Non-invasive Markers Of Liver Fibrosis Research Articles

Utility of non-invasive liver fibrosis markers to predict the incidence of chronic kidney disease (CKD): A systematic review, meta-analysis, and meta-regression

Background and aimsChronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) share common risk factors and pathogenesis mechanisms. However, the association between the degree of liver fibrosis and the incidence of CKD remains unclear. This study aims to examine the utility of non-invasive fibrosis markers to predict the occurrence of CKD. MethodsCochrane Library, Scopus, and Medline were searched up to May 20th, 2023 using combined keywords. Literature that analyzes FIB-4, NFS, and APRI to predict CKD incidence was included in this review. We used random-effect models of odds ratio (OR) with 95% confidence intervals (CI) to express the outcomes in this review. ResultsTwenty-one studies were included. Our meta-analysis showed that high FIB-4 was associated with a higher incidence of CKD (OR 2.51; 95%CI: 1.87–3.37, p < 0.00001, I2 = 96%). Further regression analysis revealed that this association was significantly influenced by hypertension (p = 0.0241), NAFLD (p = 0.0029), and body mass index (BMI) (p = 0.0025). Our meta-analysis also showed that high NFS (OR 2.49; 95%CI: 1.89–3.30, p < 0.00001, I2 = 96%) and high APRI (OR 1.40; 95%CI: 1.14–1.72, p = 0.001, I2 = 26%) were associated with a higher incidence of CKD. ConclusionsThis study suggests that these non-invasive liver fibrosis markers can be routinely measured both in NAFLD patients and the general population to enable better risk stratification and early detection of CKD.

Fibrosis-4 Index as a Predictor for Disease Severity and Mortality in Patients with COVID-19

Objective: The Fibrosis-4 (FIB-4) index is a noninvasive marker of liver fibrosis in various patient populations. We examined whether there is a relationship between the severity and prognosis of COVID-19 disease and the FIB-4 index. Materials and Methods: This stuy is a cross-sectional and retrospective. The patients were divided into two groups as those hospitalized in the intensive care unit (ICU) and those hospitalized in the clinic (non- ICU). Results: Of the total 158 cases,86(54%) were male. Age, total bilirubin, AST levels and FIB-4 index were higher in ICU patients compared to non-ICUs (p&amp;lt;0.001,p=0.002, p=0.003, p&amp;lt;0.001 respectively). FIB-4 index non-survivors were also higher (p=0.002). When the effect of the FIB-4 index on the severity of COVID-19 disease and mortality was evaluated by ROC analysis, both ICU and non-survivors were found to be significant (respectively FIB-4 score;AUC=0.705,95%CI:0.624-785,p&amp;lt;0.001;AUC=0.654,95%CI:0.566-742,p=0.002). When the FIB-4 index cut-off value for disease severity was taken as 2.19, 70.0% sensitivity and 60% specificity were found in predicting disease severity. Moreover, when the FIB-4 index cut-off value for mortality was taken as 2.19, 71.2% sensitivity and 53% specificity were found in predicting mortality. Conclusion: The FIB-4 index is an independent predictor of severity and mortality in COVID-19 patients requiring ICU.

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.

Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C

Background & aimsLife-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. Methods491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical–biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. ResultsDuring a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01–1.05), age (HR, 1.04; 95% CI, 1.01–1.08) and albumin levels (HR, 0.90; 95% CI, 0.84–0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08–1.37) and albumin (HR, 0.90; 95% CI, 0.84–0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. ConclusionSimple models based on non-invasive markers of liver fibrosis, LSM or FIB-4, together with age and albumin levels at SVR permit to identify subsets of patients with HCC risk clearly <1%/year, for whom HCC surveillance might not be cost-effective.

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated

The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers. Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements. A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9kPa (adjusted odds ratio= 3.19; 95% CI 1.95-5.20; p <0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio= 1.76; 95% CI 1.20-2.56; p= 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis. The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX. Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients' metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate.

