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The increasing number of direct-acting antiviral (DAA) regimens along with limited number of subjects and co-medications involved in clinical trials results in drug-drug interactions (DDIs) with DAAs is to be determined. We aimed to examine the prevalence and degree of DDIs between DAAs and other co-medications in a territory-wide cohort of chronic hepatitis C virus (HCV) patients.DDIs were assigned to three risk categories: Category 1-no clinically significant DDI; category 2-potential clinically significant interaction (monitoring and caution required); category 3-contraindicated (should not be co-administered).Of 2981 patients (mean age 59.3 ± 12.3 years; male 60.6%), 810 (48.8%) had genotype 1 and 552 (33.2%) genotype 6 HCV among the 1661 patients with HCV genotype tested; 769 (25.8%) received sofosbuvir/velpatasvir, 510 (17.1%) sofosbuvir/ledipasvir, and 865 (29.0%) glecaprevir/pibrentasvir. More than one-fourth (26.3%) of the patients have polypharmacy (≥ 3 co-medications) in all patients, 27.0% in patients received sofosbuvir/velpatasvir, 25.1% in elbasvir/grazoprevir, and 21.2% in glecaprevir/pibrentasvir. 2037 (68.3%) patient experienced DDI (Category 2: 53.1%; Category 3: 15.2%). The commonest drugs leading to DDIs were calcium channel blockers (31.5%) and proton pump inhibitors (23.0%) in category 2; statins (10.2%), antiplatelet/anticoagulants (3.0%) and antipsychotics (2.9%) in category 3. Changing medication was the most common response from physicians in both category 2 and 3 DDIs.The commonest co-medications leading to contraindication during DAA treatment were statins and antipsychotics. Category 2 and 3 DDIs are often managed by appropriate dose adjustments or temporary discontinuation of relevant co-medications. Careful assessment for potential DDI before DAA use is mandatory to avoid potential harmful effects.

Automatic liver tumor segmentation is of great importance for assisting doctors in liver cancer diagnosis and treatment planning. Recently, deep learning approaches trained with pixel-level annotations have contributed many breakthroughs in image segmentation. However, acquiring such accurate dense annotations is time-consuming and labor-intensive, which limits the performance of deep neural networks for medical image segmentation. We note that Couinaud segment is widely used by radiologists when recording liver cancer-related findings in the reports, since it is well-suited for describing the localization of tumors. In this paper, we propose a novel approach to train convolutional networks for liver tumor segmentation using Couinaud segment annotations. Couinaud segment annotations are image-level labels with values ranging from 1 to 8, indicating a specific region of the liver. Our proposed model, namely CouinaudNet, can estimate pseudo tumor masks from the Couinaud segment annotations as pixel-wise supervision for training a fully supervised tumor segmentation model, and it is composed of two components: 1) an inpainting network with Couinaud segment masks which can effectively remove tumors for pathological images by filling the tumor regions with plausible healthy-looking intensities; 2) a difference spotting network for segmenting the tumors, which is trained with healthy-pathological pairs generated by an effective tumor synthesis strategy. The proposed method is extensively evaluated on two liver tumor segmentation datasets. The experimental results demonstrate that our method can achieve competitive performance compared to the fully supervised counterpart and the state-of-the-art methods while requiring significantly less annotation effort.

Identifying hepatic fibrosis is crucial for nonalcoholic fatty liver disease (NAFLD) management. The fibrosis-8 (FIB-8) score, recently developed by incorporating four additional variables into the fibrosis-4 (FIB-4) score, showed better performance in predicting significant fibrosis in NAFLD.To validate the FIB-8 score in a biopsy-proven NAFLD cohort and compare the diagnostic performance of the FIB-8 and FIB-4 scores and NAFLD fibrosis score (NFS) for predicting significant fibrosis.We collected the data of biopsy-proven NAFLD patients from three Asian centers in three countries. All the patients with available variables for the FIB-4 score (age, platelet count, and aspartate and alanine aminotransferase levels) and FIB-8 score (the FIB-4 variables plus 4 additional parameters: The body mass index (BMI), albumin to globulin ratio, gamma-glutamyl transferase level, and presence of diabetes mellitus) were included. The fibrosis stage was scored using nonalcoholic steatohepatitis CRN criteria, and significant fibrosis was defined as at least fibrosis stage 2.A total of 511 patients with biopsy-proven NAFLD and complete data were included for validation. Of these 511 patients, 271 (53.0%) were female, with a median age of 51 (interquartile range: 41, 58) years. The median BMI was 29 (26.3, 32.6) kg/mWe demonstrated that the FIB-8 score had significantly better performance for predicting significant fibrosis in NAFLD patients than the NFS, as well as clinically superior performance

Several guidelines recommend screening for NAFLD in patients with type 2 diabetes (T2D). We aimed to determine if there is a threshold of age and duration of T2D for liver-related event development to guide screening strategies.We conducted a territory-wide retrospective cohort study of adult patients with NAFLD and T2D diagnosed between 2000 and 2014 in Hong Kong to allow for at least 5 years of follow-up. The primary endpoint was liver-related events, defined as a composite of HCC and cirrhotic complications. This study included 7028 patients with NAFLD with T2D (mean age, 56.1 ± 13.3 years; 3363 male [47.9%]). During a follow-up of 77,308 person-years, there was a threshold effect with 1.1%, 4.9%, and 94.0% of patients developing liver-related events at the age of40, 40-50, and ≥50 years, respectively. Similarly, 3.1%, 5.1%, and 91.8% of patients developed cirrhosis at the age of40, 40-50, and ≥50 years, respectively. In contrast, liver-related events increased linearly with diabetes duration, with no difference in the annual incidence rate between the first 10 years of T2D diagnosis and subsequent years (0.06% vs. 0.10%; p = 0.136). On multivariable analysis, baseline age ≥50 years (adjusted HR [aHR] 2.01) and cirrhosis (aHR 3.12) were the strongest risk factors associated with liver-related events. Substitution of cirrhosis with the aspartate aminotransferase-to-platelet ratio index or the Fibrosis-4 index yielded similar results.Age rather than duration of T2D predicts liver-related events in patients with NAFLD and T2D. It is reasonable to screen patients with NAFLD and T2D for advanced liver disease starting at 50 years of age.

