Definitions, Etiologies, and Outcomes of Acute on Chronic Liver Failure: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a major public health concern. We aimed to assess the definitions, etiologic spectrum, organ failure (OF), and outcomes of ACLF globally. METHODS: Three databases were searched for studies on ACLF from 1990 until September 2022. Information regarding definitions, acute precipitants, underlying chronic liver disease (CLD), OF, and mortality were extracted. Meta-analyses were performed for pooled prevalence rates (95% confidence interval [CI]) using random-effects model for each definition of ACLF. RESULTS: Of the 11,451 studies identified, 114 articles (142 cohorts encompassing 210,239 patients) met the eligibility criteria. Most studies (53.2%) used the European Association for the Study of the Liver (EASL) definition, followed by Asia-Pacific Association for the Study of the Liver (APASL) (33.3%). Systemic infection was the major acute precipitant, and alcohol use was the major cause of CLD in EASL-defined studies, whereas alcohol was both the major acute precipitant and cause of CLD in APASL-defined studies. Liver failure was the major OF in APASL-based studies, whereas renal failure was predominant in EASL-based studies. Thirty-day mortality varied across definitions: APASL: 38.9%, 95% CI, 31.2%-46.9%; EASL: 47.9%, 95% CI, 42.2%-53.5%; and NACSELD: 52.2%, 95% CI, 51.9%-52.5%. Diagnostic overlap between definitions ranged from 7.7% to 80.2%. Meta-regression suggested that the World Health Organization region influenced 30-day mortality in studies using EASL definition. CONCLUSIONS: Heterogeneity in the definition of ACLF proposed by different expert societies and regional preferences in its use result in differences in clinical phenotype and outcomes. A uniform definition would enhance the comparability and interpretation of global data.

Frailty and sarcopenia in patients with acute-on-chronic liver failure: Assessment and risk in the liver transplant setting.

Frailty and sarcopenia are well-recognized factors related to worse outcomes in patients with cirrhosis, including liver transplant (LT) candidates. Implications of pre-LT functional and muscle deterioration also affect post-LT outcomes. Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have a lower survival rate, both before and after LT. There is a need to better identify those patients with ACLF who would benefit from LT. This review aims to present the available data about frailty and sarcopenia in patients with ACLF in the LT setting. An exhaustive review of the published literature was conducted. Data regarding frailty and sarcopenia in LT candidates with ACLF are scarce and heterogeneous. Studies evaluating frailty and sarcopenia in critically ill patients outside the liver literature are also presented in this review to enrich the knowledge of this field in expansion. Frailty and sarcopenia seem to contribute to worse outcomes in LT candidates with ACLF, both before and after LT. Sarcopenia evaluation may be the most prudent approach for those very sick patients. Skeletal muscle index assessed by computed tomography is recommended to evaluate sarcopenia. The role of muscle ultrasound and bioelectrical impedance analysis is to be determined. Frailty and sarcopenia are crucial factors to consider on a case-by-case basis in LT candidates with ACLF to improve patient outcomes.

Clinical Profile, Short-term Prognostic Accuracies of CLIF-C ACLF Score and Serial CLIF-C OF Scores in Acute-on-chronic Liver Failure Patients: A Prospective Observational Study.

Background: Acute-on-chronic liver failure (ACLF) is a recently defined entity that carries high short-term mortality. The European Association for Study of Liver (EASL) has given a different definition for ACLF and derived two scores called Chronic Liver Failure-Consortium Organ Failure (CLIF-C OF) and CLIF-C ACLF to diagnose and predict the short-term outcome, respectively. Materials and methods: This was the prospective observational study, included 40 ACLF patients diagnosed as per the EASL definition and calculated CLIF-C ACLF as well as other scores (CTP, MELD, MELD-Na, CLIF-C OF) on admission. Serial CLIF-C OF scores were also calculated (Day 3 and Day 7). The 28-day and 90-day mortality was recorded. Results: Alcohol was the predominant etiology of cirrhosis (32 patients-80%). Infection was the chief precipitating factor in 19 patients (47.5%). The 28-day and 90-day mortality was 45% and 52.5%. Mean (SD) of CLIF-C ACLF scores of survivors and non-survivors on Day-90 were 44.11(6.62) and 53.86 (7.83). The prognostic accuracy of the CLIF-C ACLF score (Area Under Receiver Operating Characteristic Curve-AUROC) to predict 28-day and 90-day mortality was 0.86 and 0.84, respectively. MELD-Na and CLIF-C ACLF scores had higher AUROC for predicting 28-day and 90-day mortality, respectively. The AUROC of the CLIF-C OF score on Day 3 was found to be higher than the values of Day 1 and Day 7, but it was not statistically significant. Conclusion: CLIF-C ACLF has good short-term prognostic accuracy and it is as good as other available scores. Serial CLIF-C OF scores were equally good in predicting in short-term mortality. How to cite this article: Hareesh GJ, Ramadoss R. Clinical Profile, Short-term Prognostic Accuracies of CLIF-C ACLF Score and Serial CLIF-C OF Scores in Acute-on-chronic Liver Failure Patients: A Prospective Observational Study. Indian J Crit Care Med 2024;28(2):126-133.

