Laurentius A. Lesmana

Asian-Pacific consensus statement on the management of chronic hepatitis B: A 2012 update

Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

IntroductionThe Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations.MethodsThe working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements.ResultsParticipants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

How common is non‐alcoholic fatty liver disease in the Asia–Pacific region and are there local differences?

Risk factors for development of non‐alcoholic steatohepatitis include obesity, especially central adiposity, glucose intolerance or type 2 diabetes mellitus (T2DM), and dyslipidemia. Non‐alcoholic fatty liver disease (NAFLD) is now considered a manifestation of metabolic syndrome. During the last two decades, NAFLD has become the most common chronic liver disease in North America and Europe, but until recently was thought to be uncommon (perhaps due to the lack of study) in Asia. Fatty liver can be identified on imaging modalities (ultrasonography, computed tomography scans, and magnetic resonance imaging) with high sensitivity, but steatohepatitis and fibrosis cannot be distinguished. Thus, an inherent drawback in studying the epidemiology of NAFLD is the lack of definitive laboratory tests, no uniform definition—with different studies using cut‐off values of alcohol consumption from <20 g/week to 210 g/week, and case selections where biopsy was used for definition. In studies outside the region, the prevalence of NAFLD varies from 16% to 42% by imaging, and 15–39% of liver biopsies. The major risk factors for NAFLD, central obesity, T2DM, dyslipidemia, and metabolic syndrome, are now widely prevalent and are increasing geometrically in the Asia–Pacific region. It is therefore not surprising that NAFLD is common in this region. Estimates of current prevalence range from 5% to 30%, depending on the population studied. Central obesity, diabetes, and metabolic syndrome are the major risk factors. To date, however, data on the natural history and impact of NAFLD causing serious significant chronic liver disease are lacking and there is a need for prospective, cooperative studies.

Early Hepatitis B Virus DNA Reduction in Hepatitis B e Antigen-Positive Patients with Chronic Hepatitis B : A Randomized International Study of Entecavir Versus Adefovir

This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e antigen positive nucleoside‐naïve adults with chronic hepatitis B (CHB). Sixty‐nine nucleoside‐naïve CHB patients with baseline HBV DNA of 108 copies/mL or more were randomized 1:1 to open‐label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks. The primary efficacy analysis compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using linear regression. Entecavir was superior to adefovir for mean change from baseline in HBV DNA at week 12 (−6.23 log10 copies/mL versus −4.42 log10 copies/mL, respectively; mean difference −1.58 log10 copies/mL; P < 0.0001). Both drugs demonstrated biphasic viral kinetics, with a first phase of rapid decline lasting 10 days. A significant difference favoring ETV was reached at day 10 (day 10 ETV−ADV difference estimate: −0.66 log10 copies/mL; 95% CI [−0.30, −0.01]). Early virological response was found to be predictive of subsequent virological response, with those having lower HBV DNA levels at day 10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48. In addition, there was considerably less variability in the extent of HBV DNA reductions in patients treated with entecavir versus adefovir. Both the mean decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less than 300 copies/mL were greater in entecavir‐treated than adefovir‐treated patients at weeks 2, 4, 8, 12, 24, and 48. At week 48, one (3%) ETV‐treated versus 15 (47%) ADV‐treated patients had HBV DNA of 105 copies/mL or more. Both antivirals were well tolerated. Conclusion: Entecavir therapy resulted in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside‐naïve HBeAg‐positive patients with CHB. (HEPATOLOGY 2009;49:72‐79.)

Hepatitis C virus variants from Jakarta, Indonesia classifiable into novel genotypes in the second (2e and 2f), tenth (10a) and eleventh (11a) genetic groups.

Hepatitis C virus (HCV) isolates from 126 hepatitis patients in Jakarta, Indonesia were genotyped by PCR with genotype-specific primers deduced from the HCV core gene. Fifty-five isolates (44%) were classified as genotype II/1b, 15 (12%) as 1c, 33 (26%) as III/2a, and 1 (1%) as V/3a, while the remaining 22 (17%) were not classifiable into any of the five common genotypes (I/1a, II/1b, III/2a, IV/2b and V/3a) or 1c. Sequences of a part of the NS5b region [1093 bp (nucleotides 8279-9371)] of the 22 isolates of unclassifiable genotype were subjected to pair-wise comparison and phylogenetic analysis along with those of 62 isolates of 25 genotypes in nine genetic groups. Seven of the isolates were classified into 2e and two into 2f, representing novel genotypes in genetic group 2, while ten and three were classified into two new genetic groups, 10 and 11, respectively, and their genotypes were provisionally designated 10a and 11a. The isolates of genotype 10a (JK049) and 11a (JK046) were sequenced in full. Comparison of 24 HCV genomes including those of JK049 and JK046, over the entire genome and subgenomic regions, supported the classification of HCV into 11 genetic groups.

Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update

There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL).

Liver fibrosis is a common pathway leading to cirrhosis, which is the final result of injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Liver biopsy has been considered to be the “gold standard” to assess fibrosis. However, liver biopsy being invasive and, in many instances, not favored by patients or physicians, alternative approaches to assess liver fibrosis have assumed great importance. Moreover, therapies aimed at reversing the liver fibrosis have also been tried lately with variable results. Till now, there has been no consensus on various clinical, pathological, and radiological aspects of liver fibrosis. The Asian Pacific Association for the Study of the Liver 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 process for the development of these consensus guidelines involved the following: review of all available published literature by a core group of experts; proposal of consensus statements by the experts; discussion of the contentious issues; and unanimous approval of the consensus statements after discussion. The Oxford System of evidence-based approach was adopted for developing the consensus statements using the level of evidence from 1 (highest) to 5 (lowest) and grade of recommendation from A (strongest) to D (weakest). The consensus statements are presented in this review.

Hepatitis B: overview of the burden of disease in the Asia‐Pacific region

Abstract: Hepatitis B virus (HBV) infection and its liver‐related complications are a substantial health concern in the Asia‐Pacific region. Over the last two decades, public health interventions and the implementation of universal vaccination programs have substantially reduced the incidence of HBV infections in many countries in this region. However, large proportions of individuals remain chronically infected and subject to an increased risk for serious sequelae, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma. The management of HBV infection varies throughout the Asia‐Pacific region, with each country confronting different issues related to prevention, screening, and treatment. These issues include the availability of diagnostic testing and treatment, the cost of diagnosis and treatment, the availability of trained medical professionals and medical facilities, and disease awareness among primary care physicians and the public. This article reviews the epidemiology of HBV infection in the Asia‐Pacific region, explains factors influencing hepatitis B prevalence and prevention, and discusses barriers to prevention and treatment of chronic hepatitis B and its liver‐related complications.

Diagnostic value of a group of biochemical markers of liver fibrosis in patients with non-alcoholic steatohepatitis

OBJECTIVE: The objectives of this study were to investigate the use of non‐invasive biochemical markers to evaluate the severity of liver fibrosis in patients with non‐alcoholic steatohepatitis (NASH).

Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC)

Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate‐stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non‐response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long‐term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens.