Liver fibrosis is characterized by excessive extracellular matrix accumulation during chronic liver disease progression. Hepatic stellate cell (HSC) activation involves metabolic reprogramming, while both HMGB1 and β-catenin pathways have been implicated in HSC activation and liver fibrosis progression. Given irisin's established role in metabolic regulation and emerging evidence of its anti-fibrotic properties, we investigated its effects on HSC activation and liver fibrosis, focusing on potential metabolic regulation through the HMGB1/β-catenin pathway. Using both in vitro HSC-T6 cell culture and in vivo CCl4-induced rat liver fibrosis model, we analyzed irisin's impact on HSC metabolism and fibrosis progression. Our results demonstrated that irisin dose-dependently suppressed HSC-T6 cell viability and glycolytic metabolism, significantly reducing ATP levels, glucose consumption, and lactate production at concentrations of 80-100 nmol/L. Irisin treatment markedly inhibited HSC-T6 cell proliferation and migration while inducing cellular senescence, as evidenced by increased H3K9me3, γ-H2AX, P16, and P21 expression. Mechanistically, irisin systematically downregulated key glycolytic enzymes (HK2, PFK1, PKM2, LDHA) and modulated the HMGB1/β-catenin pathway by reducing both cytoplasmic HMGB1 expression and β-catenin nuclear translocation. In the CCl4-induced rat model, irisin treatment significantly ameliorated liver fibrosis, as evidenced by reduced collagen deposition and α-SMA expression, while improving liver function indicators and decreasing serum fibrosis markers (HA, PIIIP, HMGB1), showing therapeutic effects comparable to colchicine. These findings reveal irisin's anti-fibrotic effects through metabolic regulation and HMGB1/β-catenin pathway modulation, suggesting its potential as a therapeutic agent for liver fibrosis.

Hepatobiliary disease in dogs and cats can lead to various complications. Vomiting is a common clinical sign in liver disease, and antiemetic therapy should be considered on a case-by-case basis. Ascites is managed by feeding a moderate sodium diet, therapy with spironolactone, and judicious use of furosemide. Hepatic encephalopathy is managed by feeding an appropriate diet and treating with lactulose and possibly an antimicrobial. Because coagulant and anticoagulant factors are affected in patients with hepatic dysfunction, they may be in an altered but balanced hemostatic state. This balance is fragile and bleeding or thrombosis can occur if it is disrupted.

Conditional survival (CS) is a measure of prognosis of patients who have already survived several years since diagnosis. However, few studies have investigated the CS of patients who underwent liver resection (LR) for early-stage hepatocellular carcinoma (HCC). We enrolled 942 consecutive patients who underwent LR for HCC with pathology-defined American Joint Committee on Cancer (AJCC) 7th edition stage 1 or 2 disease. The three-year CS was calculated as CS = S(x + 3)/S(x) and represented the probability of surviving an additional three years, given that the patient had already survived x years. The one-, three-, and five-year survival rates were 97.1%, 86.7%, and 76.1%, respectively, and were lower in cases with AJCC stage 2 disease, alpha-fetoprotein level of ≥ 20 ng/ml, presence of cirrhosis, anti-hepatitis C virus positivity, age > 65 years, and Model for End-Stage Liver Disease score of > 9. However, the three-year CS indicated that these variables were associated with shortened survival only in the first two years. From the third year after LR, the probability of survival of patients was similar between subgroups. CS is useful for providing a dynamic evaluation of survival during postoperative follow-up.

Steatotic liver disease (SLD) affects ~30% of adults worldwide. The global population is continuously threatened by epidemic and endemic viral diseases. This study aims to thoroughly examine the interaction between SLD and major viral diseases.

We systematically searched databases from inception to April 2, 2024, for observational studies recording viral-infected adult patients with eligible data on the presence of hepatic steatosis.

Six hundred thirty-six eligible studies were included in the analysis of SLD prevalence. Among patients with monoinfections, the highest SLD prevalence was observed in those infected with HCV at 49% (95% CI: 47%-51%), followed by SARS-CoV-2 (39%, 95% CI [34%-44%]), HIV (39%, 95% CI [33%-44%]), and HBV (36%, 95% CI [32%-40%]). Additionally, co-infections, such as HCV-HIV and HBV-HCV, exhibit even higher SLD prevalence. The prevalence of steatohepatitis is particularly high in HIV-infected (24%, 95% CI: 17%-30%) and HCV-infected (18%, 95% CI: 13%-24%) populations. The co-existence of SLD with viral infections was associated not only with the progression of liver disease but also with more severe outcomes of the infections and poorer responses to antiviral treatment. The combination of cardiometabolic risk factors and viral-associated and host factors contributes to the higher risk of SLD in viral-infected populations.

SLD is highly prevalent in viral-infected populations, and the reciprocal interactions between SLD and viral diseases exacerbate both conditions, leading to poorer patient outcomes in general.

Liver transplantation (LT) is still limited by organ shortage and post-transplant monitoring issues. While machine perfusion techniques allow for improving organ preservation, biomarkers like donor-derived cell-free DNA (dd-cfDNA) and mitochondrial cfDNA (mt-cfDNA) may provide insights into graft injury and viability pre- and post-LT.

A prospective observational cohort study was conducted on LT recipients (n = 45) to evaluate dd-cfDNA as a biomarker of graft dysfunction during the first 6 months after LT. Dd-cfDNA was quantified on blood samples collected pre-LT and post-LT using droplet digital PCR. In livers undergoing dual hypothermic oxygenated machine perfusion (D-HOPE), total cfDNA and mt-cfDNA levels were measured on perfusate samples collected at 30-min intervals. Correlations with graft function and clinical outcomes were assessed.

Dd-cfDNA levels peaked post-LT and correlated with transaminase levels and histological injury severity. The longitudinal assessment showed that postoperative complications and rejection were associated with an increase in dd-cfDNA levels. Mt-cfDNA levels in D-HOPE perfusate correlated with graft function parameters post-LT and were higher in patients with early allograft dysfunction and severe complications.

This study confirms dd-cfDNA as a marker of graft injury after LT and suggests that perfusate mt-cfDNA levels during D-HOPE correlate with graft function and post-transplant clinical outcome. Integration of these tests into clinical practice may improve transplant management and viability assessment during hypothermic perfusion.

Antifibrotic trials rely on conventional pathology despite recognized limitations. We compared single-fiber digital image analysis with conventional pathology to quantify the antifibrotic effect of Aramchol, a stearoyl-CoA desaturase 1 inhibitor in development for metabolic dysfunction-associated steatohepatitis.

Fifty-one patients with metabolic dysfunction-associated steatohepatitis enrolled in the open-label part of the ARMOR trial received Aramchol 300 mg BID and had paired pre-post treatment liver biopsies scored by consensus among 3 hepatopathologists, and separately assessed by a digital image analysis platform (PharmaNest) that generates a continuous phenotypic Fibrosis Composite Severity (Ph-FCS) score. Fibrosis improvement was defined as: ≥1 NASH Clinical Research Network (NASH-CRN) stage reduction; "improved" by ranked pair assessment; reduction in Ph-FCS ("any" for ≥0.3 absolute reduction and "substantial" for ≥25% relative reduction). Fibrosis improved in 31% of patients (NASH-CRN), 51% (ranked pair assessment), 74.5% (any Ph-FCS reduction), and 41% (substantial Ph-FCS reduction). Most patients with stable fibrosis by NASH-CRN or ranked pair assessment had a Ph-FCS reduction (a third with substantial reduction). Fibrosis improvement increased with treatment duration: 25% for <48 weeks versus 39% for ≥48 weeks by NASH-CRN; 43% versus 61% by ranked pair assessment, mean Ph-FCS reduction -0.54 (SD: 1.22) versus -1.72 (SD: 1.02); Ph-FCS reduction (any in 54% vs. 100%, substantial in 21% vs. 65%). The antifibrotic effect of Aramchol was corroborated by reductions in liver stiffness, Pro-C3, and enhanced liver fibrosis. Changes in Ph-FCS were positively correlated with changes in liver stiffness.

Continuous fibrosis scores generated in antifibrotic trials by digital image analysis quantify antifibrotic effects with greater sensitivity and a larger dynamic range than conventional pathology.

Few studies have compared survival outcomes between liver resection (LR) and percutaneous radiofrequency ablation (RFA) for treating solitary 3-5 cm hepatocellular carcinoma (HCC). We aimed to clarify this issue.

Patients with Child-Pugh class A liver disease and a solitary HCC of 3-5 cm without macrovascular invasion or extrahepatic metastasis who underwent LR or percutaneous RFA between 2011 and 2021 were enrolled in this retrospective study; 310 patients underwent LR and 114 patients underwent percutaneous RFA. Propensity score matching (PSM) was used to balance baseline variables, including age, sex, alpha-fetoprotein level, and Model for End-Stage Liver Disease score, between the two groups.

Before PSM, 5-year overall survival (OS) and recurrence-free survival (RFS) were significantly lower in the percutaneous RFA group than in the LR group (both p < 0.001). After PSM, 5-year OS was comparable between the two modalities (p = 0.367); however, 5-year RFS was significantly lower in the RFA group than in the LR group (p = 0.001). The two modalities did not differ in severe post-treatment complications (p = 1.000).

Five-year OS did not differ between treatment modalities for patients with a solitary HCC of 3-5 cm; however, the LR group's 5-year RFS was superior. LR should be recommended as the first-line treatment for these patients.

We aimed to develop a preoperative model to predict overall survival (OS) in patients with hepatoma undergoing liver resection (LR).

Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B hepatoma were enrolled. Tumor burden score (TBS) scores were determined using the following equation: TBS (Pinna et al., 2018) 2 = (largest tumor size [in cm])(Pinna et al., 2018) 2 ​+ ​(tumor number) (Pinna et al., 2018) 22. The cutoff values for radiographic TBS were based on our recently published paper: low, <2.6; medium, 2.6-7.9; high, >7.9.

Multivariate analysis showed that radiographic TBS (low: referent; medium: HR ​= ​2.89; 95 ​% CI: 1.60-5.21; p ​< ​0.001; high, HR ​= ​7.60; 95 ​% CI: 3.80-15.2; p ​< ​0.001), AFP (<400 ​ng/mL: referent; ≧400 ​ng/mL: HR ​= ​1.67, 95 ​% CI: 1.11-2.52, p ​= ​0.014), and cirrhosis (absence: referent; presence: HR ​= ​1.88, 95 ​% CI: 1.30-2.72, p ​< ​0.001) were associated with OS. A simplified risk score was superior to BCLC system in concordance index (0.688 vs. 0.623).

We have developed a preoperative model that performs better in predicting OS than the BCLC system.

Liver stiffness measurement (LSM) has been shown to adequately predict outcomes in patients with liver disease. However, the value of LSM as a predictor of disease progression in autoimmune hepatitis (AIH) remains to be determined. This study aimed to evaluate the role of LSM as a predictor of disease progression and decompensation of cirrhosis in patients with AIH.

This multicentre cohort study included 439 patients with histologically confirmed AIH and at least one LSM during follow-up. The association between the first LSM performed at least 6 months after treatment initiation (baseline LSM [BLSM]) and cirrhosis development and poor outcomes (decompensation, liver transplantation, and/or liver-related death) was assessed using Cox regression and its discriminating capacity with a receiver-operating characteristic curve.

Most patients were female (n = 301, 70%), with a median age of 52 years. BLSM performed after a median of 2.18 (1.19-4.68) years had a median value of 6 kPa (4.5-8.5). At the time of BLSM, 332 (76%) patients had achieved a biochemical response and 57 (13%) had cirrhosis. During follow-up, eight patients (2%) presented with poor outcomes and 26 (7%) developed cirrhosis. BLSM was higher among patients with poor outcomes (13.5 kPa vs. 6 kPa; p <0.001) and was independently associated with cirrhosis development (hazard ratio 1.300; p <0.001), irrespective of the achievement of biochemical response. A cut-off of 8.5 kPa accurately predicted cirrhosis development and poor outcomes, with AUCs of 0.859 (95% CI 0.789-0.929) and 0.900 (95% CI 0.847-0.954), respectively.

BLSM could play a significant role in predicting AIH outcomes, potentially identifying a subgroup of patients at a high risk of progressing to cirrhosis and experiencing decompensation.

The value of liver stiffness measurement as a predictor of outcomes in patients with autoimmune hepatitis (AIH) remains to be determined. In this large multicentre study, liver stiffness measurement was found to be an independent predictive factor of adverse clinical outcomes and cirrhosis development in AIH, irrespective of the achievement of biochemical response. A cut-off of 8.5 kPa accurately predicted cirrhosis development and poor outcomes in AIH.

