Cirrhosis Index Research Articles

A Comparative Study of Novel Fibrosis Index and Other Non-invasive Serum Indices for Predicting Fibrosis in Patients of Chronic Liver Disease.

Introduction Chronic liver diseaseprogression leads to liver fibrosis/cirrhosis. Transient Elastography is used for staging liver fibrosis but ascites, obesity, and operator experience limit its applicability. In this study, we compared various non-invasive serum indices in predicting fibrosis in chronic liver disease patients. Materials and methods A total of 142 cases of confirmed Chronic Liver Disease were included. Quantitative determination of liver stiffness by Transient Elastography and relevant blood investigations was done. We compared the liver stiffness measurement by Transient Elastography and fibrosis indices, i.e., Aspartate Transaminase (AST) to Alanine Transaminase (ALT) Ratio (AAR), AST to Platelet Ratio Index (APRI), Fibrosis Index (FI), Fibrosis-4 (FIB-4) Index, Age-Platelet Index (API), Pohl score, and Fibrosis Cirrhosis Index (FCI) with Novel Fibrosis Index (NFI), to predict liver fibrosis stages. Results The optimum cutoff of NFI for the F4 stage was ≥ 6670 with a sensitivity of 75.8% and specificity of 81.8%, for the F3 stage was ≥ 2112 with a sensitivity of 63.6%and specificity of 72.7%, and for the F2 stage was ≥ 1334 with a sensitivity of 100% and specificity of 56.3%. The NFI had the maximum area under the curve compared to other indices in predicting fibrosis stages. Conclusion The Novel Fibrosis Index was the best in predicting fibrosis stages in Chronic Liver Disease patients, with good performance in predicting the F4 stage.

The contribution of imaging to non-invasive fibrosis biomarkers in the diagnosis and staging of chronic liver disease

Aims: Gold standard technique for determining the stage of fibrosis in cirrhosis is a biopsy. Non-invasive tests are used when a biopsy is contraindicated. However, their specificity and sensitivity still fall short of expectations. Aim of the study is to develop a model capable of determining fibrosis using serum biomarkers and liver ultrasonography. Methods: A retrospective study was designed including patients with chronic hepatitis B and C underwenting liver biopsies between the time frame of 2015 to 2020 years at Trakya University School of Medicine. Epidemilogical data, ltrasonography and pathology reports were noted. Blood values were recorded and used to calculate AST / Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4), Gothenburg University Cirrhosis Index (GUCI) noninvasive fibrosis indices. The fibrosis stages of the patients were assessed accoridng to pathology reports into three categories: advanced (F5-F6), moderate (F3-F4), and lower Ishak scores. Results: A total of 259 patients were included in the study. The median age of the patients was 54 (19-90), and 40.9% (106) were female. The median values of APRI, GUCI and FIB-4 scores were respectively: 0.6 (0-21.8), 0.6 (0-26.2) and 1.6 (0.2-8.5). The effects of ultrasonography findings were examined to improve the diagnostic performance of APRI, GUCI and FIB-4 indices. Accompanied by statistical analysis, it was observed that the FIB-4 index and the presence of hepatosteatosis in the liver had a significant effect on the detection of F?3 (respectively; p<0.001, p=0.033). A new model named FIB4u (ultrasonography) was developed. The AUC values of indices for differentiation of intermediate and advanced stages of fibrosis (?3) were respectively:FIB4u 0.760; FIB-4 0.753; GUCI 0.676; APRI 0.667 (p<0.001). The FIB4u index demonstrated considerably better performance compared to both APRI and GUCI. Conclusion: The FIB4u index, developed by combining ultrasonography and laboratory data, can be used as a new index for fibrosis assessment in the absence of advanced elastography techniques. It needs to be validated in larger patient cohorts to be used safely in the long term.

