Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) account for an increasing proportion of liver disease in the Asia‐Pacific region. Many areas in ...the region are experiencing epidemics of metabolic syndrome among rapidly ageing populations.
Aims
To estimate using modelling the growth in NAFLD populations, including cases with significant fibrosis that are most likely to experience advanced liver disease and related mortality.
Methods
A disease progression model was used to summarise and project fibrosis progression among the NAFLD populations of Hong Kong, Singapore, South Korea and Taiwan. For each area, changes in the adult prevalence of obesity was used to extrapolate long‐term trends in NAFLD incidence.
Results
In the areas studied, prevalent NAFLD cases were projected to increase 6%‐20% during 2019‐2030, while prevalent NASH cases increase 20%‐35%. Incident cases of hepatocellular carcinoma are projected to increase by 65%‐85%, while incident decompensated cirrhosis cases increase 65%‐100% by 2030. Likewise, NAFLD‐related mortality is projected to increase between 65% and 100% from 2019 to 2030. NAFLD disease burden is expected to increase alongside rising trends in metabolic syndrome and obesity among populations in the region. This leads to more cases of advanced liver disease and associated mortality.
Conclusions
Preventing the growth of diabetic and obese populations will be a key factor in reducing ongoing increases in NAFLD‐related disease burden in the Asia‐Pacific region.
The issue of best treatment for chronic hepatitis C virus (HCV) infection is in constant flux, not only in Western countries but also in Asia. Currently, pegylated-interferon plus ribavirin is the ...standard of care. Studies from Asia provide evidence to support the same broad treatment strategies for Asian patients as recommended in Western countries. Nevertheless, there is increasing evidence that Asians have a higher likelihood of achieving a sustained virological response (SVR) than their Caucasians counterparts when treated with the corresponding regimen. With the recommended 'standard dose and duration treatment regimens', SVR is achieved in Asia for around 70% of HCV genotype 1 (HCV-1) infected cases, approximately 90% of HCV-2/3, approximately 65% of HCV-4, and approximately 80% of HCV-6 patients. Difference of body weight in race might contribute the superior response in Asian patients. HCV genotype distribution in Asia also differs from North-America/Europe. HCV-6 and its variants, previously mistyped as HCV-1, needs accurate genotyping. Increasing data support the proposal that HCV genotype, baseline viral load and on-treatment virological response provide information for decision-making so that treatment can be individualized. Beyond the older recommendations, an abbreviated 24-week regimen could be suggested for HCV-1/4 patients with baseline viral loads < 400 000 IU/mL and a rapid virological response (RVR, HCV RNA undetectable at week 4), and an abbreviated 12-16 weeks of pegylated-interferon with weight-based doses of ribavirin could be suggested for HCV-2/3 patients with a RVR. Such tailored treatment regimens can reduce the costs of treatment and incidence of adverse events without compromising efficacy. Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis worldwide, and particularly in some countries of Asia (notably Japan) where it is now more prevalent than chronic hepatitis B virus infection. Hepatitis C virus infection can also lead to hepatocellular carcinoma (HCC). It is estimated that there are more than 170 million people chronically infected with HCV, and 3 to 4 million persons are newly infected each year. The risk for developing cirrhosis 20 years after initial HCV infection among those chronically infected varies between studies, but is estimated at around 10%-15% for men and 1-5% for women. Once cirrhosis is established, the rate of developing HCC is at 1%-4% per year. Approximately 280 000 deaths per year are related to HCV infection. Hepatitis C virus-related end-stage liver disease and HCC have become the leading cause for liver transplantation worldwide. In the Asia-Pacific area, the estimated prevalence of antibodies to HCV (anti-HCV) range from 0.3% in New Zealand to 5.6% in Thailand. In Japan, Middle East, Vietnam and Taiwan, several HCV hyper-endemic areas have been reported with an anti-HCV prevalence rate of 12% to as high as 58%. In addition to the well-known endemic status of HBV infection in most countries of the Asia-Pacific region, HCV infection presents another critical scenario of public health issue in this region, as outlined in Guidelines by the Asia-Pacific Association for Study of the Liver (APASL). Given the lack of an effective vaccine, optimal treatment of chronic HCV infection is now perceived as a 'must' in terms of public health strategies, as well as of the clinical setting for individual patients.