Hepatocellular carcinoma is one of the commonest cancer in the world. Despite curative resection, recurrence remains the largest challenge. Many risk factors were identified for predicting recurrence, including liver fibrosis and cirrhosis. Transient elastography (Fibroscan) is an accurate tool in measuring liver fibrosis. This study aimed to evaluate the use of preoperative liver stiffness measurement (LSM), with Fibroscan in predicting long-term recurrence of hepatocellular carcinoma (HCC) after curative resection.A prospective cohort study was conducted from February 2010 - June 2017 in Prince of Wales hospital. All consecutive patients with HCC undergone hepatectomy were included. Demographic factors, preoperative LSM, tumor characteristics and operative details were assessed. Primary outcome and secondary outcome were overall survival and disease free survival at 1 year, 3 year and 5 year respectively.A total of 401 cases were included. Patients with LSM ≥12kPa had significantly lower 5-year overall survival rate (75.1% vs 57.3%, p 0.001) and disease free survival rate (45.8% vs. 26.7%, p 0.001). On multivariate analysis, pre-operative creatinine and vascular invasion of tumor were significant factors in predicting early recurrence (p = 0.012 and p = 0.004). LSM ≥12kPa were the only significant factor in predicting late recurrence (p = 0.048).Pre-operative liver stiffness measurement could predict the late recurrence of hepatocellular carcinoma after curative resection.

The world has made significant progress in developing novel treatments for COVID-19 since the pandemic began. Some treatments target the patient's dysregulated inflammatory response during COVID-19 infection and may cause hepatitis B reactivation (HBVr) in patients with current or past hepatitis B virus (HBV) infection. This review summarizes the risk and management of HBVr due to different treatments of COVID-19 in patients who have current or past HBV infection. Abnormal liver function tests are common during COVID-19 infection. Current evidence suggests that current or past HBV infection is not associated with an increased risk of liver injury and severe disease in COVID-19 patients. Among patients who received high-dose corticosteroids, various immunosuppressive monoclonal antibodies and inhibitors of Janus kinase, the risk of HBVr exists, especially among those without antiviral prophylaxis. Data, however, remain scarce regarding the specific use of immunosuppressive therapies in COVID-19 patients with HBV infection. Some results are mainly extrapolated from patients receiving the same agents in other diseases. HBVr is a potentially life-threatening event following profound immunosuppression by COVID-19 therapies. Future studies should explore the use of immunosuppressive therapies in COVID-19 patients with HBV infection and the impact of antiviral prophylaxis on the risk of HBVr.

Summary Despite several recent meta-analyses on the topic, the comparative risk of hepatocellular carcinoma in patients with chronic hepatitis B (CHB) receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) remains controversial. The controversy partly results from the arbitrary nature of significance levels leading to contradictory conclusions from very similar datasets. However, the use of observational data, which is prone to both within- and between-study heterogeneity of patient characteristics, also lends additional uncertainty. The asynchronous introduction of ETV and TDF in East Asia, where the majority of these studies have been conducted, further complicates analyses, as does the ensuing difference in follow-up time between ETV and TDF cohorts. Researchers conducting meta-analyses in this area must make many methodological decisions to mitigate bias but are ultimately limited to the methodologies of the included studies. It is therefore important for researchers, as well as the audience of published meta-analyses, to be aware of the quality of observational studies and meta-analyses in terms of patient characteristics, study design and statistical methodologies. In this review, we aim to help clinicians navigate the published meta-analyses on this topic and to provide researchers with recommendations for future work.

Background/Aims: We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients.Methods: The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals.Results: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57).Conclusions: We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

BACKGROUND AND AIMS The uptake of antiviral treatment for patients with chronic hepatitis B (CHB) has been suboptimal. We aimed to determine the secular trend of treatment uptake in the territory-wide CHB cohort in Hong Kong from 2000 to 2017 and the factors for no treatment despite fulfilling treatment criteria. METHODS Chronic hepatitis B patients under public clinics and hospitals were identified through electronic medical records. The treatment indications were defined according to the Asian-Pacific guidelines published at the time of patients' first appearance in four periods: 2000-2004, 2005-2009, 2010-2013, and 2014-2017. RESULTS There were 135 395 CHB patients were included; 1493/12472 (12.0%), 7416/43426 (17.1%), 10 129/46559 (21.8%), 8051/32 938 (24.4%) patients fulfilled treatment criteria in the four periods, respectively. The treatment uptake rate increased with time: 35.1%, 43.4%, 60.2%, and 68.6% respectively. High fibrosis indices (APRI, FIB-4, and Forns indices) appeared to be the main factors for treatment indication in non-cirrhotic patients, with over 90% fulfilling treatment criteria due to high fibrosis indices alone. Of those fulfilling treatment criteria by high fibrosis indices, less than 60% of patients (25.2%, 36.1%, 46.0%, and 58.9%, respectively) had antiviral treatment initiated. Normal platelet count (odds ratio 0.42, P

Background & Aim Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. Methods All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. Recommendations We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT.Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch.The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to their counterpart (P0.001).The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.

