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Fulltext Peginterferon alfa-2b in the treatment of Chinese patients with HBeAg-positive chronic hepatitis B: a randomized trial

Cheng J, Wang Y, Hou J, Luo D, Xie Q, Ning Q, et al.

J Clin Virol, 2014 Dec;61(4):509-16.
PMID: 25200354 DOI: 10.1016/j.jcv.2014.08.008

In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B.
Fulltext Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update

Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al.

Hepatol Int, 2016 Jan;10(1):1-98.
PMID: 26563120 DOI: 10.1007/s12072-015-9675-4

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 of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
Findings from a large Asian chronic hepatitis C real-life study

Lim SG, Phyo WW, Shah SR, Win KM, Hamid S, Piratvisuth T, et al.

J Viral Hepat, 2018 12;25(12):1533-1542.
PMID: 30141214 DOI: 10.1111/jvh.12989

There is a paucity of information on chronic hepatitis C (CHC) patients treated with direct antiviral agents (DAAs) in Asia. We invited Asia-Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virologic and biochemical characteristics, sustained virologic response at week 12 (SVR12) and virologic failure. SVR12 outcome was based on intention to treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. A total of 2171 patients from India (n = 977), Myanmar (n = 552), Pakistan (n = 406), Thailand (n = 139), Singapore (n = 72) and Malaysia (n = 25) were collected. At baseline, mean age was 49 years, 50.2% were males, and 41.8% had cirrhosis. Overall, SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion, respectively, was 91% and 92% for GT1, 100% and 100% for GT2, 91% and 97% for GT3, 64% and 95% for GT4, 87% and 87% for GT6 and 79% and 91% for GT untested. Patients with cirrhosis had SVR12 of 85% vs 93% for noncirrhosis (P < 0.001) (RR 2.1, 95% CI 1.4-3.1, P = 0.0002). Patients with GT1 and GT3 treated with sofosbuvir/ribavirin (SR) had 88% and 89% SVR12, respectively, but those GT6 treated with sofosbuvir/ledipasvir (SL) had only 77.6% SVR12. Multivariate analysis showed absence of cirrhosis was associated with higher SVR12 (OR 2.0, 95% CI 1.3-3.1, P = 0.002). In conclusion, patients with GT1 and GT3 with/without cirrhosis had surprisingly high efficacy using SR, suggesting that Asians may respond better to some DAAs. However, poor GT6 response to SL suggests this regimen is suboptimal for this genotype.
Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial

Wei L, Lim SG, Xie Q, Văn KN, Piratvisuth T, Huang Y, et al.

Lancet Gastroenterol Hepatol, 2019 02;4(2):127-134.
PMID: 30555048 DOI: 10.1016/S2468-1253(18)30343-1

BACKGROUND: Treatment with combined sofosbuvir and velpatasvir has resulted in high sustained virological response rates in patients chronically infected with hepatitis C virus (HCV) with genotypes 1-6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes.
METHODS: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1-6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed.
FINDINGS: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94-98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72-98]) of 28 patients without cirrhosis and seven (50% [23-77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir-velpatasvir treatment.
INTERPRETATION: Consistent with data from other phase 3 studies, single-tablet sofosbuvir-velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis.
FUNDING: Gilead Sciences.
2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report

Li PK, Bavanandan S, Mohamed R, Szeto CC, Wong VW, Chow KM, et al.

Kidney Int Rep, 2020 Aug;5(8):1129-1138.
PMID: 32775812 DOI: 10.1016/j.ekir.2020.05.001

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.
Sequencing and analysis of chromosome 1 of Eimeria tenella reveals a unique segmental organization

Ling KH, Rajandream MA, Rivailler P, Ivens A, Yap SJ, Madeira AM, et al.

Genome Res, 2007 Mar;17(3):311-9.
PMID: 17284678

Eimeria tenella is an intracellular protozoan parasite that infects the intestinal tracts of domestic fowl and causes coccidiosis, a serious and sometimes lethal enteritis. Eimeria falls in the same phylum (Apicomplexa) as several human and animal parasites such as Cryptosporidium, Toxoplasma, and the malaria parasite, Plasmodium. Here we report the sequencing and analysis of the first chromosome of E. tenella, a chromosome believed to carry loci associated with drug resistance and known to differ between virulent and attenuated strains of the parasite. The chromosome--which appears to be representative of the genome--is gene-dense and rich in simple-sequence repeats, many of which appear to give rise to repetitive amino acid tracts in the predicted proteins. Most striking is the segmentation of the chromosome into repeat-rich regions peppered with transposon-like elements and telomere-like repeats, alternating with repeat-free regions. Predicted genes differ in character between the two types of segment, and the repeat-rich regions appear to be associated with strain-to-strain variation.
Tropical and subtropical Asia's valued tree species under threat

Gaisberger H, Fremout T, Kettle CJ, Vinceti B, Kemalasari D, Kanchanarak T, et al.

