Asian Pacific Association For The Study Of The Liver Research Articles

Elastography Guidelines for the Assessment of Diffuse Liver Disease

Guidelines for the use of elastography have been produced by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and the World Federation for Ultrasound in Medicine and Biology (WFUMB), as well as by clinical associations, including the European Association for Study of Liver (EASL) together with the Asociacion Latinoamericana para el Estudio del Higado (ALEH), the Asian Pacific Association for the Study of the Liver (APASL), and the American Gastroenterological Association (AGA). The guidelines produced by these clinical associations are focused on the assessment of diffuse liver disease. Moreover, the Society of Radiologists in Ultrasound (SRU) in the United States has released a consensus statement on the use of elastography in diffuse liver disease. The amount of elastography guidelines that have been issued witnesses the great interest for the use of the available techniques in several clinical settings. EFSUMB has recently produced an update of the previously published guidelines that is dedicated to the assessment of diffuse liver disease but also provides an update of the basic principles where the technology has changed. The EFSUMB and WFUMB guidelines, as well as the SRU consensus statement, describe the advantages and disadvantages associated with the use of each elastography technique and provide a practical guide for both beginners and expert users. The role of elastography in different diseases and in several clinical scenarios is analyzed.

Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update.

Hepatic fibrosis is a common pathway leading to liver cirrhosis, which is the end result of any injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Despite the fact that liver biopsy (LB) has been considered the "gold standard" of assessment of hepatic fibrosis, LB is not favored by patients or physicians owing to its invasiveness, limitations, sampling errors, etc. Therefore, many alternative approaches to assess liver fibrosis are gaining more popularity and have assumed great importance, and many data on such approaches are being generated. The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The first consensus guidelines of the APASL recommendations on hepatic fibrosis were published in 2009. Due to advances in the field, we present herein the APASL 2016 updated version on invasive and non-invasive assessment of hepatic fibrosis. The process for the development of these consensus guidelines involved review of all available published literature by a core group of experts who subsequently proposed consensus statements followed by discussion of the contentious issues and unanimous approval of the consensus statements. The Oxford System of the evidence-based approach was adopted for developing the consensus statements using the level of evidence from one (highest) to five (lowest) and grade of recommendation from A (strongest) to D (weakest). The topics covered in the guidelines include invasive methods (LB and hepatic venous pressure gradient measurements), blood tests, conventional radiological methods, elastography techniques and cost-effectiveness of hepatic fibrosis assessment methods, in addition to fibrosis assessment in special and rare situations.

Transient Elastography (Fibroscan) in Patients with Non-Cirrhotic Portal Fibrosis

Background and Aim: Non-cirrhotic portal hypertension (NCPH) is a common cause of variceal bleed in developing countries. Transient elastography (TE) using Fibroscan is a useful technique for evaluation of fibrosis in patients with liver disease. There is no study evaluating TE in patients with non-cirrhotic portal fibrosis (NCPF). The aim of this study was to evaluate the role of TE in NCPF. Methods: Retrospective data of consecutive patients of NCPF as per Asian pacific association for the study of liver (APASL) guidelines were noted. All patients had liver biopsy, TE, computed tomography of abdomen and hepatic venous pressure gradient (HVPG). Twenty age and gender matched healthy subjects and 40 age matched patients with cirrhosis with Child's A were taken as controls. Results: A total of 20 patients (30.1 ± 10.1 years, M:F = 11:9) with a diagnosis of NCPF were enrolled from January 2011 to December 2015. Of 20 patients, 18 had variceal bleed and required endoscopic band ligation. There was no difference in haemoglobin and platelet count between patients with cirrhosis and NCPF, but total leucocyte count was significantly lower in patients with NCPF compared to patients with cirrhosis (4.1 ± 2.3 vs 6.7 ± 4.3 × 103/cumm, P = 0.01). TE was high in patients with NCPF compared to healthy controls (6.6 ± 2.7 vs 4.7 ± 0.5 kPa, P = 0.001) but it was significantly low compared to cirrhotic patients (6.6 ± 2.7 vs 48.7 ± 17.8 kPa, P = 0.001). HVPG was significantly low in patients with NCPF compared to patients with cirrhosis (5.6 ± 3.0 vs 16.6 ± 2.8 mmHg, P = 0.001). Conclusion: Transient elastography (Fibroscan) is significantly low in patients with NCPF compared to patients with cirrhosis. It is a useful technique to assess whether variceal bleed is due to Child's A cirrhosis or non-cirrhotic portal fibrosis. The authors have none to declare.

Child-Pugh, MELD, and ALBI scores for predicting the in-hospital mortality in cirrhotic patients with acute-on-chronic liver failure

ABSTRACTObjectives: Our study aimed to evaluate the discriminative abilities of Child-Pugh, model for end-stage liver disease (MELD), and albumin-bilirubin (ALBI) scores in predicting the in-hospital mortality in cirrhotic patients with acute-on-chronic liver failure (ACLF).Methods: Cirrhotic patients with ACLF admitted between 2010 January and 2014 June were retrospectively reviewed. Areas under the receiver operating characteristic curves (AUROCs) with 95% confidence intervals (CIs) were calculated.Results: One hundred patients were eligible for the Asia-Pacific Association for the Study of the Liver (APASL) criteria. AUROCs of Child-Pugh, MELD, and ALBI scores in predicting the in-hospital mortality was 0.63 (95%CI: 0.52–0.72, P = 0.05), 0.75 (95%CI: 0.65–0.83, P < 0.0001), and 0.53 (95%CI: 0.42–0.63, P = 0.69), respectively. Eighty-eight patients were eligible for the EASL/AASLD criteria. AUROCs of Child-Pugh, MELD, and ALBI scores in predicting the in-hospital mortality were 0.59 (95%CI: 0.48–0.69, P = 0.14), 0.57 (95%CI: 0.46–0.68, P = 0.26), and 0.57 (95%CI: 0.46–0.67, P = 0.29), respectively. There was no significant difference among them.Conclusion: Child-Pugh, MELD, and ALBI scores might be ineffective in predicting the in-hospital mortality of cirrhosis with ACLF.

Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients.

Little is known about stopping rules of nucelos(t)ide analog (NA) treatment for chronic hepatitis B (CHB). A total of 113 consecutive patients with CHB (45 HBeAg-positive and 68 HBeAg-negative CHB patients), who met the cessation criteria of NA treatment as per the Asian-Pacific Association for the Study of the Liver (APASL) guideline, were enrolled in this prospective cohort study. The primary endpoint was to evaluate virological relapse (VR) rate within 1year, which was defined as reappearance of hepatitis B virus (HBV)-DNA>2000IU/mL after cessation of NA treatment. In this cohort, entecavir was used in 81 (71.7%) and lamivudine in 32 (28.3%) patients. Within 1year after NA treatment, VR occurred in 26 (57.8%) HBeAg-positive patients and in 37 (54.4%) HBeAg-negative patients. In univariate and subsequent multivariate analysis, age>40years [odds ratio (OR) 10.959; 95% confidence interval (CI) 2.211-54.320; P=0.003) and a pre-treatment HBV DNA level >2000,000IU/mL (OR 9.285; 95% CI 1.545-55.795; P=0.036) were identified as independent risk factors for VR in HBeAg-positive patients, and age>40years (OR 6.690; 95% CI 1.314-34.057; P=0.022) and an end-of-treatment HBcrAg level >3.7logIU/mL (OR 3.751; 95% CI 1.187-11.856; P=0.024) were identified in HBeAg-negative patients. During follow up, neither hepatic decompensation nor hepatocellular carcinoma (HCC) occurred, and HBV DNA suppression was achieved in all patients who received antiviral re-treatment. Our data suggested that the APASL stopping rule could be applied if a candidate was properly selected using individual risk factors. However, regular monitoring should be performed after cessation of NA treatment and long-term outcomes need to be evaluated further.