Analysis of liver fibrosis equations as a potential role of predictive models in Crimean-Congo hemorrhagic fever

Crimean-Congo Hemorrhagic Fever (CCHF) is a formidable global health concern, characterized by its rapid onset and high fatality rate. Distinguishing between patients at different stages remains challenging because of overlapping clinical features. This study aimed to evaluate the diagnostic efficacy of 14 hepatic fibrosis indices for distinguishing fatal cases and intensive care unit requirement (ICU) in CCHF. This study enrolled 194 patients with confirmed CCHF. Laboratory measurements were performed using auto analyzers. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas. Time-dependent receiver operating characteristic (tdROC) curve analyses were employed to evaluate the predictive effects of hepatic fibrosis indices on both intensive care unit requirement and overall survival among patients. Regarding the tdROC analyses results, the highest area under the curve statistics were obtained for the baseline S-INDEX, KING, and GPRI scores (0.920, 0.913, and 0.909 respectively) in the estimation of ten-day survival, and the baseline KING, Goteborg University cirrhosis index (GUCI), and gamma-glutamyl transferase to platelet ratio index (GPRI) scores (0.783, 0.773, and 0.769 respectively) in the estimation of intensive care requirements for up to ten days. S-index and KING index emerged as early predictors of ten-day survival, while KING, GUCI, and GPRI indices demonstrated predictive capabilities for ICU admission on the first day. The identified indices have the potential to assist healthcare providers in making timely and informed decisions regarding patient management and treatment strategies. Further research and validation are warranted to solidify the role of these hepatic fibrosis indices in the clinical setting and enhance their broader applicability in the management of CCHF.

Опыт противовирусной терапии хронического гепатита D в Республике Саха (Якутия)

Objective. To analyze the results of antiviral therapy of patients with chronic hepatitis D (CHD) in the Republic of Sakha (Yakutia). Patients and Methods. Interim treatment outcomes over 48 weeks were studied in 36 patients receiving bulevirtide monotherapy (30 patients) and in combination with peginterferon alfa (6 patients); 11 of these patients were followed for more than 48 weeks, up to 54–118 weeks (5 and 6 patients, respectively). Results. After 48 weeks of treatment, there was a decrease in the median HDV RNA level from 7.1 log10 to 4.6 log10, with a median reduction of 2.2 log10 ( p < 0.001) (2.1 log10 with monotherapy (p < 0.001), 4.1 log10 with combination therapy), a virologic response rate of 64% (53% and 100%, respectively); and an aviremia rate of 18% (2 patients in each group). The median ALT level decreased from 63.0 to 33.0 U/L, the frequency of detection of normal ALT level increased from 24 to 67% (in the monotherapy group – from 18 to 69%). When treatment was continued for more than 48 weeks (up to 54–118 weeks), maintenance and/or improvement of virologic and biochemical response was observed in the majority of patients. The treatment was characterized by good tolerability, absence of serious adverse events, cases of treatment withdrawal, worsening of liver function indices in cirrhosis. Conclusion. Analysis of interim results of bulevirtide application in real practice demonstrated efficacy, safety and good tolerability of treatment, both in combination therapy and monotherapy, including in compensated liver cirrhosis. Further accumulation of treatment experience is necessary in order to develop an optimal treatment algorithm. Key words: bulevirtide, chronic hepatitis D, combined therapy, cirrhosis, monotherapy

Machine-learning model comprising five clinical indices andliver stiffness measurement can accurately identify MASLD-related liver fibrosis.

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

Comparison of the optimized direct spectrophotometric serum prolidase enzyme activity assay method with the currently used spectrophotometric assay methods and liver fibrosis indexes to distinguish the early stages of liver fibrosis in patients with chronic hepatitis B infection.

The aim of this study was to optimize the currently used direct spectrophotometric serum prolidase enzyme activity (SPEA) assay method and compare its diagnostic accuracy with current precipitation and direct spectrophotometric assay methods, AST-to-ALT ratio, age platelet index, AST-to-platelet ratio index, cirrhosis discriminate score, Doha score, FIB-4, FibroQ, fibrosis index, Goteborg University Cirrhosis Index , King's score, and Pohl score for distinguishing Ishak F0 from F1-F3 in patients with chronic hepatitis B (CHB) infection. Liver biopsy results from 112 patients were included in this study. The SPEA values were 529(292-794) U/L, 671(486-927) U/L, and 1077(867-1399) U/L with the precipitation, current, and optimized direct spectrophotometric assay methods, respectively. According to multivariate logistic regression analysis optimized direct spectrophotometric SPEA was the only statistically significant parameter to predict the early stages of liver fibrosis. Optimized direct spectrophotometric SPEA assay method could be used to distinguish early stages of liver fibrosis in patients with CHB infection instead of the currentlyused spectrophotometric SPEA assay methods and other evaluated liver fibrosis indexes.

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial

Patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis. This double-blind, placebo-controlled phase 2 trial enrolled patients from 38 centres in Europe and the USA. Adults with biopsy-confirmed NASH-related cirrhosis and body-mass index (BMI) of 27 kg/m2 or more were randomly assigned (2:1) to receive either once-weekly subcutaneous semaglutide 2·4 mg or visually matching placebo. Patients were randomly allocated via an interactive web response system, stratified by presence or absence of type 2 diabetes. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH after 48 weeks, assessed by biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is closed and completed, and registered with ClinicalTrials.gov, number NCT03987451. 71 patients were enrolled between June 18, 2019, and April 22, 2021; 49 (69%) patients were female and 22 (31%) were male. Patients had a mean age of 59·5 years (SD 8·0) and mean BMI of 34·9 kg/m2 (SD 5·9); 53 (75%) patients had diabetes. 47 patients were randomly assigned to the semaglutide group and 24 to the placebo group. After 48 weeks, there was no statistically significant difference between the two groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH (five [11%] of 47 patients in the semaglutide group vs seven [29%] of 24 in the placebo group; odds ratio 0·28 [95% CI 0·06-1·24; p=0·087). There was also no significant difference between groups in the proportion of patients who achieved NASH resolution (p=0·29). Similar proportions of patients in each group reported adverse events (42 [89%] patients in the semaglutide group vs 19 [79%] in the placebo group) and serious adverse events (six [13%] vs two [8%]). The most common adverse events were nausea (21 [45%] vs four [17%]), diarrhoea (nine [19%] vs two [8%]), and vomiting (eight [17%] vs none). Hepatic and renal function remained stable. There were no decompensating events or deaths. In patients with NASH and compensated cirrhosis, semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo. No new safety concerns were raised. Novo Nordisk A/S.

Performance of Non-invasive Biomarkers of Liver Fibrosis Amongst Hispanics and African Americans.

Liver biopsy is the gold standard for fibrosis staging. However, it is limited by significant complications. Non-invasive markers of fibrosis have been developed as an alternative to liver biopsy. The performance of these different markers varies with the etiology of liver fibrosis and possibly amongst different ethnicities. We aim to assess the performance of non-invasive markers of liver fibrosis amongst Hispanics and African Americans. This is a retrospective cohort analysis of patients who had liver biopsy as part of their evaluation of chronic liver disease. One hundred and twenty-six records were analyzed. Univariate and multivariate analyses were performed. Probit regression receiver operating characteristic curve analysis was used to assess the sensitivity of the different non-invasive biomarkers and underlying variables with respect to liver biopsy. The following non-invasive markers for fibrosis were used: Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), age-platelet, AST/alanine aminotransferase (AST/ALT) ratio, fibrosis cirrhosis index (FCI), and fibrosis index (FI). About two-thirds of the study population were African Americans with majority of the study population having chronic liver disease from viral infection. Minimal to no fibrosis by the METAVIR (an acronym for Meta-analysis of Histological Data in Viral Hepatitis) score was found in 58% of patients compared to 42% with moderate to severe fibrosis. Hispanics were more likely than Blacks to have hepatic steatosis. Age significantly increased the sensitivity and specificity of APRI and age-platelet scores. The AST/ALT score had a lower sensitivity for liver fibrosis in women compared to men in our study population. The sensitivity of FIB-4 and age-platelet was higher in Hispanics compared to African Americans while the opposite was the case for APRI, AST/ALT, FCI, and FI. Non-invasive biomarkers are useful in detecting liver fibrosis. FIB-4 and age-platelet have a high sensitivity in Hispanics while African Americans have a high sensitivity for APRI, AST/ALT, FCI, and FI. It is worth noting that these non-invasive biomarkers had variable performances when ethnicity, age, and sex were considered in our population.

Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta.

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB). Liver stiffness was assessed by transient elastography (TE) in CHD. The ability of fibrosis markers to detect significant fibrosis and cirrhosis were evaluated in 202 CHB and 108 CHD patients using published and new cut-offs through receiver operating characteristics (ROC) analysis. The latter was also applied to obtain cut-offs for TE. APRI, Fib-4, API and Hui score were assessed for significant fibrosis, and APRI, GUCI, Lok index, CDS and AAR for cirrhosis determination. Fibrosis markers displayed weak performance in CHB for significant fibrosis with area under ROC (AUROC) curves between 0.62 and 0.71. They did slightly better for CHD. TE displayed an AUROC of 0.92 and performed better than serum fibrosis markers (p< 0.05 for fibrosis markers). For cirrhosis determination, CDS and Lok Index displayed an AUROC of 088 and 0.89 in CHB and GUCI, Lok index and APRI displayed AUROCs around 0.90 in CHD. TE displayed the best AUROC (0.95). Hence TE is superior to serum fibrosis markers for diagnosing significant liver fibrosis and cirrhosis. GUCI, Lok index and APRI displayed a reasonable performance in CHD, which needs further confirmation.

U-shaped relationship between subcutaneous adipose tissue index and mortality in liver cirrhosis.

Subcutaneous and visceral adipose tissues are important body components, but their effects on the mortality in patients with liver cirrhosis remain controversial based on the current evidence. We retrospectively identified 372 eligible patients in whom subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) could be measured by computed tomography images at the third lumbar vertebra. The association of SATI and VATI with the risk of death was evaluated on a continuous scale with restricted cubic spline curves based on Cox proportional hazards models. Cumulative probability of mortality was estimated by Nelson-Aalen cumulative risk curve analyses. Independent predictors of death were evaluated by competing risk analyses after adjusting for age, sex, and model for end-stage liver disease score. Majority of patients were male (69.4%) with a mean age of 55.40±10.68years. SATI had a U-shaped association with mortality (P for non-linearity <0.001). Cutoff values of SATI were 19.7 and 51.8cm2 /m2 at the points where hazard ratios were just <1.2. SATI was categorized as low (<19.7cm2 /m2 ), moderate (19.7-51.8cm2 /m2 ), and high (>51.8cm2 /m2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate SATI groups (Gray's test, P=0.052) and high versus moderate SATI groups (Gray's test, P=0.054). Competing risk analyses demonstrated that low SATI could increase the mortality compared with moderate SATI (subdistribution hazard ratio [sHR]=1.66, 95% confidence interval [CI]: 0.992-2.78, P=0.054) and was an independent predictor of death (sHR=1.86, 95% CI: 1.059-3.28, P=0.031). Competing risk analyses also demonstrated that high SATI could significantly increase the mortality compared with moderate SATI (sHR=1.6, 95% CI: 1-2.54, P=0.049), and was an independent predictor of death (sHR=2.007, 95% CI: 1.195-3.37, P=0.0085). VATI had an irregularly shaped association with mortality (P for non-linearity <0.001). Cutoff values of VATI were 9.8 and 40.2cm2 /m2 at the points where hazard ratios were just <1.2. VATI was categorized as low (<9.8cm2 /m2 ), moderate (9.8-40.2cm2 /m2 ), and high (>40.2cm2 /m2 ) level. There was no significant difference in the cumulative probability of mortality between low versus moderate VATI groups (Gray's test, P=0.381) and high versus moderate VATI groups (Gray's test, P=0.787). Competing risk analyses demonstrated that neither low (sHR=1.27, 95% CI: 0.599-2.7, P=0.53) nor high VATI (sHR=0.848, 95% CI: 0.539-1.34, P=0.48) was an independent predictor of death compared with moderate VATI. Both excessive deficiency and accumulation of subcutaneous adipose tissues negatively influence the outcomes of cirrhotic patients.