Dynamic changes in the liver fibrosis marker FIB-4 as a predictor of adverse cardiovascular events in patients with high and very high cardiovascular risk

The aim of the study was to assess the prognostic significance of dynamic changes in the surrogate noninvasive liver fibrosis marker FIB-4 in relation to the development of adverse cardiovascular events in patients with high and very high cardiovascular risk (CVR). Materials and Methods. Men and women aged 40-67 years with high and very high CVR were included in the study. Fibrosis-4 index (FIB-4) was used as a noninvasive marker of liver fibrosis. The combined end point was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization. Results. 105 patients with high and very high CVR were included in the study. The duration of the follow-up period was 34.6 (15.0; 52.3) months. Events constituting the combined end point occurred in 26 (24.7%) patients. During the follow-up period, FIB-4 index values of <1.45 (0.90 (0.68; 1.23) at study inclusion changed to ≥1.45 (1.66 (1.61; 1.90) in 13 (12.4%) patients. Over the follow-up period, the median FIB-4 change was -23.0% (-1.81; 11.5) and by the end of the follow-up period, the median FIB-4 values were 1.17 (0.97; 1.47). According to Kaplan-Meier analysis, the cumulative risk of events constituting the combined end point was found to be significantly higher in patients with an increase in FIB-4. By Cox single-factor regression analysis, an increase in FIB-4 (from values <1.45 to ≥1.45) was associated with a 4.42-fold increase in the relative risk (RR) of events constituting the combined end point (95% CI 1.33-14.7; p=0.015). Conclusion. In patients with high and very high CVR over 40 years of age, an increase in FIB-4 liver fibrosis index from values <1.45 to ≥1.45 during 2.8 years of follow-up was associated with a 4.42-fold increase in the RR of adverse cardiovascular events (95% CI 1.33-14.7; p=0.015).

Significance of Fib4 index as an indicator of alcoholic hepatotoxicity in health examinations among Japanese male workers: a cross-sectional and retrospectively longitudinal study

BackgroundFib4 index (Fib4) is clinically used as a noninvasive marker of liver fibrosis. In this study, we aimed to preliminarily investigate whether Fib4 can be used to detect individuals who need assessment for alcoholic liver disease (ALD) in the general population by clarifying the detailed association of Fib4 with alcohol consumption and gamma-glutamyl transferase (GGT) among male workers.MethodsWe analyzed data sets on the comprehensive medical examinations of male workers as cross-sectional and retrospectively longitudinal studies. We enrolled 10 782 males (mean age: 52.2 ± 10.2 years) in FY2019 and 7845 males (mean follow-up: 12.6 ± 6.7 years) who could be consecutively followed up for 20 years from FY2000 to FY2019. Data were evaluated using logistic regression and COX proportional analysis.ResultsIn the cross-sectional setting, the rate of Fib4 ≥ 2.67 in heavy drinkers (≥ 40 g of ethanol/day) was increased dose dependently in those over 65 years old, and that of body mass index ≥ 30 kg/m2 was increased in those over 60 years old, but not in those with fatty liver. The odds ratio (OR) (95% confidence interval [CI]) for heavy drinking was 4.30 (95% CI = 1.90–9.72), and GGT ≥ 200 IU/L was considerably high (OR = 29.05 [95% CI = 17.03–49.56]). In the longitudinal setting, heavy drinkers and those with GGT ≥ 200 IU/L at 10 years after the baseline showed an increased risk for Fib4 ≥ 2.67 (hazard ratio = 2.17 [95% CI = 1.58–2.98] and 7.65 [95% CI 5.26–11.12], respectively).ConclusionsThe development of Fib4 ≥ 2.67 after 10 years was associated with heavy alcohol drinking and GGT level ≥ 200 IU/L. Therefore, Fib4 combined with GGT could indicate high risk of ALD. However, clinical examinations and course observations are essentially needed.

Prospects for the use of drugs from the group of agonists of glucagon-like peptide-1 receptors in the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. To a large extent, the development of this disease is associated with metabolic syndrome. There is a pathogenetic association of NAFLD with obesity, type 2 diabetes mellitus (DM2), cardiovascular diseases and chronic kidney disease. Numerous studies demonstrate that an increase in the incidence of NAFLD occurs in parallel with an increase in the prevalence of obesity and DM 2. A number of scientific studies in the field of medicine have made it possible to identify the main pathogenetic mechanisms of the development of the disease, as well as the possibility of using various pharmacological drugs to correct these conditions. Currently, the possibility of using in the future a group of drugs that have a single mechanism for controlling the development of hepatic steatosis, and further progression with the formation of inflammation, cirrhosis and, in some cases, hepatocellular carcinoma, is being considered. Of particular interest is a class of drugs intended for the treatment of type 2 diabetes and obesity – glucagon-like peptide-1 receptor agonists (arGLP-1). A search was made of clinical studies, meta-analyses, literature reviews in databases and registries of medical publications over a period of 10 years. Changes in anthropometric indications, changes in non-invasive markers of liver steatosis, inflammation and fibrosis, as well as histological data on the background of the use of drugs of the arGLP-1 class were studied. It has been demonstrated that the study drug class may have a significant potential for impact on NAFLD. However, further studies with sufficient duration and histological evaluation are needed to fully evaluate the effectiveness of arGLP-1 in the treatment of NAFLD.

Thrombospondin-2 as a potential noninvasive biomarker of hepatocyte injury but not liver fibrosis in children with MAFLD: A preliminary study.

Metabolic-associated fatty liver disease (MAFLD) requires close monitoring due to its increased incidence and progression to fibrosis, cirrhosis and even hepatocellular carcinoma. The search for non-invasive markers to diagnose liver fibrosis is ongoing. The aim of our study was to evaluate the serum levels of growth differentiation factor-15 (GDF-15), thrombospondin-2 (TSP2), pentraxin 3 (PTX3) and angiopoietin-like protein 8 (ANGPTL8) in children with MAFLD. Fifty-six overweight/obese children with suspected liver disease were included in this prospective study. MAFLD was diagnosed according to the latest consensus. Vibration-controlled transient elastography (TE) was performed to detect clinically significant liver fibrosis. Serum concentrations of GDF-15, TSP2, PTX3 and ANGPTL8 were measured by enzyme-linked immunosorbent assay (ELISA). Liver steatosis was diagnosed in abdominal ultrasound in 31 (55.36%) overweight/obese patients who were classified as the MAFLD group. Aspartate aminotransferase (AST)/platelet ratio (APRI) and liver stiffness measurement (LSM) values and TSP2 concentrations showed significantly higher values in patients in MAFLD than in the non-MAFLD group. TSP2 was significantly positively correlated with alanine transaminase (ALT), AST, γ-glutamyltransferase (GGT) and APRI in the study group. The receiver operating characteristics (ROC) analysis showed that the area under the curve (AUC) of LSM, APRI and serum TSP2 was significant for predicting MAFLD in obese children. In the multivariable regression model, LSM was the only significant parameter associated with the diagnosis of MAFLD in children. TSP2 may be a potential biomarker of hepatocyte injury in pediatric patients with MAFLD. None of the examined biomarkers were found to be effective non-invasive markers of liver fibrosis in children.

FibroMeter scores are predictive noninvasive markers of advanced and significant liver fibrosis in patients with chronic viral hepatitis or metabolic dysfunction-associated steatotic liver disease.