Introduction: Non-invasive methods aim to predict the stage of liver fibrosis in line with histological findings via biopsy. Shear wave elastography and serum markers are proven as accurate non-invasive methods for determining liver fibrosis as a modern non-invasive methods compared to liver biopsy in staging hepatic fibrosis. Aims: This study aims to determine the correlation between Shear Wave Elastography and indirect and direct serum markers of fibrosis when staging liver fibrosis. Material and methods: The study was conducted in the Clinic of Gastroenterohepatology, the Institute of Immunology and Human Genetics, and the Institute of Pathology between 2021 and 2023. The study comprises 70 patients with liver lesions, diagnosed based on clinical results, laboratory tests, and ultra-sound imaging. All patients underwent liver biopsy, classified according to Ishak and Metavir score as a reference method for diagnosing liver fibrosis. Real-time shear wave elastography was also performed as a non-invasive method and serum markers were checked for liver fibrosis. Findings: The statistical analysis indicated a positive correlation between the values of direct and indirect liver fibrosis markers and Shear Wave Elastography results. Conclusion: Our study has demonstrated that shear wave elastography has a significant positive correlation with biochemical markers of liver lesions and serum markers of liver fibrosis, whereas it has a negative correlation with platelets.

Biliary atresia (BA) is a rare condition of unknown origin in newborns with jaundice. In BA bile ducts are non-functional, causing neonatal cholestasis and following liver fibrosis and failure.

This retrospective study included liver biopsies of 14 infants with BA aged [mean ± SD] 63 ± 23 days. Patients were grouped according to the clinical course (jaundice-free vs recurrent jaundice vs required liver transplantation or liver fibrosis (Ishak fibrosis score)) and followed for 1.61-5.64 years (mean 4.03). Transcriptome profiles were assessed using a panel of 768 fibrosis-specific genes, reanalyzed via qRT-PCR, and confirmed via immunostaining. Plasma from an additional 30 BA infants and 10 age-matched controls were used for amyloid precursor protein (APP) quantification by ELISA.

Different clinical outcome groups showed a homogeneous mRNA expression. Altered amyloid-metabolism-related gene expression was found between cases with Ishak fibrosis score greater than 4. Immunostaining confirmed a distinct presence of APP in the livers of all BA subjects. APP plasma levels were higher in BA than in age-matched controls and correlated with the histological fibrosis grade.

These results suggest that amyloidosis may contribute to BA and liver fibrosis, indicating that APP could serve as a potential liquid biomarker for these conditions.

Biliary atresia patients with higher fibrosis scores according to Ishak have higher hepatic expression of amyloid-related genes while amyloid precursor protein accumulates in the liver and increases in the circulation. After a recent study revealed beta-amyloid deposition as a mechanism potentially involved in biliary atresia, we were able to correlate amyloid-metabolism-related transcript levels as well as amyloid precursor protein tissue and plasma levels with the degree of hepatic fibrosis. These findings suggest that amyloid precursor protein is a fibrosis marker in infants with biliary atresia, reinforcing the role of amyloid metabolism in the pathogenesis of this serious disease.

Multiple studies have reported models for predicting early recurrence of hepatocellular carcinoma (HCC) after liver resection (LR). However, these models are too complex to use in daily practice. We aimed to develop a simple model.

We enrolled 1133 patients with newly diagnosed HCC undergoing LR. The Kaplan - Meier method and log-rank test were used for survival analysis and Cox proportional hazards analysis to identify prognostic factors associated with early recurrence (i.e., recurrence within two years after LR).

Early recurrence was identified in 403 (35.1%) patients. In multivariate analysis, alpha-fetoprotein (AFP) 20-399 vs. < 20 ng/ml (HR = 1.282 [95% confidence interval = 1.002-1.639]; p = 0.048); AFP ≥ 400 vs. < 20 ng/ml (HR = 1.755 [1.382-2.229]; p < 0.001); 7th edition American Joint Committee on Cancer (AJCC) stage 2 vs. 1 (HR = 1.958 [1.505-2.547]; p < 0.001); AJCC stage 3 vs. 1 (HR = 4.099 [3.043-5.520]; p < 0.001); and pathology-defined cirrhosis (HR = 1.46 [1.200-1.775]; p < 0.001) were associated with early recurrence. We constructed a predictive model with these variables, which provided three risk strata for recurrence-free survival (RFS): low risk, intermediate risk, and high risk, with two-year RFS of 79%, 57%, and 35%, respectively (p < 0.001).

We developed a simple model to predict early recurrence risk for patients undergoing LR for HCC.

Numerous studies have compared outcomes of liver resection (LR) of patients with non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) to those of patients with non-NAFLD-related HCC. However, results have been inconsistent. We aim to clarify this issue. We enrolled 801 patients with hepatitis B virus (HBV)-related HCC, 433 patients with hepatitis C virus (HCV)-related HCC, and 128 patients with NAFLD-related HCC undergoing LR. Overall survival (OS) and disease-free survival (DFS) of patients with different etiologies of chronic liver disease was compared using the Kaplan-Meier estimator and log-rank test after propensity score matching (PSM). After PSM, 83 patients remained in each group. The groups did not differ significantly in age, sex, the proportion of patients with pathological American Joint Committee on Cancer stage 1, tumor size > 50 mm, receipt of major resection, alpha-fetoprotein (AFP) ≥ 20 ng/ml, presence of cirrhosis, model for end-stage liver disease (MELD) score, and American Society of Anesthesiologists (ASA) classification. The five-year OS of patients with HBV-, HCV-, and NAFLD-related HCC was 78%, 75%, and 78%, respectively (p = 0.789). The five-year DFS of the HBV, HCV, and NAFLD groups was 60%, 45%, and 54%, respectively (p = 0.159). Perioperative morbidity was noted in 17 (20.5%) in the HBV group, 22 (26.5%) in the HCV group, and 15 (18.1%) in the NAFLD group (p = 0.398). The five-year OS, DFS, and perioperative morbidity of patients undergoing LR for NAFLD-related HCC and those for viral hepatitis-related HCC was similar.