Abnormal Haematological Indices in Cirrhosis in a Tertiary Care Hospital

Background: The haematological changes are common in cirrhosis of liver the cause of which is multifactorial. It should be correlated by determining the underlying pathology accordingly. Objective: The objective of the study was to evaluate the pattern of change in Haematological indices in Cirrhosis of liver. Methods: This is a cross sectional prospective study conducted on purposely selected (non-probability) hospitalized patients admitted to Medicine, Gastroenterology and hepatology departments of Dhaka Medical College Hospital, Dhaka, Bangladesh. A total of 100 cases of cirrhosis were selected as per inclusion and exclusion criteria. After selection clinical history, meticulous physical examination and rational investigations were done. Data were collected as per a structured standard questionnaire and checklist. Data analysis was done using statistical software package SPSS 22.0 and was compared with other studies. Results: Anaemia was found in 81 cases out of 100 patients. Anaemia was morphologically normocytic in 46% patients which is the highest number in this study group. It was microcytic in 40% patients and macrocytic in 14%. Regarding Leukocyte count it was normal in 70(70%) patients, Leukopenia in 12(12%) and Leukocytosis in 18(18%) patients. Regarding platelet count it was normal in 46(46%), thrombocytopenia in 51(51%) but thrombocytosis in 3(3%) of cases. The average platelet count in thrombocytopenic patients was 90 X 1091 ± 23 X 109/L. Lastly, pancytopenia was present in 14(14%) patients. Among them, 10 patients (71%) had splenomegaly. Iron Profile was done in all patients of microcytic anaemia and it revealed 68% of them were iron deficiency anaemia. Prothrombin time was done in all patients and it was prolonged in 54 (54%) and its average value was 16.13±.2.9 seconds. Conclusion: Haematological changes are common in cirrhosis of liver, the cause of which is multifactorial. Iron deficiency anaemia is the common type (68%).Prolong prothrombin time (54%) and thrombocytopenia (51%) are the common features.

Role of Non-Invasive Scoring Systems in Detecting Fibrosis in Chronic Hepatitis B

Objectives: Chronic hepatitis is a clinical and pathological condition defined by etiological, clinical, and pathological aspects, in which inflammation in the liver continues for more than six months. Hepatitis B virus is one of the most important causes of etiology. Although liver biopsy is accepted as the gold standard test, there is a need to search for an alternative method due to the risk of complications, invasiveness, and cost. Our aim in this study was; to evaluate the predictive value of calculating fibrosis four scores (FIB -4), age platelet index (API), AST ALT ratio (AAR), AST platelet ratio index (APRI), Hui score, Goteburg University cirrhosis index (GUCI) indices in relation to liver biopsy in patients with chronic hepatitis B diagnosis who have not received any treatment before. Methods: The study included treatment-naive cases who underwent liver biopsy at Ankara University School of Medicine Hospitals Gastroenterology Clinics between March 2013 and November 2017 and at Ankara City Hospital Gastroenterology Clinic between 2019-2021. Non-invasive scores of the cases were evaluated simultaneously with liver biopsy. Results: A total of 159 patients, 45 (28.3%) female and 114 (71.7%) male, were included in our study. Eight non-invasive fibrosis markers were used, including APRI, FIB-4, AAR, API, CDS, Lok, GUCI, and Hui. GUCI and Hui non-invasive fibrosis markers were numerically superior to all other parameters in differentiating mild hepatitis from severe hepatitis and patients with cirrhosis, without cirrhosis. In the comparison of area under – receiver operating characteristic (AUROC) values ​​using the Hanley-McNeal test to differentiate the cirrhosis patient from the non-cirrhosis patient, statistical superiority was found only against AAR and API (p&lt;0.001, p&lt;0.001). Conclusion: Although many markers were found successful in our study, AUC values ​​were not significantly superior to each other, and we determined that they could not be an alternative to liver biopsy on their own. Keywords: chronic hepatitis B, fibrosis, liver

