George K K Lau

• MBBS (HK), MRCP(UK), FHKCP, FHKAM (GI), MD(HKU), FRCP (Edin, Lond), FAASLD (USA)
• CEO at Humanity and Health Medical Centre

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 “A...

Background 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 AARC registry. The diagnosis of M...

Background and aims: Limited data exist regarding outcomes of acute variceal bleeding (AVB) in patients with acute-on-chronic liver failure (ACLF), especially in those with hepatic failure. We evaluated the outcomes of AVB in patients with ACLF in a multinational cohort of APASL ACLF Research Consortium (AARC). Methods: Prospectively maintained...

Background and aims Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. Methods A total of 1,621 patients were prospectivel...

Background and aimsAcute-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 p...

Background We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence.MethodsACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, includin...

Background Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients.Methods Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (...

Background COVID-19 has been giving the devastating impact on the current medical care system. There are quite many guidelines on COVID-19, but only a few on the management of hepatocellular carcinoma (HCC) during COVID-19 pandemic. Aims We develop these recommendations to preserve adequate clinical practice for the management of HCC. Methods Exp...

Background: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. Present study evaluated this effect in patients with alcohol associated acute-on-chronic liver failure(ACLF). Methodology: 1216 prospectively enrolled patients with ACLF (males 98%, mean age 42.5±9.4 years, mean CTP, MELD and AARC scores of 12±1.4,...

Background and aims COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comor-bidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. Methods Data was collected from 13 Asian c...

Background and aimsCOVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis.Methods Data was collected from 13 Asian coun...

Background and Aims: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon co morbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. Methods: Data was collected from 13 Asian...

The article Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update, written by [Shiv Sarin], was originally published electronically on the publisher’s internet portal (currently SpringerLink) on June 06, 2019 without open access.

In the direct-acting antiviral (DAA) era for hepatitis C virus (HCV) infection, sustained virological response (SVR) is very high, but close attention must be paid to the possible occurrence of hepatocellular carcinoma (HCC) and reactivation of hepatitis B virus (HBV) in patients with co-infection who achieved SVR in short term. HCC occurrence was...

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. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF...

Objectives: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of...

Chronic hepatitis C virus (HCV) infection is common among patients with chronic kidney disease (CKD) and those on hemodialysis due to nosocomial infections and past blood transfusions. While a majority of HCV-infected patients with end-stage renal disease are asymptomatic, some may ultimately experience decompensated liver diseases and hepatocellul...

Background and aimsAcute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. MethodsA total of 1402 ACLF patients, enro...

Background and aim: There is limited data on predictors of acute kidney injury(AKI) in ACLF. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting AKI in a multi-centric cohort of ACLF patients. Patients and methods: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate l...

Background: SIRS is an early marker of sepsis and ongoing inflammationand has been reported in large proportion of ACLF patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, we investigated the course and outcome of ACLF patients without SIRS/sepsis. Methods: Consecutive ACLF patie...

There is an increased awareness of hepatitis B (HBV) reactivation in chronic hepatitis C (CHC) patients coinfected with HBV treated with pan-oral direct-acting antiviral agents (DAAs). We performed a systematic review and meta-analysis to compare the rate of HBV reactivation in CHC patients coinfected with overt HBV (hepatitis B surface antigen [HB...

Background Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis. Methods One hundred forty...

Hepatitis due to reactivation of hepatitis B virus (HBV) has been reported in patients treated with direct-acting antiviral (DAA) agents for chronic hepatitis C virus (HCV) infection. We performed an observational study to determine the incidence of and factors associated with hepatitis in 327 patients receiving pan-oral DAA agents for HCV infectio...

Background: To shorten the course of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, we examined the antiviral efficacy and safety of 3 weeks of response-guided therapy with an NS3 protease inhibitor and dual NS5A inhibitor-NS5B nucleotide analogue. Methods: In this open-label, phase 2a, single centre study, Chinese...

Background: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patien...

Tornado diagram of one-way sensitivity by previous treatment history in A: All China, B: Northeastern-China, C: Central-China, D: Eastern-China and E: Western-China. (DOCX)

More details on the model. Model validation: life expectancies for chronic liver disease stage and general population (Table A). Validation of the natural history of our model (Table B). (DOCX)

The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on “APASL consensus statements and recommendations for management of hepatitis C” in March 2015 to revise the “APASL consensus statements and management algorithms for hepatitis C virus infection” (Hepatol Int 6:409–435, 2012). The working party...

The Asian-Pacific Association for the Study of the Liver (APASL) convened an international working party on the “APASL consensus statements and recommendation on management of hepatitis C” in March, 2015, in order to revise “APASL consensus statements and management algorithms for hepatitis C virus infection (Hepatol Int 6:409–435, 2012)”. The work...

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management...

Background: Many epidemiological studies have demonstrated a significant association between Type 2 diabetes mellitus and abnormal lipid profiles with chronic HCV genotype 1 (GT1) infection. We examined the impact on glucose and lipid profiles of treating Chinese patients using pegylated interferon (Peg-IFN)-a and ribavirin (RBV). Methods: We co...

Estimated hepatitis C virus (HCV) infection rates in the general populations were 1.3, 0.9, 0.4-1.0, 14.7, 0.1-0.3, 0.9-1.9, 1.0-2.0, 5, 4.4-8.6 and 0.5-1.3 % in Australia, Bangladesh, Mainland China, Egypt, Hong Kong, India, Japan, Pakistan, Taiwan and Turkey, respectively. The main HCV genotypes (Gs) are G1, G3, G1b, G4, G1b, G3, G1b, G3, G1b and...

To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma (HCC) in Chinese patients with primary biliary cirrhosis (PBC). We reviewed the data of 52 PBC-associated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders....

This proof-of-concept study compared lamivudine (LAM) with a newer antiviral agent, adefovir dipivoxil (ADF), in preventing hepatitis B virus (HBV) reactivation in chronic HBV patients undergoing chemotherapy. Hepatitis B surface antigen (HBsAg) positive patients intended to undergo chemotherapy were randomized to receive either LAM 100 mg daily or...

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Non-invasive techniques are needed to assess hepatic fibrosis in patients with chronic hepatitis B. We developed a scoring system to determine degree of fibrosis in patients with genotype B or C hepatitis B virus (HBV) infection and positive for the e antigen (HBeAg). We performed a retrospective study to identify baseline variables associated with...

Introduction: Viral kinetics has proved useful in understanding antiviral potency, determining antiviral profiles and optimizing treatment strategy. Methods: This was a randomized, open-label study comparing the viral kinetics in 46 hepatitis B e antigen-positive patients during 12-week treatment with telbivudine monotherapy, tenofovir monothera...

Background & aims: This study investigated the antiviral efficacy and safety of telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients. Methods: This was a randomized, open-label, multicentre study, in treatment-naïve patients with HBeAg-positive CHB, comparing the efficacy and safety of telb...

In 2014, seven drugs were registered for the treatment of chronic hepatitis B (CHB) infection. Two were immunomodulatory agents, conventional interferon(IFN)-α and pegylated IFN-α2a, and five were direct antiviral nucleos(t)ide analogs (NUCs), lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. Due to the high...

Unlabelled: The role of CD4(+) cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC) remains obscure. This study characterized CD4(+) CTLs in HCC patients and further elucidated the associations between CD4(+) CTLs and HCC disease progression. In all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis (LC) patients, a...

Background Hepatocellular carcinoma (HCC) is one of the most popular cancers in the world with poor prognosis, which often develops from chronic liver inflammatory diseases. Interleukin 23 (IL-23) is an inflammatory cytokine which is reported to play an important role in tumor development in animal model. While the function of IL-23 in HCC developm...

Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derive...

Hepatitis B virus (HBV)-specific T-cell responses are important in the natural history of HBV infection. The number of known HBV-specific T-cell epitopes is limited, and it is not clear whether viral evolution occurs in chronic HBV infection. We aimed to identify novel HBV T-cell epitopes by examining the relationship between HBV sequence variation...

Chronic hepatitis B (CHB) infection is a global health problem affecting more than 2 billion people worldwide. Among them, more than 75% reside in AsiaPacific countries. Although only a minority (15%–40%) of infected individuals go on to develop cirrhosis, liver failure, and hepatocellular carcinoma (HCC), which account for an estimated 0.5–1.2 mil...

Inhibiting NF-κB with helenalin could block rhIL-17A induced HCC cell lines invasion. Effect of NF-κB inhibitor on the blocking of rhIL-17A induced cell invasion was detected by cell invasive assay. Representatives of cells migrated through Matrigel-coated transwell were shown in the upper panel (magnification 100). Total invasive cell number in ea...

Primer list for qPCR. (DOC)

Background IL-17A is a pro-inflammatory cytokine that plays important role in inflammatory disease pathology and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the progression of hepatocellular carcinoma (HCC). Methodology and Principal Finding Expression pattern of IL-17A in clinical HCC samples (n = 43) w...