In the last decade tight junction proteins exposed at the surface of liver or cancer cells have been uncovered as mediators of liver disease biology: Claudin-1 and Occludin are host factors for hepatitis C virus entry and Claudin-1 has been identified as a driver for liver fibrosis and hepatocellular carcinoma (HCC). Moreover, Claudins have emerged as therapeutic targets for liver disease and HCC. CLDN1 expression is upregulated in liver fibrosis and HCC. Monoclonal antibodies (mAbs) targeting Claudin-1 have completed preclinical proof-of-concept studies for treatment of liver fibrosis and HCC and are currently in clinical development for advanced liver fibrosis. Claudin-6 overexpression is associated with an HCC aggressive phenotype and treatment resistance. Claudin-6 mAbs or chimeric antigen receptor-T cells therapies are currently being clinically investigated for Claudin-6 overexpressing tumors. In conclusion, targeting Claudin proteins offers a novel clinical opportunity for the treatment of patients with advanced liver fibrosis and HCC.

Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue.

Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder.

Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1).

Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Pre-transplant deceased donor liver biopsy may impact decision making; however, interpretation of the results remains variable and depends on accepting center practice patterns.

In this cohort study, adult recipients from 04/01/2015-12/31/2020 were identified using the UNOS STARfile data. The deceased donor liver biopsies were stratified by risk based on degree of fibrosis, macrovesicular fat content, and level of portal infiltration (low-risk: no fibrosis, no portal infiltrates, and <30% macrosteatosis; moderate-risk: some fibrosis or mild infiltrates and <30% macrosteatosis; high-risk: most fibrosis, moderate/marked infiltrates, or ≥30% macrosteatosis). Graft utilization, donor risk profile, and recipient outcomes were compared across groups.

Of the 51,094 donor livers available, 20,086 (39.3%) were biopsied, and 34,606 (67.7%) were transplanted. Of the transplanted livers, 14,908 (43.1%) were biopsied. The transplanted grafts had lower mean macrovesicular fat content (9.3% transplanted vs. 26.9% non-transplanted, P < 0.001) and less often had any degree of fibrosis (20.9% vs. 39.9%, P < 0.001) or portal infiltration (51.3% vs. 58.2%, P < 0.001) versus non-transplanted grafts. Post-transplant recipient LOS (14.2 days high-risk vs. 15.2 days low-risk, P = 0.170) and 1-year graft survival (90.5% vs. 91.7%, P = 0.137) did not differ significantly between high- versus low-risk groups. Kaplan-Meier survival estimates further revealed no differences in the 5-year graft survival across risk strata (P = 0.833). Of the 5178 grafts biopsied and turned down, PSM revealed 1338 (26.0%) were potentially useable based on biopsy results and donor characteristics.

Carefully matched deceased donor livers with some fibrosis, inflammation, or steatosis ≥30% may be suitable for transplantation. Further study of this group of grafts may decrease turndowns of potentially useable organs.

The study aimed to evaluate the role of histologic scoring of liver biopsies using Ishak-modified histological activity index (HAI) and Laennec's scoring system in predicting chronic liver disease (CLD) prognosis in South India.

A retrospective analysis of liver biopsy samples was conducted at a tertiary care hospital. The samples were scored using the Ishak-modified HAI and Laennec's scoring system for staging and grading CLD. Patient clinical data were retrieved and assessed using the Child-Pugh scoring system. Chi-squared test was used to test the association between categorical variables and the association with multiple categories was reported using Cramer's V correlation coefficient. A p-value < 0.05 was considered significant.

Out of 43 samples included in the study, 65.12% were male patients, with a mean age of 43.3 ± 13.9 years. Cirrhotic cases accounted for the highest proportion (65.12%, n = 28), followed by hepatitis cases (30%, n = 13). The predominant etiology was alcohol-related (44.19%, n = 19). Percutaneous liver biopsies constituted most of the samples (48.84%, n = 21), followed by transjugular (37.21%, n = 16) and ultrasonography-guided (11.63%, n = 6) biopsies. The correlation between Ishak-modified HAI stages and Child-Pugh scores was weak and insignificant (p = 0.71), while Laennec's scores showed a moderate but insignificant correlation with Child-Pugh scores (p = 0.066).

Histologic scoring of liver biopsies using the Ishak-modified HAI and Laennec's scoring system can provide valuable prognostic information for CLD. However, further research is needed to establish stronger correlations with clinical outcomes.

Predicting recurrence patterns of hepatocellular carcinoma (HCC) can be helpful in developing surveillance strategies. This study aimed to use the hazard function to investigate recurrence hazard and peak recurrence time transitions in patients with HCC undergoing liver resection (LR). We enrolled 1204 patients with HCC undergoing LR between 2007 and 2018 at our institution. Recurrence hazard, patterns, and peak rates were analyzed. The overall recurrence hazard peaked at 7.2 months (peak hazard rate [pHR]: 0.0197), but varied markedly. In subgroups analysis based on recurrence risk factors, patients with a high radiographic tumor burden score (pHR: 0.0521), alpha-fetoprotein level ≥ 400 ng/ml (pHR: 0.0427), and pT3-4 (pHR: 0.0656) showed a pronounced peak within the first year after LR. Patients with cirrhosis showed a pronounced peak within three years after LR (pHR: 0.0248), whereas those with Barcelona Clinic Liver Cancer stage B (pHR: 0.0609) and poor tumor differentiation (pHR: 0.0451) showed multiple peaks during the 5-year follow-up period. In contrast, patients without these recurrence risk factors had a relatively flat hazard function curve. HCC recurrence hazard, patterns, and peak rates varied substantially depending on different risk factors of HCC recurrence.

Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR.

Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features-tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis-were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram's performance was evaluated using calibration plots with bootstrapping.

Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence.

We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.

Studies have rarely reported on preoperative predictors of prognosis of patients undergoing liver resection (LR) for HCC ≥10 cm. We developed a simple model to predict overall survival (OS) of these patients.

We enrolled 305 patients with HCC ≥10 cm undergoing LR. Cirrhosis and imaging-defined AJCC stage were used to develop a preoperative model. Patients were divided into three groups based on the Kaplan-Meier estimator.

Group 1 included patients with AJCC stage 1 and no cirrhosis (n = 86), group 2 those with AJCC stage 1 and cirrhosis plus those with AJCC stage 2 or 3 and no cirrhosis (n = 166), and group 3 those with AJCC stage 2 or 3 and cirrhosis (n = 51). The five-year OS of group 1, 2, and 3 was 55%, 32%, and 25%, respectively (p < 0.001). With group 1 as the reference, multivariate analysis of OS showed that group 2 (HR = 2.043; 95% CI = 1.332-3.134; p = 0.001) and group 3 (HR = 2.740; 95% CI = 1.645-4.564; p < 0.001) were independent predictors of OS.