Background/Aims: Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients.Methods: Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort.Results: 180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence

Objective Accurate risk prediction is important for evaluating early medical treatment effects and improving health care quality. Existing methods are usually designed for dynamic medical data, which require long-term observations. Meanwhile, important personalized static information is ignored due to the underlying uncertainty and unquantifiable ambiguity. It is urgent to develop an early risk prediction method that can adaptively integrate both static and dynamic health data. Materials and Methods Data were from 6367 patients with Peptic Ulcer Bleeding between 2007 and 2016. This article develops a novel End-to-end Importance-Aware Personalized Deep Learning Approach (eiPDLA) to achieve accurate early clinical risk prediction. Specifically, eiPDLA introduces a long short-term memory with temporal attention to learn sequential dependencies from time-stamped records and simultaneously incorporating a residual network with correlation attention to capture their influencing relationship with static medical data. Furthermore, a new multi-residual multi-scale network with the importance-aware mechanism is designed to adaptively fuse the learned multisource features, automatically assigning larger weights to important features while weakening the influence of less important features. Results Extensive experimental results on a real-world dataset illustrate that our method significantly outperforms the state-of-the-arts for early risk prediction under various settings (eg, achieving an AUC score of 0.944 at 1 year ahead of risk prediction). Case studies indicate that the achieved prediction results are highly interpretable. Conclusion These results reflect the importance of combining static and dynamic health data, mining their influencing relationship, and incorporating the importance-aware mechanism to automatically identify important features. The achieved accurate early risk prediction results save precious time for doctors to timely design effective treatments and improve clinical outcomes.

Surveillance of C. difficile infections suggests correlation of incidence to antibiotic stewardship programs., We conducted a territorywide survey to investigate the epidemiology, risk factors, and clinical outcomes of Clostridioides difficile infection (CDI) among hospitalized patients in Hong Kong. A total of 17,105 cases of CDI were identified, of which 15,717 (91.9%) were healthcare-associated and 1,025 (6.0%) were community-associated. Although CDI incidence increased substantially from 2006 to 2017, it plateaued in 2018 and 2019. The 30-day mortality rates decreased from 20.1% in 2015 to 16.8% in 2019, whereas the 60-day recurrence rates remained constant at ≈11% during the study period. Cross-correlation statistic showed significant correlations between incidence trend and overall antimicrobial drug use (r = 0.865, p

Women at childbearing age and pregnant ladies living in the areas of high or intermediate prevalence of hepatitis B virus (HBV) remain at risk of getting the infection and passing the infections to their offspring via mother-to-child transmission (MTCT) of HBV. HBV infection may affect the mothers by active hepatitis, very occasionally liver cirrhosis and rarely fulminant hepatitis and liver failure. The virus may be transmitted to the babies despite immunoprophylaxis in the setting of very high maternal viral load. Tenofovir disoproxil fumarate (TDF) has been shown to be efficacious to reduce MTCT of HBV, which contributes to the elimination of chronic HBV infection by 2030, the goal set by World Health Organization.

Background/Aims: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV.Methods: We prospectively recruited patients with Child’s A cirrhosis and eGFR 2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment.Results: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed.Conclusions: GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

BACKGROUND AND AIMS Type 2 diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis. Current international guidelines recommend the use of noninvasive tests as initial assessments for NAFLD, but the role of noninvasive tests as monitoring tools has not been established. We aimed to study the role of transient elastography as a monitoring tool in patients with type 2 diabetes. APPROACH AND RESULTS We recruited patients with type 2 diabetes without viral hepatitis or excessive alcohol intake from a complication screening facility in Hong Kong in 2013-2014 and repeated the assessments in 2016-2018. The primary endpoint was an increase of liver stiffness measurement (LSM) to ≥10 kPa. The secondary endpoint was the change in the controlled attenuation parameter (CAP). A total of 611 patients with type 2 diabetes and a valid LSM (mean age, 57.7 ± 10.9 years; 342 men [56.0%]) were included in this study (568 also had a valid CAP). Overall, there was moderate correlation between the baseline and follow-up LSM (r = 0.689, P

Reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is the key ultimate goal set in essentially all treatment guidelines. There has been solid evidence supporting the relationship between serum hepatitis B virus (HBV) DNA level and risk of HCC. Antiviral treatment with oral nucleos(t)ide analogues (NAs) leads to sustained viral suppression and hence is often adopted as the secondary prevention for HCC in CHB patients. The first-generation NA, lamivudine, reduced the risk of HCC at 3 years compared to placebo; yet, its high emergence of antiviral resistance has made it no longer recommended in the international guidelines. Recent heated debate is about the two current first-line NAs—entecavir and tenofovir disoproxil fumarate (TDF)—Are they just as good to reduce HCC risk in CHB patients? A handful of cohort studies show two different kinds of observations—TDF is better than entecavir in lowering HCC risk, or these two NAs have led to similarly low risk of HCC. Tenofovir alafenamide (TAF), a modified version of TDF higher rate of ALT normalization, would be another potent nucleotide analogue is the treatment of choice for secondary prevention for HCC.

BACKGROUND AND AIM Hepatitis B core-related antigen (HBcrAg) has been shown to correlate with various viral markers in chronic hepatitis B, but its role in defining natural history is not well studied. We aimed to investigate the use of HBcrAg to define different phases of chronic hepatitis B. METHODS Stored residual serum samples from longitudinal cohorts of chronic hepatitis B patients in Hong Kong and Japan were studied. Viral markers were measured in three serial serum samples for each patient. Patients were divided into six groups for analysis: hepatitis B e antigen (HBeAg)-positive chronic infection (EPI), HBeAg-positive chronic hepatitis (EPH), HBeAg seroconversion (ES), HBeAg-negative chronic hepatitis (ENH), HBeAg-negative chronic infection (ENI), and HBsAg seroclearance (SS). RESULTS In total, 166 patients followed up for 100 (76-113) months were included. HBcrAg was correlated with hepatitis B virus DNA and HBsAg levels in both HBeAg-positive and HBeAg-negative patients. HBcrAg cut-off of ≥ 6.0 log U/mL could best differentiate HBeAg-positive from HBeAg-negative patients (area under receiver operating characteristic curve of 0.99, P

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend noninvasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.

Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear.This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions. Patients were observed for HBsAg seroclearance until death, loss to follow-up, or treatment discontinuation or switching. The incidences of HBsAg seroclearance were adjusted for competing mortality and compared between ETV and TDF cohorts with inverse probability of treatment weighting (IPTW) and also by multivariable regression analysis.The study population was followed up for a median duration of 56.1 months with 36,929 11 person-years of observation. HBsAg seroclearance occurred in 70 ETV-treated and 21 TDF-treated patients, yielding 8-year cumulative incidence of 1.69% (95% confidence interval [CI] 1.32-2.17) for ETV and 1.34% (95% CI 0.85-2.10%), for TDF (p = 0.58). In the IPTW analysis with the two study cohorts more balanced in background covariates, the age-adjusted hazard ratio (HR) of TDF versus ETV for HBsAg seroclearance was 0.91 (95% CI 0.50-1.64; p = 0.75). Furthermore, there was no significant difference between the two medications in the multivariable competing risk regression model (adjusted sub-distributional HR 0.92 for TDF vs. ETV; 95% CI 0.56-1.53; p = 0.76).ETV and TDF did not differ significantly in the incidence of HBsAg seroclearance, which rarely occurred with either regimen.

Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir for the treatment of chronic hepatitis B (CHB) infection. We aimed to evaluate the impact of switching to TAF on alanine aminotransferase (ALT) normalization and renal safety. We also described the indications of switching to TAF. Consecutive adult CHB patients switched from tenofovir disoproxil fumarate (TDF) dominant therapy to TAF for more than 12 months were identified retrospectively. A subgroup of patients newly switched to TAF was prospectively invited to perform transient elastography examination and dual-energy X-ray absorptiometry. The time of switching to TAF was defined as baseline. Among 393 patients in the retrospective cohort, the median ALT at month 12 was significantly lower (21.0 [16.0-29.9] U/L vs. 25.0 [19.0-34.0] U/L; p 0.001) and ALT normalization rate was higher (89.9% vs. 83.7%; p = 0.037) than those at baseline. Estimated glomerular filtration rate decreased from 12 months before baseline and then increased from baseline to month 12 significantly (69.7 ± 22.0 ml/min/1.73 m

Automatic liver tumor segmentation could offer assistance to radiologists in liver tumor diagnosis, and its performance has been significantly improved by recent deep learning based methods. These methods rely on large-scale well-annotated training datasets, but collecting such datasets is time-consuming and labor-intensive, which could hinder their performance in practical situations. Learning from synthetic data is an encouraging solution to address this problem. In our task, synthetic tumors can be injected to healthy images to form training pairs. However, directly applying the model trained using the synthetic tumor images on real test images performs poorly due to the domain shift problem. In this paper, we propose a novel approach, namely Synthetic-to-Real Test-Time Training (SR-TTT), to reduce the domain gap between synthetic training images and real test images. Specifically, we add a self-supervised auxiliary task, i.e., two-step reconstruction, which takes the output of the main segmentation task as its input to build an explicit connection between these two tasks. Moreover, we design a scheduled mixture strategy to avoid error accumulation and bias explosion in the training process. During test time, we adapt the segmentation model to each test image with self-supervision from the auxiliary task so as to improve the inference performance. The proposed method is extensively evaluated on two public datasets for liver tumor segmentation. The experimental results demonstrate that our proposed SR-TTT can effectively mitigate the synthetic-to-real domain shift problem in the liver tumor segmentation task, and is superior to existing state-of-the-art approaches.

For the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.

COVID-19 is caused by s-coronavirus SARS-CoV-2. Recent reports suggested that neurological diseases, in particular stroke, dementia and advanced Parkinson’s disease (PD), were important predictors of COVID-19-related mortality.1–3 SARS-CoV was another s-coronavirus which resulted in the epidemic of SARS in late 2002 to early 2003. Apparently, it remained quiescent since 2004 but its re-emergence is possible. Patients with SARS at advanced age and with multiple comorbidities were at higher risk of mortality.4 Given mortality rates and predictors may vary with regions, we investigated the impact of pre-existing neurological diseases on the mortality of patients with COVID-19 and SARS in Hong Kong, one of the most densely populated cities in the world. Studying the impact of neurological diseases on COVID-19 and SARS mortalities would have important implications on possible future pandemics caused by coronaviruses. We believe the data would provide guidance on resource allocation and healthcare policy making. With the availability of effective vaccination against COVID-19, the finding could implicate on the prioritisation of vaccination for patients with chronic neurological diseases. ### Study design and data retrieval We performed a territory-wide retrospective cohort study using data from the Clinical Data Analysis and Reporting System (CDARS) under the management of the Hospital Authority, Hong Kong. CDARS is an electronic healthcare database that covers the patients’ demographic, death, diagnoses, procedures, drug prescription and dispensing history, and laboratory results from all public hospitals and clinics in Hong Kong. It represents in-patient data of about 80%–90% of the 7.49 million population in Hong Kong. All confirmed patients with COVID-19 and SARS were reported to the Department of Health and hospitalised in public hospitals in Hong Kong. Patients were anonymised in CDARS to ensure confidentiality. ### Subjects Consecutive patients with laboratory-confirmed COVID-19 from 23 January 2020 to 31 July 2020 and patients with SARS from March to June 2003 were identified by International …