Simplifying Treatment Criteria in Chronic Hepatitis B: Reducing Barriers to Elimination.

BACKGROUND: Early, sustained hepatitis B virus (HBV) DNA suppression reduces long-term risks of hepatocellular carcinoma. Chronic hepatitis B (CHB) treatment criteria are complex. Simplifying criteria will improve timely linkage to therapy. We evaluated treatment eligibility patterns among US patients with CHB and propose stepwise simplification of CHB treatment criteria. METHODS: Using 2016-2020 Quest Diagnostics data, we evaluated treatment eligibility among patients with CHB (2 positive HBV tests [HBV surface antigen, HBV e antigen, or HBV DNA] ≥6 months apart) using American Association for the Study of Liver Disease (AASLD), European Association for Study of the Liver (EASL), Asian Pacific Association for Study of the Liver (APASL), and Asian American Treatment Algorithm (AATA) criteria. RESULTS: Among 84 916 patients with CHB, 6.7%, 6.2%, 5.8%, and 16.4% met AASLD, EASL, APASL, and AATA criteria, respectively. Among treatment-ineligible patients with CHB, proportion with significant fibrosis (aspartate aminotransferase platelet ratio index >0.5) were 10.4%, 10.4%, 10.8%, and 7.7% based on AASLD, EASL, APASL, and AATA, respectively. In the proposed treatment simplification, the proportion of patients with CHB eligible for therapy increased from 10.3% for step 1 (HBV DNA >20 000 IU/mL, elevated alanine aminotransferase [ALT] level) to 14.1% for step 2 (HBV >2000 IU/mL, elevated ALT level), 33.5% for step 3 (HBV DNA >2000 IU/mL, any ALT level), and 87.2% for step 4 (detectable HBV DNA, any ALT level). CONCLUSIONS: A large proportion of patients with CHB not meeting established treatment criteria have significant fibrosis. Simplifying criteria to treat all patients with detectable HBV DNA will reduce complexity and heterogeneity in assessing treatment eligibility, improving treatment rates and progress toward HBV elimination.

[Application of different prognostic scores in liver transplantation decision-making for acute-on-chronic liver failure].

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.

Hepatitis E case series: A UK experience.

The incidence of hepatitis E continues to increase and in immunocompromised patients can lead to chronic infection. Management of hepatitis E has evolved over time, with the first step being a reduction of immunosuppression followed by treatment with ribavirin. The European Association for the Study of Liver guidelines support treatment with ribavirin although the optimum dose and regime is unknown. This series reviews eight chronically infected cases treated between 2018 and 2021 in two UK centres (Ipswich Hospital and Addenbrooke's Hospital). Treatment response was defined primarily as sustained virological response at 12 weeks (SVR12) following the cessation of treatment and secondly as sustained virological response at 24 weeks (SVR24). The median dose of ribavirin given daily was 600 mg. The management of five of the eight cases was in line with the guidelines, and treatment was stopped after 12 weeks. Two of these five patients achieved SVR (40%). The remaining three cases were given a 24-week course based on clinical judgement, and all achieved SVR (100%). The three patients who relapsed received a second 24-week course of treatment and achieved SVR. Therefore, with a 24-week course, a 100% treatment success rate was attained. In chronic hepatitis E, a 24-week course of ribavirin would achieve optimum clearance rates with a single course of treatment. Ensuring the highest dose of ribavirin as possible (aiming to reach 800 mg daily) and attempts to reduce immunosuppressive therapy safely may also be relevant to achieving SVR.

Acute-on-chronic liver failure: A distinct clinical syndrome.

