The aspartate aminotransferase-to-platelet ratio index (APRI) is an effective non-invasive marker for chronic liver dysfunction. Given that heat stroke patients often suffer from poor prognosis due to multi-organ involvement, with liver injury and coagulation dysfunction being of particular concern, this study aims to investigate whether APRI can comprehensively reflect liver injury and coagulation dysfunction in heat stroke patients and explore its relationship with 28-day mortality.

This retrospective study analysed electronic medical records from patients treated at 57 grade A tertiary hospitals in China from May 2005 to May 2024. The primary outcome was 28-day mortality, and the secondary outcome was 7-day mortality. Restricted cubic splines (RCS) were utilized to visualize the relationship between APRI and 28-day mortality risk. The independent association between APRI and outcomes was assessed using Cox proportional hazards models, with multivariable analyses controlling for confounding factors. The predictive ability of APRI for outcomes was evaluated using receiver operating characteristic (ROC) curves.

A total of 450 eligible patients were included, with 71 deaths occurring within 28 days. RCS analysis showed a positive correlation between APRI and 28-day mortality. Participants were divided into higher (APRI ≥ 15.14) and lower (APRI < 15.14) APRI groups. Cox proportional hazards models indicated that individuals with higher APRI had a significantly increased 28-day mortality rate (HR 5.322, 95% confidence interval [CI] 2.642-10.720, p < 0.0001). Subgroup and interaction analyses confirmed the robustness of the core findings. Additionally, the areas under the ROC (AUROC) for APRI predicting 28-day mortality was 0.823 (95% CI 0.772-0.875), significantly higher than the AST to ALT ratio (0.526, 95% CI 0.448-0.605) and total bilirubin (0.694, 95% CI 0.623-0.765).

APRI is an independent predictor of early mortality risk in heat stroke.

Pien Tze Huang (PTH), a well-established traditional Chinese medicine compound, has exhibited anti-hepatic fibrosis properties both in vitro and in vivo animal models, but the randomized clinical trials to evaluate anti-hepatic fibrosis efficacy of PTH are deficient. Chronic hepatitis B (CHB) is a leading cause of hepatic fibrosis in China. Although antiviral therapies have demonstrated significant effectiveness in arresting the progression of fibrotic disease, complete regression of established fibrosis is limited to only a subset of treated patients.

To assess the efficacy of PTH in improving hepatic fibrosis in CHB patients.

We conducted a randomized, double-blind, placebo-controlled clinical trial involving 144 CHB patients with hepatic fibrosis. This study was carried out from September 2020 to April 2023. (Clinical Trials Registration: ChiCTR2000035128) METHODS: CHB patients with an Ishak score of 2-5 points were recruited from ten hospitals across China. Participants were randomized in 1:1 ratio to receive either oral PTH (0.6 g per dose, three times/day) or placebo for 48 weeks, in addition to the standard treatment of entecavir (0.5 mg/day). The primary endpoint was the change in Ishak score. Secondary outcomes included changes in Knodell HAI score, liver stiffness measurement, AST- to -platelet ratio index, Fibrosis-4 index and hepatic function indices.

Of the 144 randomized patients, 142 patients (71 in the PTH group and 71 in the placebo group) were included in the primary analysis. The PTH group exhibited lower Ishak score compared to the control group (2.37 ± 0.94 vs. 2.87 ± 1.04, F = 6.072, p = 0.015). Notably, in treatment-naive patients, the PTH group showed significant improvement in Ishak score post-treatment compared with the control group (2.13 ± 0.72 vs. 2.74 ± 1.07, F = 6.336, p = 0.014). However, no significant changes were observed in these parameters among patients already receiving antiviral therapy.

The combination of PTH and entecavir demonstrates significant improvement in hepatic fibrosis among CHB patients, especially those who are treatment-naive patients.

Bulevirtide (BLV) 2 mg/day is EMA approved for the treatment of compensated chronic HDV infection; however, real-world data in large cohorts of patients with cirrhosis are lacking.

Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day from September 2019 were included in a European retrospective multicenter real-world study (SAVE-D). Patient characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (hepatocellular carcinoma [HCC], decompensation, liver transplant) were assessed.

A total of 244 patients with HDV-related cirrhosis receiving BLV monotherapy for a median of 92 (IQR 71-96) weeks were included: at BLV start, median (IQR) age was 49 (40-58) years and 61% were men; median ALT, LSM and platelet count were 80 (55-130) U/L, 18.3 (13.0-26.3) kPa, and 94 (67-145) x103/mm3, respectively; 54% had esophageal varices, 95% Child-Pugh A cirrhosis, and 10% HIV coinfection; 92% were on nucleos(t)ide analogues; median HDV RNA and HBsAg were 5.4 (4.1-6.5) log10 IU/ml and 3.8 (3.4-4.1) log10 IU/ml, respectively. At weeks 48 and 96, virological, biochemical and combined responses were observed in 65% and 79%, 61% and 64%, 44% and 54% of patients, respectively. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Serum bile acid levels increased in most patients, but only 10% reported mild and transient pruritus, which was independent of bile acid levels. The week 96 cumulative risks of de novo HCC and decompensation were 3.0% (95% CI 2-6%) and 2.8% (95% CI 1-5%), respectively. Thirteen (5%) patients underwent liver transplantation (n = 11 for HCC, n = 2 for decompensation).

BLV 2 mg/day monotherapy for up to 96 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses increased over time, while the incidence of liver-related complications was low.

Bulevirtide 2 mg/day is EMA approved for the treatment of compensated chronic hepatitis delta; however, real-world data in large cohorts of patients with cirrhosis are lacking. Bulevirtide 2 mg/day monotherapy for up to 96 weeks was safe and effective (week 96: 79% virological, 64% biochemical and 54% combined response) in a large real-world cohort of patients with HDV-related cirrhosis, including patients with clinically significant portal hypertension. Liver function tests and liver stiffness improved, suggesting a potential clinical benefit in patients with advanced liver disease, while the incidence of de novo liver-related events (hepatocellular carcinoma and decompensation) was low during the 96-week study period.

Nonalcoholic fatty liver disease (NAFLD) cirrhosis is a significant health concern with a major impact on global morbidity and mortality. This study investigates the association of hemoglobin, albumin, lymphocyte, and platelet (HALP) with all-cause mortality, cardiovascular disease mortality, and cancer-related mortality in patients with NAFLD cirrhosis.

This retrospective cohort study used data from the National Health and Nutrition Examination Survey, assessing 11 550 adults. NAFLD cirrhosis was defined by a hepatic steatosis index greater than 36 and a NAFLD fibrosis score greater than 0.676 in participants without viral hepatitis or excessive alcohol use. The HALP score was categorized into low (<32), moderate (32-48.3), and high (>48.3). Logistic and weighted Cox regression analyses were conducted, along with subgroup and restricted cubic spline analyses.

Higher HALP scores were associated with lower all-cause mortality. Subgroup analyses revealed significant interactions with gender and age, showing a decreased risk of all-cause mortality in males and individuals aged 40 and above with higher HALP scores. A U-shaped relationship between HALP scores and all-cause mortality was observed.

The study demonstrates that HALP is associated with a lower risk of all-cause mortality in the NAFLD cirrhosis population, suggesting that HALP may be a useful predictor of mortality risk.

Liver fibrosis is a chronic fibrosing hepatic disorder following recurrent injury, characterized by the excessive accumulation of extracellular matrix. Early detection has a great clinical impact because 80-90% of hepatocellular carcinomas are known to develop in fibrotic or cirrhotic (end-stage fibrotic) livers. PET imaging with FAP ligands exhibited highly promising results in recent years to visualize fibrosis in various organs due to the crucial role of activated fibroblasts in fibrosing processes. However, still little is known about the efficacy of FAP imaging in liver fibrosis. Thus, we sought to investigate the potential of FAPI-PET in a cohort of oncological and non-oncological patients.

199 patients who underwent FAPI-PET/CT at the University Hospital of Heidelberg between July 2017 and July 2020 were retrospectively analyzed. The tracer uptake of the liver was analyzed and correlated with radiological and clinical parameters.

We observed a weak but significant negative correlation between the hepatic FAPI uptake and CT density (r = - 0.273, P < 0.001***). A positive correlation was observed between hepatic FAPI uptake and the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) (r = 0.183, P = 0.009**), an established surrogate for liver fibrosis. The liver SUV (standardized uptake value) mean and SUVmax of FAPI showed significant differences between groups of patients with low (< 0.5), middle (0.5-1.0) and higher (> 1.0) levels of APRI (both P < 0.001***).

These preliminary observational results suggest that FAPI-PET may be a viable non-invasive method to asses liver fibrosis.

Noninvasive and cost-effective markers are needed to replace esophagogastroduodenoscopy in the screening for severe esophagogastric varices (EGVs) and portal hypertensive gastropathy (PHG).

This study evaluated the performances of several commonly used fibrosis markers in assessing EGVs and PHG in cirrhosis patients.

Retrospective cohort study.

A series of 323 patients with cirrhosis were consecutively enrolled and endoscopically followed up until variceal eradication was achieved. The Fibrosis-4 (FIB-4) score, albumin-bilirubin (ALBI) index, aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI), gamma-glutamyl transpeptidase-to-platelet ratio (GPR), and Lok score were calculated for each patient upon first admission. The performances of these markers in assessing EGVs and PHG were determined.

In the screening for clinically relevant esophageal varices (CREVs), none of the markers showed a significant ability to differentiate CREVs from non-CREVs (P > .05). The AAR (area under the curve (AUC): 0.581, sensitivity: 52.0%, specificity: 66.1%, P = .033) and the GPR (AUC = 0.596, sensitivity: 64.0%, specificity: 50.0%, P = .033) fairly differentiated clinically relevant gastric varices (CRGVs) from non-CRGVs patients. Moreover, no correlation was noted between PHG and CREVs (r = .016, P = .778) or between PHG and CRGVs (r = -.024, P = .666). Furthermore, no difference in the severity of PHG before and after variceal eradication was detected (P = .224).

The studied markers revealed poor to no ability to assess EGVs or PHG. Hence, they cannot be used to substitute EGD in the screening for EGVs. Furthermore, endoscopic eradication of EGVs did not affect the severity of PHG.

Predictive capability of aspartate transaminase-to-platelet ratio index (APRI) in assessing liver fibrosis/cirrhosis. This study aims to evaluate the correlation between APRI scores and perioperative outcomes following robotic hepatectomy. Data of 530 consecutive patients undergoing robotic hepatectomy were analyzed. Patients were classified based on an APRI score threshold of 0.7 and extent of resection. Data are presented as median (mean ± SD). Of 530 patients, 166 (31%) underwent major resection. Expectedly, major resections were associated with higher expert-level operations based on IWATE system. While having statistically similar APRI scores, patients undergoing major resection had larger tumor size (p = 0.003), longer operative duration (p < 0.0001), and higher blood loss (p = 0.0002). Patients undergoing minor/technically major resections, 100 (27%) patients had an elevated APRI, which was associated with higher MELD score (p = 0.0001), Child-Pugh score (p = 0.0001), cirrhosis (p < 0.0001), and neoplastic diseases (p < 0.0001). Patients undergoing major resections, 48 (29%) had elevated APRI, which was also associated with higher Child-Pugh Score (p < 0.0001), cirrhosis (p = 0.0008), and neoplastic diseases (p = 0.001). Elevated APRI levels were indicative of cirrhosis and higher MELD score; however, outcomes following robotic major hepatectomy remain unaffected by the index.

HIV alone can induce liver fibrosis whereas co-infection with HCV presents a significant challenge in hastening the development of chronic liver disorders such a liver fibrosis, cirrhosis, and hepatic malignancy. Information on the influence of HIV on liver stiffness (LS) after treatment with direct-acting antiviral (DAAs) agents is scarce. The aim of this study was to assess the changes in LS using transient elastography (TE) and fibrosis scores (Fibrosis-4 [FIB-4] and AST-to-platelet ratio index [APRI]) before the initiation of treatment and six months after the end of treatment (EOT) with DAAs in HCV/HIV co-infected patients compared with HCV mono-infected patients.

All consecutive chronic HCV patients treated with DAAs during 2016-2020 were retrospectively recruited. TE was performed at baseline and SVR24. Fibrosis scores such as FIB-4 and APRI were calculated in parallel. Improvement of liver fibrosis was defined as any changes in the fibrosis category at baseline to a lower fibrosis category at SVR24.

Of 288 HCV-infected patients, 217 (75.3 %) were HCV mono-infected and 71 (24.7 %) were HCV/HIV co-infected. A significant decrease in TE values was noted at SVR24 compared with baseline (10.3 kPa vs. 7.9 kPa, respectively; P= <0.0001 in HCV mono-infection; 5.9 kPa vs. 5.3 kPa, respectively; P= <0.0001 in HCV/HIV co-infection). Moreover, the proportion of HCV mono-infected patients who had stable, improvement, and worsening in fibrosis stage at follow-up was 50.2 %, 43.3 %, and 6.5 %, respectively while it was 54.9 %, 32.4 %, and 12.7 %, respectively in HCV/HIV co-infection. In multivariable analysis, the higher fibrosis category was the only factor that influenced the improvement of liver fibrosis at follow-up, whereas HIV co-infection wasn't confirmed.

patients with HCV mono-infection and HCV/HIV co-infection experienced a rapid and significant improvement in LS and fibrosis indices. This improvement was more pronounced in those with high fibrosis grades at baseline.

To assess the performance of fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS) and aspartate aminotransferase to platelet ratio index (APRI) for advanced fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD) subgroups categorized by concomitant liver conditions.

We conducted a multicentered study comprising inpatients with type 2 diabetes mellitus and MAFLD. Participants were categorized into 2 groups: MAFLD with pure metabolic etiologies (MAFLD-P) and MAFLD with mixed etiologies (MAFLD-M). Diagnostic performance of FIB-4, NFS, and APRI was assessed by area under the curve (AUC), sensitivity, and specificity.

This study comprised a total of 1475 participants, with a mean (SD) age of 58.4 (13) years and 835 (56.6%) males. FIB-4 and APRI had higher AUCs for advanced fibrosis in the MAFLD-M group than in the MAFLD-P group (MAFLD-M vs MAFLD-P: FIB-4 0.680 vs 0.591, P = .0442; APRI 0.723 vs 0.631, P = .0363). No significant difference was observed in the AUC of NFS between the 2 subgroups (MAFLD-M 0.572 vs MAFLD-P 0.617; P = .3237). Besides, the sensitivity of FIB-4 (69.6% vs 54.0%; P = .019) and APRI (43.5% vs 26.1%; P = .005) was higher in the MAFLD-M group. However, no significant difference in sensitivity of NFS and specificity of FIB-4, NFS, and APRI was observed between subgroups.

In this diagnostic study of the type 2 diabetes mellitus population, FIB-4 and APRI showed better performance for identifying advanced fibrosis in MAFLD with mixed etiologies.

Chronic hepatitis C (CHC), caused by the hepatitis C virus, commonly leads to liver fibrosis. CHC is also related to T-cell exhaustion, phenotypically manifesting as overexpression of inhibitory receptors (iRs), e.g., programmed death receptor-1 (PD-1), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and lymphocyte activation gene 3 (LAG-3), which have corresponding plasma-soluble analogs. Galectin-3 (Gal-3) is a pro-fibrotic and pro-inflammatory molecule, but its role in CHC is controversial. The study aimed to assess the relationship between plasma levels of soluble PD-1 (sPD-1), sTIM-3, sLAG-3 and Gal-3 and the degree of fibrosis in CHC and successful CHC treatment effect on these markers. The study comprised 98 CHC patients, qualified for treatment with direct-acting antivirals. Plasma samples were collected prior to and six months post-treatment. iRs were determined by ELISA. sPD-1 levels were significantly higher in more advanced fibrosis (F2 + F3 vs. F0/1). Regardless of the degree of fibrosis, sPD-1 and sLAG-3 levels significantly decreased after therapy. sTIM-3 levels also decreased, however, mostly in patients with no or mild (i.e., F0/1) fibrosis. Furthermore, Gal-3 increased in patients with more advanced fibrosis (F2 + F3). sPD-1 is associated with liver disease stage in CHC and effective treatment is related to the iRs levels reduction.

This review highlights the critical considerations for monitoring patients who achieve sustained virological response (SVR) after direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection. Despite the remarkable success of DAAs, challenges persist in managing long-term risks, including hepatocellular carcinoma (HCC), liver decompensation, and extrahepatic manifestations, necessitating a tailored follow-up approach.

Recent studies emphasize that SVR does not eliminate risks for complications, particularly in patients with advanced fibrosis or cirrhosis. Advances in noninvasive tools, such as transient elastography and blood-based markers, have improved assessment of portal hypertension and liver function dynamics post-SVR. HCC surveillance remains critical for high-risk groups. Additionally, SVR improves extrahepatic conditions like mixed cryoglobulinemia and non-Hodgkin lymphoma, though careful monitoring for recurrence or associated risks is advised. Reinfection in high-risk populations underscores the importance of structured prevention and retreatment strategies.

Tailored follow-up of post-SVR patients remains essential. Future research should focus on refining predictive tools for late complications and optimizing surveillance strategies, balancing cost-effectiveness with clinical outcomes.

Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here, we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD.

A total of 230 HDV-infected RNA-positive patients from various centers who underwent liver biopsy and liver stiffness measurements (LSMs) using Fibroscan, within a period of 6 months maximum, were investigated retrospectively. Area under the receiver operating characteristic curve and Youden index were used to establish cutoff values of LSM. TE was compared with other noninvasive tests: aspartate aminotransferase to platelet ratio index, Fibrosis-4, and Delta-4 fibrosis scores.

Histologic fibrosis stage distribution was: 20.4% for F0-F1; 27.0% for F2; 18.7% for F3; and 33.9% for F4. TE demonstrated good diagnostic performance for detecting cirrhosis and advanced fibrosis with an Area under the receiver operating characteristic curve of 0.88 and 0.86, which were significantly higher than those obtained with the other noninvasive tests (P = .004 and P < .001). With a cutoff value of >12 kPa for cirrhosis, the sensitivity was 70.5%, specificity was 86.2%, positive predictive value was 72.4%, negative predictive value was 85.1%, and accuracy was 80.9%. Using 10.4 kPa as the cutoff value for F3, the sensitivity was 70.2%, specificity was 83.5%, positive predictive value was 82.5%, negative predictive value was 71.7%, and accuracy was 76.5%. In 89% of patients with LSM ≤6.2 kPa, liver biopsy disclosed only absent or minimal fibrosis.

TE demonstrated good diagnostic performance for advanced fibrosis and cirrhosis in patients with CHD. Advanced fibrosis is highly probable for LSM values ≥10 kPa. LSM values <6 kPa almost totally exclude significant fibrosis. Between 6 and 10 kPa, liver biopsy should be discussed.

Background: Chronic liver disease (CLD) is a major global health concern, contributing significantly to morbidity and mortality. Cirrhosis and liver cancer are the leading causes of liver-related deaths, with various etiological factors, such as metabolic disorders and alcohol-related and viral hepatitis, driving its global prevalence. Non-invasive biomarkers and scoring systems have emerged as key tools for assessing liver disease severity and differentiating CLD from cirrhosis. This study evaluates biomarkers and non-invasive scores and their utility in distinguishing CLD from cirrhosis. Methods: This retrospective observational study included 250 adult patients hospitalized between January 2021 and December 2023 at Cluj County Emergency Clinical Hospital, Romania. Patients were diagnosed with either cirrhosis or CLD of viral, autoimmune, or primary biliary cholangitis (PBC) etiology. Non-invasive biomarkers, scores, and various hemogram-derived ratios were evaluated. Statistical analysis involved descriptive statistics, comparative tests, and receiver operating characteristic (ROC) curve analysis. Results: Among the 250 patients, 137 had liver cirrhosis (54.8%) and 113 had CLD without cirrhosis (45.2%). Significant differences were observed in laboratory parameters, with cirrhosis patients showing lower hemoglobin, platelet count, and albumin levels alongside higher liver enzymes and INR values. Non-invasive scores such as APRI, FIB-4, and NFS demonstrated higher values in the cirrhosis group, indicating more advanced liver damage. Hemogram-derived ratios, particularly the neutrophil-to-lymphocyte ratio (NLR), were higher in cirrhosis patients. ROC analysis revealed that the Lok index had the highest discriminatory power (AUC 0.89), followed by the King score (AUC 0.864) and the Fibrosis index (AUC 0.856), which effectively distinguished cirrhosis from CLD. Conclusions: This study underscores the utility of non-invasive biomarkers and scoring systems in differentiating CLD from cirrhosis. The Lok index, King score, and Fibrosis index demonstrated excellent diagnostic accuracy, while hemogram-derived ratios, such as NLR, offer insights into systemic inflammation associated with liver disease progression. These findings support the integration of non-invasive markers into clinical practice for improved risk stratification and management of liver diseases.

Background: Existing non-invasive tests (NITs) for liver fibrosis offer moderate precision and accessibility but are often limited by complexity, reducing their practicality in routine clinical use. This study aimed to evaluate the diagnostic performance of current fibrosis assessment methods and develop a novel, simplified scoring system-the Aspartate Aminotransferase (AST)-Thrombocytopenia-Albumin (ATA) score-to enhance ease of use and clinical applicability. Methods: This study examined past cases of patients with chronic liver disease (CLD) by using magnetic resonance elastography (MRE) to evaluate fibrosis stages. Serum biomarkers were collected, and common fibrosis scores were calculated. Logistic regression identified potential predictors of significant fibrosis, forming the ATA score. Diagnostic performance was assessed, and internal validation was conducted via bootstrap resampling. Results: Among 70 patients, 31.4% had significant fibrosis. Hepatitis B was the most common cause (60.0%), followed by hepatitis C (18.6%) and nonalcoholic fatty liver disease (NAFLD, 15.7%). The ATA score demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.872, comparable to the AST-to-platelet ratio index (APRI; 0.858) and fibrosis-4 index (FIB-4; 0.847). The recommended cut-offs for identifying high-risk patients were ATA score ≥ 2 (specificity 95.8%, sensitivity 50.0%), APRI ≥ 0.50 (specificity 89.6%, sensitivity 68.2%), and FIB-4 ≥ 1.3 (specificity 58.3%, sensitivity 90.9%). Internal validation confirmed model robustness, with an optimism-corrected AUROC of 0.8551. Conclusions: The ATA score offers a straightforward and efficient method for detecting significant fibrosis, demonstrating comparable diagnostic capability to APRI and FIB-4, while being more user-friendly in clinical practice. A score of 0-1 indicates low risk, suitable for clinical follow-up, whereas a score of ≥2 suggests high risk, warranting further evaluation. Integrating the ATA score into clinical workflows can enhance early detection, optimize resource utilization, and improve patient care.

Many studies have shown a close relationship between type 2 diabetes mellitus and obesity. Glucagon-like peptide-1 (GLP-1) agonists are particularly preferred as antidiabetic medications for obese patients with type 2 diabetes because they not only help with glycemic control but also promote weight loss by slowing gastric emptying. Fatty liver disease, a significant complication of obesity, can progress to hepatic fibrosis and cirrhosis in later stages. Platelets ratio index (APRI), fibrosis-4 index (FIB-4), indices are two of the most studied indirect markers of hepatic fibrosis. Our study aimed to investigate the effect of exenatide, a GLP-1 agonist, on the APRI and FIB-4 indices in obese patients with type 2 diabetes mellitus. We included obese patients with type 2 diabetes treated with exenatide at the endocrinology and metabolism outpatient clinics of Bakırköy Dr. Sadi Konuk Training and Research Hospital between January 2015 and May 2018. We calculated the APRI and FIB-4 indexes retrospectively using data on aspartate aminotransferase, alanine aminotransferase, platelet counts, and ages. The study included 170 patients, with an average age of 48.27 ± 11 years. We compared the APRI and FIB-4 indices at the third and sixth months after the onset of exenatide and before the treatment. While there was no significant change in the FIB-4 index with treatment, the APRI index showed a significant decrease. In conclusion, our study observed a significant decrease in the APRI index with exenatide treatment, while the FIB-4 index remained unchanged. More research is needed on liver fibrosis indices in the obese population.

The development of accurate noninvasive tests to identify individuals with metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis is of great clinical importance. In this study, we aimed to develop 2 noninvasive diagnostic models on the basis of routine clinical and laboratory data, using machine learning, to identify patients with MASH and significant fibrosis (fibrosis stages 2 to 4), respectively.

This analysis included the training (n=456) and the validation (n=105) sets of patients who underwent liver biopsy and laboratory testing for liver disease at 2 hospitals in China. Logistic regression, random forest, support vector machine, and the XGBoost algorithm were used to construct models, respectively. The best diagnostic models for MASH and significant fibrosis were compared with 7 existing noninvasive scoring systems including AAR, AST to platelet ratio index (APRI), BARD score, fibrosis-4 (FIB-4), fibrotic non-alcoholic steatohepatitis (NASH) index (FNI), homeostatic model assessment of insulin resistance (HOMA-IR), and non-alcoholic fatty liver disease fibrosis score (NFS). Performance was estimated by the area under the receiver operating characteristic curve (AUROC).

The final noninvasive diagnostic model integrated 19 indicators derived from routine clinical and laboratory tests. The XGBoost models exhibited superior performance in MASH and significant fibrosis with an improved AUROC value (MASH, 0.670, 95% CI 0.530-0.811; significant fibrosis, 0.713, 95% CI 0.611-0.815) compared with other noninvasive scoring systems in the validation set.

Utilizing machine learning can assist in diagnosing MASH and significant fibrosis based on clinical epidemiological information with good diagnostic performance.

Current treatments for chronic hepatitis B (CHB) virus involve nucleos(t)ide analogs and pegylated interferon-alpha (PEG-IFNα). This study compares the efficacy and safety of PEG-IFNα monotherapy with its combinations with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in managing CHB. We included 147 treatment-naïve patients divided into three groups: Group A (PEG-IFNα-2b with ETV), Group B (PEG-IFNα-2b with TDF), and Group C (PEG-IFNα-2b monotherapy). Evaluations occurred every 12 weeks up to 48 weeks. The Kaplan-Meier method showed no significant differences in cumulative HBsAg loss, but HBV DNA clearance rates were higher in the TDF group than in the ETV group (P = 0.01). Higher incidences of elevated alanine aminotransferase (ALT), aspartate aminotransferase, and thrombocytopenia were observed in the TDF group compared to other groups. After propensity score matching, the TDF group had a higher undetectable HBV DNA rate than the IFN group, but no significant differences in HBsAg clearance rates. Both TDF and ETV groups achieved more significant HBsAg reductions from baseline to week 48 than the IFN group (P < 0.05). ETV showed a lower HBeAg clearance rate (30.00% vs 87.50%, P < 0.05) but higher ALT normalization (76.92% vs 45.45%, P < 0.05). In the TDF group, patients with lower baseline HBsAg levels, high ALT levels, and lower aspartate aminotransferase-to-platelet ratio index (APRI) scores were more likely to achieve HBsAg loss. These findings suggest that TDF and ETV are effective for viral suppression, with TDF showing superior HBV DNA clearance but more adverse events.

