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Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies., (© 2025. The Author(s).)

Introduction: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute-on-chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied., Methods: Patients with MAFLD-ACLF were recruited from the Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC registry). The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease as MAFLD (or previous nomenclature such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or non-alcoholic steatohepatitis-cirrhosis). Patients with coexisting other etiologies of chronic liver disease (such as alcohol, hepatitis B virus, hepatitis C virus, etc.) were excluded. Data were randomly split into derivation (n = 258) and validation (n = 111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered., Results: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27% and hypertension in 29%. The dominant precipitants included viral hepatitis (hepatitis A virus and hepatitis E virus, 32%), drug-induced injury (drug-induced liver injury, 29%), and sepsis (23%). Model for End-Stage Liver Disease-Sodium (MELD-Na) and AARC scores on admission averaged 32 ± 6 and 10.4 ± 1.9. At 90 days, 51% survived. Nonviral precipitant, diabetes, bilirubin, international normalized ratio, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for nonviral precipitant), and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts., Discussion: Almost half of patients with MAFLD-ACLF die within 90 days. Diabetes and nonviral precipitants such as drug-induced liver injury and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for patients with MAFLD-ACLF., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Early detection of esophageal varices (EV) before the first attack of bleeding is crucial for primary prophylaxis. The current work aims to investigate the use of a combination of FibroScan and platelet count as noninvasive means to identify EV in patients with compensated cirrhosis., Methods: Sixty-two patients with compensated hepatitis C virus (HCV)-related cirrhosis were divided into two groups with and without EV. All patients were exposed to complete history, physical examination, laboratory, and endoscopic evaluation. FibroScan was performed for all patients, and the two groups were compared., Results: A statistically significant higher mean liver stiffness measurement (LSM) (KPa), lower mean platelet count to splenic diameter ratio (PSR), and higher mean fibrosis-4 (FIB4) score were noticed in those with EV with P < 0.0005. A cutoff value of ≥23.1 for LSM, ≥3.71 for FIB4, and ≥130 mm for splenic diameter have a sensitivity of 94%, 97%, and 97% and a specificity of 81%, 81%, and 68%, respectively, in the detection of varices. Platelet count of ≥112,500 (×10 3 /dl) and of ≥771.33 for PSR have a sensitivity of 84% and 77% and a specificity of 87% and 90%, respectively, to rule out the presence of varices. LSM, FIB4 score, and splenic diameter are predictors of the presence of varices where platelet count and PSR are negative predictors., Conclusion: The combination of LSM by transient elastography (TE), PSR, or platelet count can be used to detect a relevant category of patients with compensated cirrhosis who have a very low possibility of EV where endoscopy can be avoided., Competing Interests: The authors have none to declare., (© 2021 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Objectives: The objective of this study was to screen for significant hepatic fibrosis or steatosis in asymptomatic, apparently healthy subjects by using Vibration-controlled transient elastography and controlled attenuation parameter (CAP)., Methods: Prospectively, 433 asymptomatic apparently healthy adults were included. Fibroscan/CAP examination was performed for all of them. Subjects with liver stiffness measurement > 6 kPa or CAP >248 dB/m were further evaluated to assess underlying chronic liver disease., Results: According to fibroscan/CAP examination, subjects were classified into four subgroups: normal (119) with CAP score of 215.85 ± 24.81 dB/m and fibrosis score of 4.47 ± 0.81 kPa, subjects with steatosis only 133 with CAP score of 309.41 ± 42.6 dB/m and fibrosis score of 4.74 ± 0.82 kPa, subjects with both steatosis and fibrosis 95 with CAP score of 318.20 ± 39.89 dB/m and fibrosis score of 7.92 ± 2.58 kPaand subjects with fibrosis only 86 with CAP score of 213.48 ± 22.62 dB/m and fibrosis score of 6.96 ± 1.11 kPa. S0 was present in 205 (47.3%), S1 in 48 (10.2%), S2 in 16 (3.7%) and S3 in 168 (38.8%) of studied subjects, whereas F0-1 was present in 371 (85.7%), F2 in 44 (10.16%), F3 in 16 (3.7%) subjects and F4 in only one (0.23%) subject. Subjects with both steatosis and fibrosis showed significantly higher transaminases, triglycerides and total cholesterol levels than other subgroups., Conclusions: Most asymptomatic, apparently healthy subjects (72%) have significant steatosis and fibrosis. Liver stiffness measurement and CAP might represent promising first-line