FibroMeter and FibroMeter vibration-controlled transient elastography (FibroMeter VCTE) were assessed in a Greek cohort of patients with chronic viral hepatitis (CVH) B and C or metabolic dysfunction-associated steatotic liver disease (MASLD) to evaluate their accuracy in predicting advanced liver fibrosis against other well-validated noninvasive markers. Group 1: n=83 CVH and group 2: n=38 MASLD patients underwent liver biopsy and transient elastography (TE) on the same day as sera collection. FibroMeter scores APRI and FIB-4 were calculated in all 121 patients, while MASLD fibrosis score (MFS) was also calculated in group 2. In CVH, FibroMeter VCTE performed equivalently to TE and better than the other markers in predicting advanced (≥F3) and significant (≥F2) fibrosis (area under the receiver operating characteristic curve [AUC] 0.887, P<0.001 for F3; AUC 0.766 P<0.001 for F2). FibroMeter Virus (cutoff 0.61) had lower sensitivity (20%) but performed equivalently to APRI and FIB-4. In MASLD, all markers but APRI performed equivalently in predicting advanced fibrosis. FibroMeter VCTE >0.2154 had the same sensitivity (100%) and specificity (81%) as TE (cutoff >7.1 kPa). FibroMeter MASLD >0.25 performed equivalently to MFS and FIB4, but with higher specificity (100%). Both FibroMeter and FibroMeter VCTE correlated with liver histology but not with liver enzymes. FibroMeter VCTE predicts accurately advanced fibrosis in CVH and MASLD, irrespectively of transaminase levels. FibroMeter Virus can be applied only as an alternative marker in CVH, while FibroMeter MASLD performs equally to TE and calculated scores (MFS, FIB-4) in predicting advanced fibrosis in MASLD patients.

The FINDRISC scale as a risk assessment tool for liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which includes changes from hepatic steatosis and nonalcoholic steatohepatitis to fibrosis and cirrhosis. Attempts to find noninvasive markers of liver fibrosis have led to a variety of scales, diagnostic algorithms, and imaging techniques. Individual studies have analyzed the relationship between the FINDRISC scale and hepatic steatosis and concluded that this questionnaire can be used as part of population screening to identify individuals at risk for hepatic steatosis. However, our review of the literature did not reveal any clinical studies on the use and effectiveness of the FINDRISC in liver fibrosis screening.AIM: To evaluate diagnostic value of FINDRISC for liver fibrosis detection.MATERIALS AND METHODS: The study enrolled patients aged 40–60 years from unorganized outpatient population. The sample of patients was formed randomly according to the inclusion and noninclusion criteria. All patients were assessed with standard anthropometric parameters. The FINDRISC questionnaire was used. All patients underwent transabdominal ultrasound examination of the liver and transient liver elastometry. The degree of steatosis was evaluated using Hamaguchi ultrasound scale. RESULTS: The study included 100 patients. An increased risk of type 2 DM (≥7 points) was detected in 68% of patients using the FINDRISC scale. Liver steatosis was diagnosed in 41% of patients. Median values of hepatic elastic modulus by transient elastometry were 4.50 (4.00; 5.25) kPa. At the same time, liver elasticity modulus values ≥5.9 kPa were registered in 11 (11.0%) patients. When analyzing the array of sensitivity and specificity values using the ROC-curve, it was found that for the FINDRISC scale the maximum LR+ and the minimum LRvalues were observed when the number of points on the indicated scale exceeded 10. At this cutoff, the FINDRISC scale had a sensitivity of 81.8% and specificity of 61.8% for detecting liver fibrosis (liver modulus of elasticity ≥5.9 kPa). The scale was of good diagnostic value (AUC 0.699; 95% CI 0.530–0.815).CONCLUSION: In an unorganized sample of patients aged 40–60 years the FINDRISC can serve as a diagnostic tool for liver fibrosis and steatosis. Sum of FINDRISC scores &gt;10 allowed to diagnose liver fibrosis (liver elastic modulus ≥5.9kPa) with sensitivity 81.8% and specificity 61.8%. The probability of absence of hepatic fibrosis with FINDRISC scale values &lt;10 was 96.5%.