There are different operating definitions for acute-on-chronic liver failure (ACLF) in different geographic regions. Consortia in Western countries have developed definitions that apply to patients with cirrhosis, while consortia in Asia have developed definitions that apply to patients with chronic liver diseases with or without cirrhosis. Investigators of the Chinese and Western Consortia believe that ACLF can be precipitated by acute insults that are intrahepatic (e.g. alcoholic hepatitis) or extrahepatic (e.g. bacterial infection, gastrointestinal haemorrhage), and that extrahepatic organ system failures can be used to define ACLF. In contrast, the Asia Pacific consortium believe that ACLF is only defined by an acute onset of liver failure in response to an acute hepatic insult. Of note, although ACLF has received different operating definitions, every definition recognises that ACLF is a distinct clinical entity. This article provides an updated overview of the distinctive features of ACLF according to the definitions used to characterise it. In addition, we discuss future directions for research aimed at identifying the hallmarks of ACLF.

'Equity' and 'Justice' for patients with acute-on chronic liver failure: A call to action.

Acute-on-chronic liver failure (ACLF) occurs in hospitalised patients with cirrhosis and is characterised by multiorgan failures and high rates of short-term mortality. Without liver transplantation (LT), the 28-day mortality rate of patients with ACLF ranges from 18-25% in those with ACLF grade 1 to 68-89% in those with ACLF grade 3. It has become clear that patients with ACLF do not have equitable access to LT because of current allocation policies, which are based on prognostic scores that underestimate their risk of death and a lack of appreciation of the clear evidence of transplant benefit in carefully selected patients (who can have excellent post-LT outcomes). In this expert opinion, we provide evidence supporting the argument that patients with ACLF should be given priority for LT based on prognostic models that define the risk of death for these patients. We also pinpoint risk factors for poor post-LT outcomes, identify unanswered questions and describe the design of a global study, the CHANCE study, which will provide answers to the outstanding issues. We also propose the worldwide adoption of new organ allocation policies for patients with ACLF, as have been initiated in the UK and recommended in Spain.

EASL-CLIF criteria outperform NACSELD criteria for diagnosis and prognostication in ACLF.

BACKGROUND & AIMS: There is no consensus on the best definition for acute-on-chronic liver failure (ACLF). In this study, we compared the prevalence and 30-day all-cause and transplant-free mortality of patients with ACLF identified by European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) and North American Consortium for the Study of End-stage Liver Disease (NACSELD) criteria. METHODS: We performed this comparative analysis using the United Network for Organ Sharing (UNOS) data from January 11, 2016 to August 31, 2020. RESULTS: A total of 10,198 (21%) adult patients had EASL-CLIF ACLF grade 1-3, but of these only 15.3% had ACLF by NACSELD. Of the 2,562 with EASL-CLIF ACLF grade 3, only 48.8% had NACSELD-ACLF, 16.8% had no organ failure (OF) and 34.4% had 1 OF. The 30-day all-cause mortality was 1.5%, 7.7%, 13.3% and 25.8% for EASL-CLIF grade 0-3, respectively, and it was 15.4% and 28.1% in those without and with NACSELD-ACLF. When EASL-CLIF grade 3 patients were stratified by NACSELD OF, the mortality ranged from 18.6% with no OF to 41.0% with 4 OFs. The 30-day transplant-free mortality in those with no OF by NACSELD was 2.7%, but when the same group is stratified by EASL-CLIF grades 0-3, the mortality rates were 1.5%, 10.5%, 43.5% and 86%, respectively; the mortality rates ranged from 3.0% to 75.7% in those with 1 OF by NACSELD. CONCLUSIONS: There is a clear discordance in the prevalence and 30-day mortality rates of patients with ACLF identified by the EASL-CLIF and NACSELD criteria. EASL-CLIF criteria have a better sensitivity to detect ACLF and have a better prognostic capability. LAY SUMMARY: There is no consensus on the definition of acute-on-chronic liver failure. European (EASL-CLIF) and North American (NACSELD) consortia have each proposed a commonly used definition. In this study, we compared the prevalence and short-term (30-day) mortality based on these definitions. Using a very large data set, we observed that there was a significant discordance in the prevalence and mortality based on these criteria. EASL-CLIF criteria appeared to be more sensitive to identify acute-on-chronic liver failure, and were better at predicting all-cause and short-term mortality.

EASL versus LI-RADS: Intra-individual comparison of MRI with extracellular contrast and gadoxetic acid for diagnosis of small HCC.