noninvasive procedures to screen for silent liver diseases in the general population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aim: Indeterminate biliary stricture (IBS) is a frequently encountered clinical problem. In this study, we aimed to highlight the clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture., Method: A Retrospective multicenter study included all patients diagnosed with IBS in the participating centers between 2017 and 2021. Data regarding IBS such as presentations, patient characteristics, diagnostic and therapeutic modalities were collected from the patients' records and then were analyzed., Results: Data of 315 patients with IBS were retrospectively collected from 7 medical centers with mean age: 62.6 ± 11 years, females: 40.3% and smokers: 44.8%. For diagnosing stricture; Magnetic resonance imaging/Magnetic resonance cholangiopancreatography (MRI/MRCP) was the most frequently requested imaging modality in all patients, Contrast enhanced computerized tomography (CECT) in 85% and endoscopic ultrasound (EUS) in 23.8%. Tissue diagnosis of cholangiocarcinoma was achieved in 14% only. The used therapeutic modalities were endoscopic retrograde cholangiopancreatography (ERCP)/stenting in 70.5%, percutaneous trans-hepatic biliary drainage (PTD): 17.8%, EUS guided drainage: 0.3%, and surgical resection in 8%. The most frequent type of strictures was distal stricture in 181 patients, perihilar in 128 and intrahepatic in 6. Distal strictures had significant male predominance, with higher role for EUS for diagnosis and higher role for ERCP/stenting for drainage, while in the perihilar strictures, there was higher role for CECT and MRI/MRCP for diagnosis and more frequent use of PTD for drainage., Conclusion: Indeterminate biliary stricture is a challenging clinical problem with lack of tissue diagnosis in most of cases mandates an urgent consensus diagnostic and treatment guidelines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tag-Adeen, Malak, Abdel-Gawad, Abu-Elfatth, Eldamarawy, Alzamzamy, Elbasiony, Elsharkawy, El-Raey, Basiony, Qasem, Shady, Abdelmohsen, Abdeltawab, Farouk, Fouad, Rabie, Erian, Sapra, Shaibat-Alhamd, Aboubakr, Omran and Alboraie.)

Background: Hepatitis C virus (HCV) is a known risk factor for hepatocellular carcinoma. Several epidemiological studies have pointed out to an association of HCV infection with other extrahepatic malignancies. The role of chronic HCV in breast cancer causation is less clear. Egypt is an endemic area of HCV infection with resulting significant morbidity. The association between HCV status and breast cancer risk in Egyptian women is hitherto unknown., Methods: A retrospective study was performed. The prevalence of anti-HCV seropositivity was estimated in a sample of women with a breast cancer diagnosis, retrieved from the hospital records, and was compared to the raw data of a population study in Egypt. Anti-HCV negative and positive patients were compared regarding the disease course and outcome., Results: Retrospective analysis revealed a markedly high prevalence of anti-HCV seropositivity in young breast cancer patients. In patients younger than 45 years, 13.4% were anti-HCV positive. Seropositivity was 6-fold higher in these patients than in adult females of the same age without cancer diagnosis ( P  = .003). The biological type, tumor size, nodal status, and disease-free survival were not affected by the patients' HCV status., Conclusion: Young Egyptian breast cancer patients have a dramatically high prevalence of HCV seropositivity. Further population studies are strongly required to investigate the epidemiological association of these two significant health problems., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

The new anti-hepatitis C virus (HCV) molecules improve treatment regimens and outcomes, but there are drawbacks. New combinations should target the HCV infectious cycle and be effective against all HCV genotypes. We developed the novel formulation Catvira, composed of epigallocatechingallate (EGCG) + sofosbuvir + ribavirin. Here, we compared Catvira to sofosbuvir + ribavirin tablets in patients with CHC genotype 4 in a randomized open-label efficacy and safety study. Treatment-naïve and treatment-experienced patients (n = 80) were randomly assigned to receive a single daily fixed dose of Catvira or sofosbuvir + ribavirin for 12 or 24 weeks. Both Catvira and sofosbuvir + ribavirin yielded similar outcomes of viral load (p < 0.001). Patients receiving Catvira had a significantly more rapid rate of viral load decline with sustained virologic response (SVR12) achieved by 90% of patients receiving 12 weeks of treatment. Catvira did not impact hemoglobin levels while sofosbuvir + ribavirin showed significant decline in hemoglobin levels after 24 weeks (p < 0.05). In this clinical trial (ClinicalTrials.gov Identifier NCT02483156), we found that Catvira administered daily for 12 or 24 weeks is safe, effective, and well-tolerated in both naïve and treatment-experienced patients with HCV genotype 4.