Genetic Analysis of Restriction Fragment Length Polymorphism of TLL1 Gene (rs17047200) in Patients of Hepatocellular Carcinoma

To find out the association of polymorphism of the TLL1 gene in hepatocellular carcinoma. A cross-sectional study was conducted from January 2020 to September 2020. Subjects were enrolled from Mayo Hospital, Lahore, Jinnah Hospital Lahore and the Liver Transplant Unit of Sheikh Zayed Hospital, Lahore. A total of 200 individuals were registered and segregated into the Control group (n=100) and hepatocellular carcinoma (HCC) group (n=100). DNA was extracted from obtained blood samples and Restriction Fragments Length Polymorphism (RFLP) was carried out at the laboratories of LCWU by using specific primers and restriction endonuclease enzymes. The data were analyzed statistically. The high proportion of smoking, hepatitis B, hepatitis C, cirrhosis and Body Mass Index (BMI) were established risk factors in the HCC group. Subjects with hepatocellular carcinoma had low socioeconomic status. Heterozygous bands in the HCC group were observed after RFLP. TLL1 genotype was AA (72 %) and AT/TT (28 %). The patient’s clinical aspects were similar across TLL1 genotypes. It was concluded that RFLP on the exon region by using their specific enzymes HpyCH4III showed heterozygous bands in the HCC group that indicated a mutation in the TLL1 gene though this mutation does have a significant association with HCC.

Transferrin saturation as a surrogate marker for assessment of labile nontransferrin bound iron in chronic liver disease.

Increased transferrin saturation (TS) and ferritin are common in hereditary hemochromatosis (HH) but also in chronic liver diseases (CLD). Nontransferrin bound iron (NTBI) is believed to be associated with iron-induced cell damage. We aimed to evaluate NTBI in CLD and their relationship with liver damage. Two groups of patients were studied. Group 1 (G1): 94 CLD patients from an Outpatient Hepatology Unit. Group 2 (G2): 36 healthy individuals form a Medical Checkup Clinic. Transferrin iron-binding capacity, TS, ferritin, AST, ALT, and red cell count were performed using standard tests. NTBI was assessed as enhanced labile plasma iron (eLPi). Levels of eLPi less than 0.4 µmol/l were considered within the normal range. Prevalence of increased iron tests (elevated TS and ferritin) was 14% in G1 and 5.5% in G2 ( P = 0.19). Positive NTBI was found in 12 patients (11 in G1 and 1 in G2). Positivity to NTBI was associated with increased iron tests ( P = 0.03), cirrhosis ( P = 0.03) and AST index (ASTI) ( P = 0.03). NTBI was associated with TS of more than 70% ( P = 0.002) but not to elevated ferritin ( P = 0.74). Variables strongly associated with a positive NTBI in univariate analysis (TS > 70%, cirrhosis and ASTI) were submitted to binary regression analysis. TS of more than 70% was the only independent predictive factor ( P = 0.049; odds ratio, 6.8). NTBI was associated with TS in CLD, but not with ferritin. NTBI testing could be useful for CLD patients with increased iron tests. Alternatively, a TS of more than 70% can be used as a surrogate marker.

Moving computed tomography-based quantification of muscle mass to the mainstream: Validation of a web-based platform to calculate skeletal muscle index in cirrhosis.