We developed a simple model to predict OS of patients undergoing LR for HCC ≥10 cm.

The updated Barcelona Clinic Liver Cancer guidelines recommend liver resection (LR) for patients with single hepatocellular carcinoma (HCC) of any size. This study developed a preoperative model for predicting early recurrence in patients undergoing LR for single HCC.

We identified 773 patients undergoing LR for single HCC between 2011 and 2017 from the cancer registry database of our institution. Multivariate Cox regression analyses were performed to construct a preoperative model for predicting early recurrence, i.e., recurrence within 2 years of LR.

Early recurrence was identified in 219 patients (28.3%). The final model of early recurrence included four predictive factors-alpha-fetoprotein level of ≥20 ng/mL, tumor size of >30 mm, Model for End-Stage Liver Disease score of >8, and cirrhosis. Preoperative application of this model provided three risk strata for recurrence-free survival (RFS): low risk, with 2-year RFS of 79.8% (95% confidence interval [CI]: 75.7-84.2%); intermediate risk, with 2-year RFS of 66.6% (95% CI: 61.1-72.6%); and high risk, with 2-year RFS of 51.1% (95% CI: 43.0-60.8%).

We developed a preoperative model for predicting early recurrence after LR for single HCC. This model provides useful information for clinical decision-making.

The aim is to study the cellular and molecular features of toxic liver fibrosis in rats and its dependence on development stages of this pathological condition.

Liver fibrogenesis in male Wistar rats was induced with the thioacetamide solution by introducing into the stomach with a probe at a dose of 200 mg/kg of animal body weight 2 times per week. The process dynamics was studied at 5 time points (control, week 3, week 5, week 7, and week 9). The mRNA levels of tweak, fn14, ang, vegfa, cxcl12, and mmp-9 genes in liver were detected by real-time polymerase chain reaction. Immunohistochemical study was performed on paraffin sections. The CD31, CD34, CK19, α-SMA, FAP, CD68, CD206, CX3CR1, and CD45 cells were used as markers. Fibrosis degree was determined in histological sections, stained in line with the Mallory technique, according to the Ishak's semi-quantitative scale.

Two simultaneously existing morphologically heterogeneous populations of myofibroblasts expressing different types of markers (FAP, α-SMA) were identified in rat liver. Prior to the onset of transformation of fibrosis into cirrhosis (F1-F4, weeks 3-7), FAP+ and SMA+ cells were localized in different places on histological specimens. All stages of liver fibrosis development were accompanied by an increase in the number (p=0.0000), a change in the phenotypic structure and functional properties of macrophages. The CK19+ cells of the portal areas differentiated into cholangiocytes that formed interlobular bile ducts and ductules, as well as hepatocytes that formed rudiments of new hepatic microlobules. Pathological venous angiogenesis and heterogeneity of endotheliocytes of the intrahepatic vascular bed were detected. Two options for changes in mRNA expression of the selected genes were identified. The level of the fn14 and mmp-9 mRNAs at all stages of fibrosis was higher (p=0.0000) than in control rats. For tweak, ang, vegfa, and cxcl12 mRNAs, the situation was the opposite - the level of genes decreased (p=0.0000). There were strong and moderate correlations between the studied target genes (p<0.05).

It was established that the stages of toxic fibrosis had morphological and molecular genetic features. The FAP+ cells make the main contribution to development of portal and initial stage of bridging fibrosis. The stellate macrophages and infiltrating monocytes/ macrophages can potentially be used for development of new therapeutic strategies for liver pathology treatment. One should take into account the features of the markers' expression by endothelial cells during the study of the intrahepatic vascular bed. Joint study of genes is a necessary ad-hoc parameter in fundamental and preclinical research.

Fibroblast activity is a key feature of fibrosis progression and organ function loss, leading to liver-related complications and mortality. The fibrogenesis marker, PRO-C3, has been shown to have prognostic significance in relation to fibrosis progression and as a treatment efficacy marker. We investigated whether PRO-C3 was prognostic for clinical outcome and mortality in two distinct cohorts of compensated cirrhosis.

Cohort 1 was a rapid fibrosis progression cohort including 104 patients with HCV and biopsy-proven Ishak fibrosis stage ≥3 without prior clinical events. Cohort 2 was a prospective cohort including 172 patients with compensated cirrhosis of mixed aetiology. Patients were assessed for clinical outcomes. PRO-C3 was assessed in serum at baseline in cohorts 1 and 2, and compared with model for end-stage liver disease and albumin-bilirubin (ALBI) scores.

In cohort 1, a 2-fold increase in PRO-C3 was associated with 2.7-fold increased hazard of liver-related events (95% CI 1.6-4.6), whereas a one unit increase in ALBI score was associated with a 6.5-fold increased hazard (95% CI 2.9-14.6). In cohort 2, a 2-fold increase in PRO-C3 was associated with a 2.7-fold increased hazard (95% CI 1.8-3.9), whereas a one unit increase in ALBI score was associated with a 6.3-fold increased hazard (95% CI 3.0-13.2). A multivariable Cox regression analysis identified PRO-C3 and ALBI as being independently associated with the hazard of liver-related outcomes.

PRO-C3 and ALBI were independent prognostic factors for predicting liver-related clinical outcomes. Understanding the dynamic range of PRO-C3 might enhance its use for both drug development and clinical practice.

We tested novel proteins of liver scarring (PRO-C3) in two groups of liver patients with advanced disease to see if they could predict clinical events. We found that this marker and an established test called ALBI were both independently associated with future liver-related clinical outcomes.

The Barcelona Clinic Liver Cancer (BCLC) staging system has been recommended for prognostic prediction. However, prognosis is variable at different BCLC stages. We aimed to evaluate whether the radiographic tumor burden score (TBS) could be used to stratify prognosis in different BCLC stages.

Hepatocellular carcinoma (HCC) patients undergoing liver resection (LR) at BCLC-0, -A, or -B stage in our institution in 2007-2018 were divided into derivation and validation cohorts. Overall survival (OS) was analyzed according to the TBS and BCLC stage. TBS cutoff values for OS were determined with X-tile.