A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis

Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1-F3 fibrosis. The primary objective of the BALANCED Cohort C was to assess the safety and tolerability of efruxifermin in patients with compensated NASH cirrhosis. Patients with NASH and stage 4 fibrosis (n= 30) were randomized 2:1 to receive efruxifermin 50mg (n= 20) or placebo (n= 10) once-weekly for 16 weeks. The primary endpoint was safety and tolerability of efruxifermin. Secondary and exploratory endpoints included evaluation of non-invasive markers of liver injury and fibrosis, glucose and lipid metabolism, and changes in histology in a subset of patients who consented to end-of-study liver biopsy. Efruxifermin was safe and well-tolerated; most adverse events (AEs) were grade 1 (n= 7, 23.3%) or grade 2 (n= 19, 63.3%). The most frequent AEs were gastrointestinal, including transient, mild to moderate diarrhea, and/or nausea. Significant improvements were noted in key markers of liver injury (alanine aminotransferase) and glucose and lipid metabolism. Sixteen-week treatment with efruxifermin was associated with significant reductions in non-invasive markers of fibrosis including Pro-C3 (least squares mean change from baseline [LSMCFB]-9μg/L efruxifermin vs.-3.4μg/L placebo; p= 0.0130) and ELF score (-0.4 efruxifermin vs.+0.4 placebo; p= 0.0036), with a trend towards reduced liver stiffness (LSMCFB-5.7kPa efruxifermin vs.-1.1kPa placebo; n.s.). Of 12 efruxifermin-treated patients with liver biopsy after 16 weeks, 4 (33%) achieved fibrosis improvement of at least one stage without worsening of NASH, while an additional 3 (25%) achieved resolution of NASH, compared to 0 of 5 placebo-treated patients. Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and lipid metabolism following 16 weeks of treatment, warranting confirmation in larger and longer term studies. Cirrhosis resulting from non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease, represents a major unmet medical need. Currently there are no approved drugs for the treatment of NASH. This proof-of-concept randomized, double-blind clinical trial demonstrated the potential therapeutic benefit of efruxifermin treatment compared to placebo in patients with cirrhosis due to NASH. NCT03976401.

Serum non-coding RNAs for diagnosis and stage of liver fibrosis.

BackgroundAll chronic liver diseases could lead to liver fibrosis. Accurate diagnosis and stage of fibrosis were important for the medical determination, management, and therapy. Liver biopsy was considered to be the gold criteria of fibrosis diagnosis. However, liver biopsy was an invasive method with some drawbacks. Non‐invasive tests for liver fibrosis included radiologic method and serum‐based test. Radiologic examination was influenced by obesity, cost, and availability. Serum‐based test was widely used in the screening and diagnostic of liver fibrosis. However, the accuracy was still needed to be improved.MethodsRecent studies showed serum non‐coding RNAs: microRNA, long non‐coding RNA(lncRNA), and circular RNA(circRNA), which have the potentiality to be non‐invasive markers for liver fibrosis. The recent progress was summarized in this review.ResultsThese studies showed serum non‐coding RNAs exerted a good diagnostic performance for liver fibrosis. A panel that included several non‐coding RNAs could increase the accuracy of single marker.ConclusionsSerum microRNAs, lncRNAs, and circRNAs could be potential non‐invasive markers for diagnosis and stage of liver fibrosis. More high‐quality clinical study is needed for further research.

Impact of aspartate aminotransferase–to–platelet ratio index based score to assess posthepatectomy liver failure in patients with hepatocellular carcninoma

BackgroundPosthepatectomy liver failure (PHLF) is a life-threatening complication following hepatic resection. The aspartate aminotransferase-to-platelet ratio index (APRI) is a non-invasive model for assessing the liver functional reserve in patients with hepatocellular carcinoma (HCC). This study aimed to establish a scoring model to stratify patients with HCC at risk for PHLF.MethodsThis single-center retrospective study included 451 patients who underwent hepatic resection for HCC between 2004 and 2017. Preoperative factors, including non-invasive liver fibrosis markers and intraoperative factors, were evaluated. The predictive impact for PHLF was evaluated using receiver operating characteristic (ROC) curves of these factors.ResultsOf 451 patients, 30 (6.7%) developed severe PHLF (grade B/C). Multivariate logistic analysis indicated that APRI, model for end-stage liver disease (MELD) score, operating time, and intraoperative blood loss were significantly associated with severe PHLF. A scoring model (over 0–4 points) was calculated using these optimal cutoff values. The area under the ROC curve of the established score for severe PHLF was 0.88, which greatly improved the predictive accuracy compared with these factors alone (p < 0.05 for all).ConclusionsThe scoring model-based APRI, MELD score, operating time, and intraoperative blood loss can predict severe PHLF in patients with HCC.

