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We examined the long-term trend of incident hepatocellular carcinoma (HCC) and hepatic decompensation among chronic hepatitis B (CHB) patients who have achieved hepatitis B surface antigen (HBsAg) seroclearance.All adult CHB monoinfected patients who cleared HBsAg between January 2000 and December 2020 were identified using a territory-wide database in Hong Kong. Patients with liver transplantation and/or HCC before HBsAg seroclearance or follow-up less than 6 months were excluded. The primary and secondary endpoints were HCC and hepatic decompensation respectively.We identified 9,769 CHB patients with HBsAg seroclearance (mean age 57 years, 60.0% male, 13.2% cirrhosis); most had compensated liver function at HBsAg loss. At a median (25HCC risk persists in patients after HBsAg loss, whereas the risk of hepatic decompensation decreases over time.Patients with chronic hepatitis B (CHB) still have a non-negligible risk of hepatocellular carcinoma (HCC) after 12 years of hepatitis B surface antigen (HBsAg) seroclearance, especially among those with cirrhosis. The risk of developing hepatic decompensation decreases over time after HBsAg seroclearance. In clinical practice, although CHB patients who cleared HBsAg have a more favourable clinical outcome than those who remain chronically infected, long-term HCC surveillance would still be necessary for cirrhotic patients and high-risk subgroups of non-cirrhotic patients after HBsAg seroclearance.

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 AND AIMS: We compared risk of acute liver injury and mortality in patients with COVID-19 and current, past, and no HBV infection. APPROACH AND RESULTS: This was a territory-wide retrospective cohort study in Hong Kong. Patients with COVID-19 between January 23, 2020, and January 1, 2021, were identified. Patients with hepatitis C or no HBsAg results were excluded. The primary outcome was mortality. Acute liver injury was defined as alanine aminotransferase or aspartate aminotransferase ≥2 × upper limit of normal (ULN; i.e., 80 U/L), with total bilirubin ≥2 × ULN (i.e., 2.2 mg/dL) and/or international normalized ratio ≥1.7. Of 5,639 patients included, 353 (6.3%) and 359 (6.4%) had current and past HBV infection, respectively. Compared to patients without known HBV exposure, current HBV-infected patients were older and more likely to have cirrhosis. Past HBV-infected patients were the oldest, and more had diabetes and cardiovascular disease. At a median follow-up of 14 (9-20) days, 138 (2.4%) patients died; acute liver injury occurred in 58 (1.2%), 8 (2.3%), and 11 (3.1%) patients with no, current, and past HBV infection, respectively. Acute liver injury (adjusted HR [aHR], 2.45; 95% CI, 1.52-3.96; P

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

It is unclear if the leading causes of death in patients with NAFLD differ by age. We aimed to investigate if the relative importance of liver-related deaths is lower and overshadowed by cardiovascular and cancer-related deaths in the elderly population.We conducted a territory-wide retrospective cohort study of adult patients with NAFLD between 2000 and 2021 in Hong Kong. The outcomes of interest were all-cause and cause-specific mortality. Age groups at death were studied at 10-year intervals. During 662,471 person-years of follow-up of 30,943 patients with NAFLD, there were 2097 deaths. The top three causes of death were pneumonia, extrahepatic cancer, and cardiovascular diseases. Liver disease was the sixth leading cause of death in patients aged 70-79 and 80-89 years, accounting for 5.1% and 5.9% of deaths, respectively, but only accounted for 3% or fewer of the deaths in the other age groups. Nonetheless, liver disease was the leading cause of death in patients with NAFLD-related cirrhosis, accounting for 36.8% of all deaths. The incidence of liver-related death was higher in men younger than age 70 but higher in women afterwards. The incidence of liver-related death in women increased from 0.62 to 7.14 per 10,000 person-years from age 60-69 to 70-79 years.The relative importance of liver-related death increases with age in patients with NAFLD, especially among women. In patients with cirrhosis, liver disease is the leading cause of death.