This study investigates how different treatments for chronic hepatitis B (CHB), a widespread liver infection, compare in effectiveness and safety. By evaluating the use of pegylated interferon-alpha alone and in combination with two other drugs, entecavir and tenofovir disoproxil fumarate (TDF), researchers found that TDF offers better viral suppression but also comes with more side effects. For patients receiving TDF combined with PEG-IFN therapy, low HBsAg levels, elevated alanine aminotransferase levels, and lower APRI scores were associated with a higher likelihood of achieving HBsAg loss. Consistent with previous findings, this study confirms the benefits of nucleos(t)ide analog plus PEG-IFN therapy for CHB treatment and further explores which patients are more likely to benefit from combination therapy. Furthermore, this study underscores the importance of further monitoring adverse events in patients receiving combination therapy.

To investigate the association of four liver fibrosis scores - Fibrosis-4 (FIB-4), AST/ALT ratio, AST-to-platelet ratio index (APRI) and Gamma-glutamyl transferase-to-platelet ratio index (GPRI) - and clinical outcomes in ambulatory patients with heart failure (HF).

We conducted a retrospective study involving 2379 patients with HF referred to a specialized clinic from January 2010 to June 2022. We used multivariable Cox´s regression models to study the association between liver fibrosis scores and long-term clinical outcomes (all-cause death and the combined endpoints all-cause death or HF hospitalization and cardiovascular death or heart transplantation). Areas under receiver-operator curves were used to evaluate the discriminative capacity of each score for predicting 1-year clinical outcomes, as well as to analyze their incremental predictive value in addition to the broadly validated MAGGIC risk score.

Median follow up was 1568 days. GPRI was identified as an independent predictor of all-cause death or HF hospitalization (HR 1.12, 95% CI 1.07-1.18), all-cause death (HR 1.14, 95% CI 1.08-1.20) and cardiovascular death or heart transplantation (HR 1.10, 95% CI 1.03-1.17). FIB-4 and AST/ALT ratios were also independently associated with all-cause mortality. According to receiver-operator curve analyses, GPRI showed the best discriminative capacity among the four liver fibrosis scores evaluated in the study to predict 1-year clinical outcomes. The predictive value of GPRI was incremental to the one of the MAGGIC risk score.

Liver fibrosis scores are associated with long-term clinical outcomes in ambulatory patients with HF. In our study, the predictive capacity of GPRI outperformed the one of FIB-4, APRI and AST/ALT and was incremental to the one of the MAGGIC risk score.

To identify risk factors associated with liver complications in patients with chronic hepatitis B infection in an unselected cohort of hepatitis B patients in southern Spain.

A prospective open-cohort study was conducted on 437 patients with uncomplicated chronic hepatitis B infection in two hospitals in Málaga, southern Spain. The follow-up time ranged from 0.5 to 31.5 years (mean: 13.8±9.5 years; median: 11.4 years). The aim of this study was to evaluate the occurrence of the initial liver complication during follow-up, which is defined as the emergence of liver cancer or complications resulting from portal hypertension. Survival curves were obtained using a time-to-event method through Kaplan-Meier analysis. Multivariate Cox regression was conducted to estimate the hazard ratios of risk factors associated with complications after adjusting for multiple variables. The follow-up of the patients was carried out under conditions of usual clinical practice. Based on the weighted adjustment of these factors, we developed a Hepatitis B Complication Score (HBCS) from which it was possible to identify patients with low and high risk of complications during follow-up.

33 out of 437 patients (7.55%) experienced liver complications, 12 (36.3%) were secondary to portal hypertension, and 21 patients (63.7%) developed liver cancer. A Multivariate Cox regression identified the following independent risk factor: Age above 45 years: HR 7.10 (2.9-17.3); low platelet count: HR 4.88 (2.1-10.9); hepatitis C coinfection: HR 4.68 (2.0-10.9); Male gender: HR 4.64 (1.5-14.2); alkaline phosphatase above 147 UI/mL: HR 4.33 (2.0-8.9); and Child score above 5 points: HR 3.83 (1.7-8.4). The Risk of Complications Score (HBCS) was developed with a high predictive capacity AUROC 0.92 (0.87-0.97).

An HBCS score greater than 3.07 points identifies patients at high risk of developing complications and with an increased risk of liver and all-cause mortality.

The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD.

This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed.

Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis ≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis ≥F3, and 0.890, 0.884, and 0.889 for fibrosis ≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis ≥F2, 0.788, 0.814, and 0.79 for fibrosis ≥F3, and 0.846, 0.859, and 0.856 for fibrosis ≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64 years for fibrosis ≥F4.

The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis.

Introduction Hepatitis C virus (HCV) infection is still a worldwide health issue, leading to progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma. Detection at early stages of advanced liver fibrosis is critical for early treatment and appropriate management. Liver biopsy, though still considered the gold standard for fibrosis staging, is invasive and costly and poses possible risks and complications. The application of non-invasive biomarkers such as the platelet-to-lymphocyte ratio (PLR) as substitute tools for fibrosis staging is on the rise. This study aimed to determine the utility of PLR in predicting advanced liver fibrosis in HCV infection. Methodology This retrospective observational study was carried out at the department of hepatogastroenterology, Sindh Institute of Urology and Transplantation (SIUT), Pakistan, in patients aged ≥18 years old who had established chronic infection of HCV and had undergone liver biopsy and shear wave elastography (SWE) in the period between January 2018 and December 2023. Exclusion criteria consisted of coexisting liver and hematological disorders and incomplete patient clinical records. Laboratory parameters, demographic variables, and fibrosis scores were compared. The ratio of PLR was calculated. Area under the receiver operating characteristic (AUROC) curve analysis was done for PLR, and at an optimal cutoff, diagnostic accuracy was obtained for PLR and was compared to aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4). Results A total of 107 HCV-infected patients, who had a mean age of 49.1 ± 8.9 years, were enrolled in the study. Liver biopsy confirmed significant fibrosis (meta-analysis of histological data in viral hepatitis (METAVIR) score ≥ 2) in 56 (52.3%) patients. The PLR was significantly lower in patients with advanced fibrosis (4.17 ± 1.44 vs. 6.8 ± 1.99, p ≤ 0.001). The AUROC for PLR was 0.879 (p ≤ 0.001). At an optimal cutoff of ≤5.41, PLR showed a high sensitivity of 85.71%, specificity of 86.27%, and an excellent diagnostic accuracy of 85.98%. The diagnostic accuracy of PLR was far superior to APRI (37%) and FIB-4 (40%) in predicting advanced liver fibrosis in HCV patients. Conclusion PLR is a simple, cost-effective, highly sensitive, non-invasive marker for advanced liver fibrosis in chronic infection with HCV. It is superior to currently established non-invasive markers such as APRI and FIB-4 and can be utilized as a good screening tool for fibrosis in resource-limited situations.