Impact of HIV-1 Infection on the Natural Progress of an Anti-HCV Positive Population in an Impoverished Village in China from 2009 to 2017.

Our study aimed to determine the impact of HIV coinfection on the natural progression of liver disease in treatment-naive HCV-infected patients. From 2009 to 2017, we tracked non-invasive markers of liver fibrosis and end-stage liver disease (ESLD)-associated mortality among HCV mono-infected and HIV/HCV coinfected patients in an impoverished village in China. The study cohort consisted of 355 HBsAg-negative and anti-HCV (+) or anti-HIV (+) patients recruited in July 2009, 164 of whom were diagnosed with HIV-1 infection. The surviving patients were re-evaluated in August 2017. During the follow-up, the disease status, liver biochemical, and non-invasive indicators of liver fibrosis (APRI and FIB-4) were measured. The transaminases ALT and AST were significantly higher in HIV-positive HCV resolvers (HIV+ HCVr) than in HIV-negative HCV resolvers (HCVr) (p = 0.019 and p < 0.0001, respectively). APRI and FIB-4 scores of HIV-positive chronic HCV carriers (HIV+ HCVc) were significantly higher than in HIV-negative chronic HCV carriers (HCVc) (p < 0.001). Similarly, APRI and FIB-4 scores were higher in the HIV+ HCVr group than in the HCVr group (ps < 0.001). From 2009 to 2017, the levels of ALT (p = 0.006), AST (p = 0.003), APRI (p = 0.015), and FIB-4 (p = 0.025) were significantly elevated in the HIV/HCV coinfected patients with CD4+ T counts below 500 cells/l. ESLD-related mortality was significantly greater in HIV/HCV-infected cases than in HCV mono-infected patients (73.3% vs. 31.3%, p = 0.009) among patients (n = 45) who died between 2009 and 2017 during follow-up. These findings suggest a higher risk of ESLD-related death and rapid progression of liver fibrosis in HIV/HCV coinfected individuals compared with HCV mono-infected patients. During HIV/HCV coinfection, HIV infection may aggravate HCV-associated liver injury.

Impact of Hepatitis C Treatment Uptake on Cirrhosis and Mortality in Persons Who Inject Drugs : A Longitudinal, Community-Based Cohort Study.

Hepatitis C virus (HCV) infection can be cured, and the United States has joined the World Health Organization in calling for HCV elimination by 2030. However, historically low uptake of HCV treatment among people who inject drugs (PWID) threatens HCV elimination and exacerbates social and racial health disparities. To assess whether all-oral HCV treatments were accessed by PWID and reduced liver disease burden and mortality. Community-based, longitudinal cohort study of persons with a history of injection drug use. Baltimore, Maryland. 1323 participants enrolled in the ALIVE (AIDS Linked to the IntraVenous Experience) study from 2006 to 2019 and chronically infected with HCV. Liver stiffness measures (LSMs) by transient elastography, HCV RNA, and mortality from the National Death Index. Among 1323 persons with evidence of chronic HCV infection at baseline, the median age was 49 years. Most were Black (82%), male (71%), and HIV-negative (66%). The proportion in whom HCV RNA was detected decreased from 100% (by definition) in 2006 to 48% in 2019. Across 10350 valid LSMs, cirrhosis was detected in 15% of participants in 2006, 19% in 2015, and 8% in 2019. Undetectable HCV RNA was significantly associated with reduced odds of cirrhosis (adjusted odds ratio, 0.28 [95% CI, 0.17 to 0.45]) and reduced all-cause mortality risk (adjusted hazard ratio, 0.54 [CI, 0.38 to 0.77]). Noninvasive markers of liver fibrosis have not been validated in persons with sustained virologic response. Many community-based PWID in Baltimore are receiving HCV treatment, which is associated with sharp decreases in liver disease and mortality. Additional efforts will be needed to reduce residual barriers to treatment and to eliminate HCV as a public health threat for PWID. National Institutes of Health.