Recall strategies for patients found to have a nodule in cirrhosis: is there still a role for CEUS?

Development of liver tumors and their evolution to hepatocellular carcinoma (HCC) is a multi-step process in which different HCC-etiologies induce continuous rounds of hepatocyte damage and regeneration. Over an extended time, this triggers cirrhosis which is a pathological state of the liver in which lesions can progress to become dysplastic nodules. Later, these nodules may evolve into HCC and occasionally generate metastatic events. To provide optimal care, patients with liver cancer should be managed using a multidisciplinary approach in specialized centers in which all the diagnostic and therapeutic resources are available. Among the different imaging modalities the introduction on contrast agents for ultrasound use has opened new further applications in different clinical settings. In fact, contrast enhanced ultrasound (CEUS) has been applied for more than ten years and plays increasingly important roles in the management of HCC. Since early 2000, international societies including the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific association for the Study of the Liver (APASL), the Japanese society of Hepatology (JSH), the Italian society for the study of the liver (AISF), the World Federation for Ultrasound in Medicine and Biology (WFUMB), and the European Federation of Societies for Ultrasound in Medicine and Biology (EFUSMB) have discussed the important role of CEUS in the diagnosis of HCC. In the present review an update of the literature and a detailed discussion of the present Guidelines regarding the role of CEUS in the evaluation of nodules in cirrhotic patients is offered.

Acute-On-Chronic Liver Failure (ACLF) in a Tertiary Care Hospital in Resource Constrained Region

Introduction: Acute-On-Chronic Liver Failure (ACLF) is an emerging entity. There is limited data on ACLF in the literature. The present study was undertaken to analyze the clinical profile and natural course of ACLF patients. Methods: ACLF was defined as per modified Asian Pacific Association for the Study of Liver (APASL) consensus criteria 2008. Patients fulfilling the criteria were included and prospectively evaluated for three months to study short term outcome. Results: Out of 159 patients with ACLF (mean age: 46.06±11.64 years; male: female-139:20), 38.36% cases had prior decompensation, whereas 61.63% presented first time as ACLF. Etiologies of cirrhosis were alcohol, cryptogenic and chronic hepatitis B virus infection in 67.29%, 22% and 10.69% cases respectively. Active alcohol drinking within 4 weeks (43%) followed by bacterial infection (37.39%) ware the common acute insults. Only 122 cases could be followed up, out of which 72.13% cases died by 3 months (Early mortality). Most of deaths occurred in alcoholics compared to non alcoholics (80% vs. 55.88%; p=0.007). Early mortality was significantly higher in cases with prior decompensation compared to newly diagnosed ACLF cases (84.78% vs. 64.47%; p=0.01). Early mortality was not significantly different between cases with single and multiple acute predispositions (p=0.13). The mean CTP and MELD score were 12.33±1.27 and 27.64±6.81 respectively. The prognostic markers (MELD, MELD-Na, CTP) were not significantly different between survivors and non-survivors. Conclusion: ACLF patients in our region had high short term mortality with majority of death in alcoholics and in cases with prior decompensation. Alcohol intake and bacterial infections were mainly responsible for acute decompensation in our region.

Changing Nomenclature for PBC: From 'Cirrhosis' to 'Cholangitis'.

Changing Nomenclature for PBC: From 'Cirrhosis' to 'Cholangitis'.

