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Enhanced liver fibrosis (ELF) score is a noninvasive assessment for liver fibrosis. We aimed to evaluate the performance of changes in ELF score 3 years apart in combination with liver stiffness measurement (LSM)‐hepatocellular carcinoma (HCC) score to predict HCC in chronic hepatitis B (CHB) patients. This is a prospective cohort study. Patients who underwent transient elastography (TE) examinations and at intermediate or high risk of HCC defined by LSM‐HCC score were invited to repeat the examination about 3 years later. Their serum samples at these two time points were retrieved to assess the ELF score changes. The primary endpoint was HCC. There were 445 CHB patients (males: 73.9%; mean age: 51.6 ± 10.3 years) who received two TE examinations and ELF scores. Among them, 252 (56.6%) and 193 (43.4%) patients were at intermediate and high HCC risk at first assessment defined by LSM‐HCC score, respectively. Kaplan–Meier analysis showed that the changes in ELF score could stratify the HCC risk in both intermediate‐ and high‐risk patients defined by LSM‐HCC score (p < 0.001 for intermediate‐risk group; p = 0.011 for high‐risk group). Patients remained having mild or moderate fibrosis at both assessments had the lowest risk of HCC (4.0%), followed by patients with fibrosis regressed (11.3%; p = 0.014) during a mean follow‐up of 163 months. Patients remained having or progressed to severe fibrosis were at highest risk of HCC (> 20%). Consistent findings were demonstrated in patients at both intermediate and high risk of HCC defined by LSM‐HCC score. Dynamic changes in ELF score provided additional value to LSM‐HCC score for stratifying HCC risk in CHB patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Risk of hepatocellular carcinoma (HCC) persists after hepatitis B surface antigen (HBsAg) seroclearance in patients with chronic hepatitis B (CHB). Aims: To identify risk factors and construct a predictive model for HCC development. Methods: We retrospectively analysed patients with CHB with HBsAg seroclearance. Primary outcome was HCC development. Factors identified from a multivariate Cox model in the training cohort, consisting of 3476 patients from two Korean hospitals, were used to construct the prediction model. External validation was performed using data from 5255 patients in Hong Kong. Results: In the training cohort, HCC occurred in 102 patients during 24,019 person‐years of observation (0.43%/year). Risk scores were assigned to cirrhosis (C:3), age ≥50 years (A:2), male sex (M:3) and platelet count <150,000/mm3 (P:1); all were independently associated with an increased risk of HCC in multivariate analysis The time‐dependent area under receiver operating characteristic curves for 5, 10 and 15 years in the training and validation cohorts were 0.782, 0.817 and 0.825 and 0.785, 0.771 and 0.796, respectively. In the validation cohort, 85 patients developed HCC (0.24%/year). The corresponding incidence of HCC in the low‐, intermediate‐ and high‐risk groups were 0.07%, 0.37% and 0.90%, respectively. Conclusions: The CAMP‐B score (cirrhosis, age ≥50 years, male sex and platelet count <150,000/mm3/L) was significantly associated with HCC development after HBsAg seroclearance. CAMP‐B score can be easily implemented in real‐world clinical practice and helps stratify HCC risk in patients with CHB following HBsAg seroclearance. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction‐associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N‐terminal propeptide of collagen type 3 (PRO‐C3) is a biomarker of advanced fibrosis in MAFLD and PRO‐C3 may be involved in renal fibrosis. We aimed to use PRO‐C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD–CKD). Methods: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy‐confirmed MAFLD were included. Serum PRO‐C3 concentration was measured and regression analyses were performed to examine associations with MAFLD–CKD. A derivative algorithm for MAFLD–CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. Results: The study included two Asian cohorts (n = 180 with MAFLD–CKD; mean‐eGFR: 94.93 mL/min/1.73 m2; median‐urinary albumin‐to‐creatinine ratio: 6.58 mg/mmol). PRO‐C3 was associated with the severity of MAFLD‐CKD and independently associated with MAFLD–CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08–1.23, p <.001). A new non‐invasive score (termed PERIOD) including PRO‐C3 efficiently predicted MAFLD‐CKD (AUROC =.842, 95% CI:.805–.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC =.807, 95% CI:.691–.893) with similar results in all patient subgroups. In the MAFLD–CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO‐C3‐based ADAPT with the Agile 3+ scores (AUROC =.90, 95% CI:.836–.964). Conclusions: The PERIOD score is helpful for accurately predicting the risk of MAFLD–CKD. PRO‐C3 can also be used to assess liver fibrosis in people with MAFLD–CKD. [ABSTRACT FROM AUTHOR]