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

BackgroundNonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH.MethodsThis is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers.ResultsOf 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75–1); CAP, 0.94 (0.88–1); FLI, 0.81 (0.58–1); HSI, 0.74 (0.62–0.87); and TyG, 0.75 (0.49–1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82–1), 0.96 (0.90–1), 0.97 (0.93–1), and 0.85 (0.68–1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97–1, P < .001) and 0.92 (0.77–1, P < .001).ConclusionsUltrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index for Detecting Liver Fibrosis in Patients With Autoimmune Hepatitis: A Meta-Analysis

BackgroundAspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are the two most widely studied noninvasive markers of liver fibrosis. We aimed to assess the diagnostic accuracy of APRI and FIB-4 for liver fibrosis in patients with autoimmune hepatitis (AIH) using liver biopsy as the reference standard.MethodsPubMed, EMBASE, Cochrane Library and Web of Science databases were searched for studies (published as of May 1st, 2021) that assessed the diagnostic performance of APRI and FIB-4 for liver fibrosis in AIH. The summary area under receiver operating characteristics curve (AUROC), sensitivity, specificity, diagnostic odds ratios were used to assess the diagnostic accuracy of APRI and FIB-4 for detecting liver fibrosis.ResultsFourteen studies (including 1015 patients) were selected with 13 studies each evaluating the use of APRI and FIB-4 for detecting different stages of fibrosis in AIH. For prediction of significant fibrosis, advanced fibrosis, and cirrhosis, the summary AUROC value was 0.66 [95% confidence interval (CI): 0.61–0.70], 0.71 (95% CI: 0.67–0.75), and 0.75 (95% CI: 0.71–0.79) for APRI, and the summary AUROC value was 0.75 (95% CI: 0.71–0.79), 0.73 (95% CI: 0.69–0.77) and 0.79 (95% CI: 0.75–0.82) for FIB-4, respectively. The summary sensitivity and specificity for diagnosis of significant fibrosis, advanced fibrosis, and cirrhosis were 90% and 36%, 78% and 55%, and 77% and 61% for APRI, and 70% and 70%, 65% and 70%, and 78% and 65% for FIB-4, respectively.ConclusionsAPRI and FIB-4 showed suboptimal diagnostic performance for identifying liver fibrosis in AIH with mediocre sensitivity and specificity.

Trends in indirect liver function marker testing in Wales from 2000 to 2017 and their association with age and sex: an observational study

ObjectiveIf non-invasive markers of liver fibrosis were recorded frequently enough in clinical practice, it might be feasible to use them for opportunistic community screening for liver disease. We aimed to...

24-month decline of non-invasive liver fibrosis markers in HCV-mono and HCV/HIV coinfection after direct-acting antiviral therapy

Long term liver fibrosis (LF) changes and their best -monitoring non-invasive markers (NILFM) after effective anti-HCV DAA therapy are little- known. Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs) are pivotal in liver inflammation repair. Their plasma levels might assess long-term LF changes after therapy. Overall 374 HCV-infected adult patients, 214 HCV-HIV coinfected, were followed-up for 24 months after starting DAA. LF was assessed by transient elastometry (TE), biochemical indexes (APRI, Forns, FIB-4) and, in 61 individuals, by MMPs and TIMP-1 plasma levels. Several MMPs and TIMP-1 SNPs were genotyped in 319 patients. TE was better than biochemical indexes for early and long-term LF monitoring. MMPs-2,-8,-9 and-TIMP-1 levels and TE displayed parallel declining curves although only TIMP-1 correlated with TE (P = 0.006) and biochemical indexes (P < 0.02). HCV monoinfected had significantly higher baseline NILFM and TIMP-1 plasma values, but lower MMPs levels than coinfected patients. No differences in NILFM course were observed between mono-and coinfected or between different DAA regimens. Only the MMP-2 (-1306 C/T) variant TT genotype associated with higher values of NILFM NILFM decline extends 24 months after therapy. TE and TIMP1 are reliable LF-monitoring tools. NILFM courses were similar in mono-and coinfected patients, DAA regimens type did not influence NILFM course.