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

To provide an updated overview on the current status of risk prediction scores for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus infection. More HCC risk scores have been developed, validated, and optimized (e.g., with liver stiffness measurement) in different patient and ethnic groups. Risk scores for treated patients with high negative predictive values would be able to identify patients who may not need HCC surveillance anymore as their HCC risk has been reduced by antiviral therapy. Current HCC risk scores can accurately predict HCC in specific populations, in both treatment-naive patients and those receiving antiviral therapy. Different levels of care and different intensities of HCC surveillance should be offered according to the risk profile of patients.

Background & Aims PAGE-B and modified PAGE-B (mPAGE-B) scores were developed to predict the risk of hepatocellular carcinoma (HCC) in patients on nucleos(t)ide analogue therapy. However, how and when to use these risk scores in clinical practice is uncertain. Methods Consecutive adult patients with chronic hepatitis B who had received entecavir or tenofovir for at least 6 months between January 2005 and June 2018 were identified from a territory-wide database in Hong Kong. The performance of PAGE-B and mPAGE-B scores for HCC prediction at 5 years was assessed by area under the time-dependent receiver operating characteristic curve (AUROC), and different cut-off values of these 2 scores were evaluated by survival analysis. Results Of 32,150 identified patients with chronic hepatitis B, 20,868 (64.9%) were male. Their mean age was 53.0 ± 13.2 years. At a median (IQR) follow-up of 3.9 (1.8–5.0) years, 1,532 (4.8%) patients developed HCC. The AUROCs (95% CI) for the prediction of HCC at 5 years were 0.77 (0.76–0.78) and 0.80 (0.79–0.81), with PAGE-B and mPAGE-B scores, respectively (p Conclusions PAGE-B and mPAGE-B scores can be applied to identify patients on antiviral therapy who are at low risk of developing HCC. These patients could be exempted from HCC surveillance due to their very low HCC risk. Lay summary Risk scores have been developed to predict the likelihood of patients with chronic hepatitis B developing hepatocellular carcinoma (HCC). We investigated the role of 2 such scores, PAGE-B and modified PAGE-B, in predicting the risk of HCC in 32,150 nucleos(t)ide analogue-treated patients with chronic hepatitis B. These scores identified a group of patients at very low risk of developing HCC who could therefore be exempted from HCC surveillance.

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.

Background and Aims Metformin is an oral anti‐hyperglycemic recommended by the American Diabetes Association (ADA) as a preferred initial pharmacologic agent for type 2 diabetes. Metabolic acidosis is a rare yet severe side effect of it. We examined the association of metformin use and dosage on the risk of metabolic acidosis in diabetic patients with different degrees of chronic hepatitis B (CHB)‐related cirrhosis and chronic kidney disease (CKD). Methods Metabolic acidosis was defined by blood pH ≤7.35, together with lactate >5 mmol/L or arterial bicarbonate ≤18 mmol/L or venous bicarbonate ≤21 mmol/L, and/or diagnosis codes. Child‐Pugh class and CKD stage were included in the model as time‐dependent covariates. Age, gender, comorbidities, and use of relevant medications were adjusted as covariates. Maximum daily dose of metformin was classified into ≤1000 mg and >1000 mg. Results We identified 4431 diabetic patients with CHB‐related cirrhosis between 2000 and 2017 from a territory‐wide database in Hong Kong. The risk of metabolic acidosis increased with Child‐Pugh class B and C cirrhosis regardless of CKD stage (adjusted subdistribution hazard ratio [aSHR] ranged from 3.50 to 86.16). Metformin use was associated with a higher risk in patients with Child‐Pugh class B or C cirrhosis and stage 3A CKD or above (aSHR ranged from 1.55 to 2.46). In stage 4/5 CKD, a daily dose of metformin ≤1000 mg was still associated with a higher risk of metabolic acidosis regardless of the severity of cirrhosis (aSHR ranged from 2.45 to 3.92). Conclusion In conclusion, patients with Child‐Pugh class B cirrhosis or above were at a higher risk of metabolic acidosis. Metformin further increased the risk in patients with Child‐Pugh class B cirrhosis or above and stage 3A CKD or above. Dose adjustment in stage 4/5 CKD did not reduce the risk of metabolic acidosis.

