Advanced Fibrosis Group Research Articles

Development of a diagnostic support system for the fibrosis of nonalcoholic fatty liver disease using artificial intelligence and deep learning.

Liver fibrosis is a pathological condition characterized by the abnormal proliferation of liver tissue, subsequently able to progress to cirrhosis or possibly hepatocellular carcinoma. The development of artificial intelligence and deep learning have begun to play a significant role in fibrosis detection. This study aimed to develop SMART AI-PATHO, a fully automated assessment method combining quantification of histopathological architectural features, to analyze steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD) core biopsies and employ Metavir fibrosis staging as standard references and fat assessment grading measurement for comparison with the pathologist interpretations. There were 146 participants enrolled in our study. The correlation of Metavir scoring system interpretation between pathologists and SMART AI-PATHO was significantly correlated (Agreement = 68%, Kappa = 0.59, p-value <0.001), which subgroup analysis of significant fibrosis (Metavir score F2-F4) and nonsignificant fibrosis (Metavir score F0-F1) demonstrated substantial correlated results (agreement = 80%, kappa = 0.61, p-value <0.001), corresponding with the correlation of advanced fibrosis (Metavir score F3-F4) and nonadvanced fibrosis groups (Metavir score F0-F2), (agreement = 89%, kappa = 0.74, p-value <0.001). SMART AI-PATHO, the first pivotal artificially intelligent diagnostic tool for the color-based NAFLD hepatic tissue staging in Thailand, demonstrated satisfactory performance as a pathologist to provide liver fibrosis scoring and steatosis grading. In the future, developing AI algorithms and reliable testing on a larger scale may increase accuracy and contribute to telemedicine consultations for general pathologists in clinical practice.

Assessment of Metabolic and Bariatric Surgery Safety in Patients with Advanced Liver Fibrosis.

The well-established relationship between obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) is a key etiological factor in the development of liver cirrhosis. Bariatric surgery is an effective treatment for weight loss in patients with moderate-to-severe obesity, also playing a role in controlling MASLD. However, surgical safety in patients with advanced fibrosis remains to be established. This study aimed to evaluate the safety and repercussions of bariatric surgery according to fibrosis stage. Patients undergoing bariatric surgery who had an intraoperative liver biopsy were retrospectively evaluated. Preoperative and postoperative data were collected from medical records, and results were stratified according to fibrosis stage into early fibrosis (no fibrosis or stages 1 and 2) and advanced fibrosis (stages 3 and 4). The study included 1185 patients: 1129 with early fibrosis and 56 with advanced fibrosis. The advanced fibrosis group had higher percentage of men (35.7% vs 21.6%, p = 0.014) and of people with diabetes (42.9% vs 16.5%, p < 0.001) and hypertension (57.1% vs 41.4%, p = 0.012). Patients with advanced fibrosis also required longer hospitalizations (4.64 vs 4.06days, p < 0.001) and were more frequently admitted to the intensive care unit (7.1% vs 2.9%, p = 0.038). The groups did not differ significantly in other outcomes. There were no deaths in either group. Bariatric surgery proved to be safe, with similar complication rates in patients with advanced fibrosis and in those with early fibrosis.

The relationship between advanced liver fibrosis and osteoporosis in type 2 diabetes patients with MAFLD.

To investigate the relationship between advanced liver fibrosis and osteoporosis in metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). A total of 1144 T2DM patients were divided into the MAFLD and non-MAFLD groups, 460 T2DM patients with MAFLD (277 males aged ≥50 years and 183 postmenopausal females) were divided into N1 (advanced liver fibrosis excluded), N2 (indeterminate advanced liver fibrosis), and N3 (advanced liver fibrosis) groups according to the non-alcoholic fatty liver fibrosis score (NFS), the differences in bone mineral density (BMD) levels and prevalence of osteoporosis were compared. Based on the tertile levels of BMD of the lumbar spine (L), T2DM patients were divided into three groups (T1, T2, and T3), and the differences in the prevalence of advanced liver fibrosis were compared. The BMD levels of the L4, and L1-4 in the MAFLD group were lower than those of the non-MAFLD groups in male and female T2DM patients .The BMD levels of the total hip, L4, and L1-4 in the N3 group were lower than those of the N2 and N1 groups in male and female T2DM patients with MAFLD, and the prevalence of osteoporosis in the N3 group of males was higher than that in the N1 group. The BMD levels of the total hip, L4, and L1-4 were negatively correlated with NFS in both males and females. The BMD levels of the total hip and L4 in males, and the BMD level of L4 in females were negatively associated with NFS. The prevalence of advanced liver fibrosis was higher in the T1 group than in the T2 and T3 groups in T2DM patients with MAFLD. The BMD levels in male aged ≥50 years or postmenopausal female diabetic patients with MAFLD were negatively correlated with the degree of advanced liver fibrosis, which means an increased risk of liver fibrosis with decreasing BMD.