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can inhibit liver fibrogenesis in animal models. We aimed to evaluate the impact of ACEI/ARB use on the risk of liver cancer and cirrhosis complications in patients with NAFLD.We conducted a retrospective, territory-wide cohort study of adult patients with NAFLD diagnosed between January 2000 and December 2014 to allow for at least 5 years of follow-up. ACEI or ARB users were defined as patients who had received ACEI or ARB treatment for at least 6 months. The primary endpoint was liver-related events (LREs), defined as a composite endpoint of liver cancer and cirrhosis complications. We analyzed data from 12,327 NAFLD patients (mean age, 54.2 ± 14.7 years; 6163 men [50.0%]); 6805 received ACEIs, and 2877 received ARBs. After propensity score weighting, ACEI treatment was associated with a lower risk of LREs (weighted subdistribution hazard ratio [SHR], 0.48; 95% CI, 0.35-0.66; p 0.001), liver cancer (weighted SHR, 0.46; 95% CI, 0.28-0.75; p = 0.002), and cirrhosis complications (weighted SHR, 0.42; 95% CI, 0.27-0.66; p 0.001), but ARB was not. In subgroup analysis, ACEI treatment was associated with greater reduction in LREs in patients with chronic kidney diseases (CKDs) than those without (CKD-weighted SHR, 0.74; 95% CI, 0.52-0.96; p = 0.036; non-CKD-weighted SHR, 0.15; 95% CI, 0.07-0.33; p 0.001).ACEI, rather than ARB, treatment is associated with a lower risk of LREs in NAFLD patients, especially among those with CKD.

ObjectivesTo investigate the association between baseline use of glucose-lowering drugs and serious clinical outcome among patients with type 2 diabetes.DesignTerritory-wide retrospective cohort of confirmed cases of COVID-19 between January 2020 and February 2021.SettingAll public health facilities in Hong Kong.Participants1220 patients with diabetes who were admitted for confirmed COVID-19.Primary and secondary outcome measuresComposite clinical endpoint of intensive care unit admission, requirement of invasive mechanical ventilation and/or in-hospital death.ResultsIn this cohort (median age 65.3 years, 54.3% men), 737 (60.4%) patients were treated with metformin, 385 (31.6%) with sulphonylureas, 199 (16.3%) with dipeptidyl peptidase-4 (DPP-4) inhibitors and 273 (22.4%) with insulin prior to admission. In multivariate Cox regression, use of metformin and DPP-4 inhibitors was associated with reduced incidence of the composite endpoint relative to non-use, with respective HRs of 0.51 (95% CI 0.34 to 0.77, p=0.001) and 0.46 (95% CI 0.29 to 0.71, pConclusionsUsers of metformin and DPP-4 inhibitors had fewer adverse outcomes from COVID-19 compared with non-users, whereas insulin and sulphonylurea might predict a worse prognosis.

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.

Background and aims Improvement in Model for End-Stage Liver Disease (MELD) score during antiviral treatment is associated with reduced hepatic decompensation and death in patients with chronic hepatitis B (CHB)-related cirrhosis. We aimed to identify factors associated with transplant-free survival and on-treatment MELD score improvement. Methods We identified patients with CHB-related cirrhosis and MELD score ≥ 15 at the start of entecavir and/or tenofovir disoproxil fumarate treatment between 2005 and 2017. The primary endpoint was transplant-free survival at month 6. The secondary endpoints at month 6 were transplant-free survival with > 5-point improvement in MELD score and transplant-free survival with MELD score Results Of 999 cirrhotic CHB patients, 605 (60.6%) achieved transplant-free survival at month 6. Proportion of transplant-free survival at month 6 stabilized at 10% in patients with high MELD. Patients who achieved transplant-free survival at month 6 were younger, had lower MELD score, lower alanine aminotransferase (ALT), and higher albumin at baseline. Of 605 patients with transplant-free survival, 276 (45.6%) achieved > 5-point improvement in MELD score; 183 (30.2%) had 1-point to 5-point improvement in MELD score; 146 (24.1%) had no improvement or a worsened MELD score. Also, 321 (53.1%) patients with transplant-free survival had a MELD score Conclusion On top of lower MELD score, patients with CHB-related cirrhosis who are younger, have higher albumin, and lower ALT are more likely to achieve transplant-free survival after 6 months of antiviral treatment.

Background & Aims Systemic corticosteroids may cause HBV reactivation, but the impact on patients with previous HBV exposure is poorly defined. We aimed to study the risk of HBsAg seroreversion and hepatitis flare in patients with previous HBV exposure. Methods Patients who were negative for HBsAg and received corticosteroids between 2001–2010 were included. Patients who were positive for antibody to HBsAg (anti-HBs) and/or to HBcAg (anti-HBc) were defined as having previous HBV exposure. The primary endpoint was HBsAg seroreversion; the secondary endpoint was hepatitis flare (alanine aminotransferase >80 U/L) at 1 year. Results A total of 12,997 patients fulfilled the inclusion criteria: anti-HBs positive only (n = 10,561); anti-HBc positive only (n = 970); anti-HBs & anti-HBc positive (n = 830) and anti-HBs & anti-HBc negative (n = 636). HBsAg seroreversion occurred in 165 patients. Patients who were anti-HBc positive only had a higher risk of HBsAg seroreversion (1-year incidence 1.8%) than those negative for both anti-HBs & anti-HBc (0%; p = 0.014). Patients with previous HBV exposure had a similarly low risk of liver failure as unexposed individuals (1.1% vs. 0.9%). The risk of a hepatitis flare started to increase in those receiving corticosteroids at peak daily doses of 20–40 mg (adjusted hazard ratio [HR] 2.19, p = 0.048) or >40 mg (aHR 2.11, p = 0.015) prednisolone equivalents for 28 days (aHR 2.02–3.85; p Conclusions In HBsAg-negative patients who were only anti-HBc positive, high peak daily doses of corticosteroids increased the risk of hepatitis flare, but not seroreversion. The rate of liver failure was low and similar in HBV exposed and unexposed individuals; there were no deaths, nor any requirement for liver transplantation. Lay summary It is important to know the hepatitis B virus (HBV) status before starting corticosteroid therapy. Patients with resolved HBV infection without detectable immunity are at an increased risk of HBV surface antigen seroreversion after corticosteroid therapy. High peak daily doses of corticosteroids (>40 mg prednisolone equivalents) increase the risk of hepatitis flare, but not seroreversion, in patients with previous exposure to HBV, irrespective of the duration of treatment. Interval monitoring of liver biochemistries is essential for the early detection of hepatitis flares in these patients.