Background & Aims: Hepatocellular carcinoma (HCC) risk persists after hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs), particularly in patients with cirrhosis. Identifying those who are likely to develop HCC is a critical unmet medical need. Our aim is to develop a score that offers individualized patient HCC risk prediction., Methods: This two-centre prospective study included 4400 patients, with cirrhosis and advanced fibrosis who achieved a sustained virologic response (SVR), including 2372 patients (derivation cohort). HCC-associated factors were identified by multivariable Cox regression analysis to develop a scoring model for prediction of HCC risk; and subsequently internally and externally validated in two independent cohorts of 687 and 1341 patients., Results: In the derivation cohort, the median follow-up was 23.51 ± 8.21 months, during which 109 patients (4.7%) developed HCC. Age, sex, serum albumin, α fetoprotein and pretreatment fibrosis stage were identified as risk factors for HCC. A simple predictive model (GES) score was constructed. The 2-year cumulative HCC incidence using Kaplan-Meier method was 1.2%, 3.3% and 7.1% in the low-risk, medium-risk and high-risk groups respectively. Internal and external validation showed highly significant difference among the three risk groups (P < .001) with regard to cumulative HCC risk. GES score has high predictive ability value (Harrell's C statistic 0.801), that remained robustly consistent across two independent validation cohorts (Harrell's C statistic 0.812 and 0.816)., Conclusion: GES score is simple with validated good predictive ability for the development of HCC after eradication of HCV and may be useful for HCC risk stratification in those patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%-8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long-term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis-related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow-up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow-up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow-up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942-2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407-3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333-1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy., (© 2020 John Wiley & Sons Ltd.)

Emergence of new molecules acting directly on the hepatitic C virus (HCV) has improved treatment outcomes. However, there is a risk of selecting viral escape mutants, so a new combination is needed using different inhibitors that target different steps of the HCV infectious cycle. Novel single tablet formulations were developed: Dactavira, composed of sofosbuvir (SOF) 400 mg/daclatisvir (DCV) 60 mg/epigallocatechin gallate (EGCG) 400 mg without ribavirin (RBV); and Dactavira plus, which includes RBV 800 mg. A randomized, open-label study was carried out on treatment-naïve non-cirrhotic (Group A, n = 50) and treatment-naïve cirrhotic (Group B, n = 22) patients with genotype 4 HCV infection. Group A was randomly assigned to receive a single daily fixed-dose (Dactavira, n = 25) or the standard of care [SOF 400 mg/DCV 60 mg] (n = 25) daily for 12 weeks. Group B was randomly assigned to receive a single daily fixed-dose (Dactavira plus, n = 11) or the standard of care + RBV 800 mg (n = 11) daily for 12 weeks. Patients receiving Dactavira or Dactavira plus had a significantly more rapid rate of viral load decline as compared to patients receiving the standard of care therapy. Sustained virological response for 12 weeks for Dactavira or Dactavira plus showed no statistically significant difference when compared to the standard of care. Also, they did not affect normal hemoglobin levels (p < 0.001) versus the standard of care. The incorporated EGCG interferes with the viral entry mechanisms, as reported by several investigators, and in turn enhances efficacy and prevents relapse as compared to the standard of care. Also, its antihemeolytic and antifibrotic activities may improve the safety and tolerability of the therapy.