High coffee consumption is not associated with less liver fibrosis in non-alcoholic steato-hepatitis: Results of the COCANASH study

BackgroundThe beneficial effect of coffee consumption on the progression of liver fibrosis in NASH is controversial. AimsTo compare coffee consumption in NASH patients with and without advanced fibrosis. MethodsCross-sectional observational study on 97 patients with NASH diagnosed by histology or the association of steatosis, metabolic syndrome, elastometry>6kPa, and exclusion of other liver diseases. Usual coffee and caffeine intake were assessed using a standardized questionnaire. Liver fibrosis was evaluated by elastometry (advanced fibrosis if ≥10kPa). ResultsAmong the 97 patients, 49 patients (51%) had non-advanced fibrosis (group 1) and 48 (49%) advanced fibrosis (group 2). The mean consumption of caffeine from coffee was 251mg±293 per day in group 1 and 257mg±286 per day in group 2 (P=0.92). In multivariable analysis, the odds ratio for the mean consumption of caffeine from coffee (100mg/d) between groups was 1.00 (1.00–1.00, P=0.92). There was no correlation between elastometry and the consumption of caffeine from coffee. ConclusionWe found no relationship between caffeine or coffee consumption and the degree of liver fibrosis in NASH. Our result does not support a beneficial effect of coffee consumption on the progression of fibrosis in NASH.

Agile 3+ and Agile 4, noninvasive tests for liver fibrosis, are excellent formulae to predict liver-related events in nonalcoholic fatty liver disease.

The noninvasive tests (NITs) Agile 3+ and Agile 4 effectively identify patients with nonalcoholic fatty liver disease (NAFLD) complicated with advanced fibrosis (F3-4) and cirrhosis (F4), respectively. Little information is available on associations between Agile scores and intra-/extrahepatic events. The aim of this study was to determine the predictive performance of Agile scores for intra-/extrahepatic events in Asian patients with biopsy-proven NAFLD. We undertook a retrospective multicenter cohort study to investigate associations between intra-/extrahepatic events and two Agile scores, Agile 3+ and Agile 4. The scores were obtained by combining clinical parameters and liver stiffness measurement using transient elastography. Among 403 enrolled patients, 11 had liver-related events (LREs), including seven with hepatocellular carcinoma (HCC). The incidence of LREs and HCC showed a stepwise increase in the advanced fibrosis group (F3-4), Agile 3+ rule-in (F3-4, highly suspected), and Agile 4 rule-in (F4, highly suspected) groups, compared to their counterparts. Hazard ratios for LREs in the advanced fibrosis group, Agile 3+ rule-in, and Agile 4 rule-in groups were 4.05 (p=0.03), 23.5 (p=0.003), and 45.5 (p<0.001), respectively. The predictive performance results for Agile 3+ and Agile 4 were 0.780 and 0.866, respectively, which were higher than for fibrosis (0.595). Unlike for LREs, Agile scores failed to identify patients with extrahepatic events, including cardiovascular events and extrahepatic cancer. Agile 3+ and Agile 4 scores are excellent NITs for predicting LREs in patients with NAFLD, possibly without histological assessment.

Multi-omics profiling of primary hepatic stellate cells from advanced liver fibrosis patients reveals distinctive molecular signatures.