Background Acute variceal bleeding (AVB) is a medical emergency and associated with a mortality of 20% at 6 weeks. Significant advances have occurred in the recent past and hence there is a need to update the existing consensus guidelines. There is also a need to include the literature from the Eastern and Asian countries where majority of patient...

Liver grafts from donors positive for antibody to hepatitis B core antigen (anti-HBc) may be used for transplantation in patients with hepatitis B virus (HBV)-related liver disease, and an occult HBV infection may develop from either source. Liver biopsy was performed for 31 patients who remained seronegative for hepatitis B surface antigen for a m...

HIV infection has a significant impact on the natural progression of hepatitis B virus (HBV) related liver disease. In HIV-HBV co-infected patients, little is known about mutations in the HBV genome, which can influence severity of liver disease. The aim of this study was to characterize and to determine the frequency of known clinically significan...

Clevudine is a pyrimidine analogue with potent activity against hepatitis B virus (HBV) replication in vitro. In a previous pivotal phase III clinical study, 24 weeks treatment with clevudine 30 mg has been shown to profoundly suppress HBV replication and normalize serum alanine aminotransferase level. In this study, we compare the efficacy and saf...

Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains...

HBeAg seroconversion, in association with undetectable levels of hepatitis B virus DNA as determined by polymerase chain reaction, is an important goal in the treatment of patients with HBeAg-positive chronic hepatitis B (CHB). Achievement of sustained HBeAg seroconversion at an early age (<40 years) is associated with a reduced incidence of hepati...

Replication of hepatitis B virus (HBV) is the primary driver of disease progression and clinical outcomes in patients with chronic hepatitis B (CHB), but other factors, such as hepatitis B e antigen (HBeAg) status, also influence disease course. The importance of HBeAg seroconversion is underscored by current CHB treatment guidelines that recommend...

Biomarkers for accurate diagnosis of early hepatocellular carcinoma (HCC) are limited in number and clinical validation. We applied SELDI-TOF-MS ProteinChip technology to identify serum profile for distinguishing HCC and liver cirrhosis (LC) and to compare the accuracy of SELDI-TOF-MS profile and alpha-fetoprotein (AFP) level in HCC diagnosis. Seru...

No data on antiviral response of HBV genotypes E-H are available so far although these HBV genotypes contribute significantly to the global HBV burden. Of 49 patients with HBV genotypes E-H, 23 received interferon (IFN)-alpha, 12 nucleos(t)ide analogues and 14 patients were untreated. HBV genotype was determined by direct sequencing of the HBV S ge...

Therapy with pegylated interferon (PEG-IFN)-alfa results in sustained response in a minority of patients with chronic hepatitis B virus (HBV) infection and has considerable side effects. We analyzed data from the 2 largest global trials of hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B to determine which are most likely to...

Hepatic fibrosis is a consequence of severe liver damage that occurs in many patients with chronic liver diseases. TCM 319 recipe is a Chinese Medicine formula which consists of six Chinese herbs. In this study, we investigated the anti-fibrotic efficacy and mechanisms of TCM 319 recipe. Hepatic fibrosis in rats was induced by carbon tetrachloride...

Coptidis rhizoma (CR, Chinese name is Huanglian) has been used in treating infectious and inflammatory diseases for two thousand years in Traditional Chinese Medicine (TCM). Its related pharmacological basis for the therapeutics has been studied intensively, but CR can also be used for vomiting of "dampness-heat type or acid regurgitation" due to "...

Patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B treated with peginterferon alpha-2a with or without lamivudine achieve significantly higher 6-month posttreatment rates of response compared with those treated with lamivudine alone. The durability of <or=3-year posttreatment response was investigated in this study. Patients r...

Adoptive immune transfer plays an important role in clearance of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. However, it is unclear whether cytokine-induced killer (CIK) cells could suppress HBV replication in CHB patients, especially if drug resistance develops. In this study, functional CIK cells were efficiently generated from...

Unlabelled: We investigated the relationship between hepatitis B virus surface antigen (HBsAg) serum level decline and posttreatment response in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B from a large multinational study of pegylated interferon alfa-2a (peginterferon alfa-2a), with or without lamivudine, versus lamivu...

Programmed death-1 (PD-1) upregulation can impair virus-specific CD8 T-cell responses during chronic viral infection. Whether and how PD-1 affects virus-specific memory CD8 T cells in humans with acute viral infection, however, remains largely undefined. The association between PD-1 expression and HBV-specific memory CD8 T-cell responses were longi...