Objective: We evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens., Design: In this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12)., Results: We enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin., Conclusion: Among non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir., Trial Registration Number: NCT02487030., Competing Interests: Competing interests: GS has served as a principal investigator for AbbVie and Gilead. GE has served as a principal investigator for AbbVie, Gilead, BMS and Pharco Pharmaceuticals, and has served as a speaker for Gilead and BMS, and has served on advisory boards for Gilead and MSD. MH has served as an investigator for AbbVie, Janssen and Gilead, and has served as a speaker for AbbVie. RS has served as an investigator for AbbVie and Gilead. ME has served as an investigator for Gilead. RF has served as an investigator for Gilead, Abbie and Pharco Pharmaceuticals. AE has served as an investigator for Gilead, Abbvie and Janssen. RH declares no conflicts of interest. WA-R has served as a co-investigator for Gilead, Janssen and AbbVie. TZ has served as a co-investigator for Janssen and AbbVie. IW has served as an investigator, speaker and on advisory boards for AbbVie, Eva Pharma, Gilead, Janssen, Marcyrl, Onxio, Pharco and Roche. WD has served as an investigator for AbbVie, Janssen and Gilead. The following coauthors are employees of and hold stock interest in Gilead Sciences: KK, BM, AO, SL, DMB and JGMcH., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Egypt has one of the highest prevalences and burdens of hepatitis C virus (HCV) worldwide, and a large government treatment programme. However, identifying and treating people who are infected in rural communities can be a substantial challenge. We designed and evaluated a comprehensive community-led outreach programme for prevention, testing, and treatment of HCV infection in one village in northern Egypt, with the goal to eliminate HCV infection from all adult villagers, and as a model for potential adoption in rural settings., Methods: A community-based education and test-and-treat project was established in Al-Othmanya village. The programme consisted of community mobilisation facilitated by a network of village promoters and establishment of partnerships; an educational campaign to raise awareness and promote behavioural changes; fundraising for public donations in the local community; and comprehensive testing, diagnosis, and treatment. For the educational campaign, we used public awareness events, house-to-house visits, and promotional materials (eg, booklets, cartoons, songs) to raise awareness of HCV and its transmission, and changes in knowledge, attitudes, and practices were measured through the use of a survey done before and after the educational campaign. Comprehensive testing, linkage to care, and treatment was offered to all eligible villagers (ie, those aged 12-80 years who had not previously been treated for HCV). Testing was done by use of HCV antibody and hepatitis B surface antigen (HBsAg) rapid diagnostic tests, with HCV-RNA PCR confirmation of positive cases, and staging of liver disease by use of transient elastography. HCV-RNA-positive participants were offered a 24-week course of sofosbuvir (400 mg orally, daily) and ribavirin (1000-1200 mg orally, daily) with an assessment of cure (sustained virological response) at 12 weeks after completion of treatment (SVR12)., Findings: Between June 6, 2015, and June 9, 2016, 4215 (89%) of 4721 eligible villagers were screened for HCV antibodies and HBsAg. Of these participants, 530 (13%) were HCV antibody positive and eight (<1%) were HBsAg positive. All HCV-antibody-positive individuals had an HCV-RNA assay, and 312 (59%) were HCV-RNA positive. All 312 completed a full baseline assessment with staging of liver disease, and 300 (96%) were given 24 weeks of sofosbuvir and ribavirin treatment within a median of 2·3 weeks (IQR 0·0-3·7) from serological diagnosis. 293 (98%) of the treated participants achieved SVR12. 42 (13%) HCV-RNA-positive participants had cirrhosis as determined by transient elastography, of whom 12 (29%) were diagnosed with hepatocellular carcinoma on the basis of α-fetoprotein measurement and ultrasound. 3575 (85%) of 4215 eligible villagers completed the baseline and after educational campaign survey, and awareness, knowledge, and adoption of safer practices to prevent HCV transmission all significantly increased (p<0·0001)., Interpretation: This community-led educate, test-and-treat demonstration project achieved high uptake of HCV testing, linkage to care and treatment, and attainment of cure in one village, as well as awareness and adoption of practices to prevent transmission in the community. This approach could be an important strategy for adoption in rural settings to complement the national government programme towards the elimination of HCV in Egypt., Funding: Egyptian Liver Research Institute and Hospital., (Copyright © 2018 World Health Organization. Published by Elsevier Ltd.. All rights reserved.)