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•TAF is a new prodrug of tenofovir developed to treat patients with chronic HBV.•A lower dose of TAF can be used because it delivers tenofovir more efficiently to hepatocytes than ...TDF.•At week 48, TAF had non-inferior efficacy to TDF with improved renal and bone safety.•Efficacy and safety results at week 96 confirm the 48-week results in both studies.
Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials.
In two international trials, patients with chronic HBV infection were randomized 2:1 to receive 25 mg TAF or 300 mg TDF in a double-blinded fashion. One study enrolled HBeAg-positive patients and the other HBeAg-negative patients. We assessed efficacy in each study, and safety in the pooled population.
At week 96, the differences in the rates of viral suppression were similar in HBeAg-positive patients receiving TAF and TDF (73% vs. 75%, respectively, adjusted difference −2.2% (95% CI −8.3 to 3.9%; p = 0.47), and in HBeAg-negative patients receiving TAF and TDF (90% vs. 91%, respectively, adjusted difference −0.6% (95% CI −7.0 to 5.8%; p = 0.84). In both studies the proportions of patients with alanine aminotransferase above the upper limit of normal at baseline, who had normal alanine aminotransferase at week 96 of treatment, were significantly higher in patients receiving TAF than in those receiving TDF. In the pooled safety population, patients receiving TAF had significantly smaller decreases in bone mineral density than those receiving TDF in the hip (mean % change −0.33% vs. −2.51%; p <0.001) and lumbar spine (mean % change −0.75% vs. −2.57%; p <0.001), as well as a significantly smaller median change in estimated glomerular filtration rate by Cockcroft-Gault method (−1.2 vs. −4.8 mg/dl; p <0.001).
In patients with HBV infection, TAF remained as effective as TDF, with continued improved renal and bone safety, two years after the initiation of treatment. Clinicaltrials.gov number: NCT01940471 and NCT01940341.
At week 96 of two ongoing studies comparing the efficacy and safety of tenofovir alafenamide (TAF) to tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B patients, TAF continues to be as effective as TDF with continued improved renal and bone safety.
Registration: Clinicaltrials.gov number: NCT01940471 and NCT01940341.
Abstract
Background
Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen HBsAg seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) ...treatment are incompletely understood.
Methods
This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.
Results
The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%–2.88%) and an annual rate of 0.22% (.17%–.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 95% confidence interval, 1.80–5.49), elevated serum alanine aminotransferase >200 U/L (3.68 2.07–6.53), serum bilirubin (1.11 per mg/dL; 1.06–1.17 mg/dL), and fatty liver (1.84 1.03–3.29).
Conclusion
HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.
Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.
LINKED CONTENT
This article is linked to Mederacke et al and Mederacke and Mederacke papers. To view these articles, visit https://doi.org/10.1111/apt.15722 and https://doi.org/10.1111/apt.15873.
Background and aims
COVID-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 countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19.
Results
Altogether
,
228 patients 185 CLD without cirrhosis and 43 with cirrhosis were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes 57.7% vs 39.7%, OR = 2.1 (1.1–3.7), p = 0.01 and in cirrhotics, obesity, 64.3% vs. 17.2%, OR = 8.1 (1.9–38.8), p = 0.002 predisposed more to liver injury than those without these
.
Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure 5 (11.6%) or acute decompensation 4 (9%). Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality AUROC 0.94, HR = 19.2 (95 CI 2.3–163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients.
Conclusions
SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.
Background & Aims
Hepatocellular carcinoma (HCC) surveillance is associated with improved outcomes and long‐term survival. Our goal is to evaluate adherence rates to HCC surveillance.