Moving computed tomography-based quantification of muscle mass to the mainstream: Validation of a web-based platform to calculate skeletal muscle index in cirrhosis.

Cairo University fibrosis index (CUFI): A score based on microRNA for diagnosis of significant hepatic fibrosis

Introduction: Identification of HCV- induced liver fibrosis is mandatory for tailoring therapy, and management of complications. The current study evaluated the accuracy of circulating miRNAs; in diagnosis of hepatic fibrosis. Patients and methods: Seventy HCV patients were subjected to routine laboratory investigations, HCV-RNA, serum miRNA-122, 221, 192, 224 , 375, and 885 by PCR, liver biopsy and calculation of the following scores: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), aspartate to platelet ratio index (APRI), FIB-4 score, Hui index, Fibrosis Index (FI), Fibro-Q , Fibro-Alfa Biotechnology Research Center (BRC) score and Gotebörg University Cirrhosis Index (GUCI). Results: Patients with significant and advanced fibrosis have significantly lower miR-122 (P &lt; 0.0001 and P= 0.007, respectively). miR-122, bilirubin and miR-855 were found to be independent predictors of significant fibrosis in univariate analysis. A novel score; Cairo University Fibrosis Index (CUFI) based on microRNA 122, bilirubin and microRNA 855 were formulated for predicting significant liver fibrosis. The AUC of this score, for predicting significant and advanced hepatic fibrosis was 0.83 and 0.80 respectively. This AUC was higher than those of other fibrosis scores. Conclusion: Cairo University Fibrosis Index is better than the existing scores in assessing fibrosis in chronic HCV patients.

Sarcopenia in Liver Cirrhosis: A Prospective Study

Background and aim: Liver diseases are associated with low testosterone. However, little is known about risk factors of changes in testosterone. This study determined skeletal mass index in liver cirrhosis and associated risk factors with the abnormal testosterone levels. Methods: In this descriptive hospital-based study, 50 patients with evidence of liver cirrhosis diagnosed on history, imaging and investigations were included for a period of 12 months. Sarcopenia was defined as value of ≤36.5 cm2/m2 in males and ≤30.2 cm2/m2 in females. Results: The mean age was 50.4±10.1 years. The most common symptom was abdominal distension (50%) followed by upper GI bleed (30%), altered sensorium (20%), and jaundice (10%). Majority of the patients (58%) in our study were in CTP class C, followed by 16 patients (32%) in CTP class B, and 5 patients (10%) in CTP class A. 66% of the patients had low skeletal mass index. SMI was not associated with CTP class (P=0.463). Conclusion: There is a significantly higher prevalence of loss of skeletal mass in liver cirrhotic patients in this region

Impact of antiviral therapy for disease progression and non-invasive liver fibrosis index in patients with chronic hepatitis C: Markov chain model analysis.

Antiviral therapy advancements resulted in an era in which eradication of hepatitis C has become a goal, however, there are few reports on the long-term course of liver disease progression with antiviral therapy. The aim of this study was to use the Markov model to analyze disease progression and non-invasive liver fibrosis index in hepatitis C Patients. Patients with chronic hepatitis C (n=1432) were diagnosed between January 2012 and May 2021 in the Musashino Red Cross Hospital. Patients with other hepatitis virus co-infection, chronic liver disease, and hepatocellular carcinoma (HCC) at the beginning of the study were excluded. A total of 618 patients with a 1-year or longer observation period were studied. The liver disease state was defined as chronic hepatitis (CH), compensated liver cirrhosis (CLC), decompensated liver cirrhosis (DLC), and HCC. Cirrhosis and high FIB-4 index (≥3.61) were 42 cases (6.8%) and 208 cases (33.6%), respectively at the start of the study. The 40years estimated transition analysis of 40-year-old CH low FIB-4 level (<3.61) revealed that the proportion of CH low/high, CLC low/high, DLC low/high, and HCC were 10.83%/10.86%, 0.35%/2.64%, 0%/3.21% 72.11% in untreated unit and 47.83%/9.21%, 6.69%/1.32%, 0.70%/0.99%, 33.27% in treated unit, respectively. Antiviral therapy suppressed liver fibrosis, disease progression, and HCC development significantly. Markov model analysis of hepatitis C virus patients showed the impact of antiviral therapy on the suppression of disease progression in the order of CH, CLC, and DLC.