This multicentre study investigated the dynamics of thrombospondin 2 (TSP2) levels during direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV) infected patients and evaluated TSP2's potential as a predictive marker for hepatocellular carcinoma (HCC). All 134 participants achieved sustained virological response at 12 weeks (SVR12) with DAA therapy, and serum TSP2 levels significantly decreased from before and after treatment (p < 0.001). During the median follow-up period of 6.0 years, HCC after DAA therapy was observed in 16 patients (11.9%). Patients with serum TSP2 High (≥ 32 ng/mL) at SVR12 had a significantly higher cumulative occurrence of HCC than did those without (26.5% vs. 7.0%, p = 0.0033). A multivariate Cox proportional hazards model identified male gender (HR 4.84, p = 0.005), HCC history (HR 4.61, p = 0.017) and TSP2 High (HR 3.93, p = 0.009) as significant independent predictors of HCC occurrence after DAA therapy. The model had a high concordance index of 0.878. Additionally, combining TSP2 High and FIB-4 High (≥ 3.538) at SVR12 yielded high specificity and negative predictive value (0.941 and 0.917, respectively) for predicting HCC. Kaplan-Meier analysis showed a higher HCC incidence in the TSP2 High + FIB-4 High group (log-rank p < 0.0001). In conclusion, TSP2 may be a promising biomarker for personalised HCC surveillance in DAA-treated hepatitis C patients.

Fontan circulation (FC) in complex congenital heart disease is characterized by altered hemodynamics and associated with Fontan-associated liver disease. Patients with FC may exhibit abnormalities in cholate clearance due to abnormal perfusion. We aimed to compare cholate clearance in adults with FC to healthy controls and explore associations between cholate clearance and clinical features.

This is a prospective cohort study of patients with FC ≥18 years of age between 2019 and 2022. Systemic and portal hepatic clearance of cholate was assessed using a dual cholate clearance assay (HepQuant Shunt), measuring systemic and portal hepatic filtration rates (HFRs). Systemic HFR/portal HFR ratio (SHUNT%) was calculated. Participants with FC and healthy controls were compared using the Fisher exact test and Wilcoxon test. Univariable regression and multivariable analyses determined associations with clinical variables. There were 35 participants with FC (54% women; median age 29.0 years [interquartile range, 24.0-36.0], 91% White) and 26 controls. In addition to lower platelet counts and higher aspartate aminotransferase to platelet ratio index, and Fibrosis-4 indices, FC participants had lower systemic HFR and portal HFR. SHUNT% was comparable with controls but ranged from 8% to 76%, with 8 (23%) having SHUNT% >30%. In those with FC, increase in SHUNT% was associated with elevated Fontan pressure, higher aortopulmonary collateral flow, decreased oxygen saturation, elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, thrombocytopenia, and Fibrosis-4 ≥1.45.

Cholate clearance, as defined by systemic and portal HFR, is impaired in those with FC. Features of worse Fontan physiology correlate with higher SHUNT%, supporting the hypothesis that hemodynamic derangements play a role in progression of Fontan-associated liver disease.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03726229.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent pediatric liver disease, yet accurate risk scores for referral of children/adolescents with suspected clinically significant liver fibrosis are currently lacking.

Clinical and biochemical variables were collected in a prospective cohort of 327 children and adolescents with severe obesity, in whom liver fibrosis was evaluated by transient elastography. Logistic regression was performed to establish continuous (pFIB-c) and simplified (pFIB-6) diagnostic scores that accurately exclude significant (≥F2) fibrosis. Performance for each was compared to established noninvve fibrosis scores. These scores were validated in elastography (n=504) and multiple biopsy-proven MASLD (n=261) cohorts. Patient sex, ethnicity, weight z-score, homeostatic model assessment of insulin resistance index, ALT, and presence of hypertension were included in the scores. The pFIB-c and pFIB-6 exhibited good discriminatory capacity (c-statistic of 0.839 and 0.826), outperforming existing indices. Negative predictive values were >90% for both scores in the derivation and elastography validation cohorts. Performance in the histological cohorts varied (AUROCs for the pFIB-c between 0.710 and 0.770), as the scores were less accurate when applied to populations in tertiary referral centers characterized by a high prevalence of significant fibrosis and high ALT levels.

Analyzing several cohorts totaling approximately 1100 children and adolescents, we developed novel risk scores incorporating readily available clinical variables. In accordance with the aim of excluding pediatric MASLD-associated fibrosis, the scores performed better in nonselected cohorts of children and adolescents living with obesity than in patients referred to tertiary liver units.

Existing hepatocellular carcinoma (HCC) prediction models for the general population without traditional risk factors for chronic liver disease are limited. This study aimed to develop an HCC prediction model for individuals lacking these traditional risk factors.

The total of 138 452 adult participants without chronic viral hepatitis or significant alcohol intake who underwent regular health checkup at a tertiary hospital in South Korea were followed up for the development of HCC. Risk factors for HCC development were analyzed using Cox regression analysis, and prediction model was developed using the risk factors.

Significant predictors of HCC development included older age, male sex, higher body mass index, presence of diabetes mellitus, and levels of aspartate aminotransferase, total cholesterol, and platelet count. A new HCC prediction model using these variables was developed. Harrell's concordance index and Heagerty's integrated area under the receiver operating characteristics (AUROC) curve of the model were 0.88 (95% confidence interval [CI] 0.85-0.91) and 0.89 (95% CI 0.86-0.91), respectively. The 5- and 10-year AUROC were 0.89 (95% CI 0.88-0.89) and 0.87 (95% CI 0.87-0.88), respectively. This model significantly outperformed the FIB-4 scoring model in predicting HCC and effectively stratified individuals into low-, intermediate-, and high-risk groups with significantly different cumulative incidences of HCC.

The new model, based on clinical parameters, provides a valuable tool for clinicians to stratify HCC risk in the general population without risk factors for chronic liver disease.

FibraChek is a newly developed mass spectrometry (MS) assay kit approved by the National Medical Products Administration (NMPA) of China for quantifying L-tyrosine (Tyr) and taurocholic acid (TCA) in serum, aiding liver fibrosis diagnosis. This study aimed to assess its analytical performance.

The analytical performance was investigated based on NMPA and CLSI guidelines. Method suitability in the clinical context was tested by analyzing clinical samples from liver fibrosis patients confirmed via liver biopsy.