BACKGROUND & AIMS: Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study (EASL) criteria for hepatocellular carcinoma (HCC) diagnosis have been updated in 2018. We aimed to compare the HCC diagnostic performance of LI-RADS and EASL criteria with extracellular contrast agents-MRI (ECA-MRI) and hepatobiliary agents-MRI (HBA-MRI). METHODS: We prospectively evaluated 179 participants with cirrhosis (n = 105) or non-cirrhotic chronic hepatitis B (CHB) (n = 74) who underwent both ECA-MRI and HBA-MRI before surgery for de novo nodule(s) measuring 10-30 mm. We compared the HCC diagnostic performance of EASL and LR-5 in both MRIs. RESULTS: In an analysis of 215 observations (175 HCCs, 17 non-HCC malignancies and 23 benign lesions) identified from cirrhotic or non-cirrhotic CHB participants, LR-5 with ECA-MRI provided the highest sensitivity (80.7%), followed by EASL with ECA-MRI (76.2%), LR-5 with HBA-MRI (67.3%) and EASL with HBA-MRI (63.0%, all P < .05). The specificities were comparable (89.4%-91.5%). When the analysis is limited to participants with pathological cirrhosis (123 observations), the sensitivity of LR-5 with ECA-MRI was similar to that of EASL with ECA-MRI (82.7% vs 80.2%, P = .156), but higher than LR-5 with HBA-MRI (65.1%) or EASL with HBA-MRI (62.8%, both P < .001), with comparable specificities (87.5%-91.7%). CONCLUSIONS: The LR-5 with ECA-MRI yielded the highest sensitivity with a similar specificity for HCC diagnosis in cirrhosis and non-cirrhotic CHB participants, while the sensitivities of LR-5 and EASL with ECA-MRI are similar for cirrhosis participants. This indicates non-invasive diagnosis criteria can differ by contrast agents and presence of cirrhosis.

Risk prediction scores for acute on chronic liver failure development and mortality.

BACKGROUND & AIMS: Acute on chronic liver failure (ACLF) causes high short-term mortality in patients with previously stable chronic liver disease. To date there are no models to predict which patients are likely to develop ACLF, and existing models to predict ACLF mortality are based on limited cohorts. We sought to create novel risk prediction scores using a large cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of 74 790 patients with incident cirrhosis in the Veterans Health Administration database using randomized 70% derivation/30% validation sets. ACLF events were identified per the European ACLF criteria. Multivariable logistic regression was used to derive prediction models for developing ACLF at 3, 6 and 12 months, and ACLF mortality at 28 and 90 days. Mortality models were compared to model for end-stage liver disease (MELD), MELD-sodium and the Chronic Liver Failure Consortium (CLIF-C) ACLF score. RESULTS: Models for the developing ACLF had very good discrimination (concordance [C] statistics 0.83-0.87) at all timepoints. Models for ACLF mortality also had good discrimination at 28 and 90 days (C-statistics 0.79-0.82), and were superior to MELD, MELD-sodium and the CLIF-C ACLF score. The calibration of the novel models was excellent at all timepoints. CONCLUSION: We have obtained highly-predictive models for developing ACLF, as well as for ACLF short-term mortality in a diverse United States cohort. These may be used to identify outpatients at significant risk of ACLF, which may prompt closer follow-up or early transplant referral, and facilitate decision making for patients with diagnosed ACLF, including escalation of care, expedited transplant evaluation or palliation.

Alcohol-related liver diseases (ALD).

The main aim of this educational article ( narrative review ) is to reflect clinical practice guidelines of the European Association for the Study of the Liver (EASL) published in J Hepatol 2018, contrasting with the 2012 guidelines especialy in the new terminology of alcohol-related liver diseases (ALD). The strong emphasis on prevention of alcohol use disorders (AUD) may be exert at all stages of public health care. Another aim of the article are ALD history, epidemiology, metabolism of alcohol and clinical pictures of ALD.

Predniso(lo)ne Dosage and Chance of Remission in Patients With Autoimmune Hepatitis.