Key Points: Question: What are the clinical implications of single or serial measurements of vibration–controlled transient elastography (VCTE)–based scores in metabolic dysfunction-associated steatotic liver disease (MASLD)? Findings: In this cohort study of 16 603 patients with MASLD who underwent VCTE examination, the VCTE-based scores outperformed most noninvasive tests and were at least similar if not better than histologic fibrosis staging in predicting liver-related events. On repeated testing, the scores were largely stable, and patients with improvement in the scores had substantial reduction in the risk of liver-related events. Meaning: Findings of this study suggest that the VCTE-based scores are generally accurate for predicting liver-related events, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis. Importance: Metabolic dysfunction–associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)–based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis. This cohort study evaluates the prognostic implications of baseline and repeated vibration-controlled transient elastography scores and liver stiffness measurements in a large cohort of patients with metabolic dysfunction–associated steatotic liver disease. [ABSTRACT FROM AUTHOR]

Background & Aims: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B‐related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction‐associated steatotic liver disease (MASLD; formerly NAFLD)‐related fibrosis diagnosis and establish a machine‐learning (ML) model to improve the diagnostic performance. Methods: A total of 946 biopsy‐proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). Results: The AUROCs of aMAP versus fibrosis‐4 index (FIB‐4) and aspartate aminotransferase‐platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut‐off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB‐4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM‐plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM‐plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM‐plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). Conclusions: The aMAP score is capable of diagnosing MASLD‐related fibrosis. The LSM‐plus model could accurately identify MASLD‐related cirrhosis and advanced fibrosis. [ABSTRACT FROM AUTHOR]

Context Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce. Objective We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM. Method PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool. Results A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (−0.09%/mg), weight (−2.2 kg/mg), and TDI (−4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (−0.51% vs −0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse. Conclusion Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits. [ABSTRACT FROM AUTHOR]

Summary: Background: Early screening may prevent fibrosis progression in metabolic‐associated fatty liver disease (MAFLD). Aims: We developed and validated MAFLD fibrosis score (MFS) for identifying advanced fibrosis (≥F3) among MAFLD patients. Methods: This cross‐sectional, multicentre study consecutively recruited MAFLD patients receiving tertiary care (Malaysia as training cohort [n = 276] and Hong Kong and Wenzhou as validation cohort [n = 431]). Patients completed liver biopsy, vibration‐controlled transient elastography (VCTE), and clinical and laboratory assessment within 1 week. We used machine learning to select 'highly important' predictors of advanced fibrosis, followed by backward stepwise regression to construct MFS formula. Results: MFS was composed of seven variables: age, body mass index, international normalised ratio, aspartate aminotransferase, gamma‐glutamyl transpeptidase, platelet count, and history of type 2 diabetes. MFS demonstrated an area under the receiver‐operating characteristic curve of 0.848 [95% CI 0.800–898] and 0.823 [0.760–0.886] in training and validation cohorts, significantly higher than aminotransferase‐to‐platelet ratio index (0.684 [0.603–0.765], 0.663 [0.588–0.738]), Fibrosis‐4 index (0.793 [0.735–0.854], 0.737 [0.660–0.814]), and non‐alcoholic fatty liver disease fibrosis score (0.785 [0.731–0.844], 0.750 [0.674–0.827]) (DeLong's test p < 0.05). MFS could include 92.3% of patients using dual cut‐offs of 14 and 15, with a correct prediction rate of 90.4%, resulting in a larger number of patients with correct diagnosis compared to other scores. A two‐step MFS‐VCTE screening algorithm demonstrated positive and negative predictive values and overall diagnostic accuracy of 93.4%, 89.5%, and 93.2%, respectively, with only 4.0% of patients classified into grey zone. Conclusion: MFS outperforms conventional non‐invasive scores in predicting advanced fibrosis, contributing to screening in MAFLD patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Baveno VII was proposed for non‐invasive identification of clinically significant portal hypertension. However, a substantial proportion of patients is classified in the grey zone (i.e., liver stiffness 15–24.9 kPa and/or platelet count <150 × 109/L). Aims: To evaluate the risk and predictors of hepatic decompensation in patients in the grey zone, and to determine the prognostic role of spleen stiffness measurement. Methods: We included prospective cohorts (from Hong Kong, Korea and France) of patients who had undergone transient elastography examination for chronic liver disease. We estimated risk of hepatic decompensation using competing risk regression with hepatocellular carcinoma and non‐liver‐related death as competing events. Results: We identified 2763 patients with compensated advanced chronic liver disease (cACLD). There were 1243 (44.9%) and 536 (19.4%) patients in the Baveno VII grey zone and high‐risk groups, respectively. The cumulative incidence of decompensation at 5 years was significantly different among low‐risk (0.6% [95% CI: 0.2%–1.3%]), grey zone 4.2% (95% CI: 3.1%–5.4%) and high‐risk groups (11.4% [95% CI: 8.7%–14.6%]). By competing risk analysis, aetiology of liver disease (alcohol‐related liver disease), albumin–bilirubin score and alkaline phosphatase level were independently associated with decompensation among patients in the grey zone. The combination of Baveno VII and spleen stiffness significantly reduced patients classified into grey zone (12.8% in cACLD patients), while maintaining high discrimination of decompensation in low‐ and high‐risk groups. Conclusions: Patients in grey zone of Baveno VII criteria remain at high risk of hepatic decompensation. Clinical risk factors and spleen stiffness can further stratify the risk in such patients. [ABSTRACT FROM AUTHOR]

