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 (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).
Conclusions
ACEI, rather than ARB, treatment is associated with a lower risk of LREs in NAFLD patients, especially among those with CKD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Data on serial liver biochemistries of patients infected by different human coronaviruses (HCoVs) are lacking. The impact of liver injury on adverse clinical outcomes in coronavirus disease 2019 ...(COVID-19) patients remains unclear.
This was a retrospective cohort study using data from a territory-wide database in Hong Kong. COVID-19, severe acute respiratory syndrome (SARS) and other HCoV patients were identified by diagnosis codes and/or virological results. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2 × upper limit of normal (ie, 80 U/L). The primary end point was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation and/or death.
We identified 1040 COVID-19 patients (mean age 38 years, 54% men), 1670 SARS patients (mean age 44 years, 44% men) and 675 other HCoV patients (mean age 20 years, 57% men). ALT/AST elevation occurred in 50.3% SARS patients, 22.5% COVID-19 patients and 36.0% other HCoV patients. For COVID-19 patients, 53 (5.1%) were admitted to ICU, 22 (2.1%) received invasive mechanical ventilation and 4 (0.4%) died. ALT/AST elevation was independently associated with primary end point (adjusted OR (aOR) 7.92, 95% CI 4.14 to 15.14, p<0.001) after adjusted for albumin, diabetes and hypertension. Use of lopinavir-ritonavir ±ribavirin + interferon beta (aOR 1.94, 95% CI 1.20 to 3.13, p=0.006) and corticosteroids (aOR 3.92, 95% CI 2.14 to 7.16, p<0.001) was independently associated with ALT/AST elevation.
ALT/AST elevation was common and independently associated with adverse clinical outcomes in COVID-19 patients. Use of lopinavir-ritonavir, with or without ribavirin, interferon beta and/or corticosteroids was independently associated with ALT/AST elevation.
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 < 0.001), but not current (aHR, 1.29; 95% CI, 0.61‐2.70; P = 0.507) or past (aHR, 0.90; 95% CI, 0.56‐1.46; P = 0.681) HBV infection, was associated with mortality. Use of corticosteroid, antifungal, ribavirin, or lopinavir–ritonavir (adjusted OR aOR, 2.55‐5.63), but not current (aOR, 1.93; 95% CI, 0.88‐4.24; P = 0.102) or past (aOR, 1.25; 95% CI, 0.62‐2.55; P = 0.533) HBV infection, was associated with acute liver injury.
Conclusion
Current or past HBV infections were not associated with more liver injury and mortality in COVID‐19.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background and aims
In non‐alcoholic fatty liver disease (NAFLD), fibrosis is the strongest prognostic factor and can be assessed by non‐invasive methods. We evaluated the ability of liver stiffness ...measurement (LSM) to predict overall survival and liver, cardiovascular and oncologic complications.
Methods
We prospectively collected data on 2251 consecutive NAFLD patients (mean age 59 years, male 53%, mean body mass index 28 kg/m2) in two centres. At inclusion, all patients had LSM, clinical and biological evaluation. During follow‐up, we recorded cardiovascular events, cancers, liver complications, liver transplantation and death. The primary endpoint was overall survival. Survival curves according to LSM were first performed using Kaplan‐Meier method for the primary endpoint, and Aalen‐Johansen method for secondary outcomes to take into account competitive risks. In a second step, a Cox proportional hazard model analysis was done to identify independent predictors of overall survival.
Results
Median follow‐up was 27 months IQR: 25‐38. Fifty‐five patients died and three patients had liver transplantation. Overall survival significantly decreased as baseline LSM increased. Twenty‐one patients (0.9%) had a liver event, 142 (6.3%) developed cancer (excluding HCC) and 151 (6.7%) had a cardiovascular event during follow‐up. By multivariable analysis, independent predictors of overall survival were as follows: baseline LSM (adjusted HR (aHR) = 2.85 1.65‐4.92, P = .0002), age (aHR = 1.11 1.08‐1.13, P < .0001) and male sex (aHR = 2.05 1.17‐3.57, P = .012). Patients with elevated LSM were also more likely to develop cardiovascular, and liver events but not other cancers.
Conclusion
LSM can be used to predict survival, cardiovascular and liver complications in NAFLD patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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.
Diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and its severity. However, it is difficult to screen every diabetic patient for NAFLD because of the large number of patients. In a study of 7028 patients with NAFLD and type 2 diabetes from Hong Kong, we showed that the vast majority of patients developed liver‐related complications after the age of 50 years. In contrast, liver‐related events increased linearly with the duration of diabetes with no threshold effect. Our study suggests that screening for liver disease should be based on age instead of the duration of diabetes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Background
In clinical trials involving patients with preserved renal function, tenofovir disoproxil fumarate (TDF) use was associated with mild renal impairment in 1% of patients.
Aim
To ...compare serial renal function of entecavir (ETV)‐treated, TDF‐treated, and untreated patients with chronic hepatitis B.
Methods
We studied the risk of chronic kidney disease (CKD) progression in a territory‐wide cohort of patients with chronic hepatitis B without treatment and of those on ETV or TDF treatment. Estimated glomerular filtration rate (eGFR) was determined by the CKD Epidemiology Collaboration equation and was classified into five CKD stages. CKD progression, defined as an increase of at least one CKD stage, was compared among treated and untreated patients.
Results
After propensity score matching, 2254 ETV‐treated, 2254 TDF‐treated, and 2254 untreated patients were included in the analysis. Their mean baseline eGFR was 90.3 ± 19.6, 91.3 ± 20.6, and 92.2 ± 20.0 mL/min/1.73 m2, respectively. During a mean follow‐up of 2.4 ± 1.5 years, 639 ETV‐treated, 706 TDF‐treated, and 564 untreated patients exhibited CKD progression ≥1 stage. The 5‐year cumulative incidence (95% confidence interval) of CKD progression was 43% (40%‐46%) in ETV‐treated, 48% (45%‐51%) in TDF‐treated, and 43% (39%‐47%) in untreated patients (reference group), respectively (P = 0.267 and <0.001, respectively). The number of patients who exhibited CKD progression ≥2 stages was 92 (4.1%) in the untreated cohort, 95 (4.2%) in the ETV‐treated cohort, and 51 (2.3%) in the TDF‐treated cohort.
Conclusions
The use of TDF was associated with mild renal impairment in a minority of patients; those treated with ETV had a similar risk compared to untreated patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background
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.
Methods
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.
Results
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 log
10
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.
Conclusion
Serum HBcrAg level predicts the risk of HCC accurately in NA-treated HBeAg-negative CHB patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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.
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%).
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.
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