Of the 749 patients in the derivation cohort, 138 (18.4%) had BCLC-0, 542 (72.3%) BCLC-A, and 69 (9.2%) BCLC-B HCC; 76 (10.1%) had a high TBS (> 7.9), 477 (63.7%) a medium TBS (2.6-7.9), and 196 (26.2%) a low TBS (< 2.6). OS worsened progressively with increasing TBS in the cohort (p < 0.001) and in BCLC-A (p = 0.04) and BCLC-B (p = 0.002) stages. Multivariate analysis showed that the TBS was associated with OS of patients with BCLC-A (medium vs. low TBS: hazard ratio [HR] = 2.390, 95% CI = 1.024-5.581, p = 0.04; high vs. low TBS: HR = 3.885, 95% CI = 1.443-10.456, p = 0.007) and BCLC-B (high vs. medium TBS: HR = 2.542, 95% CI = 1.077-6.002, p = 0.033) HCC. The TBS could also be used to stratify the OS of patients in the validation cohort (p < 0.001).

The TBS could be used to stratify the OS of the entire cohort and BCLC stages A and B of HCC patients undergoing LR.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue.

We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan-Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis.

This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p = 0.694), cirrhotic patients (p = 0.753), non-cirrhotic patients (p = 0.146), patients with alpha-fetoprotein (AFP) > 20 ng/ml (p = 0.562), patients with AFP ≤ 20 ng/ml (p = 0.967), patients with Edmondson grade 1 or 2 (p = 0.615), patients with Edmondson grade 3 or 4 (p = 0.825), patients positive for hepatitis B surface antigen (HBsAg; p = 0.308), in patients positive for anti-hepatitis C virus (HCV) antibody (p = 0.781), or patients negative for both HBsAg and anti-HCV antibody (p = 0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio (HR): 1.338; 95% confidence interval (CI):0.737-2.431; p = 0.339).

No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.

To demonstrate that patients with pre-cirrhotic bridging fibrosis (Meta-analysis of Histological Data in Viral Hepatitis, METAVIR stage F3) and clinically significant portal hypertension (CSPH, Hepatic Venous Pressure Gradient ≥10 mmHg) experience a higher rate of clinical decompensation than patients without CSPH.

128 consecutive patients with pathology proven bridging fibrosis without cirrhosis between 2012 and 2019 were reviewed. Inclusion criteria were patients with HVPG measurement obtained during the same outpatient transjugular liver biopsy and clinical follow up of at least two years. Primary endpoint included rate of overall complication related to portal hypertension including evidence of either ascites, presence of varices on imaging or endoscopy, or evidence of hepatic encephalopathy.

Among 128 patients with bridging fibrosis (67 females and 61 males; average age 56 years), 42 (33%) and 86 (67%) were with and without CSPH (HVPG ≥10 mmHg). Median follow-up time was 4 years. Rate of overall complication (either ascites, varices or hepatic encephalopathy) in patients with and without CSPH was 36/42 (86%) and 39/86 (45%) (p < .001) respectively. Rate of developing ascites, varices and hepatic encephalopathy in patients with and without CSPH was 21/42 (50%) vs 26/86 (30%) (p = .034), 32/42 (76%) vs 26/86 (30%) (p ≤ .001) and 18/42 (43%) vs 12/86 (14%) (p = .001) respectively.

Patients with pre-cirrhotic bridging fibrosis and CSPH were associated with higher rates of developing ascites, varices and hepatic encephalopathy. Measuring HVPG during transjugular liver biopsy provides additional prognostic value in anticipating clinical decompensation in patients with pre-cirrhotic bridging fibrosis.

Developing liver disease treatments, in which fibrosis is a key pathogenetic link, still remains an urgent problem in hepatology. In the present study, the level of mmp-9 mRNA expression and the number of FAP+, α-SMA+, CD45+ cells were analyzed at nine time points of fibrosis and cirrhosis. It was found that in the case of liver fibrosis, the choice of the optimal reference gene depended on the stage of fibrogenesis. When studying the specific stages rather than the entire process in a long-term experiment, it was shown that choosing an optimal reference gene has to be done additionally. In this case, the mmp-9 mRNA expression level should be considered as a marker of liver fibrosis initiation and development but not as that of cirrhosis progression. In the liver, two morphologically heterogeneous populations of myofibroblasts were simultaneously identified as able to synthesize various types of immunohistochemical markers. It was found that the FAP+ cells were the main contributor to the development of portal fibrosis and the initial stages of bridging fibrosis. In the selected experimental model, fibrosis initiation and the development stages preceding parenchyma restructuring were accompanied by a low level of inflammation.

Tumor necrosis has been associated with poor prognosis in hepatocellular carcinoma (HCC) patients undergoing liver resection (LR). However, more evidence is needed to clarify this issue.

Patients who underwent upfront LR between 2010 and 2018 for newly diagnosed HCC without undergoing neoadjuvant therapy were enrolled in this retrospective study. Tumor necrosis was classified as present or absent according to retrospective examinations. The association between tumor necrosis, pathologic characteristics, overall survival (OS), and recurrence-free survival (RFS) were analyzed.

Among 756 patients who underwent LR for HCC, tumor necrosis was present in 279 (36.9%) patients. Compared with patients without tumor necrosis, patients with tumor necrosis had higher proportions of tumors sized >5.0 cm (P < 0.001), multiple tumors (P < 0.001), microvascular or macrovascular invasion (P < 0.001), poorly differentiated or undifferentiated tumors (P < 0.001), and T stage 3 or 4 (P < 0.001) on pathological examination. The presence of tumor necrosis was associated with worse OS and RFS compared with the absence of tumor necrosis: 5-y OS was 56% versus 78% (P < 0.001); 5-y RFS was 42% versus 55% (P < 0.001). In multivariate analysis, the presence of tumor necrosis was an independent factor associated with worse OS (hazard ratio: 1.956; 95% confidence interval: 1.409-2.716; P < 0.001) and RFS (hazard ratio: 1.422; 95% confidence interval: 1.085-1.865; P = 0.011).

Tumor necrosis was associated with worse OS and RFS among patients who underwent LR for HCC.