Background Cure rates of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared with HCV/non-HCC patients. Methods Using data from the Real-World Evidence from the Asia Liver Consortium (REAL-C) registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin levels to evaluate DAA treatment outcomes in a large population of HCV/HCC compared with HCV/non-HCC patients. Results We included 6081 patients (HCC, n = 465; non-HCC, n = 5 616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs 93.7%; P = .03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR, 0.28; P = .01) when compared with non-HCC. Conclusions Active HCC but not inactive HCC was independently associated with lower SVR compared with non-HCC patients undergoing DAA therapy, although cure rate was still relatively high (85%) in active HCC patients.

Achieving hepatitis B e antigen (HBeAg) seroconversion is a satisfactory endpoint during antiviral treatment for chronic hepatitis B (CHB). This study aimed to develop and validate a novel scoring system to predict HBeAg seroconversion during entecavir (ETV) treatment. A total of 526 patients with HBeAg-positive CHB treated with ETV for at least 1 year were randomly assigned to the training and validation cohorts. Baseline parameters including hepatitis B virus DNA, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and alanine aminotransferase level were quantified. Patients who achieved HBeAg seroconversion were compared with those without HBeAg seroconversion. A prediction model was established to predict HBeAg seroconversion during ETV treatment. After a median follow up of 2.67 years, 93 (36.0%) and 87 (32.5%) patients in the training and validation cohorts developed HBeAg seroconversion. A prediction score composed of age, HBsAg and HBcAb quantification was derived. Areas under receiver operating characteristic curve at 5 years of this prediction score were 0.70 and 0.72 in the training and validation cohorts. By using the dual cutoff values of 0.28 and 0.58, the model was endowed with high sensitivity and specificity to exclude or identify patients developing HBeAg seroconversion (90.3% sensitivity and 90.2% specificity in the training cohort as well as 92.8% sensitivity and 84.4% specificity in the validation cohort, respectively). A novel prediction score that uses baseline clinical variables was developed and validated. The score accurately estimates the probabilities of developing HBeAg seroconversion at 5-years ETV therapy in patients with CHB.

ObjectiveFibrosis stage is strongly associated with liver-related outcomes and is a key surrogate endpoint in drug trials for non-alcoholic steatohepatitis. Dual-photon microscopy allows automated quantification of fibrosis-related parameters (q-FPs) and may facilitate large-scale histological studies. We aim to validate the performance of q-FPs in a large histological cohort.Design344 patients with non-alcoholic fatty liver disease (NAFLD) underwent 428 liver biopsies (240 had paired transient elastography examination). Fibrosis stage was scored using the NASH Clinical Research Network system, and q-FPs were measured by dual-photon microscopy using unstained slides. Patients were randomly assigned to the training and validation cohorts to test the performance of individual q-FPs and derive optimal cut-offs.ResultsOver 25 q-FPs had area under the receiver-operating characteristics curves >0.90 for different fibrosis stages. Among them, the perimeter of collagen fibres and number of long collagen fibres had the highest accuracy. At the best cut-offs, the two q-FPs had 88.3%–96.2% sensitivity and 78.1%–91.1% specificity for different fibrosis stages in the validation cohort. q-FPs and histological scoring had nearly identical correlations with liver stiffness measurement, suggesting that the accuracy of q-FPs approached that of histological assessment. Among patients with paired liver biopsies, changes in the same q-FPs were associated with changes in fibrosis stage. At a median follow-up of 5.6 years, baseline q-FPs predicted liver-related events.Conclusionq-FP is highly accurate in the assessment of fibrosis in NAFLD patients. This automated platform can be used in future studies as objective and reliable evaluation of histological fibrosis.

One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia. Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR

Background The Liver stiffness measurement hepatocellular carcinoma (LSM-HCC) score predicts HCC accurately in patients with chronic hepatitis B (CHB). Aim To assess the ability of LSM-HCC combined with enhanced liver fibrosis (ELF) score to predict HCC in CHB patients who received anti-viral treatment. Methods CHB patients who had transient elastography examinations in 2006-2013 with intermediate and high risk of HCC by LSM-HCC score (ie 11 or above) were assessed by repeat transient elastography at least 3 years later. ELF score was assessed by retrieving the stored serum samples 4 weeks within transient elastography examination. The primary endpoint was the cumulative incidence of HCC. Results A total of 453 CHB patients (mean age 51.7 ± 10.3 years; male 74.4%) were recruited, 45 patients (9.9%) developed HCC during the mean follow-up of 56 months. Regarding LSM-HCC score, 71.4%, 24.3% and 4.3% of patients had LSM-HCC score improved, remained static and deteriorated respectively; whereas 36.9%, 57.8% and 5.3% of patients had ELF score improved, remained static and deteriorated respectively. The sensitivity (86.7%) and negative predictive value (NPV) (95.3%) of combined LSM-HCC and ELF score were higher than that of each score alone. Kaplan-Meier analysis showed that ELF score would help further differentiate the HCC risk in patients with intermediate risk by LSM-HCC score (P = 0.026), but not in patients with high risk by LSM-HCC score (P = 0.770). Conclusions The two-step algorithm combining LSM-HCC score and ELF score could improve the accuracy of predicting HCC of CHB patients receiving anti-viral treatment.

ImportanceSome patients treated with nirmatrelvir-ritonavir have experienced rebound of COVID-19 infections and symptoms; however, data are scarce on whether viral rebound also occurs in patients with COVID-19 receiving or not receiving molnupiravir.ObjectiveTo examine the incidence of viral rebound in patients with COVID-19 who were treated with the oral antiviral agents nirmatrelvir-ritonavir and molnupiravir.Design, Setting, and ParticipantsThis cohort study identified 41 255 patients with COVID-19 who were hospitalized from January 1, 2022, to March 31, 2022, in Hong Kong and assessed 12 629 patients with serial cycle threshold (Ct) values measured. Patients were followed up until the occurrence of the clinical end point of interest, death, date of data retrieval (July 31, 2022), or up to 30 days of follow-up, whichever came first.ExposuresMolnupiravir or nirmatrelvir-ritonavir treatment.Main Outcomes and MeasuresViral rebound, defined as a Ct value greater than 40 that decreased to 40 or less.ResultsOf 12 629 patients (mean [SD] age, 65.4 [20.9] years; 6624 [52.5%] male), 11 688 (92.5%) were oral antiviral nonusers, 746 (5.9%) were molnupiravir users, and 195 (1.5%) were nirmatrelvir-ritonavir users. Compared with nonusers, oral antiviral users were older, had more comorbidities, and had lower complete vaccination rates. The mean (SD) baseline Ct value was slightly higher in nirmatrelvir-ritonavir users (22.2 [6.0]) than nonusers (21.0 [5.4]) and molnupiravir users (20.9 [5.4]) (P = .04). Viral rebound occurred in 68 nonusers (0.6%), 2 nirmatrelvir-ritonavir users (1.0%), and 6 molnupiravir users (0.8%). Among 76 patients with viral rebound, 12 of 68 nonusers, 1 of 6 molnupiravir users, and neither of the nirmatrelvir-ritonavir users died of COVID-19.Conclusions and RelevanceIn this cohort study, viral rebound was uncommon in patients taking molnupiravir or nirmatrelvir-ritonavir and was not associated with increased risk of mortality. Given these findings, novel oral antivirals should be considered as a treatment for more patients with COVID-19 in the early phase of the infection.

BACKGROUND & AIMS How adiposity influences the effect of genetic variants on non-alcoholic fatty liver disease (NAFLD) in the Asian population remains unclear. We aimed to study the association between genetic risk variants and susceptibility/severity of NAFLD in the lean, overweight and obese individuals. METHODS Nine hundred and four community subjects underwent proton-magnetic resonance spectroscopy and transient elastography examination. Lean (

Although the association between fatty pancreas and metabolic syndrome has been suggested in retrospective studies, long-term prospective data on the effect of fatty pancreas on various metabolic outcomes are lacking. We aimed to prospectively investigate the association between fatty pancreas and the development of major metabolic outcomes.A total of 631 subjects from a population study using fat-water magnetic resonance imaging to quantify pancreatic and liver fat content during 2008 to 2010 were followed up prospectively until December 2020 (mean follow-up time, 11.1 ± 1.1 y). Subjects with significant alcohol intake and diabetes mellitus (DM) at baseline were excluded. Incidence of newly diagnosed DM, hypertension, dyslipidemia, ischemic heart disease, cardiovascular accidents, pancreatic cancer, and mortality were evaluated.Among the 631 subjects (mean age, 48 ± 11 y), 93 (14.7%) had fatty pancreas. The fatty pancreas group had a higher incidence of DM (33.3% vs 10.4%; P.001), hypertension (37.7% vs 22.7%; P = .003), and dyslipidemia (37.7% vs 14.6%; P.001) during long-term follow-up evaluation. Individuals with both fatty liver and pancreas had the highest DM incidence, followed by fatty liver only and fatty pancreas only groups (P.001). Fatty pancreas was associated independently with DM (adjusted hazard ratio, 1.81; 95% CI, 1.10-3.00; P = .020), but not hypertension or dyslipidemia on multivariate analysis. Each percentage increase of pancreatic fat increased the risk of incident DM by 7% (adjusted hazard ratio, 1.07; 95% CI, 1.01-1.13; P = .016). No participants developed pancreatic cancer during the follow-up period.Fatty pancreas is associated independently with subsequent DM development, but not hypertension or dyslipidemia.

Currently, there is no well-established algorithm predicting hepatocellular carcinoma (HCC) development in untreated hepatitis C virus (HCV) patients. We aimed to validate an algorithm (risk evaluation of viral load elevation and associated liver disease/HCV [REVEAL-HCV]: age, AST, ALT, HCV RNA, HCV genotype, and cirrhosis) developed in Taiwanese patients. We analyzed 1381 (50.1% White, 14.7% Hispanic, 13.8% Asian of diverse origin, and 7.8% African American) adult treatment-naive HCV patients (no viral co-infection, no HCC within 6 months) at 4 U.S. and one Hong Kong centers (11/1994-10/2017). Compared to the non-Asian cohort, the Asian cohort had a higher percentage of patients in the low-risk group (46.1% vs. 26.1%) and a lower percentage in the high-risk group (12.0% vs. 20.3%, p

Fibrosis-4 (FIB-4) and the nonalcoholic fatty liver disease fibrosis score (NFS) are the 2 most popular noninvasive blood-based serum tests proposed for widespread fibrosis screening. We therefore aimed to describe the accuracy of FIB-4 and NFS to detect elevated liver stiffness as an indicator of hepatic fibrosis in low-prevalence populations.This study included a total of 5129 patients with concomitant measurement of FIB-4, NFS, and liver stiffness measurement (LSM) by Fibroscan (Echosens, France) from 5 independent population-based cohorts from Spain, Hong Kong, Denmark, England, and France; 3979 participants from the general population and 1150 from at-risk cohorts due to alcohol, diabetes, or obesity. We correlated LSM with FIB-4 and NFS, and calculated pre- and post-test predictive values of FIB-4 and NFS to detect elevated LSM at 8 kPa and 12 kPa cutoffs. The mean age was 53 ± 12 years, the mean body mass index was 27 ± 5 kg/mFIB-4 and NFS are suboptimal for screening purposes due to a high risk of overdiagnosis and a non-negligible percentage of false-negatives, especially in patients with risk factors for chronic liver disease. Waist circumference emerged as a potential first step to identify patients at risk for liver fibrosis in the general population.