Hepatic fibrosis is a common pathogenic outcome of almost all chronic liver diseases and a growing public health problem globally. However, the key genes or proteins driving liver fibrosis and cirrhosis are not well understood. We aimed to identify novel hepatic fibrosis genes of human primary hepatic stellate cells (HSCs). Human primary HSCs were isolated from surgically resected advanced fibrosis liver tissues (n=6) and surgical resection of normal liver tissue around hemangioma (n=5). Differences in the expression levels of mRNA and proteins from HSCs in advanced fibrosis group and the control group were analyzed using RNA sequencing and mass spectrometry as transcriptomic and proteomic approaches. The obtained biomarkers were further validated through real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and Western blot. A total of 2156 transcripts and 711 proteins were found to be differently expressed between the advanced fibrosis group and the control group patients. The Venn diagram shows that a total of 96 upregulated molecules are overlapped in both the transcriptomic and proteomic datasets. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis indicated that those overlapped genes were mainly involved in wound healing, cell adhesion regulation, and actin binding, which reflects the major biological conversions in liver cirrhosis process. Pyruvate kinase M2 and EH domain-containing 2 were identified as potential new markers for advanced liver cirrhosis, which have been validated in primary human HSCs and in vitro cellular hepatic fibrosis model Lieming Xu-2 (LX-2) cells. Our results revealed the major transcriptomic and proteomic changes during liver cirrhosis process and identified new biomarkers and potential therapeutic targets for advanced liver fibrosis.

Impact of Biopsy Proven Liver Fibrosis on Patients Undergoing Evaluation and Treatment for Advanced Heart Failure Surgical Therapies

There is a paucity of data regarding the impact of liver fibrosis on patients with stage D heart failure (HF). We conducted a retrospective study (January 1, 2017 to December 12, 2020) in patients with stage D HF who underwent liver biopsy as part of their advanced HF therapy evaluation. Baseline characteristics and 1-year outcomes were compared between no- or mild-to-moderate-fibrosis (grade 0 to 2) and advanced-fibrosis (grade 3 to 4) groups. Of 519 patients with stage D HF, 136 who underwent liver biopsy (113 [83%] no or mild-to-moderate fibrosis and 23 [17%] advanced fibrosis) were included. A total of 71 patients (52%) received advanced HF therapies (23 heart transplantation, 48 left ventricular assist devices). One-year mortality was higher among patients with advanced fibrosis (52% vs 18%, p <0.001). Further subgroup analysis suggested a trend toward increased 1-year mortality among patients with advanced fibrosis who underwent advanced therapies (37% vs 13%, p=0.09). There was a trend of lower likelihood of receiving advanced HF therapies in the advanced-fibrosis group, only 1 heart transplantation and 7 left ventricular assist devices, but it did not reach statistical significance (35% vs 56%, p=0.06). After adjustment for confounders, degree of liver fibrosis was an independent predictor of mortality (odds ratio 6.2; 95% 1.27 to 30.29, p=0.02). We conclude that advanced liver fibrosis is common among patients with stage D HF who undergo evaluation for advanced HF surgical therapies and significantly increases 1-year mortality. Further larger studies are needed to support our findings.

Ultrasound Radiomics for the Detection of Early-Stage Liver Fibrosis.

Objective: The study evaluates quantitative ultrasound (QUS) texture features with machine learning (ML) to enhance the sensitivity of B-mode ultrasound (US) for the detection of fibrosis at an early stage and distinguish it from advanced fibrosis. Different ML methods were evaluated to determine the best diagnostic model. Methods: 233 B-mode images of liver lobes with early and advanced-stage fibrosis induced in a rat model were analyzed. Sixteen features describing liver texture were measured from regions of interest (ROIs) drawn on B-mode images. The texture features included a first-order statistics run length (RL) and gray-level co-occurrence matrix (GLCM). The features discriminating between early and advanced fibrosis were used to build diagnostic models with logistic regression (LR), naïve Bayes (nB), and multi-class perceptron (MLP). The diagnostic performances of the models were compared by ROC analysis using different train-test sampling approaches, including leave-one-out, 10-fold cross-validation, and varying percentage splits. METAVIR scoring was used for histological fibrosis staging of the liver. Results: 15 features showed a significant difference between the advanced and early liver fibrosis groups, p < 0.05. Among the individual features, first-order statics features led to the best classification with a sensitivity of 82.1−90.5% and a specificity of 87.1−89.8%. For the features combined, the diagnostic performances of nB and MLP were high, with the area under the ROC curve (AUC) approaching 0.95−0.96. LR also yielded high diagnostic performance (AUC = 0.91−0.92) but was lower than nB and MLP. The diagnostic variability between test-train trials, measured by the coefficient-of-variation (CV), was higher for LR (3−5%) than nB and MLP (1−2%). Conclusion: Quantitative ultrasound with machine learning differentiated early and advanced fibrosis. Ultrasound B-mode images contain a high level of information to enable accurate diagnosis with relatively straightforward machine learning methods like naïve Bayes and logistic regression. Implementing simple ML approaches with QUS features in clinical settings could reduce the user-dependent limitation of ultrasound in detecting early-stage liver fibrosis.

Low plasma growth/differentiation factor 1 levels are associated with liver fibrosis in patients with stable angina.

Growth differentiation factor 1 (GDF1) is a member of the transforming growth factor-β (TGF-β) superfamily and a protective mediator against the development of post-infarction cardiac remodeling by negatively regulating MEK-ERK1/2 and Smad signaling pathways in the heart. The TGF-β/SMAD pathway has been shown to play a key role in the development of hepatic fibrosis. In addition, fatty liver disease has been associated with reduced MEK/ERK1/2 signaling. However, no previous study has investigated the association between GDF1 and liver fibrosis. Therefore, the aim of this study was to investigate the association between plasma GDF1 and liver fibrosis in patients with stable angina. We included 327 consecutive patients with stable angina. ELISA was used to measure circulating levels of GDF1, and the fibrosis-4 index was used to assess liver fibrosis. The advanced liver fibrosis group had lower median plasma GDF1 levels than those with minimal liver fibrosis. There was a significant negative association between GDF1 plasma level and fibrosis-4 index (r=-0.135, p=0.019). A lower concentration of GDF1 was significantly and independently associated with an increased risk of liver fibrosis when concentration was analyzed as a continuous variable and by tertile. In addition, fibrosis-4 index, aspartate aminotransferase (AST)-to-platelet ratio index, and AST/alanine aminotransferase ratio were significantly associated with GDF1 concentration. Our results indicated an association between low plasma GDF1 and liver fibrosis in the enrolled patients. Further investigations into the role of plasma GDF1 in the pathogenesis of liver fibrosis are warranted.

Characterization of Nutrient Intake in Biopsy-Confirmed NAFLD Patients.

Objectives: Weight loss improves the liver pathophysiological status of nonalcoholic fatty liver disease (NAFLD) patients. However, there are few studies that investigate the accurate relationships between nutritional intake and disease progression in NAFLD patients. Methods: A total of 37 biopsy-confirmed NAFLD patients were enrolled in this study. Clinical and nutritional control data of 5074 persons were obtained from the National Institute of Health and Nutrition. Each NAFLD subject recorded dietary intake for seven consecutive days using a dietary questionnaire and photographs of each meal. A dietitian analyzed and quantified the nutritional data in each patient. We further analyzed the nutritional intake of NAFLD patients in three groups according to the following criteria: (1) liver fibrosis degree (advanced, early), (2) gender (male, female), and (3) body mass index (BMI) (high, low). Results: Excesses or deficiencies of multiple nutrients were found in NAFLD patients compared with control subjects. In addition, there were variations in nutritional intake. (1) The intake of vitamins A, B6, and E, pantothenic acid, soluble dietary fiber, and salt was lower in the advanced fibrosis group than in the early fibrosis group. (2) Fat intake was higher in male patients, and dietary fiber intake was lower in both male and female patients compared with control subjects. (3) Saturated fatty acid intake was higher, and copper and vitamin E intakes were lower in patients with high BMI than with low BMI. Conclusions: Our study demonstrates that differences were found in some nutrient intake of NAFLD patients and controls and according to the severity of the conditions (liver fibrosis degree, BMI).

Association of Serum and Fecal Bile Acid Patterns With Liver Fibrosis in Biopsy-Proven Nonalcoholic Fatty Liver Disease: An Observational Study.

No reports on both blood and fecal bile acids (BAs) in patients with nonalcoholic fatty liver disease (NAFLD) exist. We simultaneously assessed the serum and fecal BA patterns in healthy participants and those with NAFLD. We collected stool samples from 287 participants from 5 hospitals in Japan (healthy control [HC]: n = 88; mild fibrosis: n = 104; and advanced fibrosis group: n = 95). Blood samples were collected and analyzed for serum BAs and 7α-hydroxy-4-cholesten-3-one (C4)-a surrogate marker for BA synthesis ability-from 141 patients. Concentrations of BAs, including cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid, ursodeoxycholic acid, and lithocholic acid (LCA), were measured using liquid chromatography-mass spectrometry. The total fecal BA concentration was significantly higher in the NAFLD group with worsening of fibrosis than in the HC group. Most of the fecal BAs were secondary and unconjugated. In the fecal BA fraction, CA, DCA, chenodeoxycholic acid, ursodeoxycholic acid, and LCA were significantly higher in the NAFLD than in the HC group. The total serum BA concentration was higher in the NAFLD group with worsening of fibrosis than in the HC group. In the serum BA fraction, CA, LCA, and C4 concentrations were significantly higher in the NAFLD than in the HC group. Fecal and serum BA and C4 concentrations were high in patients with NAFLD with worsening of fibrosis, suggesting involvement of abnormal BA metabolism in NAFLD with fibrosis progression. Abnormalities in BA metabolism may be a therapeutic target in NAFLD with fibrosis.

Gamma-glutamyl transpeptidase dynamics as a biomarker for advanced fibrosis in non-alcoholic fatty liver disease.

It is unclear whether changes in lipid profile and liver biochemistry are associated with advanced fibrosis. Patients diagnosed with non-alcoholic fatty liver disease (NAFLD) between 2009 and 2017 were included. The changes in blood tests were calculated as follows: [(value at 6months-value at baseline)/value at baseline]×100. The endpoint was advanced fibrosis determined by the NAFLD fibrosis score, calculated every year from diagnosis until 2019. Cox proportional hazards models were used to identify factors predicting advanced fibrosis. After a median follow-up of 31.7 (19.4-50.8) months, advanced fibrosis occurred in 64 (6.3%) of 1021 patients. Gamma-glutamyl transpeptidase (GGT) levels (72.9 vs 51.1IU/L; P=0.23) and ΔGGT (+6.0% vs -6.9%; P=0.06) were higher in the advanced fibrosis group. ΔGGT (hazard ratio [HR] 1.03; P<0.001) was significantly associated with advanced fibrosis after adjusting for age and platelet count. The positive ΔGGT group showed a higher incidence of advanced fibrosis and the 1-standard deviation increment in ΔGGT showed a significant association with advanced fibrosis both in statin users (HR, 1.35) and in non-users (HR, 1.31; Ps<0.05). The restricted cubic spline model identified a positive correlation between ΔGGT and the NAFLD fibrosis scores (P<0.001). ΔGGT showed sensitivity of 64.2%, specificity of 52.6%, and negative predictive value of 98.3% in predicting advanced fibrosis. ΔGGT calculated at 6months following NAFLD diagnosis is associated with advanced fibrosis.

Advanced Liver Fibrosis Is Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.

BackgroundNonalcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). However, the causal relationship between NAFLD and CKD is uncertain, particularly in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between the presence and severity of NAFLD and incident CKD in patients with T2DM.MethodsIn this longitudinal cohort study of patients with T2DM, 3,188 patients with preserved renal function were followed up for the occurrence of incident CKD. NAFLD was defined as the presence of hepatic steatosis on ultrasonography, without any other causes of chronic liver disease. Advanced liver fibrosis of NAFLD was defined as a fibrosis-4 index ≥2.67. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2.ResultsAt baseline, 1,729 (54.2%) patients had NAFLD, of whom 94 (5.4%) had advanced liver fibrosis. During the follow-up of 8.3±3.6 years, 472 (14.8%) patients developed incident CKD: 220 (15.1%) in the non-NAFLD group, 231 (14.1%) in the NAFLD without advanced fibrosis group and 28 (31.1%) in the NAFLD with advanced fibrosis group. There was no increased risk of incident CKD in the NAFLD group compared to the non-NAFLD group (P=0.435). However, among patients with NAFLD, advanced liver fibrosis was associated with an increased risk of CKD (adjusted hazard ratio, 1.75; 95% confidence interval, 1.15 to 2.66; P=0.009).ConclusionAdvanced liver fibrosis in patients with NAFLD is independently associated with an increased risk of incident CKD in patients with T2DM.

Prediction of Fibrosis in Chronic Hepatitis C by Mean Platelet Volume and Platelet to Lymphocyte Ratio

Abstract: Introduction: Hepatitis C is a chronic inflammatory condition that associated with fibrosis. Novel inflammatory markers have been suggested to be related inflammatory condition. Therefore, we aimed to investigate hemogram derived indices, such as, Mean Platelet Volume (MPV) and Platelet to Lymphocyte ratio (PLR) in hepatitis C subjects and to compare those in healthy controls. Materials and Methods: In present retrospective study, 17 HCV patients having mild fibrosis, 23 patients having advanced fibrosis and 68 control subjects were included whom visited outpatient clinics of our institution between 1.10. 2017 and 30.11.2019. Hemogram indices and laboratory characteristics were compared. Results: Median MPV values of the advanced fibrosis patients [8.3 (6.5-14) fL] was significantly higher than that of the mild fibrosis patients [7.9 (6.5-11.1) fL] (p=0.002) and control subjects [7.2 (4.6-10.7) fL] p&lt;0.001) whereas MPV values of mild and advanced fibrosis patients were similar (p=0.750). Median PLR values of the mild fibrosis, advanced fibrosis and control groups were 103 (58-223) %, 86 (45-358) %, and 77 (64-96) %, respectively (p=0.010). A ROC analysis revealed that a MPV value greater than 7.3 fL determines advanced fibrosis with 76% sensitivity and 59% specificity. A PLR greater than 92% determines advanced fibrosis with 73% sensitivity and 64% specificity. Conclusion: We suggest that elevated PLR and MPV could predict of advanced fibrosis in chronic hepatitis C. Keywords: Hepatitis C, Fibrosis, Platelet to lymphocyte ratio, Mean platelet volume, Hemogram indices, Liver cirrhosis.

Serum soluble cluster of differentiation 163 (sCD163), matrix metalloproteinase 9 (MMP9) and cytokeratin 18 (CK18) levels as biomarkers for liver fibrosis in Egyptian chronic hepatitis C patients

Abstract Liver fibrosis is a pathological disease in which extracellular matrix proteins, such as collagen, build up in the liver, causing tissue remodeling and the creation of persistent scar tissue. It has been associated to HCV infection, As a result, the objective of this study is to evaluate the levels of sCD163, MMP9, and CK18 as noninvasive biomarkers . A total of 100 subjects were divided into 4 groups for investigation. Group 1 consisted of healthy control subjects (Control group). Patients with HCV infection were divided into 3 groups based on their fibrosis grade: Group 2 (F0), Group 3 (F1-F2), and Group 4 (F3-F4). The ELISA technique was used to assess the levels of direct serum indicators sCD163, MMP9, CK18, and AFP. A complete blood count, serum ALT, AST, albumin, total bilirubin, and INR were measured. In addition, as indirect biomarkers, the FIB-4 score and the AST/ALT Ratio (AAR) were reported. Results indicated that the levels of sCD163, CK18, and AFP were increased significantly in all HCV infected groups, compared to controls, with the highest levels in the advanced groups. MMP9 was decreased in low grade fibrotic HCV groups, but significantly increased in advanced liver fibrosis group. FIB-4 and AAR showed a significant increase in all HCV patients, compared to control group. From the obtained data, the performance of MMP9 was the most accurate direct blood biomarker for evaluating the advanced fibrosis (Group 4). In addition, CK18 and sCD136 showed promising results.

Serum Peptidyl-prolyl Cis-trans Isomerase NIMA-interacted 1 (Pin1) as a Non-invasive Marker for Liver Fibrosis due to Chronic Hepatitis C Virus.