BACKGROUND & AIMS: Patients with autoimmune hepatitis (AIH) commonly receive induction therapy with predniso(lo)ne followed by maintenance therapy with azathioprine. European Association for Study of the Liver clinical practice guidelines advise a predniso(lo)ne dose range of 0.50-1 mg/kg/day, which leaves room for practice variation. We performed a multicenter study to determine the efficacy of different dose ranges of predniso(lo)ne induction therapy in a large European cohort of patients with AIH. METHODS: We performed a retrospective cohort study using a comparative effectiveness design. We collected data from 451 adults with AIH who began treatment from 1978 through 2017 at 9 centers in 5 European countries. We assigned patients to a high-dose group (initial predniso(lo)ne dose ≥0.50 mg/kg/day; n = 281) or a low-dose group (<0.50 mg/kg/day; n = 170). Logistic regression was performed to determine difference in outcomes between the groups. The primary outcome was normal serum levels of transaminases at 6 months after initiation of therapy. RESULTS: There was no significant difference in rates of normalization of transaminases between the high-dose predniso(lo)ne group and the low-dose group (70.5% vs 64.7%; P = .20). After multivariable logistic regression with correction for confounders, there was no difference in the likelihood of normalization of transaminases between the groups (odds ratio, 1.21; 95% CI, 0.78-1.87; P = .38). Patients given an initial high dose of predniso(lo)ne received more predniso(lo)ne over time than patients started on a lower dose (median doses over 6 months: 3780 mg vs 2573 mg) (P < .01). CONCLUSIONS: In a retrospective study of patients with AIH in Europe, we found that the dose of predniso(lo)ne to induce remission in patients with AIH is less relevant than assumed. An initial predniso(lo)ne dose below 0.50 mg/kg/day substantially decreases unnecessary exposure to predniso(lo)ne in patients with AIH.

Reproducibility of European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors in patients treated with sorafenib.

BACKGROUND & AIMS: The European Association for the Study of the Liver criteria and the modified Response Evaluation Criteria in Solid Tumors are used for assessing the treatment outcomes of hepatocellular carcinoma. We investigated the inter- and intra-observer reproducibility of the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors in patients with advanced hepatocellular carcinoma treated with sorafenib. METHODS: A total of 99 patients with treatment-naive advanced hepatocellular carcinoma receiving sorafenib were included. The κ-values for the inter- and intra-observer agreement of the treatment response were calculated. RESULTS: Inter-observer agreement for baseline tumour number was excellent, as reflected by the high κ-value. The κ-statistics showed "excellent" concordance between the 2 sets of measurements by observer A regarding the overall responses using the European Association for the Study of the Liver criteria (κ = .948, agreement rate = 84.8%) and modified Response Evaluation Criteria in Solid Tumors (κ = .944, agreement rate = 83.8%; all P < .001). In addition, high κ-values indicated concordance between the first sets of measurements by observers A and B (κ = .991 by the European Association for the Study of the Liver criteria and .988 by modified Response Evaluation Criteria in Solid Tumors, all P < .001). When agreements in radiological overall responses between the 2 sets of measurements by observer B and between the second sets of measurements by observers A and B were calculated, similar results regarding high κ-values (>.8) were obtained. CONCLUSIONS: The reproducibility of the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors in assessing treatment outcomes was high in patients with advanced hepatocellular carcinoma treated with sorafenib.

A multicenter pilot survey to clarify the clinical features of patients with acute-on-chronic liver failure in Japan.

AIM: To establish diagnostic criteria for acute-on-chronic liver failure (ACLF) in Japan, a multicenter pilot survey was carried out to examine the usefulness of overseas criteria in patients with chronic liver diseases manifesting acute decompensation. METHODS: Patients fulfilling the Asian-Pacific Association for the Study of the Liver (APASL), European Association for the Study of the Liver (EASL), or Chinese Medical Association (CMA) criteria for decompensation were enrolled from eight institutions in Japan, and the clinical features were evaluated. RESULTS: Among 112 patients, 109 patients (97.3%) fulfilled the APASL criteria for decompensation; 7 patients were excluded because the decompensation had been provoked by gastrointestinal bleeding. Consequently, 102 patients (91.1%) were diagnosed as having ACLF according to the APASL definition. Among the patients who fulfilled the APASL criteria for decompensation, the etiologies of the underlying liver diseases were alcohol abuse in 59 cases (54.1%) and hepatitis B or hepatitis C virus infection in 24 (22.0%). The acute insults were alcohol abuse in 50 (45.9%), bacterial infection in 26 (23.9%), and exacerbation of underlying liver disease in 14 (12.8%). Fifty-four patients (49.5%) satisfied the CMA criteria, but the survival rates were similar between patients who did and those who did not meet the criteria. When 84 patients with underlying cirrhosis were classified according to the EASL-Chronic Liver Failure (Clif) Consortium criteria, the survival rates differed according to grade: 67.6% (23/34) for patients without ACLF, and 41.2% (14/34) and 18.8% (3/16) for those with grade 1/2 and grade 3 ACLF, respectively. CONCLUSION: The APASL definition was suitable for screening Japanese patients with ACLF, including those whose conditions were triggered by gastrointestinal bleeding, and the EASL-Clif Consortium criteria were useful for predicting outcome.