Methods
We ...performed a systematic search of the PubMed and Scopus databases and search of relevant studies from recent major liver meetings. All searches and data extraction were performed independently by two authors. Analysis was via random‐effects models and multivariate meta‐regression.
Results
A total of 22 studies (n = 19 511) met inclusion criteria (original non‐interventional studies with defined cirrhosis or chronic hepatitis B or chronic hepatitis C with advanced fibrosis populations, and surveillance tests and intervals). Overall adherence rate was 52% (95% CI 38%‐66%). Adherence was significantly higher in cirrhotic patients compared to chronic hepatitis B and other high‐risk patients, in European compared to North American studies, in less than 12‐month compared to yearly surveillance intervals, and in prospective compared to retrospective studies (71%, 95% CI 64%‐78% vs 39%, 95% CI 26%‐51%, P < .001). The between‐study heterogeneity of all above analyses was significant (P < .001). Only the study design (retrospective vs prospective cohort) had statistical significance in a multivariate meta‐regression model (P < .05) and could account for some of the differences above.
Conclusions
Overall adherence rate to HCC surveillance was suboptimal at 52% with no significant differences by liver disease aetiology or study location in multivariate meta‐regression analysis. Further research and educational efforts are needed to improve the current rate of HCC surveillance.
Hepatitis C virus (HCV) infection is a silent killer that leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (HCC). High prevalence of HCV infection has been reported in ...Taiwan, especially in high-risk populations including people who inject drugs (PWID) and patients requiring dialysis. Besides, certain populations merit special considerations due to suboptimal outcome, potential drug–drug interaction, or possible side effect. Therefore, in the second part of this 2-part consensus, the Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era. Special populations include patients with acute or recent HCV infection, previous DAA failure, chronic kidney disease, decompensated cirrhosis, HCC, liver and other solid organ transplantations, receiving an HCV viremic organ, hepatitis B virus (HBV) and HCV dual infection, HCV and human immunodeficiency virus (HIV) coinfection, active tuberculosis infection, PWID, bleeding disorders and hemoglobinopathies, children and adolescents, and pregnancy. Moreover, future perspectives regarding the management of hepatitis C are also discussed and summarized in this consensus statement.
During the progression from hepatitis to fibrosis, cirrhosis, and liver failure, the accumulation of stressed/damaged hepatocyte elements associated with liver inflammation is critical. The causes of ...hepatocyte injuries include viral hepatitis infections, alcoholic hepatitis, and non-alcoholic fatty liver disease. Hepatocyte-derived extracellular vesicles (Hep-EVs) released from stressed/damaged hepatocytes are partly responsible for liver disease progression and liver damage because they activate non-parenchymal cells and infiltrate inflammatory cells within the liver, which are in turn are an important source of EVs. This cell-to-cell signaling is prevalent during inflammation in many liver diseases. Accordingly, special emphasis should be placed on liquid biopsy methods for the long-term monitoring of chronic liver diseases. In the present review, we have highlighted various aspects of current liquid biopsy research into chronic liver diseases. We have also reviewed recent progress on liquid biopsies that focus on cell-free DNA (cfDNA), long non-coding RNA (lncRNA), and the proteins in EVs as potential diagnostic tools and novel therapeutic targets in patients with viral hepatitis, fatty liver steatosis, and alcoholic liver diseases.
The Nobel Prize for Physiology or Medicine, in the year 2020, has been awarded to three scientists, Harvey Alter, Michael Houghton, and Charles Rice, for jointly discovering the hepatitis C virus ...(HCV). This remarkable achievement is a huge breakthrough in the fight against hepatitis C. Most importantly, their pioneering works have successfully saved millions of lives by acting as the foundation for sensitive blood tests and effective antivirals. Inspired by the 2020 Nobel Prize winners, this review article honors their great efforts and discusses several unmet needs in the path toward HCV elimination. In Taiwan, we adopted a micro‐elimination approach plus patient‐centric outreach program to tackle the obstacles that stand in the way of HCV elimination. With its significant results, HCV elimination could be achieved in the near future.
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