A recent study from the US showed a decreasing trend in the elevated serum alpha-fetoprotein (AFP) level (i.e., ≥20 ng/mL) in hepatocellular carcinoma (HCC) patients at the time of diagnosis. Furthermore, advanced tumor stage and severe underlying liver disease were associated with elevated AFP levels. We aimed to evaluate this issue in an area endemic for hepatitis B virus (HBV). Between 2011 and 2020, 4031 patients were newly diagnosed with HCC at our institution. After excluding 54 patients with unknown AFP data, the remaining 3977 patients were enrolled in this study. Elevated AFP level was defined as ≥20 ng/mL. Overall, 51.2% of HCC patients had elevated AFP levels; this proportion remained stationary between 2011 and 2020 (51.8% vs. 51.1%). Multivariate analysis showed that female gender (odds ratio (OR) = 1.462; p < 0.001), tumor size per 10 mm increase (OR = 1.155; p < 0.001), multiple tumors (OR = 1.406; p < 0.001), Barcelona Clinic Liver Cancer stages B-D (OR = 1.247; p = 0.019), cirrhosis (OR = 1.288; p = 0.02), total bilirubin > 1.4 mg/dL (OR = 1.218; p = 0.030), and HBV- or hepatitis C virus (HCV)-positive status (OR = 1.720; p < 0.001) were associated with elevated AFP levels. In conclusion, a stationary trend in elevated serum AFP level in HCC patients has been noted in the past 10 years. Advanced tumor stage, severe underlying liver disease, viral etiology, and female gender are associated with elevated AFP levels in HCC patients.

We evaluated whether combining the radiographic tumor burden score (TBS) and alpha-fetoprotein (AFP) level could be used to stratify overall survival (OS) among hepatocellular carcinoma (HCC) patients after liver resection (LR). Patients who underwent LR for Barcelona Clinic Liver Cancer stage 0, A, or B HCC between 2011 and 2018 were enrolled. TBS scores were calculated using the following equation: TBS2 = (largest tumor size (in cm))2 + (tumor number)2. Among 743 patients, 193 (26.0%) patients had a low TBS (<2.6), 474 (63.8%) had a moderate TBS (2.6-7.9), and 75 (10.1%) had a high TBS (>7.9). Those with a TBS ≤ 7.9 and AFP < 400 ng/mL had a significantly better OS than those with a TBS > 7.9 and an AFP < 400 ng/mL (p = 0.003) or ≥ 400 ng/mL (p < 0.001). A multivariate analysis using TBS ≤ 7.9 and AFP < 400 ng/mL as the reference values showed that a TBS > 7.9 and an AFP < 400 ng/mL (hazard ratio (HR): 2.063; 95% confidence interval [CI]: 1.175-3.623; p = 0.012) or ≥ 400 ng/mL (HR: 6.570; 95% CI: 3.684-11.719; p < 0.001) were independent predictors of OS. In conclusion, combining radiographic TBSs and AFP levels could stratify OS among HCC patients undergoing LR.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies.

Demographic, clinicopathological features, and survival outcomes of patients with surgically resected HCC were collected. NAFLD activity score (NAS) and fibrosis score were assessed by focused pathologic review in a subset of patients.

Among 492 patients screened, 260 met eligibility (NAFLD/NASH [n = 110], and other etiologies [n = 150]). Median age at diagnosis was higher in the NAFLD/NASH HCC cohort compared with the other etiologies cohort (66.7 vs. 63.4 years, respectively, P = .005), with an increased percentage of female patients (36% vs. 18%, P = .001). NAFLD/NASH-related tumors were more commonly >5 cm (66.0% vs. 45%, P = .001). There were no significant differences in rates of lymphovascular or perineural invasion, histologic grade, or serum AFP levels. The NAFLD/NASH cohort had lower rates of background liver fibrosis, lower AST and ALT levels, and higher platelet counts (P < .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant.

Patients with NAFLD/NASH-related HCC more commonly lacked liver fibrosis and presented with larger HCCs compared with patients with HCC from other etiologies. No differences were seen in rates of other high-risk features or survival. With the caveat of sample size and retrospective analysis, this supports a similar decision-making approach regarding surgical resection for NAFLD/NASH and other etiology-related HCCs.

To determine the impact of microvascular invasion (MVI) on outcome in patients with solitary hepatocellular carcinoma (HCC) of ≤ 2 cm undergoing liver resection (LR).

This retrospective study enrolled consecutive patients between 2007-2019 with newly diagnosed solitary HCC ≤ 2 cm who were undergoing LR at our institution. Overall survival (OS) and recurrent-free survival (RFS) were compared between patients with or without MVI.

Of the 229 patients included in this study, 71 had MVI. The median follow-up period was 28.8 months (interquartile range: 13.5-70.1). Although the 90-day mortality rate was 0, 18 deaths occurred during the study, and the 5-year survival rate was 87.1%. Tumor recurrence occurred in 45 cases, and 5-year RFS was 71.9%. The presence or absence of MVI did not significantly affect the OS and RFS rates (log rank test, p = 0.10 and 0.38, respectively). In univariate and multivariate analysis, the presence of MVI was not associated with OS and RFS.

The presence of MVI was not associated with OS and RFS in patients with solitary HCC ≤ 2 cm who underwent LR in this cohort.

Barcelona Clinic Liver Cancer (BCLC) guidelines designate monofocal hepatocellular carcinoma (HCC) > 2 cm as BCLC A, and large monofocal HCC is defined at > 5 cm. We aimed to evaluate the optimal cutoff value for large monofocal HCC based on prognosis stratification.

From 2011 to 2018, 3055 patients with newly diagnosed HCC, who were managed in our institution, including 868 patients with monofocal HCC > 2 cm and 330 patients with BCLC B, were enrolled in this retrospective study.

Monofocal HCC > 5 cm patients had worse overall survival (OS) than monofocal HCC 2-5 cm patients (5-year OS: 54% vs. 57%; p = 0.047), confirmed by multivariate analysis (hazard ratio (HR): 1.492, 95% confidence interval (CI): 1.055-2.110; p = 0.024). Monofocal HCC > 5 cm patients had better OS than BCLC B HCC patients (5-year OS: 54% vs. 25%; p < 0.001), confirmed by multivariate analysis (HR: 0.670, 95% CI: 0.481-0.934; p = 0.018). Using 7 cm as the monofocal HCC cutoff value resulted in worse OS than monofocal HCC 2-7 cm (5-year OS: 50% vs. 57%; p = 0.02), confirmed by multivariate analysis (HR: 1.625, 95% CI: 1.039-2.540; p = 0.033). Monofocal HCC > 7 cm patients had better OS than BCLC B patients (p = 0.006). However, no significant difference was identified in the multivariate analysis (HR: 0.726; 95% CI: 0.473-1.115; p = 0.144).