Background: Hepatitis C virus (HCV) may remain asymptomatic or cause liver fibrosis and cirrhosis. Objectives: We aimed to assess the relationship between serum peptidyl-prolyl cis-trans isomerase NIMA-interacted 1 (Pin1) levels and liver fibrosis due to HCV. Methods: Serum samples of successive patients with HCV genotype 1b and healthy volunteers were collected, and Pin1 levels were measured using ELISA kits. Liver fibrosis stages were calculated by the Ishak Scoring System and subdivided into two groups; stage &lt; 3 (mild fibrosis) and ≥ 3 (advanced fibrosis). Correlation and area under receiver operating characteristics (AUROC) analysis were used to investigate the relationship between Pin1 and clinical and histopathological properties of HCV infection. Results: Ninety-four patients with HCV and 47 age- and sex-matched volunteers were included. The median age of the participants was 52, and 55% of whom were females. The mean (SD) of Pin1 serum level was significantly higher in the HCV group compared with healthy volunteers (33.94 (21.15) vs. 26.82 (8.85) pg/mL, respectively, P = 0.007). Seventy-seven (82%) and 17 (18%) of the participants showed mild and advanced fibrosis, respectively. Pin1 serum levels were significantly lower in the mild compared with advanced fibrosis group (29 (17.88) vs. 43.59 (7.98) pg/mL, respectively, P &lt; 0.001). We found a significantly positive correlation between Pin1 serum level and liver fibrosis stage (r = 0.71, P &lt; 0.001). The cut off of 33.04 pg/mL of Pin1 serum level showed the best sensitivity (100%) and specificity (68.4%) (AUROC = 0.81 [95% confidence interval: 0.72 - 0.90], P &lt; 0.001) for distinguishing advanced from mild liver fibrosis. Conclusions: Serum Pin1 level may be a relevant marker for predicting liver fibrosis in HCV infected patients.

A novel non-invasive score for the prediction of advanced fibrosis in patients with chronic hepatitis B

Introduction and objectivesEvaluation of liver fibrosis is important for treatment decisions, complications and to predict prognosis in patients with chronic hepatitis B (CHB). Our aim was to develop a new non-invasive fibrosis scoring method and prove its accuracy in the differentiation of no/low grade and advanced fibrosis in patients with CHB. Patients and methodsOur study included 273 chronic hepatitis B patients who underwent liver biopsy from February, 2007 to February, 2019 with medical records retrospectively reviewed. Preparations of these patients were divided into two groups as ≤ 3 no-low grade fibrosis (n=236) and ≥ 4 advanced fibrosis (n=37) according to histological ISHAK fibrosis scoring system. ResultsThe newly developed AGAP score and other non-invasive fibrosis scores; Fibrosis-4 index, Aspartate aminotransferase to platelets ratio, Gamma glutamyl transpeptidase to platelet ratio, Goteborg University Cirrhosis Index, King's score, Albumin-bilirubin index, Fibrosis cirrhosis index, Fibrosis index, Fibrosis quotient, Lok score and mean and/or median values of Fibroindex were significantly higher in the advanced fibrosis group compared to the no/low grade fibrosis group (p<0.001). However, there was no significant difference in AAR score among the groups (p=0.265). With cut-off value of 4.038, AUROC value of 0.803, sensitivity of 75.7%, specificity of 73.7% and accuracy of 0.740, AGAP score showed the best performance in advanced fibrosis differentiation compared to 12 other non-invasive fibrosis scoring methods. ConclusionsThe newly developed AGAP score showed better performance in patients with CHB compared to 12 other non-invasive fibrosis scores in differentiation of no/low grade fibrosis and advanced fibrosis.

Type 2 diabetes mellitus increases the risk of hepatic fibrosis in individuals with obesity and nonalcoholic fatty liver disease.