Conserv Biol, 2021 Dec 05.
PMID: 34865262 DOI: 10.1111/cobi.13873

Tree diversity in Asia's tropical and subtropical forests is central to nature-based solutions. Species vulnerability to multiple threats, which affect provision of ecosystem services, is poorly understood. We conducted a region-wide, spatially explicit assessment of the vulnerability of 63 socioeconomically important tree species to overexploitation, fire, overgrazing, habitat conversion, and climate change. Trees were selected for assessment from national priority lists, and selections were validated by an expert network representing 20 countries. We used Maxent suitability modeling to predict species distribution ranges, freely accessible spatial data sets to map threat exposures, and functional traits to estimate threat sensitivities. Species-specific vulnerability maps were created as the product of exposure maps and sensitivity estimates. Based on vulnerability to current threats and climate change, we identified priority areas for conservation and restoration. Overall, 74% of the most important areas for conservation of these trees fell outside protected areas, and all species were severely threatened across an average of 47% of their native ranges. The most imminent threats were overexploitation and habitat conversion; populations were severely threatened by these factors in an average of 24% and 16% of their ranges, respectively. Our model predicted limited overall climate change impacts, although some study species were likely to lose over 15% of their habitat by 2050 due to climate change. We pinpointed specific natural areas in Borneo rain forests as hotspots for in situ conservation of forest genetic resources, more than 82% of which fell outside designated protected areas. We also identified degraded areas in Western Ghats, Indochina dry forests, and Sumatran rain forests as hotspots for restoration, where planting or assisted natural regeneration will help conserve these species, and croplands in southern India and Thailand as potentially important agroforestry options. Our results highlight the need for regionally coordinated action for effective conservation and restoration.
Strategies to manage hepatitis C virus infection disease burden-Volume 4

Chen DS, Hamoudi W, Mustapha B, Layden J, Nersesov A, Reic T, et al.

J Viral Hepat, 2017 10;24 Suppl 2:44-63.
PMID: 29105286 DOI: 10.1111/jvh.12759

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.
Historical epidemiology of hepatitis C virus in select countries-volume 4

Maaroufi A, Vince A, Himatt SM, Mohamed R, Fung J, Opare-Sem O, et al.

J Viral Hepat, 2017 10;24 Suppl 2:8-24.
PMID: 29105285 DOI: 10.1111/jvh.12762

Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.
The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4

Chan HLY, Chen CJ, Omede O, Al Qamish J, Al Naamani K, Bane A, et al.

J Viral Hepat, 2017 10;24 Suppl 2:25-43.
PMID: 29105283 DOI: 10.1111/jvh.12760

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.
The Global ACLF Consensus : the 'Istanbul Document'

Kulkarni AV, Choudhury A, Arora V, Dokmeci AK, Koshy A, Gurakar A, et al.

Hepatol Int, 2026 Oct;20(5):1281-1294.
PMID: 42782569 DOI: 10.1007/s12072-026-11136-x

The Kyoto Consensus introduced a key conceptual shift in characterizing acute-on-chronic liver failure (ACLF) patients into Type-A and Type-B phenotypes. A day-long meeting was convened at Istanbul during APASL 2026 to assess the real-world applicability of Type-A and Type-B ACLF across continents. The objective was that physicians could recognize ACLF as a unified disease entity, and quality research and new therapeutic options with defined end-points could be undertaken. Data from APASL ACLF Research Consortium (AARC), EASL-CLIF and NACSELD were assessed and discussed in detail. While the applicability of Type-A and Type-B varied across cohorts, the definition required to be appended. The experts unanimously agreed that 'liver failure' as identified by serum bilirubin of ≥ 5 mg/dl and INR ≥ 1.5 should be the 'core' for both Type-A and Type-B ACLF. Type-A ACLF is considered when "a patient with compensated advanced chronic liver disease or compensated cirrhosis presents with index decompensation as liver failure followed by development of ascites and/or hepatic encephalopathy within 4 weeks." Type-B ACLF is considered when "a patient with prior or concurrent decompensated cirrhosis presents with acute decompensation as liver failure accompanied by one or more extrahepatic organ failures." New definitions of organ dysfunction and failure, as well as endpoints for clinical trials, were also deliberated and finalized. The "Istanbul Report", presents a milestone evidence based consensus document carrying harmonization of various aspects of ACLF, incorporating current evidence, critically analyzed unanimous recommendations, and key areas for future studies.

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