Summary: Background: It is uncertain whether people with HIV infection have a higher incidence of hepatocellular carcinoma (HCC) than the general population. Aims: To compare the incidence of HCC between people infected with HBV and/or HCV with and without HIV Methods: We performed a retrospective population‐based cohort study, involving people with HBV and/or HCV infection from 2001 to 2018. The primary endpoint was incidence of HCC; secondary endpoint was all‐cause mortality. We performed Cox proportional hazard regression models to estimate the hazard ratios (HR) of HIV for the primary and secondary endpoints. Results: We identified 1374 people infected with HIV and 39,908 people without HIV with HBV and/or HCV infection. Among those with HIV, 654 (47.6%) had HBV, 649 (47.2%) HCV and 71 (5.2%) HBV‐HCV‐co‐infection; they were younger, and had a higher prevalence of HCV and a lower prevalence of cirrhosis. The incidence rate estimates of HCC were, respectively, 1.5 (95% CI: 0.8–2.5) and 7.6 (95% CI 7.3‐8.0) per 1000 person‐years for those with and without HIV infection. Using multivariate Cox proportional hazard regression models, among people with HBV, HIV was associated with lower risk of HCC (adjusted HR: 0.376, 95% CI: 0.201–0.704, p = 0.01) and death (adjusted HR: 0.692, 95% CI: 0.552–0.867, p = 0.007). Risks of HCC were similar for HCV and HBV‐HCV co‐infection for people with and without HIV. Conclusions: Among individuals with HBV infection, the Incidence of HCC was lower in those with HIV. For HCV infection, incidence of HCC was similar between those with and without HIV. [ABSTRACT FROM AUTHOR]

Background: Baveno VII criteria for predicting varices needing treatment (VNT) have not been tested in hepatocellular carcinoma (HCC) population. We evaluated Baveno VII consensus for VNT in HCC patients of different stages according to Barcelona Clinic Liver Cancer (BCLC) stages undergoing curative hepatectomy. Methods: This was a prospective cohort study of patients with HCC. Patients underwent transient elastography examination before HCC treatment and received at least one upper endoscopic examination afterwards. Patients were prospectively followed for clinical events including VNT. Results: Six hundred and seventy‐three patients (83.1% male, median age 62 years) with HCC of BCLC stage 0 (10%), A (57%), B (17%) and C (15%) were recruited and followed for 47 months. The median (range) LSM was 10.5 (6.9–20.4) kPa; 74% had LSM ≤ 20 kPa and 58% had platelet count ≥150 × 10/L, respectively. VNT occurred in 51 (7.6%) patients. In patients who fulfilled Baveno VII criteria, that is, LSM ≤ 20 kPa and platelet count above 150 × 10/L, only 11 (1.6%) patients had VNT. In all BCLC stages of HCC, the proportion of patients with VNT was below 5%, which support the validity and applicability of Baveno VII criteria in all BCLC stages of HCC. Conclusions: The Baveno VII criteria are valid and applicable in HCC patients undergoing curative hepatectomy for selecting patients to undergo screening endoscopy for VNT. The validity was consistent across different BCLC stages of HCC. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to determine the trends in risk factor control and treatment among patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) in 2000-2020. Methods: We conducted a territory-wide cohort study of adult patients with NAFLD and T2D diagnosed between 1 January 2000 and 31 July 2021 in Hong Kong. T2D was defined by use of any anti-diabetic agents, laboratory tests and/or diagnosis codes. Results: This study included 16,084 patients with NAFLD and T2D (mean age, 54.8 ± 12.0 years; 7124 male [44.3%]). The percentage of patients achieving individualised haemoglobin A1c (HbA1c) targets increased from 44.5% (95% confidence interval [CI], 42.9-46.1) to 64.8% (95% CI, 64.1-65.5), and percentage of patients achieving individualised low-density lipoprotein-cholesterol (LDL-C) targets increased from 23.3% (95% CI, 21.9-24.7) to 54.3% (95% CI, 53.5-55.1) from 2000-2005 to 2016-2020, whereas percentage of patients achieving blood pressure control (<140/90 mm Hg) remained static at 53.1-57.2%. Combination therapy for diabetes increased, especially among those with poor glycaemic control, but there was no increase in combination therapy for hypertension. Fewer cirrhotic patients achieved blood pressure control and individualised LDL-C targets, but they were more likely to achieve individualised HbA1c targets than non-cirrhotics. Metformin and statins were underused in cirrhotic patients. Younger patients (18-44 years) were less likely to achieve individualised HbA1c targets than middle-aged (45-64 years) and older ones (=65 years). Conclusions: From 2000 to 2020, glycaemic and lipid control improved significantly, whereas blood pressure control remained static among patients with NAFLD and T2D. [ABSTRACT FROM AUTHOR]