ObjectiveThis study assessed the impact of diabetes mellitus (DM) on nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) with advanced fibrosis prevalence in adults with overweight or obesity in the United States.MethodsParticipants (National Health and Nutrition Examination Survey [NHANES] 2015‐2016 database) included 834 middle‐aged patients with DM (21.7%) and 3,007 without DM (78.3%). NAFLD was defined by Fatty Liver Index (FLI) ≥ 60 or United States FLI (USFLI) ≥ 30. Moderate‐to‐high and high risk of advanced fibrosis was defined by fibrosis‐4 index (FIB‐4) ≥ 1.67 and ≥ 2.67, respectively, and NAFLD fibrosis scores > 0.676 also indicated a high risk.ResultsNAFLD prevalence increased with BMI. Steatosis was higher in individuals with overweight with DM versus without DM (USFLI ≥ 30: 48.3% vs. 17.4%; p < 0.01) and in individuals with obesity with DM versus without DM (USFLI ≥ 30: 79.9% vs. 57.6%; p < 0.01). DM significantly increased the proportion of individuals at moderate‐to‐high risk of fibrosis (FIB‐4 ≥ 1.67: 31.8% vs. 20.1%; p < 0.05). In the high risk of advanced fibrosis group (FIB‐4 ≥ 2.67), the risk almost doubled (3.8% vs. 7.1%). Among individuals with obesity, DM increased the proportion of adults with moderate and high risk of fibrosis by 1.8‐ and 2.5‐fold, respectively (p < 0.01 and p = 0.39, respectively, vs. without DM).ConclusionsIn this US cohort, DM modestly impacted steatosis, which was primarily obesity‐driven. DM added a significant risk of fibrosis to individuals with overweight or obesity, suggesting that screening is imperative in adults with DM.

Alteration of prognostic efficacy of albumin-bilirubin grade and Child-Pugh score according to liver fibrosis in hepatocellular carcinoma patients with Child-Pugh A following hepatectomy.

BackgroundThe albumin‐bilirubin (ALBI) grade was developed to predict the prognosis of patients with hepatocellular carcinoma (HCC), which can stratify the prognosis even in HCC patients with Child‐Pugh A. We evaluated the prognostic efficacy of the ALBI grade and Child‐Pugh classification in HCC patients with Child‐Pugh A stratified by the presence or absence of advanced fibrosis or a preoperative biomarker for advanced fibrosis.MethodsWe retrospectively analyzed 490 consecutive HCC patients with Child‐Pugh A who underwent initial hepatectomies. The accuracy of prognostic prediction using both models was compared by the presence or absence of advanced fibrosis (F3‐4) and its predictor, the preoperative platelet count (PLT).ResultsThe prognostic accuracy of the ALBI grade was better in patients without advanced fibrosis (F3‐4; likelihood ratio: 4.39, corrected Akaike information criterion [AICc]: 453.0, P = .074), but Child‐Pugh score was better in the advanced fibrosis group (likelihood ratio: 10.67, AICc: 915.2, P = .0014). In the high PLT group (≥140 × 103/μL), the prognostic accuracy using the ALBI grade was better in overall survival (OS) and relapse‐free survival (RFS), but in the low PLT group, the Child‐Pugh score was the more accurate model in OS and RFS.ConclusionsDepending on the degree of fibrosis or preoperative PLT, the ALBI grade and Child‐Pugh score may provide more accurate prognoses after initial hepatectomy in HCC patients with Child‐Pugh A.

Evaluation of the Impact of Metabolic Syndrome on Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic syndrome (MS) is a condition that consists of several disorders, and the individual impact of these disorders on metabolic dysfunction-associated fatty liver disease (MAFLD) is still not clear in a combined diagnosis of MS. In this study, we aimed to investigate the effect of MS on advanced fibrosis in patients with MAFLD. We recruited the patients from our gastroenterology out-patient clinic who were being followed up for MAFLD. MAFLD was diagnosed with liver biopsy in all patients. The frequency of MS and other metabolic parameters were also compared between groups with advanced fibrosis and groups in which fibrosis was not as advanced. In total, we enrolled 424 biopsy-proven MAFLD patients to the study. In univariate analysis, individuals with greater age, body mass index (BMI), higher aspartate transaminase (AST), MS, impaired fasting glucose, hypertension, enlarged waist circumference (WC), diabetes mellitus (DM), and women had significantly increased risk for fibrosis. In multivariate analysis, it was found that DM, greater age, higher BMI, and increased AST were seen more commonly in MAFLD patients with advanced fibrosis. Greater age, a higher BMI, higher AST and a diagnosis of diabetes were more commonly associated with advanced fibrosis. However, DM was found to be the strongest predictive factor of advanced fibrosis in our cohort (OR: 2.495). Multivariate analyses did not indicate a significantly common occurrence of MS in the advanced fibrosis group, despite its important role in MAFLD pathophysiology.