The severity of COVID-19 infections could be exacerbated by the epidemic of chronic diseases and underlying inequalities in social determinants of health. Nonetheless, there is scanty evidence in regions with a relatively well-controlled outbreak. This study examined the socioeconomic patterning of COVID-19 severity and its effect modification with multimorbidity in Hong Kong. 3074 local COVID-19 cases diagnosed from 5 July to 31 October 2020 were analyzed and followed up until 30 November 2020. Data on residential addresses, socio-demographic background, COVID-19 clinical conditions, and pre-existing chronic diseases of confirmed cases were retrieved from the Centre for Health Protection and the Hospital Authority. Results showed that, despite an independent adverse impact of multimorbidity on COVID-19 severity (aOR = 2.35 [95% CI = 1.72–3.19]), it varied across the socioeconomic ladder, with no significant risk among those living in the wealthiest areas (aOR = 0.80 [0.32–2.02]). Also, no significant association of the area-level income-poverty rate with severe COVID-19 was observed. In conclusion, the socioeconomic patterning of severe COVID-19 was mild in Hong Kong. Nonetheless, socioeconomic position interacted with multimorbidity to determine COVID-19 severity with a mitigated risk among the socioeconomically advantaged. Plausible explanations include the underlying socioeconomic inequalities in chronic disease management and the equity impact of the public-private dual-track healthcare system.

Recent data suggest that non-alcoholic fatty liver disease (NAFLD) has become a major public health problem in Asia, with an updated population prevalence of 34%. In parallel, NAFLD-associated hepatocellular carcinoma (HCC) is also on the rise. In this review, we describe the changing epidemiology of HCC in Asia over the past 30 years. While traditional risk factors for HCC (older age, male sex and metabolic factors) are also important in Asia, the PNPLA3 gene polymorphism is particularly prevalent in East Asia and may increase the risk of HCC. NAFLD among non-obese individuals is also commonly described in Asia. Because NAFLD is often undiagnosed, few patients receive HCC surveillance, and the target surveillance population beyond patients with cirrhosis remains poorly defined. As a result, NAFLD-associated HCC is often diagnosed at an advanced stage, rendering curative treatment impossible. Finally, despite around 20-30 years of universal vaccination, chronic HBV infection remains prevalent in Asia, and emerging evidence highlights the importance of metabolic factors and concomitant hepatic steatosis on HCC development in infected patients. Future studies should explore the role of metabolic treatments in HCC prevention among patients with hepatic steatosis and concomitant liver diseases.

Background Recently, Papatheodoridi et al proposed to refine the Baveno VI elastography dual-cutoffs and introduce an algorithm for the detection of compensated advanced chronic liver disease (cACLD) in asymptomatic European patients with chronic liver diseases. Aims To validate the performance of the dual-cutoffs (8/12 kPa) and the proposed algorithm to identify patients with cACLD in three well-characterised Asian nonalcoholic fatty liver disease (NAFLD) cohorts. Methods We included 830 patients with biopsy-proven NAFLD. Liver stiffness was measured using transient elastography (FibroScan). Results cACLD was found in 21.8% of patients. Compared with the original Baveno VI elastography criteria (10/15 kPa), the new cutoffs showed a comparable specificity and a higher sensitivity for identifying cACLD. We developed a simplified risk model incorporating age, liver stiffness value, and platelet count, which outperformed liver stiffness measurement alone in two Chinese cohorts (P = 0.001), and was further validated in a Malaysian cohort (P = 0.04). Overall, the "two-step" screening of cACLD improved classification rates from 73.5% by the original dual-cutoffs to 86.7%. Notably, usage of our simplified risk model resulted in significantly lower false-negative rate than the refined screening approach by Papatheodoridi et al (27.1% vs 41.4%; P = 0.01). Conclusions The dual elastography cutoffs of 8 and 12 kPa are more appropriate to identify cACLD in Asian patients with NAFLD. In combination with a simplified risk model in unclassified patients, the two-step approach showed a classification rate of about 85%.

BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis.METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284.FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard.FUNDING: The German Federal Ministry of Education and Research and Echosens.

Introduction Aspirin may reduce the risk of chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in patients receiving antiviral treatment. We aimed to investigate the impact of aspirin on reducing HCC risk in patients treated with first-line oral nucleos(t)ide analogs (NAs; entecavir and/or tenofovir disoproxil fumarate). Methods We conducted a territorywide, retrospective cohort study in NA-treated CHB patients between 2000 and 2018 from the electronic healthcare data repository in Hong Kong. Subjects were classified into aspirin users for at least 90 days during NA treatment (aspirin group) or no aspirin or any other antiplatelet use during follow-up period (no aspirin group). Incidence rates of HCC and gastrointestinal bleeding (GIB) in 2 groups with propensity score matching with 1:3 ratio. Results Of 35,111 NA-treated CHB patients of mean age of 53.0 years and 61.6% men, sixty-nine (4.0%) and 1,488 (4.5%) developed HCC at a median (interquartile range) of 2.7 (1.4-4.8) years and 3.2 (1.8-6.0) years in the aspirin group and no aspirin group, respectively. A duration-dependent association between aspirin and the risk of HCC was observed (subhazard ratio [sHR] 3 months-2 years: 0.65; 95% confidence interval [CI] 0.47-0.92; sHR 2-5 years: 0.63; 95% CI 0.43-0.94; sHR from ≥5 years: 0.41; 95% CI 0.18-0.91). Patients who took aspirin for ≤2 years had significantly higher risk of GIB (sHR: 1.73, 95% CI 1.07-2.79) than those not receiving aspirin. The risk of GIB started declining with the longer use of aspirin and becoming insignificant for ≥5 years' use (sHR: 0.79, 95% CI 0.19-3.21). Discussion Long-term aspirin use is associated with a lower risk of HCC in a duration-dependent manner in NA-treated CHB patients without a significant increase in the risk of gastrointestinal adverse effects.