Changing Nomenclature for PBC: From ‘Cirrhosis’ to ‘Cholangitis’

Changing Nomenclature for PBC: From ‘Cirrhosis’ to ‘Cholangitis’

A Review on Therapeutic Management of Chronic Hepatitis B Infection

The current therapeutic goal in the management of chronic hepatitis B (CHB) infection is to persistently suppress hepatitis B virus (HBV) replication and prevent its progression to liver failure and the development of hepatocellular carcinoma (HCC). At present, the therapeutic strategies for CHB includes either a short course of pegylated-interferon-alfa (PEG-IFNa) and/or a long term course of nucleos(t)ide analogues (NA’s). NA’s are more preferable to PEG-IFNa, majorly for its easier route of administration and excellent tolerance and safety profiles. Entecavir (ETV) and tenofovir (TDF) are the current first line options for its potency to maintain sustained virological response (SVR) in almost 100% of the adherent individuals along with minimal to no long-term resistance. These sustained inhibitions of HBV replication have been shown to be associated with histological improvement, modifying the long-term outcomes. However, HBsAg seroconversion, the best surrogate marker for viral clearance is still unachievable with the current first line agents and hence the risk for hepatocellular carcinoma (HCC) still exists among them. This makes us to still consider, a finite duration of PEG-IFN a that has shown considerable results with regards to HBsAg loss, as an attractive add-on or monotherapy option despite its adverse events profile. Existing evidences do not recommends its usage. However, numerous studies are ongoing and also further studies to evaluate the reliable baseline predictors of response to PEG-IFNa and early on-treatment stopping rules based on age, alanine aminotransferase levels (ALT), HBV DNA levels and HBsAg kinetics would be ideal. existing practice guidelines such as that of American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL) assist physicians in the diagnosis and optimal management of CHB; they are still expected to individualize the management considering various factors like cost-effectiveness, compliance, efficacy and duration of anti-viral agents, existence of coinfections etc. [1,3,4]. This article reviews the basis for those guideline recommendations, the natural history of the disease, treatment options and what we do in our practice to illustrate factors that may influence the management of CHB. Natural history of chronic hepatitis B infection

Residual amount of HBV DNA in serum is related to relapse in chronic hepatitis B patients after cessation of nucleos(t)ide analogs.

To investigate the relationship between relapse and the levels of the residual amount of HBV DNA in serum at cessation in chronic hepatitis B patients meeting 2008 Asian Pacific Association for the Study of the Liver (APASL) nucleos(t)ide analogs (NAs) cessation criteria. A total of 72 chronic hepatitis B patients who took NAs and had reached 2008 APASL cessation criteria entered the study. Patients were followed up for 6 months or longer after antiviral therapy was stopped. Serum HBV DNA level at cessation was detected by a highly sensitive polymerase chain reaction assay with detection limitation of 2 IU/mL. Of all the 72 patients, 42 patients (65.3%) relapsed after NA cessation. The detectable rate of the trace amount of HBV DNA at cessation was 41.7% by highly sensitive polymerase chain reaction reagents. The detectable rate of patients with consolidation treatment duration of <18 months was higher than that with consolidation duration of ≥18 months (47.5% vs. 15.4%, P=0.034), and the detectable rate of patients with HBeAg seroconversion within 6 months of treatment was lower than that of ≥6 months (25.0% vs. 61.5%, P=0.036). The residual amount of HBV DNA and detectable rate at cessation showed significant differences between relapsed and nonrelapsed patients (130.4±420.90 vs 44.6±155.16 IU/mL, P=0.004; 55.3% vs. 16.0%, P=0.001). The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840. Residual amount of HBV DNA in serum at NA cessation is associated with HBV relapse. The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840.

Reimbursement policies in the Asia-Pacific for chronic hepatitis B.