Area Deprivation Index and Gut-Brain Axis in Cirrhosis.

INTRODUCTION:Neighborhood deprivation has been associated with chronic diseases and with gut microbial alterations. Although cirrhosis is associated with gut microbiome changes and hepatic encephalopathy (HE), their association is unclear.METHODS:Demographics and cirrhosis details (model for end-stage liver disease [MELD], prior HE, and medications) were recorded from outpatients with cirrhosis. Area deprivation index (ADI), which ranks neighborhoods by socioeconomic disadvantage, was recorded as state decile and national percentile (high = worse for both) and dichotomized on the median. Patients underwent cognitive testing to diagnose minimal HE (MHE). Stool microbiota was analyzed using 16S ribosomal RNA for α/β-diversity. Multivariable analysis was used to evaluate the factors independently associated with MHE.RESULTS:A total of 321 people with cirrhosis (60 years, 78% men, 75% non-Hispanic White, 24% non-Hispanic African American, 4% Hispanic) were included. 45% had prior HE and 56% MHE. For ADI, the national percentile was 49.1 ± 21.8 while the state decile was 6.1 ± 2.3. ADI was not associated with race, ethnicity, MELD, or HE-related variables on regression. Regarding microbiota, α-diversity was lower in MHE and prior HE patients but similar across ADI rankings. Low vs high ADIs were associated with different β-diversity in univariable but not multivariable analyses. Multivariable analyses showed positive associations with MELD, prior HE, and lactate producers (Lactobacillus and Lacticaseibacillus) and negative associations with short-chain fatty acid producers (Blautia, Lachnoclostridium, and Anaerobutyricum) with MHE.DISCUSSION:Cirrhosis-related variables may be more influential in determining gut microbiome composition and cognitive impairment than ADI. Therefore, the focus should be on improving cirrhosis care, regardless of ADI, but studies evaluating other measures of social determinants are needed in cirrhosis.

High serum fibroblast growth factor 21 is associated with inferior hepatocellular carcinoma survival: A prospective cohort study.

Epidemiological evidence linking fibroblast growth factor 21 (FGF21) with hepatocellular carcinoma (HCC) prognosis lacked. We aimed to evaluate the associations between serum FGF21 levels and HCC survival in a large prospective cohort. 825 newly diagnosed, previously untreated HCC patients from the Guangdong Liver Cancer Cohort were enrolled between September 2013 and April 2017. Serum FGF21 levels were measured by ELISA. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Multivariable Cox proportional hazards models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with patients in the lowest tertile of serum FGF21 levels, patients in the highest tertile had inferior survival outcomes. HRs in the fully adjusted models were 1.44 (95% CI: 1.07, 1.94; P-trend =.014) and 1.48 (95% CI: 1.12, 1.97; P-trend =.002) for LCSS and OS, respectively. The associations were not significantly modified by selected metabolic disorder diseases or state such as arterial hypertension, diabetes, dyslipidemia, fatty liver, cirrhosis, and body mass index ≥25.0kg/m2 , except for that stronger associations were observed in patients co-occurred more than three metabolic disorder diseases (P-interaction =.046 for OS and .151 for LCSS), with an HR of 2.01 (95% CI: 1.04, 3.85; P-trend =.009) for OS and 1.51 (95% CI: 0.73, 3.10; P-trend =.195) for LCSS. Higher serum FGF21 levels were associated with worse survival in HCC patients, suggesting that serum FGF21 may be used as a novel metabolism-related prognostic biomarker for HCC.