0.015; for both). Escherichia coli was the commonest organism isolated from SBP (n = 14; 21.5%), urinary tract infection (n = 5; 45.5%), and bacteremia (n = 3; 20%). There was a trend toward higher 28-day mortality in infected cohort as compared with non-infected cohort (48 [52.7%] vs 28 [32%]; P = 0.152). Multidrug-resistant organisms (MDROs) were isolated in 63% of all culture-positive infections. The presence of MDRO was an independent predictor of 28-day mortality. CONCLUSIONS: Infections are the leading reason for the occurrence of AD; SBP is the most common infection, and E. coli is the commonest microorganism based on this single-center study of Indian patients with AD of cirrhosis. There is a high prevalence of MDROs among culture-positive infections that independently predict 28-day mortality in AD of cirrhosis.

Valproate-induced Drug Rash Eosinophilia with Systemic Symptoms Syndrome: An Unknown Hepatotoxicity.

Drug rash eosinophilia with systemic symptoms (DRESS syndrome) presents as an acute febrile illness with leukocytosis, eosinophilia, lymphadenopathy, skin rash with acute hepatitis, renal failure, myositis, or systemic organ involvement. Aromatic anticonvulsants like phenytoin, carbamazepine, and phenobarbital cause drug-induced hypersensitivity or DRESS syndrome. However, sodium valproate being nonaromatic compound although known hepatotoxic drug in preexisting chronic liver disease has never been reported to cause DRESS syndrome alone. Here we report an interesting case of DRESS syndrome caused by valproate, which presented as an acute hepatitis illness with rash, renal dysfunction, and typical hematological features of DRESS syndrome within 2 months of the introduction of the drug in an epileptic patient. Patient initially showed a good response to intravenous steroids with improvement in the liver and renal dysfunction. However, later on, developed pancytopenia either due to steroid-induced sepsis or DRESS syndrome-related secondary hemophagocytosis (HPS) due to involvement of bone marrow as a rare occurrence and succumbed to illness. HOW TO CITE THIS ARTICLE: Gupta T. Valproate-induced Drug Rash Eosinophilia with Systemic Symptoms Syndrome: An Unknown Hepatotoxicity. Euroasian J Hepato-Gastroenterol 2019;9(2):102-103.

Managing Encephalopathy in the Outpatient Setting.

In cirrhosis of liver, hepatic encephalopathy (HE) has an important impact on health-related quality of life. It is important to define whether HE is episodic, recurrent, or persistent; types A, B, or C; overt HE or covert HE; and spontaneous or precipitated. The overt HE is clinically evident and needs hospitalization. Nonabsorbable disaccharides, rifaximin, and probiotics are proven to be useful in the treatment of overt HE. Covert HE includes both minimal HE and grade I HE. It is not apparent on routine clinical examination. Presence of poor work productivity, increased accidental injuries on complex machinery and driving, etc., raise the suspicion of cognitive dysfunction. Specialized neurocognitive testing like psychometric HE, computerized tests like critical flicker frequency tests, inhibitory control tests, Stroop encephalopathy tests, and electroencephalography are needed to diagnose overt HE. Various studies have shown lactulose and rifaximin to be useful in overt HE. However, presence of persistent and recurrent HE in cirrhosis is an indication for liver transplant. Lactulose is effective both in improving reversal of minimal HE and in reducing the risk of development of overt HE. How to cite this article: Gupta T, Rathi S, Dhiman RK. Managing Encephalopathy in the Outpatient Setting. Euroasian J Hepato-Gastroenterol 2017;7(1):48-54.

Characterization of Cerebral Edema in Acute-on-Chronic Liver Failure.

BACKGROUND AND AIMS: The nature of cerebral edema in acute-on-chronic liver failure (ACLF) is not well studied. We aimed to characterize cerebral edema in ACLF using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). METHODS: Forty-six patients with cirrhosis and acute decompensation were included. Patients were divided into groups A (no cerebral failure, n = 39) and B (cerebral failure, n = 7). Group A was subdivided into no-ACLF (n = 11), grade 1 (n = 10), grade 2 (n = 9) and grade 3 (n = 9) ACLF as per CANONIC study. MRI brain and plasma TNF-alpha, IL-1beta and IL-6 were measured at baseline and 7-10 days after admission. Ten age- and sex-matched healthy controls were also included. RESULTS: Mean diffusivity (MD) values, an MRI marker of water content, progressively increased from controls to no-ACLF to ACLF grade 1, 2 and 3 in group A in frontal white matter (FWM) and basal ganglia (P < 0.0001). MD values improved only in survivors on follow-up. MD values correlated with IL-6 levels at baseline. On multivariate analysis MELD score ≥28 and MD values (>8 × 10-9 M2/s) in FWM were independent predictors of 90-day mortality. There was no significant difference in clinical and MRI parameters between group A and B. CONCLUSION: Cerebral edema increases with severity of ACLF. Correlation between MD values and IL-6 levels suggests pathogenic role of inflammation in cerebral edema. Patients with grade 3 ACLF have cerebral edema irrespective of presence of clinically evident cerebral failure. MELD score and cerebral edema have prognostic significance in ACLF.