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.

The benefit of colonoscopy and/or polypectomy for colorectal cancer (CRC) prevention in patients with nonalcoholic fatty liver disease (NAFLD) remains unclear. We aimed to estimate the incidence rate of CRC in patients with NAFLD who had and had not undergone colonoscopy. We conducted a retrospective territory‐wide cohort study for patients aged over 40 years with NAFLD identified with the International Classification of Diseases, Ninth Revision, Clinical Modification codes between January 1, 2000, and December 31, 2014. Patients were followed until CRC diagnosis, death, or December 31, 2017. We estimated CRC incidence and standardized incidence ratio (SIR) using the general population of Hong Kong as reference. We included 8,351 patients with NAFLD in the final analysis (median age, 56.2 years; interquartile ratio [IQR], 49.2‐65.3 years; 45.4% male; median follow‐up, 7.4 years; IQR, 5.4‐9.6 years). Compared with the general population, patients with NAFLD who had not undergone colonoscopy had a higher incidence of CRC (SIR, 2.20; 95% confidence interval [CI], 1.64‐2.88; P 2.67) had a significantly higher risk of CRC after adjusting for demographic and metabolic factors. Conclusion: Patients with NAFLD who had undergone colonoscopy had a lower incidence of CRC than the general population, especially among those aged ≥50 years or with DM. A high FIB‐4 index was associated with a higher risk of CRC.

INTRODUCTION Immunotherapy has dramatically improved the survival of patients with advanced or metastatic malignancies. Recent studies suggest that immunotherapy may increase the risk of hepatitis, whereas it may also induce functional cure of chronic hepatitis B virus (HBV) infection. We evaluated the incidence of hepatitis flare, HBV reactivation, hepatitis B surface antigen (HBsAg) seroclearance or seroreversion in patients with current or past HBV infection who had received immunotherapy. METHODS This was a territory-wide observational cohort study in Hong Kong. We identified patients through electronic medical records based on the prescriptions of immune checkpoint inhibitors from July 1, 2014, to December 31, 2019. Patients who were HBsAg positive or HBsAg negative with results for antibody to hepatitis B surface or core antigen (anti-HBs or anti-HBc) were included. RESULTS A total of 990 patients (397 HBsAg-positive, 593 HBsAg-negative with 482 anti-HBc and/or anti-HBs positive, and 111 both anti-HBc and anti-HBs negative) were identified. All of HBsAg-positive and 15.9% HBsAg-negative patients were put on oral antiviral treatment. Hepatitis flare (alanine aminotransferase >2 times of the upper limit of normal) occurred in 39.3% HBsAg-positive and 30.4% HBsAg-negative patients. High baseline alanine aminotransferase and combination of immunotherapy increased the risk of hepatitis. HBV reactivation (≥2 log increase in HBV DNA from baseline) occurred in 2 HBsAg-positive patients; HBsAg seroclearance and seroreversion was observed in 1 HBsAg-positive and 1 HBsAg-negative patient, respectively (