The assay enables simultaneous determination of Tyr and TCA, demonstrating compliance with performance parameters such as linearity, dynamic range, limit of detection (LOD), limit of quantification (LOQ), recovery, repeatability, reproducibility, and stability. It validated a linear range of 20-1000 μmol/L for Tyr and 10.3-618 ng/ml for TCA, maintaining stability after 5 freeze-thaw cycles for 14 months. Components remained stable for up to 7 days at room temperature and 30 days at 2-8 °C. TCA and Tyr were stable for up to 36 months at -20 °C or -80 °C. The method effectively quantified Tyr and TCA in serum from liver fibrosis patients and healthy controls.

This is the first MS-based assay for non-invasive liver fibrosis detection validated for clinical use, providing a rapid and reliable analytical protocol suitable for routine analysis.

Non-invasive tests (aspartate aminotransferase-to-platelet ratio index [APRI] and transient elastography [FibroScan]) were recommended in the 2015 WHO guidelines to guide treatment decisions in people with chronic hepatitis B. We updated the systematic review and meta-analysis that informed the 2015 guidelines to inform new cutoffs for non-invasive tests for the diagnosis of significant fibrosis and cirrhosis for the 2024 WHO guidelines for chronic hepatitis B.

We searched PubMed (MEDLINE), Embase, and Science Citation Index Expanded (Web of Science) for studies published in any language between Jan 1, 2014, and Feb 15, 2023. We included all studies that reported cross-sectional data on the staging of fibrosis or cirrhosis with APRI, Fibrosis-4 (FIB-4), and FibroScan compared with liver biopsy as the reference standard in people with chronic hepatitis B. We excluded studies in which the maximum interval between liver biopsy and non-invasive fibrosis test was more than 6 months; that reported on fewer than ten patients with advanced fibrosis or cirrhosis; that were done exclusively in children; and did not report diagnostic accuracy across our prespecified ranges of test cutoffs. The results of this updated search were collated with the meta-analysis that informed the 2015 guidelines. Outcomes of interest were the sensitivity and specificity of non-invasive tests using defined index test cutoffs for detecting significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) based on the METAVIR staging system. We performed meta-analyses using a bivariate random-effects model.

Of 19 933 records identified by our search strategy, 195 were eligible for our systematic review and combined with the 69 studies from the previous meta-analysis to total 264. Two studies were at low risk of bias, 31 studies had unclear risk of bias, and 231 studies had a high risk of bias. Of these 264, 211 studies with 61 665 patients were used in the meta-analysis. For the diagnosis of significant fibrosis (≥F2), sensitivity and specificity were 72·9% (95% CI 70·2-75·5) and 64·7% (95% CI 61·0-68·2) for the APRI low cutoff (>0·3 to 0·7), 30·5% (23·7-38·3) and 92·3% (89·3-94·6) for the APRI high cutoff (>1·3 to 1·7), and 75·1% (72·2-77·7) and 79·3% (76·2-82·2) for FibroScan (>6·0 to 8·0 kPa), respectively. For the diagnosis of cirrhosis (F4), sensitivity and specificity were 59·4% (53·2-65·2) and 73·9% (70·1-77·4) for the APRI low cutoff (>0·8 to 1·2), 30·2% (24·2-36·9) and 88·2% (85·4-90·6) for the APRI high cutoff (>1·8 to 2·2), and 82·6% (77·8-86·5) and 89·0% (86·3-91·2) for FibroScan (>11·0 to 14·0 kPa), respectively. Using a hypothetical population of 1000 unselected patients with chronic hepatitis B with a 25% prevalence of significant fibrosis (≥F2), the APRI low cutoff for significant fibrosis (≥F2) would result in 262 (26·2%) false positives but only 68 (6·8%) false negatives. The FibroScan cutoff would result in 158 (15·8%) false positives and 63 (6·3%) false negatives. In a population with a 5% prevalence of cirrhosis (F4), the APRI low cutoff for cirrhosis (F4) would result in 247 (24·7%) false positives and 21 (2·1%) false negatives and the FibroScan cutoff would result in 105 (10·5%) false positives and nine (0·9%) false negatives.

These findings have informed new thresholds of APRI and FibroScan for diagnosis of significant fibrosis and cirrhosis in the 2024 WHO guidelines on chronic hepatitis B, with an APRI score greater than 0·5 or a FibroScan value greater than 7·0 kPa considered to identify most adults with significant fibrosis (≥F2) and an APRI score greater than 1·0 or a FibroScan value greater than 12·5 kPa to identify most adults with cirrhosis (F4). These patients are a priority for antiviral treatment.

WHO.

The Fontan operation is a surgical procedure to palliate single ventricle congenital heart disease. Hepatocellular carcinoma (HCC) is a rare complication of Fontan-associated liver disease (FALD).

The authors aim to examine characteristics of individuals with Fontan circulation diagnosed with HCC and to describe tumor characteristics, treatment, and survival outcomes of these patients.

This was a multicenter retrospective case-control study of adults with Fontan circulation between 2005 and 2021. HCC cases were included based on histology or imaging-based diagnosis. Controls were randomly selected in a 3:1 ratio from the center in which the case was derived. Descriptive statistics were used to compare groups and Kaplan-Meier survival analysis was performed.

There were 58 cases of HCC diagnosed at a median age of 31 (IQR: 26-38) years. Diagnosis was made at very early or early stage disease in 68%. Compared to controls, cases had higher prevalence of advanced FALD including varices, ascites, splenomegaly, and decreased platelets. Treatment with curative intent (combined heart-liver transplantation, resection, or ablation) was performed in 41%. Survival at 1 year was 78.9% and highest among those diagnosed at very early or early stage. Over half were undergoing active surveillance at diagnosis, which showed a nonsignificant trend toward higher survival (P = 0.088).

We describe the clinical characteristics, treatment, and survival in patients with FALD-HCC. Results suggest that adults with FALD-HCC diagnosed with early stage disease may have survival benefit. Our findings underscore the importance of HCC screening for early detection in individuals after the Fontan operation.

To explore the value of preoperative Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) in predicting short-term prognosis of children with biliary atresia (BA) undergoing Kasai portoenterostomy (KPE).

Clinical data from children who underwent KPE were analyzed. Patients were divided into two groups based on their 2-year native liver survival after KPE. General information and laboratory findings were collected before KPE. The difference in liver fibrosis between the two groups was analyzed. The predictive efficacy of each index for short-term prognosis of children with BA was evaluated using the receiver operating characteristic curve.