The prognosis of monofocal HCC > 7 cm was similar to that of BCLC B, indicating that 7 cm represents an optimal cutoff value for prognosis stratification in large monofocal HCC.

Analysis of host genetic polymorphisms is an increasingly important tool for understanding and predicting pathogenesis and treatment response of viral diseases. The gene locus of scavenger receptor class B type I (SR-BI), encoding a cell entry factor and receptor for hepatitis C virus (HCV), contains several genetic polymorphisms. We applied a probe extension assay to determine the frequency of six single nucleotide polymorphisms (SNPs) within the SR-BI gene locus in 374 individuals with history of HCV infection. In addition, SR-BI messenger RNA (mRNA) levels were analyzed in liver biopsy specimens of chronically infected HCV subjects. The rs5888 variant allele T was present at a higher frequency in subjects with advanced fibrosis (χ² , p = 0.016) and after adjusting for age, duration of infection and alcohol intake as confounding factors. Haplotype analysis of SNP frequencies showed that a haplotype consisting of rs61932577 variant allele C and rs5888 variant allele T was associated with an increased risk of advanced liver fibrosis (defined by an Ishak score 4-6) (adjusted odds ratio 2.81; 95% confidence interval 1.06-7.46. p = 0.038). Carriers of the rs5888 variant allele T displayed reduced SR-BI mRNA expression in liver biopsy specimens. In conclusion the rs5888 polymorphism variant is associated with decreased SR-BI expression and an increased risk of development of advanced fibrosis in chronic HCV infection. These findings provide further evidence for a role of SR-BI in HCV pathogenesis and provides a genetic marker for prediction of those infected individuals at greater risk of developing severe disease.

Advanced liver disease and portal hypertension (PH) are seen as a relative contraindication for bariatric and metabolic surgery. Several studies have shown significant improvement in liver function and liver histology after bariatric surgery. There are very few studies describing bariatric surgery in patients with PH. The purpose of this retrospective study is to evaluate the feasibility and results of laparoscopic sleeve gastrectomy (SG) in patients with PH.

We present our experience of performing laparoscopic SG in 15 patients with evidence of PH. All the patients were Childs Pugh Criteria A. PH was confirmed by the presence of dilated esophageal varices on endoscopy.

The mean operative time was 77.33 ± 15.22 min and mean blood loss was 80.67 ± 37.12 ml. The mean length of stay was 2.73 ± 0.59 days. There were no intraoperative or immediate postoperative complications. None of the patients required blood transfusion in the postoperative period. The weight, BMI, Excess body weight loss% (EBWL%), Total weight loss (TWL) and TWL% at 1 year were 86.05 ± 14.40 kg, 31.16 kg/m² ± 3.82, 63.84% ± 15.24, 31.49 ± 9.54 kg and 26.50 ± 5.42%, respectively. Diabetes and hypertension resolution at 1 year was 80% and 72.72%, respectively. All the patients were followed up for mean 3 ± 1.5 years. There were no immediate or long-term morbidity and mortality noted.

SG is a feasible and safe option for the treatment of obesity in carefully selected patients with PH with good weight loss and comorbidity resolution.

Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels.

This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017.

The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC.

This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.

A French study found that three preoperative factors (i.e. alpha-fetoprotein (AFP) > 100 ng/ml, image-diagnosed tumor number > 1, and cirrhosis) could predict non-transplantable recurrence (NTR) after liver resection (LR) for early-stage hepatocellular carcinoma (HCC). We aimed to evaluate whether this model could be applicable in an East Asian cohort from a country in which the majority of patients undergo living donor liver transplantation (LT). This retrospective study enrolled consecutive patients who underwent LR for transplantable HCC between 2011 and 2018 in our institution. The occurrence of NTR after LR was analyzed in a competing risks analysis, with death and transplantable recurrence as competing events. A total of 309 patients were included. The five-year overall survival and recurrence-free survival were 79.0% and 51.4%, respectively (median follow-up: 32.0 months). Recurrence was noted in 94 (30.4%) patients. NTR was noted in 35 (11.3%) patients. Univariate analysis showed that cirrhosis (sub-distribution hazard ratio (SHR) = 2.301, 95% CI = 1.046-5.065; p = 0.038) and image-diagnosed tumor number > 1 (SHR = 2.32; 95% CI = 1.11-4.86; p = 0.026) were associated with NTR, whereas AFP > 100 ng/ml (SHR = 1.56; 95% CI = 0.59-4.10; p = 0.37) was not associated with NTR. In the presence of 0, 1, and 2 factors (i.e. cirrhosis or image-diagnosed tumor number > 1), the NTR rates were 7.2%, 10.8%, and 29.0%, respectively. The results showed that the French model was applicable to our cohort. In the presence of two factors (i.e. cirrhosis and image-diagnosed tumor number > 1), risks and benefits of upfront LT could be discussed with the patient and the living donor.

To estimate the optimal density coefficient for conversion of liver volume into liver weight in patients with chronic liver disease based on semiautomated CT-liver volumetry data and the histologic Ishak score of explanted liver.

A total of 114 patients (39 female; age, 46±20 years) with chronic liver diseases who underwent liver transplantation between January 2010 and September 2020 were identified over a patient chart search at our institution and subsequently analyzed in retrospect. All patients had contrast-enhanced CT-examinations (mean, 24 days) to liver transplantation. Liver volume was calculated by a semiautomated software and results compared with the liver weight registered by the pathologist. Each explanted liver was histologically scored into six classes according to the Ishak classification where the categories were subgrouped based on recommendation of the pathologists into the following categories 0-3, 4-5 and 6.

Mean liver volume was 1,870±1,195, 1,162±679 and 1,278±510 mL for the categories 0-3, 4-5 and 6, respectively. Mean liver weight was 1,624±999, 1,082±669 and 1,346±559 g for the categories 0-3, 4-5 and 6, respectively. A coefficient of 0.92±0.22, 0.98±0.28 and 1.06±0.20 g/mL was found at best for conversion of liver volume into liver weight in these subgroups. Differences between Ishak-subgroups proved significant (0.002). In 4 patients with cystic liver disease, density coefficients varied significantly and were found generally lower compared to the other liver disorders.

Our results yielded significant differences between the density coefficients calculated along with the Ishak score and also for the subgroup with cystic liver disease.