Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the ...clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.
The Malaysian Society of Gastroenterology and Hepatology saw the need for a consensus statement on metabolic dysfunction‐associated fatty liver disease (MAFLD). The consensus panel consisted of ...experts in the field of gastroenterology/hepatology, endocrinology, bariatric surgery, family medicine, and public health. A modified Delphi process was used to prepare the consensus statements. The panel recognized the high and increasing prevalence of the disease and the consequent anticipated increase in liver‐related complications and mortality. Cardiovascular disease is the leading cause of mortality in MAFLD patients; therefore, cardiovascular disease risk assessment and management is important. A simple and clear liver assessment and referral pathway was agreed upon, so that patients with more severe MAFLD can be linked to gastroenterology/hepatology care, while patients with less severe MAFLD can remain in primary care or endocrinology, where they are best managed. Lifestyle intervention is the cornerstone in the management of MAFLD. The panel provided a consensus on the use of statin, angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, sodium–glucose cotransporter‐2 inhibitor, glucagon‐like peptide‐1 agonist, pioglitazone, vitamin E, and metformin, as well as recommendations on bariatric surgery, screening for gastroesophageal varices and hepatocellular carcinoma, and liver transplantation in MAFLD patients. Increasing the awareness and knowledge of the various stakeholders on MAFLD and incorporating MAFLD into existing noncommunicable disease‐related programs and activities are important steps to tackle the disease. These consensus statements will serve as a guide on MAFLD for clinicians and other stakeholders.
Background and Aims
We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute‐on‐chronic liver failure (ACLF).
Methods
We ...recruited ACLF patients between 2009 and 2020 from APASL‐ACLF Research Consortium (AARC). Their clinical data, investigations and organ involvement were serially noted for 90‐days and utilized for AI modelling. Data were split randomly into train and validation sets. Multiple AI models, MELD and AARC‐Model, were created/optimized on train set. Outcome prediction abilities were evaluated on validation sets through area under the curve (AUC), accuracy, sensitivity, specificity and class precision.
Results
Among 2481 ACLF patients, 1501 in train set and 980 in validation set, the extreme gradient boost‐cross‐validated model (XGB‐CV) demonstrated the highest AUC in train (0.999), validation (0.907) and overall sets (0.976) for predicting 30‐day outcomes. The AUC and accuracy of the XGB‐CV model (%Δ) were 7.0% and 6.9% higher than the standard day‐7 AARC model (p < .001) and 12.8% and 10.6% higher than the day 7 MELD for 30‐day predictions in validation set (p < .001). The XGB model had the highest AUC for 7‐ and 90‐day predictions as well (p < .001). Day‐7 creatinine, international normalized ratio (INR), circulatory failure, leucocyte count and day‐4 sepsis were top features determining the 30‐day outcomes. A simple decision tree incorporating creatinine, INR and circulatory failure was able to classify patients into high (~90%), intermediate (~60%) and low risk (~20%) of mortality. A web‐based AARC‐AI model was developed and validated twice with optimal performance for 30‐day predictions.
Conclusions
The performance of the AARC‐AI model exceeds the standard models for outcome predictions in ACLF. An AI‐based decision tree can reliably undertake severity‐based stratification of patients for timely interventions.
Globally according to the WHO progress report on viral hepatitis in 2021, 296 million people are living with chronic hepatitis B virus (HBV) infection and 820,000 deaths per year were due to HBV ...related liver cirrhosis and cancer. These estimated numbers for HBV are 5.1 folds and 2.8 folds higher than the respective estimates for hepatitis C, HBV needs greater efforts and attention if we are to eliminate viral hepatitis.
Mother-to-child transmission (MTCT) is responsible for the majority of chronic HBV infection especially in endemic regions. Perinatal transmission of HBV results in chronic infection in 90% of cases where else HBV infection in adulthood carries a much lower risk of chronicity at 10%.
About 6 million children younger than five years old are living with HBV. Therefore the prevention of MTCT is an essential step towards HBV elimination.
Complete and timely HBV vaccination is the most cost-effective way to prevent MTCT of HBV and in hepatitis B endemic populations with universal hepatitis B vaccination there are evidence showing reduction in the incidence of hepatitis-B-related childhood hepatocellular carcinoma.