Proposed diagnostic criteria for acute-on-chronic liver failure in Japan.

To establish diagnostic criteria for acute-on-chronic liver failure (ACLF) in Japan, the Intractable Hepato-Biliary Disease Study Group of Japan undertook a multicenter pilot survey for patients fulfilling the Asian Pacific Association for the Study of the Liver (APASL), Association for the Study of the Liver-Chronic Liver Failure (EASL-Clif) Consortium, or Chinese Medical Association (CMA) diagnostic criteria for ACLF. The APASL criteria were suitable for screening Japanese patients with ACLF when patients whose conditions were triggered by gastrointestinal bleeding were included within the disease entity, and the EASL-Clif Consortium criteria were useful for classifying the severity of the patients' conditions. Based on these observations, the Study Group proposed the following diagnostic criteria for ACLF in Japan: patients with cirrhosis and a Child-Pugh score of 5-9 should be diagnosed as having ACLF when a deterioration of liver function (serum bilirubin level ≥5.0 mg/dL and prothrombin time value ≤40% of the standardized values and/or international normalization rate ≥1.5) caused by severe liver damage develops within 28 days after acute insults, such as alcohol abuse, bacterial infection, gastrointestinal bleeding, or the exacerbation of underlying liver diseases. The severities of the patients can be classified into four grades depending on the extent of the deterioration in organ functions, including kidney, cerebral, blood coagulation, circulatory and respiratory functions, as well as liver function. The usefulness of these novel criteria should be validated prospectively in a large-scale cohort in the future.

Evaluation of HCC response to locoregional therapy: Validation of MRI-based response criteria versus explant pathology.

BACKGROUND AND AIMS: This study evaluates the performance of various magnetic resonance imaging (MRI) response criteria for the prediction of complete pathologic necrosis (CPN) of hepatocellular carcinoma (HCC) post locoregional therapy (LRT) using explant pathology as a reference. METHODS: We included 61 patients (male/female 46/15; mean age 60years) who underwent liver transplantation after LRT with transarterial chemoembolization plus radiofrequency or microwave ablation (n=56), or 90Yttrium radioembolization (n=5). MRI was performed <90days before liver transplantation. Three independent readers assessed the following criteria: RECIST, EASL, modified RECIST (mRECIST), percentage of necrosis on subtraction images, and diffusion-weighted imaging (DWI), both qualitative (signal intensity) and quantitative (apparent diffusion coefficient [ADC]). The degree of necrosis was retrospectively assessed at histopathology. Intraclass correlation coefficient (ICC) and Cohen's kappa were used to assess inter-reader agreement. Logistic regression and receiver operating characteristic analyses were used to determine imaging predictors of CPN. Pearson correlation was performed between imaging criteria and pathologic degree of tumor necrosis. RESULTS: A total of 97HCCs (mean size 2.3±1.3cm) including 28 with CPN were evaluated. There was excellent inter-reader agreement (ICC 0.77-0.86, all methods). EASL, mRECIST, percentage of necrosis and qualitative DWI were all significant (p<0.001) predictors of CPN, while RECIST and ADC were not. EASL, mRECIST and percentage of necrosis performed similarly (area under the curves [AUCs] 0.810-0.815) while the performance of qualitative DWI was lower (AUC 0.622). Image subtraction demonstrated the strongest correlation (r=0.71-0.72, p<0.0001) with pathologic degree of tumor necrosis. CONCLUSIONS: EASL/mRECIST criteria and image subtraction have excellent diagnostic performance for predicting CPN in HCC treated with LRT, with image subtraction correlating best with pathologic degree of tumor necrosis. Thus, MR image subtraction is recommended for assessing HCC response to LRT. LAY SUMMARY: The assessment of hepatocellular carcinoma (HCC) tumor necrosis after locoregional therapy is essential for additional treatment planning and estimation of outcome. In this study, we assessed the performance of various magnetic resonance imaging (MRI) response criteria (RECIST, mRECIST, EASL, percentage of necrosis on subtraction images, and diffusion-weighted imaging) for the prediction of complete pathologic necrosis of HCC post locoregional therapy on liver explant. Patients who underwent liver transplantation after locoregional therapy were included in this retrospective study. All patients underwent routine liver MRI within 90days of liver transplantation. EASL/mRECIST criteria and image subtraction had excellent diagnostic performance for predicting complete pathologic necrosis in treated HCC, with image subtraction correlating best with pathologic degree of tumor necrosis.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.

Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors including vaccination policies and migration. This Clinical Practice Guideline presents updated recommendations for the optimal management of HBV infection. Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis and (V) HBsAg-negative phase. All patients with chronic HBV infection are at increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC), depending on host and viral factors. The main goal of therapy is to improve survival and quality of life by preventing disease progression, and consequently HCC development. The induction of long-term suppression of HBV replication represents the main endpoint of current treatment strategies, while HBsAg loss is an optimal endpoint. The typical indication for treatment requires HBV DNA >2,000IU/ml, elevated ALT and/or at least moderate histological lesions, while all cirrhotic patients with detectable HBV DNA should be treated. Additional indications include the prevention of mother to child transmission in pregnant women with high viremia and prevention of HBV reactivation in patients requiring immunosuppression or chemotherapy. The long-term administration of a potent nucleos(t)ide analogue with high barrier to resistance, i.e., entecavir, tenofovir disoproxil or tenofovir alafenamide, represents the treatment of choice. Pegylated interferon-alfa treatment can also be considered in mild to moderate chronic hepatitis B patients. Combination therapies are not generally recommended. All patients should be monitored for risk of disease progression and HCC. Treated patients should be monitored for therapy response and adherence. HCC remains the major concern for treated chronic hepatitis B patients. Several subgroups of patients with HBV infection require specific focus. Future treatment strategies to achieve 'cure' of disease and new biomarkers are discussed.

Report from European Association for the Study of the Liver: HCC Summit, Geneva, Switzerland, 2-5 February 2017.

The European Association for the Study of the Liver Hepatocellular Carcinoma (HCC) international meeting held in Geneva in February 2017 focused on the state of the art of HCC management, from diagnosis to treatment and the potential development of clinical research in this field. This report reviews some of the most interesting topics discussed at the meeting such as the role of hepatitis C viral infection treatment with direct-acting antivirals in enhancing HCC risk, current prognostic systems, early diagnosis techniques, curative therapies for early HCC and the systemic treatments for advanced disease with a look into future perspectives.

Treatment Response and Outcome with Two Different Prednisolone Regimens in Autoimmune Hepatitis.

BACKGROUND: Beyond available guidelines, therapy of autoimmune hepatitis (AIH) shows wide variation among physicians. We compared two regimens for treatment naive AIH: one recommended protocol with an initial prednisolone dose of 30 mg/day and our own 40 mg/day prednisolone with a slow dose tapering protocol. We analyzed the safety, response rates, and outcomes for two groups of treated patients. PATIENTS AND METHODS: We retrospectively evaluated data of 71 AIH patients including, group I (n = 32, prednisone 30 mg/day) and group II (n = 39, prednisone 40 mg/day). All patients also received azathioprine. RESULTS: The frequency of complete biochemical response was significantly higher in group II than in group I (69.2 vs. 43.8%, p = 0.031) after 3 months of therapy, but not after 6 and 12 months (79.5 vs. 59.4%, p = 0.065 and 89.5 vs. 80.6%, p = 0.30). In patients with severe interface hepatitis, the complete response rates were significantly higher in group II than in group I after 3 (63.6 vs. 23.1%, p = 0.02) and 6 months (72.7 vs. 38.5%, p = 0.046), but not after 12 months of therapy (86.4 vs. 69.2%, p = 0.221). Relapses were observed in 50% of group I and in 35.9% of group II during maintenance therapy (p = 0.23). Overall survival was significantly better in group II than in group I (100 vs. 87.5%, log-rank, p = 0.048). No severe steroid-related side effects were observed in either group. CONCLUSIONS: Our real-world experience suggests that an initial prednisolone dose of 40 mg/day with a slower tapering protocol induces earlier biochemical response, tends to result in less relapses during maintenance, and is associated with a better disease outcome.