Impact of Hepatic and Extrahepatic Insults on the Outcome of Acute-on-Chronic Liver Failure.

BACKGROUND: To study the differences in outcome and predictors of mortality in acute-on-chronic liver failure (ACLF) precipitated by hepatic or extrahepatic insults. METHODS: Consecutive patients of cirrhosis with acute decompensation were prospectively included and followed up for 90 days from admission. ACLF was defined based on chronic liver failure (CLIF) acute-on-chronic liver failure in cirrhosis (CANONIC study) criteria. Acute worsening due to acute viral hepatitis A and E, hepatitis B flare, alcoholic hepatitis, autoimmune hepatitis flare, or drug-induced liver injury were categorized as hepatic ACLF and that due to bacterial infection, upper gastrointestinal bleed or surgery as extrahepatic ACLF. Patients with both hepatic and extrahepatic insults were included in combined insult group. RESULTS: Of 179 patients of acute decompensation, 122 had ACLF (hepatic insults 47 and extrahepatic insults 51). Alcohol (64.8%) was the most common etiology of cirrhosis while infection (36%) was the most common acute insult followed by alcoholic hepatitis (24.6%). Higher proportion of extrahepatic ACLF patients had history of prior decompensation than hepatic ACLF patients (62.7% vs. 27.7%, P < 0.001). There was no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days (53.2% vs. 56.9%, P = 0.715 and 85% vs. 74.5%, P = 0.193, respectively). Area under receiver-operating curve (AUROC) for 28-day mortality in extrahepatic ACLF group was 0.788, 0.724, 0.718, 0.634, and 0.726 and in hepatic-ACLF group was 0.786, 0.625, 0.802, 0.761, and 0.648 for chronic liver failure-sequential organ failure assessment (CLIF-SOFA), model for end stage liver disease (MELD), integrated MELD score (iMELD), acute physiology and chronic health evaluation score (APACHE-II), and Child-Turcotte-Pugh score scores, respectively. CONCLUSION: There is no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days. iMELD and CLIF-SOFA have highest AUROC to predict 28-day mortality in hepatic and extrahepatic ACLF groups, respectively.

Simple organ failure count versus CANONIC grading system for predicting mortality in acute-on-chronic liver failure.

BACKGROUND AND AIM: This study assessed the utility of a simple organ failure count (SOFC) in predicting the in-hospital mortality in patients with acute-on-chronic liver failure (ACLF) compared with Chronic Liver Failure Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) ACLF grading system. METHODS: Consecutive patients of ACLF were included prospectively from 2012 to 2013. The diagnosis was based on Asian-Pacific Association for the Study of the Liver (APASL) criteria except for the inclusion of non-hepatic insults as acute events. Organ failures were defined as per the Chronic Liver Failure-Sequential Organ Failure Assessment system. SOFC was calculated as the simple number of organ failures from 0 to 6. In-hospital mortality was recorded. RESULTS: Majority (92[87%]) of the 106 patients included were males, had alcohol (76[72%]) as the etiology of cirrhosis, and alcoholic hepatitis (58[55%]) as the acute precipitating event. Overall, 51(48%) patients died in-hospital. In-hospital mortality in patients with SOFC of 0 (n = 9), 1 (n = 39), 2 (n = 24), 3 (n = 24), 4 (n = 7), and 5 (n = 3) was 0%, 26%, 58%, 71%, 100%, and 100% respectively (P < 0.001), whereas it was 10%, 30%, 58%, and 79% in patients with no-ACLF (n = 21), grades 1 (n = 27), 2 (n = 24), and 3 ACLF (n = 34) respectively (P < 0.001). Patients with no-ACLF (n = 21) had higher mortality than SOFC 0 as they included 9 patients with SOFC 0 (0% mortality) and 12 patients with SOFC 1 (17% mortality). Mortality was similar between 12 no-ACLF and 27 grade 1 ACLF patients (P = 0.462) that comprised SOFC 1. CONCLUSION: SOFC is a simpler and better method than the CANONIC grading system for predicting the in-hospital mortality in patients with ACLF defined as per APASL criteria.