Studies reported the risks of failure to prevent MTCT even with passive and active HBV vaccinations are maternal's high viral load, HBeAg positivity and delay in the administration of the HBV birth dose.
Concerted efforts and adoption of newer widely available technologies are required to overcome the accessibility of testing, the challenges when delivery occurred outside health facilities, in rural or remote communities and the inconsistent cold chain for vaccines.
Randomized controlled studies and real world practice showed the prevention of MTCT of HBV are enhanced by using prophylaxis anti-HBV therapies at 2nd or 3rd trimester of pregnancies in women with high viral load.
Ante-natal testing for hepatitis B is an invaluable opportunity to diagnose and contact trace cases for linkage to care which is key to achieve the elimination targets on morbidity and mortality of HBV.
Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. ...We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH‐ACLF. Patients with AIH‐ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child‐Turcotte‐Pugh score was 11.7 ± 1.4, and Model for End‐Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7‐12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty‐eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90‐day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.
The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. Due ...to the rapid advancements in the knowledge and available information, a consortium of members from countries across Asia Pacific, “APASL ACLF Research Consortium (AARC),” was formed in 2012. A large cohort of retrospective and prospective data of ACLF patients was collated and followed up in this data base. The current ACLF definition was reassessed based on the new AARC data base. These initiatives were concluded on a 2-day meeting in February 2014 at New Delhi and led to the development of the final AARC consensus. Only those statements which were based on the evidence and were unanimously recommended were accepted. These statements were circulated again to all the experts and subsequently presented at the annual conference of the APASL at Brisbane, on March 14, 2014. The suggestions from the delegates were analyzed by the expert panel, and the modifications in the consensus were made. The final consensus and guidelines document was prepared. After detailed deliberations and data analysis, the original proposed definition was found to withstand the test of time and identify a homogenous group of patients presenting with liver failure. Based on the AARC data, liver failure grading, and its impact on the "Golden therapeutic Window," extra-hepatic organ failure and development of sepsis were analyzed. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals, and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information are presented here.
To describe the clinical manifestations and outcome of acute liver failure (ALF) associated with dengue viral infection, a rare but severe complication.
One hundred and fifty five consecutive ...patients with ALF admitted to the national liver centre from 2001 to 2009 were reviewed retrospectively. Eight cases due to dengue infection were identified and their clinical characteristics are described.
All patients had severe dengue with one dengue shock syndrome. The median (minimum, maximum) age was 33.5 (17, 47) years with 50% female. The median (minimum, maximum) duration from the onset of fever to development of ALF was 7.5 (5, 13) days and the maximum hepatic encephalopathy (HE) grade were III in five patients and II in three patients. Three patients had systemic inflammatory responses (SIRS) on admission and were in grade III HE. The presence of SIRS on admission was associated with higher grade of HE and its development during the course of hospitalization was associated with worsening HE grade. The hepatitis was characterized by marked elevations in: alanine transaminase median admission 1140.5u/L (639, 4161); median peak 2487u/L (998, 5181), serum bilirubin median admission 29μmol/L (23, 291); median peak 127μmol/L (72, 592), and prothrombin time median admission 16.8s (15.3, 26.2); median peak 22s (15.3, 40.7). The survival rate with standard medical therapy alone was 100%.
Dengue associated ALF manifest about one week after the onset of fever with severe hepatitis and encephalopathy. In our experience, the outcome with standard medical therapy alone is excellent.
Idiosyncratic drug-induced liver injury mimics acute and chronic liver disease. It is under recognized and underrecognised because of the lack of pathognomonic diagnostic serological markers. Its ...consequences may vary from being asymptomatic to self-limiting illness to severe liver injury leading to acute liver failure. Its incidence is likely to be more common in Asia than other parts of the world, mainly because of hepatotoxicity resulting from the treatment of tuberculosis disease and the ubiquitous use of traditional and complimentary medicines in Asian countries. This APASL consensus guidelines on DILI is a concise account of the various aspects including current evidence-based information on DILI with special emphasis on DILI due to antituberculosis agents and traditional and complementary medicine use in Asia.
End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection ...can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia–Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.
Background and aims
Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various ...indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT).
Methods
Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant.
Results
The ACLF cohort mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (
p
< 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (
n
= 41) and conditional survival in the absence of transplant (
n
= 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (
p
< 0.01).
Conclusions
ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. ‘Emergent LT’ should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.
Graphic abstract
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