Background & Aims Antiviral treatment is known to improve survival in patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). Yet, the treatment uptake in CHB patients remains low. We aimed to report the secular trend in antiviral treatment uptake from 2007–2017, and to compare the effect of different nucleos(t)ide analogue (NA) initiation times (before vs. after HCC diagnosis) on survival. Methods A 3-month landmark analysis was used to compare overall survival in patients not receiving NA treatment (i.e. no NA), patients receiving NAs after their first HCC treatment (i.e. post-HCC NA), and patients receiving NAs ≤3 months before their first HCC treatment (i.e. pre-HCC NA). A propensity score-weighted Cox proportional hazards model was used to balance clinical characteristics between the 3 groups and to estimate hazard ratios (HRs). Results The uptake of antiviral treatment in HCC patients increased from 47.3% in 2007 to 98.3% in 2017. The pre-HCC NA group contributed mostly to the uptake rate, which increased from 72.7% to 96.0% in the past decade. In addition, 3,843 CHB patients (407 no NA; 2,932 pre-HCC NA; 504 post-HCC NA) with HCC, receiving at least 1 type of HCC treatment, were included in the analysis. Lack of NA treatment at the time of HCC diagnosis increased the risk of death (weighted HR 3.05; 95% CI 2.70–3.44; p, Graphical abstract, Highlights • Antiviral treatment improves survival in patients with chronic hepatitis B-related HCC. • The uptake of antiviral treatment in HCC patients was suboptimal in the past (47.3% in 2007), but dramatically improved to 98.3% in 2017. • The timing of antiviral treatment (before or after HCC occurrence) does not matter that much in terms of patient survival. • Antivirals should be started soon after HCC has been diagnosed in patients with chronic hepatitis B who are not already on them.

Hepatitis B core-related antigen (HBcrAg) is a novel serum viral marker. Recent studies showed that its level correlates with the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to evaluate the accuracy of serum HBsAg and HBcrAg levels at baseline to predict HCC. 1400 CHB patients who received nucleos(t)ide analogues (NA) treatment since December 2005 were included. Their stored serum samples at baseline were retrieved to measure HBsAg and HBcrAg levels. The primary endpoint was the cumulative incidence of HCC. 85 (6.1%) patients developed HCC during a mean (± SD) follow-up duration of 45 ± 20 months. Serum HBcrAg level above 2.9 log10 U/mL at baseline was an independent factor for HCC in hepatitis B e antigen (HBeAg)-negative patients by multivariable analysis (adjusted hazard ratio 2.13, 95% CI 1.10–4.14, P = 0.025). HBcrAg above 2.9 log10 U/mL stratified the risk of HCC in HBeAg-negative patients with high PAGE-B score (P = 0.024 by Kaplan–Meier analysis), and possibly in cirrhotic patients (P = 0.08). Serum HBsAg level did not show any correlation with the risk of HCC in all patients or any subgroups. Serum HBcrAg level predicts the risk of HCC accurately in NA-treated HBeAg-negative CHB patients.

Thiazolidinediones (TZDs) improve glycaemic control and ameliorate liver steatosis, inflammation and fibrosis in patients with fatty liver disease. We aimed to study the impact of TZD and glycaemic control on the risk of hepatocellular carcinoma (HCC) and hepatic events in diabetic patients with chronic hepatitis B (CHB). We performed a retrospective cohort study on diabetic patients with CHB in 2000-2017 using a territory-wide electronic healthcare database in Hong Kong. Diabetes mellitus was identified by use of any antidiabetic medication, haemoglobin A1c (HbA1c ) ≥6.5%, fasting glucose ≥7 mmol/L in two measurements or ≥11.1 mmol/L in one measurement and/or diagnosis codes. Use of antidiabetic medications was modelled as time-dependent covariates. Of 28 999 diabetic patients with CHB, 3963 (13.7%) developed liver-related events (a composite endpoint of HCC and hepatic events) at a median (interquartile range) follow-up of 7.1 (3.7-11.8) years; 1153 patients received TZD during follow-up. After adjusted for important confounders, TZD use was associated with a reduced risk of liver-related events (adjusted hazard ratio [aHR] 0.46, 95% confidence interval [CI] 0.24-0.88; P = .019). Similar trends were observed in HCC (aHR 0.57) and hepatic events (aHR 0.35) separately. Compared to HbA1c of 6.5% at baseline, patients with HbA1c ≥7% had an increased risk of liver-related events; the risk further increased in 5795 (20.0%) patients with HbA1c ≥9% at baseline (aHR 1.14, 95% CI 1.04-1.26; P = .006). TZD use is associated with a lower risk of liver-related events in diabetic patients with CHB. Liver-related events are more common in patients with high HbA1c levels.