There is considerable variation in reimbursement policies in Asian countries and this is likely to have an impact on treatment practice for chronic hepatitis B (CHB). Consequently a survey of leading hepatologists was performed to evaluate such policies and their impact on management of CHB in the Asia Pacific region. A questionnaire was sent to key hepatologists in Asia Pacific for information on CHB reimbursement policy-its nature, coverage, funding source, duration, review strategy and impact on Asia Pacific Association for the Study of the Liver (APASL) CHB guidelines. The results were analysed and described. Leading hepatologists from 16 Asia Pacific countries responded. Almost all of the countries have reimbursement policies but eligibility varied from only a limited group (e.g. civil servants only) to universal access. In most instances reimbursement was from the central government (except China, Pakistan and Hong Kong). Reimbursement policies were usually created by Ministry of Health committees, who received input from medical professionals, although they may not be aware of the APASL guidelines. Policies were limited by available resources, funds and prioritization. Where there was a regular review this occurred between 1 and 5 years. The quantum of reimbursement varied from 50% in Singapore to 100% in the majority of other countries. The criteria for treatment reimbursement were based on doctor's opinion alone (Bangladesh, India, Pakistan, Philippines, Singapore and Vietnam) or specific clinical/laboratory criteria in the rest of the countries. In general, most countries offered unlimited duration for reimbursement except Taiwan, Indonesia and Pakistan. Monitoring tests for treatment response were reimbursed in all countries other than Vietnam. Viral resistance was diagnosed by viral or biochemical breakthrough, and viral resistance testing was uncommon. The main rescue therapy was adefovir. Reimbursement policies differed from country to country, the quantum and the proportion of patients who received reimbursement also varied significantly. Asia Pacific countries were able to follow APASL guidelines with variable success based on their reimbursement policies.

HBV DNA level could predict significant liver fibrosis in HBeAg negative chronic hepatitis B patients with biopsy indication.

BackgroundNon-invasive models and methods to substitute liver biopsy in chronic hepatitis B (CHB) patients were investigated but their roles as predictors of significant liver histology for diagnosis of HBeAg-negative CHB patients who had indication for liver biopsy according to The American Association for the Study of Liver Diseases (AASLD) and The Asian Pacific Association for the Study of the Liver (APASL) guidelines are still unknown. This study was designed to identify predictors of significant liver necroinflammation as defined by a Histology Activity Index of necroinflammatory score ≥ 4 or Metavir necroinflammatory activity score ≥ 2 and significant liver fibrosis as defined by a Metavir fibrosis score ≥ 2 in HBeAg-negative CHB patients that had a hepatitis B virus (HBV) DNA level ≥ 2,000 IU/ml and age ≥ 40 years or elevated alanine aminotransferase level between 1–2 times the upper limit of normal.MethodsTwenty-two patients were prospectively included and performed liver biopsies. Clinical and laboratory parameters including age, gender, underlying disease, family history of cirrhosis or hepatocellular carcinoma, body mass index (BMI), HBV DNA level, HBsAg level, liver function test, complete blood count, aspartate aminotransferase-to-platelet ratio index and transient elastography were collected and analyzed with liver histology profiles.ResultsFive patients (23%) had significant liver inflammation and 7 patients (32%) had significant liver fibrosis. Factors associated with significant liver inflammation were a lower BMI and higher alkaline phosphatase level while a factor associated with significant liver fibrosis was lower age. On multivariate analysis, only HBV DNA level > 5.5 log IU/ml could predict significant liver fibrosis (odds ratio 28.012, 95% CI, 1.631-481.240, p = 0.022) and its sensitivity, specificity, positive predictive value and negative predictive value were 71.4%, 93.3%, 83.3% and 87.5% respectively.ConclusionsAn HBV DNA level of > 5.5 log IU/ml was able to predict significant liver fibrosis for treatment of HBeAg-negative CHB patients that had indication for liver biopsy as recommended by AASLD and APASL guidelines.

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014.

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.

Hepatitis B and C in pregnancy: a review and recommendations for care.