The APRI and FIB-4 in the good prognosis group were lower than those in the poor prognosis group (p=0.008 and 0.023, respectively), and postoperative jaundice clearance rate was higher (p=0.002). In the poor prognosis group, gamma-glutamyl transpeptidase levels in the F3+F4 fibrosis subgroup were significantly higher than those in the F1 subgroup (p=0.038). The area under the curve (AUC) for preoperative APRI in predicting short-term prognosis was the highest at 0.667, with a cut-off value of 1.190. The AUC for preoperative FIB-4 was predicted to be 0.642. The combination of preoperative APRI and alanine aminotransferase showed a higher AUC for prognosis prediction compared with either marker alone.

Preoperative APRI and FIB-4 may havepredictive values for short-term prognosis. The predictive value of APRI and FIB-4 combined with liver function indicators for the short-term prognosis of children is superior to that of a single indicator, but the results are not satisfactory.

Early forms of alcohol-associated liver disease (ALD) include different stages in the progression of compensated liver disease ranging from steatosis to steatohepatitis and fibrosis. ALD has been classically diagnosed at advanced stages more frequently than other liver diseases. This fact probably contributed to the scarcity of studies on early forms of ALD. Recent studies have investigated the prevalence of early ALD in the general population and have described the natural history of alcohol-induced steatosis and fibrosis, which have been linked to worse prognosis compared with early stages of other chronic liver diseases. In addition, studies on screening and early diagnosis of ALD in at-risk populations have shown that these strategies allow early detection and intervention. Of note, up to 28% of the United States population has concurrent alcohol use and metabolic syndrome, and estimated prevalence of advanced fibrosis among heavy drinkers with metabolic syndrome has increased from 3% in the 1990s to more than 10% in the 2010s. Therefore, new challenges and treatment opportunities will emerge for patients with ALD. In this review, we provide an overview of the state of the art in early ALD, focusing on natural history, diagnosis, and management, and provide insights into future perspectives.

The objective of this study was to validate the diagnostic accuracy of the acFibroMASH index in a population of metabolic dysfunction-associated steatotic liver disease (MASLD) patients with at-risk metabolic dysfunction-associated steatohepatitis (MASH) and to compare it with other scoring systems.

394 patients with biopsy-proven MASLD were retrospectively enrolled. The patients were divided into the at-risk MASH (NAFLD activity score ≥ 4 and significant fibrosis) group (n = 103) and the non-at-risk MASH group (n = 291). The diagnostic performance of the acFibroMASH index was compared to that of fibroScan-aspartate aminotransferase (FAST) and other noninvasive fibrosis scores by plotting the receiver operating characteristic curve (ROC), including the area under the curve (AUC), sensitivity, and specificity. Cut-offs of the acFibroMASH index for sensitivity (≥ 0.90) and specificity (≥ 0.90) were obtained in our cohort.

The AUC of the acFibroMASH index in assessing at-risk MASH was 0.780, while the AUC of FAST was 0.770. The comparison of acFibroMASH with FAST showed no significant difference (P = 0.542). When the cut-off value for acFibroMASH was < 0.15, 95.5% of at-risk MASH patients could be excluded in 89 patients correctly. Conversely, when the cut-off value was set at > 0.39, 49.3% of at-risk MASH patients could be diagnosed in 140 patients correctly. When the NPV was set at 0.900, the critical value for exclusion was determined to be 0.23, with a sensitivity of 0.835 and a specificity of 0.526.

This study validated the efficacy of the acFibroMASH index in predicting at-risk MASH in a population of MASLD patients, demonstrating comparable performance to that of the FAST. The acFibroMASH index may provide a valuable clinical basis for screening and identifying at-risk MASH in primary care settings.

Approximately 95% of patients with chronic hepatitis C achieve viral eradication through direct-acting antiviral (DAA) treatment. Ensuing clinical benefits include halting liver fibrosis, thereby reducing the need for liver transplantation, and decreasing both liver-related and overall mortality. It is well established that, although ameliorated, the risk of developing hepatocellular carcinoma (HCC) persists, particularly among patients with pre-treatment advanced fibrosis/cirrhosis. Current guidelines recommend indefinite HCC surveillance in these patients. However, a recent Markov model evaluation shows that HCC surveillance is cost-effective only for patients with cirrhosis but not so for those with F3 fibrosis, a finding which points out the need to better define the risk of HCC in hepatitis C patients after cure and further characterize pre- and post-treatment factors that might affect the incidence of HCC in this setting. We reviewed the literature analyzing this aspect. Here we summarize the main findings: male gender and older age are independent predictors of increased risk of post-cure HCC development. Moreover, non-invasive tests for hepatic fibrosis, namely FIB4, APRI, and liver stiffness, measured before and after treatment and their post-therapy change, contribute to better stratifying the risk of HCC occurrence. Furthermore, low serum albumin, as well as an AFP above 7 ng/mL prior to and after DAA therapy, also constitute independent predictors of HCC development. Considering these findings, we propose to classify patients with HCV viral eradication and advanced fibrosis/cirrhosis into groups of low, medium, or high risk of HCC and to adopt adequate surveillance strategies for each group, including protocols for abbreviated magnetic resonance imaging (MRI) for those at the highest risk.

Leptin replacement therapy with metreleptin improves metabolic abnormalities in patients with generalized lipodystrophy (GLD).

Determine how timing of metreleptin initiation in the clinical course of GLD affects long-term metabolic health.

Retrospective analysis of patients ≥6 months old with congenital (n = 47) or acquired (n = 16) GLD treated with metreleptin at the National Institutes of Health since 2001. Least squares means for glycated hemoglobin (HbA1c), insulin area under the curve from oral glucose tolerance tests, triglycerides, urine protein excretion, platelets, transaminases, and aspartate aminotransferase (AST) to Platelet Ratio Index for early and late treatment groups, defined by baseline metabolic health, were analyzed during median 72 (24-108) months' follow-up.

Compared to late groups, early groups based on metabolic status had higher mean ± SEM insulin area under the curve (20 831 ± 1 vs 11 948 ± 1), lower HbA1c (5.3 ± 0.3 vs 6.8 ± 0.3%), triglycerides (101 ± 1 vs 193 ± 1 mg/dL), urine protein excretion (85 ± 1.5 vs 404 ± 1.4 mg/24 h), alanine aminotransferase (30 ± 1 vs 53 ± 1 U/L), AST (23 ± 1 vs 40 ± 1 U/L), and AST to Platelet Ratio Index (0.22 ± 1.3 vs 0.78 ± 1.3), and higher platelets (257 ± 24 vs 152 ± 28 K/µL) during follow-up (P < .05). Compared to patients ≥6 years old at baseline, patients <6 years had lower HbA1c (4.5 ± 0.5 vs 6.4 ± 0.2%) and higher AST (40 ± 1vs 23 ± 1 U/L) during follow (P < .05).

Patients with GLD who initiated metreleptin before the onset of severe metabolic complications had better long-term control of diabetes, proteinuria, and hypertriglyceridemia. Early treatment may also result is less severe progression of liver fibrosis, but further histological studies are needed to determine the effects of metreleptin therapy on liver disease.