Background and aim Male sex is a risk factor for hepatocellular carcinoma (HCC). Diabetes mellitus (DM) is associated with a doubled risk of HCC in patients with chronic hepatitis B (CHB). We examined the relationship between serum total testosterone and HCC risk in male CHB patients with DM. Methods We performed a retrospective cohort study of male CHB patients with DM between 2000 and 2017 using a territory-wide electronic health-care database in Hong Kong. DM was defined by use of anti-diabetic medications, hemoglobin A1c ≥ 6.5%, and/or fasting glucose ≥ 7 mmol/L in two measurements or ≥ 11.1 mmol/L in one measurement. Results Of 928 male CHB patients with DM, 83 (8.9%) developed HCC at a median (interquartile range) of 10.7 (6.1-14.6) years. Higher testosterone was associated with an elevated risk of HCC (adjusted hazard ratio [aHR] per 1 SD increase 1.23, 95% confidence interval [CI] 1.03-1.46, P = 0.024). The upper tertile of testosterone (aHR 1.86, 95% CI 1.02-3.39, P = 0.043), but not middle tertile (aHR 0.84, 95% CI 0.41-1.69 P = 0.620), was associated with a higher risk of HCC than the lower tertile. The cumulative incidence (95% CI) of HCC at 5, 10, and 15 years was 4.4% (2.5-7.2%), 12.4% (8.7-16.7%), and 19.1% (14.2-24.5%), respectively, in patients in the upper tertile of testosterone. By subgroup analysis, the association between testosterone and HCC was stronger in patients aged ≥ 50 years and those not receiving antiviral therapy. Conclusion Higher serum testosterone is associated with a higher incidence of HCC in male CHB patients with DM.

Background The rates of hepatitis B surface antigen (HBsAg) seroclearance after stopping nucleos(t)ide analogues (NA) in European (19% in 2 years) and Asian (13% in 6 years) patients with chronic hepatitis B (CHB) vary dramatically. We evaluated the incidence of hepatitis flare and HBsAg seroclearance in hepatitis B e antigen (HBeAg)-negative Chinese CHB patients who had stopped NA. Methods This was a territory-wide retrospective study in Hong Kong. We identified HBeAg-negative CHB patients from January 2000 to December 2017 who had stopped NA treatment for more than 3 months. Hepatitis flare was defined as ALT >2×ULN. Results The 1076 patients were predominantly middle-aged men (mean age 52 years, male 74.8%) when starting NA; they stopped NA after 82 ± 35 months of treatment. At 44.3 ± 24.6 months after stopping NA, 147 (13.6%) patients had hepatitis flare, which led to resumption of NA; whereas 77 (7.2%) patients had flare but did not resume NA. Decompensation occurred in 7/914 (0.8%) patients. A total of 695 (64.6%) patients remained on NA treatment at the last visit. Eleven patients had achieved HBsAg seroclearance (6 of them had hepatitis flare and 1 of these 6 patients achieved HBsAg seroclearance after NA was restarted). Hepatic events developed in 75/695 (10.8%) patients who had NA resumed vs 43/381 (11.3%) patients who did not resume NA (P = .677). Conclusions Hepatitis flare and retreatment were common in HBeAg-negative CHB patients who stopped NA treatment; whereas HBsAg seroclearance rarely occurred. Stopping NA to achieve functional cure should not be recommended at this moment.

