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, SAZU, 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, SAZU, 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, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background
Lamivudine and entecavir reduce hepatic events and death in chronic hepatitis B (CHB) patients with cirrhosis, but the impact of tenofovir disoproxil fumarate (TDF) is less well ...studied.
Aim
To investigate the effectiveness of TDF therapy in CHB patients with cirrhosis.
Methods
We studied TDF‐treated and untreated CHB patients with cirrhosis from three tertiary centres. TDF cohort included consecutive patients who received TDF for ≥12 months while the untreated cohort were historical controls receiving routine clinical care prior to the availability of anti‐viral therapy. The primary outcome was 5‐year cumulative probability of hepatocellular carcinoma (HCC) with secondary outcomes being hepatic decompensation and death or liver transplantation (LT).
Results
A total of 1088 (291 untreated and 797 TDF‐treated) patients were included in the study. Five‐year cumulative probabilities in untreated vs TDF‐treated cohorts were 14.9% vs 9.8% for HCC (P = .07), 22.3% vs 5.9% for decompensation (P < .01) and 13.1% vs 1.1% for death or LT (P < .01) respectively. On multivariable Cox regression, TDF treatment was independently associated with reduced risks of HCC (adjusted hazard ratio aHR 0.46, P < .01), decompensating events (aHR 0.28, P = .01) and death or LT (aHR 0.06, P < .01). On sensitivity analyses, these risk reductions with TDF treatment were consistently demonstrated regardless of severity of liver disease and prior anti‐viral treatment. TDF treatment led to sustained improvements in most validated prognostic scores for predicting HCC, decompensation and death.
Conclusions
Compared to untreated patients, TDF treatment reduces the risks of HCC, hepatic decompensation and death in CHB patients with cirrhosis at 5 years.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, 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
LINKED CONTENT
This article is linked to Kuo et al papers. To view these articles, visit
https://doi.org/10.1111/apt.17637
and
https://doi.org/10.1111/apt.17742
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, 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, SAZU, SBCE, SBMB, UL, UM, UPUK
LINKED CONTENT
This article is linked to Fan et al and Fan & Hou papers. To view these articles, visit https://doi.org/10.1111/apt.16469 and https://doi.org/10.1111/apt.16548
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK