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.

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Background and Aims: 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. Approach and Results: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

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 (<1%). DISCUSSION: Hepatitis flare occurs in approximately 40% of HBsAg-positive patients and 30% of HBsAg-negative patients during immunotherapy. HBV reactivation, HBsAg seroclearance, and HBsAg seroreversion are rare. Current or past HBV infection has no impact on the emergence of hepatic flare associated with immunotherapy.

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.

Background and Aims 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. Approach and Results 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 of <40, 40–50, and ≥50 years, respectively. Similarly, 3.1%, 5.1%, and 91.8% of patients developed cirrhosis at the age of <40, 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. Conclusions 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.

Background and Aims: 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. Approach and Results: 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 personyears 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. Conclusion: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.

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.