Patients with chronic hepatitis B (CHB) are aging because of improved survival under better health care. This has an important implication on the choice of antiviral treatment (AVT), given that long-term safety would be a concern in the presence of multiple comorbidities. We aimed to determine the prevalence of key comorbidities and concomitant medications in a territory-wide CHB cohort in Hong Kong in 2000-2017. CHB patients who have been under the care at primary, secondary, and tertiary medical centers in the public sector were identified through the Clinical Data Analysis and Reporting System of the Hospital Authority, Hong Kong. The demographics and prevalence of key comorbidities, including diabetes mellitus, hypertension, chronic kidney disease, osteopenia/osteoporosis based on diagnosis codes, relevant medications, and/or laboratory parameters, were determined according to CHB patients' first appearance in four time periods: 2000-2004, 2005-2009, 2010-2013, and 2014-2017. In the final analysis, 135,395 CHB patients were included; the mean age increased with time: 41 ± 15 years in 2000-2004; 46 ± 17 years in 2005-2009; 51 ± 16 years in 2010-2013; and 55 ± 15 years in 2014-2017. There was a trend of increasing prevalence of several common comorbidities over the four periods: hypertension 25.5%, 23.8%, 27.2%, and 28.6%; diabetes mellitus 10.6%, 12.5%, 16.1%, and 20.1%; cardiovascular disease 12.5%, 16.9%, 20.9%, and 22.2%; and malignancy 7.0%, 13.2%, 17.3%, and 23.6%, respectively (all P < 0.001). Conclusion: CHB patients are getting older with increasing prevalence of common comorbidities. These comorbidities should be taken into account when choosing AVT.

Despite all these exciting developments, there remain some unmet needs in the management for patients with chronic hepatitis B (CHB). As majority of CHB patients are going to use oral nucleos(t)ide analogues (NAs) for decades, Safety profile of NAs is of no doubt an important issue. The newest nucleotide analogue tenofovir alafenamide is potent in terms of viral suppression, together with favourable renal and bone safety profile. Biochemical response as reflected by alanine aminotransferase (ALT) normalization is recently found to be prognostically important. Patients who achieved ALT normalization have reduced the risk of hepatic events by 49%. Functional cure as reflected by hepatitis B surface antigen seroclearance not only implies patients may stop NA treatment, it also confers to a reduced risk of hepatocellular carcinoma and other hepatic events. Hence functional cure should be the ultimate treatment goal in CHB patients. Preemptive antiviral treatment may reduce mother-to-child transmission of hepatitis B virus, especially if birth dose of vaccination cannot be given in the first two hours after delivery. Lastly, despite the currently first-line NAs have high-genetic barrier to drug resistance mutations, there are still are many patients who were previously treated with low barrier of resistance including lamivudine, telbivudine or adefovir dipivoxil which could lead to antiviral resistance and affecting the choice of NAs.

We previously demonstrated the possible noninferiority of a screening strategy for varices guided by liver and spleen stiffness measurement (LSSM) compared to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. We now report the long-term outcome of the patients recruited in this trial for incident variceal bleeding and other hepatic events. This was a prospective follow-up study of a noninferiority, open-label, randomized controlled trial (NCT02024347) of 548 adult patients with known chronic liver diseases, radiological evidence of liver cirrhosis, and compensated liver function. The primary outcome of this prospective study was incident variceal bleeding confirmed with upper endoscopy. Between October 2013 and June 2016, 548 patients were randomized to an LSSM arm (n = 274) and a conventional arm (n = 274). Patients in both study arms were predominantly middle-aged men (mean age 59 years, male 68.9%) with viral hepatitis-related cirrhosis (85%). Upper endoscopy examination was performed in 127 (46.4%) patients in the LSSM arm and 263 (96.0%) in the conventional arm. During the follow-up period of 41.3 ± 12.6 months, 12/274 patients in the LSSM arm (4.4%) and 11/274 in the conventional arm (4.0%) developed incident variceal bleeding (log-rank test P = 0.724). The incident rates of hepatic events were also similar in both arms (P = 0.327). Conclusions: Patients with liver cirrhosis who had undergone LSSM-guided variceal screening were at similarly low risk of incident variceal bleeding in the future; patients with cirrhosis may first have LSSM measured to save up to half of the upper endoscopy examinations.