Our objective was to provide a comprehensive review of the current knowledge regarding pregnancy and hepatitis B virus (HBV) or hepatitis C virus (HCV) infection as well as recent efforts to reduce the rate of mother-to-child transmission (MTCT). Maternal infection with either HBV or HCV has been linked to adverse pregnancy and birth outcomes, including MTCT. MTCT for HBV has been reduced to approximately 5% overall in countries including the US that have instituted postpartum neonatal HBV vaccination and immunoprophylaxis with hepatitis B immune globulin. However, the rate of transmission of HBV to newborns is nearly 30% when maternal HBV levels are greater than 200 000 IU ml(-1) (>6 log10 copies ml(-1)). For these patients, new guidelines from the European Association for the Study of the Liver (EASL) and the Asian Pacific Association for the Study of the Liver (APASL) indicate that, in addition to neonatal vaccination and immunoprophylaxis, treating with antiviral agents such as tenofovir disoproxil fumarate or telbivudine during pregnancy beginning at 32 weeks of gestation is safe and effective in preventing MTCT. In contrast to HBV, no therapeutic agents are yet available or recommended to further decrease the risk of MTCT of HCV, which remains 3 to 10%. HCV MTCT can be minimized by avoiding fetal scalp electrodes and birth trauma whenever possible. Young women with HCV should be referred for treatment post delivery, and neonates should be closely followed to rule out infection. New, better-tolerated treatment regimens for HCV are now available, which should improve outcomes for all infected individuals.

Consensus cost-effectiveness model for treatment of chronic hepatitis B in Asia Pacific countries.

The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party to develop a consensus cost-effectiveness model for treatment of Hepatitis B in Asia Pacific countries in March 2010. The working party consisted of expert hepatologists, virologists and epidemiologists from 11 representative countries in the Asia Pacific region. Meetings were conducted at the 20th APASL Annual Meeting in 2010 to determine consensus estimates for modeling and at the 21st and 22nd APASL meetings in 2011 and 2012, respectively to review and approve the models. The consensus cost-effectiveness model used Singapore as base case analysis and was validated using actual data from the Singapore Cancer, Diseases and Death Registries. Simulation for Singapore, China, Thailand, Pakistan, Taiwan and Korea were performed. Antivirals with high resistance barriers like entecavir and tenofovir had the highest retail cost but were the most cost-effective therapy in developed countries such as Singapore, Taiwan and Korea while generic tenofovir was most cost effective in Thailand and Pakistan. The cost effectiveness of different treatment strategies varied significantly between countries and was affected by medication cost, economic affordability, access to liver transplantation and the prevailing health of the general population. Choosing treatment strategies for hepatitis B based on low retail drug cost can be misleading because more expensive drugs may be more cost effective when considering long-term health outcomes and costs. Cost-effectiveness data should be individualized to countries based on their unique socio-economic conditions. Governmental policies which subsidize more costly drugs that have lower risk of drug resistance can benefit more patients.

Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: Is the glass half full or half empty?

Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: Is the glass half full or half empty?

Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients

The optimal duration of nucelos(t)ide analog (Nuc) treatment in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B virus (HBV) infection is unknown. The Asian Pacific Association for the Study of the Liver (APASL) guidelines recommend that treatment can be discontinued if undetectable HBV-DNA has been documented on three occasions ≥ 6 months apart. This study aimed to test this stopping rule in HBeAg-negative chronic hepatitis B (CHB) patients treated with entecavir (ETV). Ninety-five patients (39 cirrhosis) were treated with ETV for a median of 721 (395-1,762) days before stopping therapy and were then monitored with serum HBV DNA and alanine aminotransferase (ALT) at least every 3 months. Within 1 year after stopping ETV therapy, "clinical relapse" (an episode of ALT elevation >2 × upper limit of normal plus HBV-DNA >2,000 IU/mL) occurred in 43 (45.3%) of the 95 patients. Of the 39 cirrhosis patients, 17 (43.6%) relapsed and one (2.6%) developed decompensation. The median duration until relapse was 230 days (74.4% >6 months). Logistic regression analysis showed that baseline HBV-DNA ≤ 2 × 10(5) IU/mL was the only significant independent factor for sustained response. The 1-year relapse rate was 29% in patients with a baseline HBV DNA ≤ 2 × 10(5) IU/mL versus 53% in those with HBV DNA >2 × 10(5) IU/mL (P = 0.027). For the latter, consolidation therapy >64 weeks reduced the relapse rate to 33.3% in patients without cirrhosis. With an overall 1-year relapse rate of 45% and 29% in those with a baseline serum HBV DNA ≤ 2 × 10(5) IU/mL, the APASL stopping rule for HBeAg-negative CHB patients with proper off-therapy monitoring is adequate even in patients with cirrhosis. Consolidation therapy >64 weeks seems more appropriate for those with higher baseline HBV DNA.

Acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with chronic liver disease. Although there are no widely accepted diagnostic criteria for ACLF, the Asia.Pacific Association for the Study of the Liver (APASL) and the American Association for the Study of Liver Disease and the European Association for the Study of the Liver (AASLD/EASL) consensus definitions are commonly used. It is obvious that the APASL and the AASLD/EASL definitions are based on fundamentally different features. Two different definitions in two different parts of the world hamper the comparability of studies. Recently, the EASL-Chronic Liver Failure Consortium proposed new diagnostic criteria for ACLF based on analyses of patients with organ failure. There are areas of uncertainty in defining ACLF, such as heterogeneity of ACLF, ambiguity in qualifying underlying liver disease, argument for infection or sepsis as a precipitating event, etc. Although the exact pathogenesis of ACLF remains to be elucidated, alteration of host response to injury, infection, and unregulated inflammation play important roles. The predisposition, infection/inflammation, response, organ failure (PIRO) concept used for sepsis might be useful in describing the pathophysiology and clinical categories for ACLF. Treatment strategies are limited to organ support but better understanding of the pathophysiology is likely to lead to discovery of novel biomarkers and therapeutic strategies in the future.

Performance of Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH‐B) score in classifying treatment eligibility under 2012 Asian Pacific Association for the Study of the Liver (APASL) guideline for chronic hepatitis B patients

REACH-B [Risk Estimation for Hepatocellular Carcinoma (HCC) in Chronic Hepatitis B] scoring system was developed to predict the risk of HCC in noncirrhotic chronic hepatitis B (CHB) patients. To evaluate the discriminatory performance of REACH-B scoring system in classifying anti-viral treatment eligibility of CHB patients according to the 2012 Asian Pacific Association for the Study of the Liver (APASL) treatment guideline. A total of 904 noncirrhotic CHB were enrolled. Patients' age, gender, liver biochemistry, HBeAg status and HBV DNA levels were recorded. The minimum REACH-B risk score for patients to be eligible for anti-viral treatment was 7 for HBeAg-positive and 6 for HBeAg-negative patients. Among them, increasing REACH-B score was not significantly associated with eligibility for treatment [adjusted odds ratio (OR): 1.210, 95% confidence interval (CI): 0.979-1.494, P=0.078] in HBeAg-positive patients, as shown by logistic regression analysis after adjusting for gender. In HBeAg-negative patients, REACH-B score significantly predicted the treatment eligibility (adjusted OR: 1.783, 95% CI: 1.607-1.979, P<0.001). Discriminatory ability of REACH-B score to classify eligibility was poor for HBeAg-positive patients ≥40years [area under receiver operating characteristic (AUC): 0.664, 95% CI: 0.533-0.795], but good/excellent for HBeAg-positive patients <40years (AUC: 0.903; 95% CI: 0.841-0.964), HBeAg-negative patients ≥45years (AUC: 0.883; 95% CI: 0.848-0.917) and HBeAg-negative patients <45years (AUC: 0.907; 95% CI: 0.874-0.940). The discriminatory performance of the REACH-B scoring system in classifying anti-viral treatment eligibility based on the 2012 APASL guideline was good/excellent, except for ≥40years old HBeAg-positive patients.