Forns Index Research Articles

Association between birth weight, preterm birth, and nonalcoholic fatty liver disease in a community-based cohort.

The association between birth weight (BW) and metabolic outcomes has been described since the 1980s but NAFLD has been rarely studied. This study aimed to investigate the association between BW and NAFLD occurrence in adult subjects. The study population consisted of participants from the French nationwide Constances cohort from 2012 to 2019. Participants with a history of chronic viral hepatitis or excessive alcohol consumption were excluded. Noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The relationship between BW and NAFLD was analyzed with a sex-stratified logistic regression model adjusted for sociodemographic parameters, lifestyle, and birth term, whereas liver fibrosis was analyzed with a sex-stratified linear regression model. In total, 55,034 individuals with reliable BW were included (43% men, mean age: 38 years). NAFLD (FLI≥60) was present in 5530 individuals (10%). Multivariate logistic regression showed a significant U-shaped relationship between BW and NAFLD, with no significant interaction with sex. A significant and slightly decreasing association was found between BW and Forns Index (β=-0.05; p=0.04). Premature birth (OR, 1.23; 95% CI, 1.03-1.48 for birth between 33 and 37 weeks versus≥37 weeks) was associated with NAFLD, with a significant direct effect of premature birth, and without an indirect effect of low BW in mediation analysis. Forns Index was not significantly higher in participants with preterm birth compared to full-term birth. This large prospective adult-based cohort confirms the relationship between BW and NAFLD occurrence.

Prevalence and Prognostic Significance of Liver Fibrosis in Patients With Aneurysmal Subarachnoid Hemorrhage.

ObjectivesTo report the prevalence, clinical associations, and prognostic consequences of liver fibrosis in patients with aneurysmal subarachnoid hemorrhage (aSAH).MethodsIn a retrospective study of patients with aSAH, we evaluated three validated liver fibrosis indices and modeled them as continuous-exposure variables, including the aspartate aminotransferase/platelet ratio index (APRI), the fibrosis-4 (FIB-4) index, and the Forns index. The primary outcome was mortality at 90 days. We compared the addition of fibrosis indices to the predictors of the full Subarachnoid Hemorrhage International Trialists model.ResultsA total of 3,722 patients with aSAH were included in the study. According to the APRI, FIB-4 index, and Forns index, 21.7, 17.7, and 11.4% of patients had liver fibrosis. After adjusting for potential confounding factors, liver fibrosis indices were associated with increased 90-day mortality, with odds ratios of 1.35 (95% CI 1.02–1.77) for the FIB-4 index, 1.39 (95% CI.08–1.78) for APRI, and 1.53 (95% CI 1.11–2.12) for the Forns index. Similarly, high liver fibrosis indices were associated with an increased risk of rebleeding. However, the Forns index was not significantly associated with mortality and rebleeding. The addition of FIB-4 indices and APRI into the standard model improved the mortality prediction.ConclusionsLiver fibrosis is common in patients with aSAH, and high liver fibrosis indices are associated with mortality and rebleeding. The addition of liver fibrosis indices to a standard clinical model significantly improves risk stratification.

Systematic screening for advanced liver fibrosis in patients with coronary artery disease: The CORONASH study.

Although coronary artery disease (CAD) and advanced liver fibrosis (AdLF) are commonly associated in patients with non-alcoholic fatty liver disease (NAFLD), the prevalence of AdLF and the diagnostic performance of non-invasive fibrosis tests (NITs) in CAD patients remains unknown. We aimed to prospectively screen for AdLF in patients with documented CAD using NITs and Fibroscan. High and intermediate zones of NITs were combined to define AdLF. AdLF was suspected whenever APRI ≥ 0.5, Forns index ≥ 4.2, NAFLD fibrosis score (NFS) ≥ -1.455/0.12 for age </≥ 65 yrs), Fib4 (≥ 1.30/2.0 for age </≥ 65 yrs) and eLIFT≥ 8. A presumed AdLF assessed by Fibroscan ≥ 8 kPa was the primary outcome measure. Results were given on the basis of intent-to-diagnose liver stiffness ≥ 8 kPa. Among 189 patients (age 60±7years), 10 (5.3%) had a Fibroscan ≥ 8 kPa, of whom 5 underwent liver biopsy (F3/F4: n = 3; no fibrosis: n = 2). AdLF was suspected in 31% of cases using eLIFT (specificity, Sp 70%), 85% with Forns (Sp 16%), 38% with NFS (Sp 63%), 25% with Fib4 (Sp 74%), and 10% with APRI (Sp 91%). In 149 patients “at-risk” of NAFLD (i.e., elevated ALT or diabetes or hypertriglyceridemia or BMI ≥25 kg/m2), AdLF ranged between 10% (APRI) to 84% (Forns). In this subgroup, the most efficient NITs to predict Fibroscan ≥ 8 kPa were eLIFT (Se 60%, Sp 70%) and NFS (Se 70%, Sp 60%). Finally, in CAD patients with risk factors for NAFLD, NFS or the more user-friendly eLIFT are the most attractive first-line biochemical NITs to discriminate good candidates for Fibroscan.

OPTIONS OF INTERFERON-FREE THERAPY FOR HCV INFECTION. A CASE STUDY. COMPARISON OF NON-INVASIVE METHODS FOR LIVER FIBROSIS ASSESSMENT

The incidence of hepatitis C virus infection in Russia is 2–3 %. In our country the socio-economic damage caused by the increase in the incidence of chronic hepatitis and its consequences, such as liver cirrhosis and hepatocarcinoma, is enormous. The goal of antiviral therapy for chronic hepatitis C is a sustained virological response, which is associated with a biochemical response and regression of hepatic tissue fibrosis, which leads to a decrease in the liver cirrhosis development.&#x0D; The purpose of the study is to determine the efficacy of interferon-free therapy; to compare the efficacy of non-invasive methods for liver fibrosis diagnostics in chronic hepatitis C.&#x0D; Materials and Methods. The study included 63 patients who underwent direct antiviral therapy (dasabuvir and ombitasvir + paritaprevir + ritonavir (3D-therapy)) in combination with ribavirin or without it, depending on the hepatitis C virus genotype and the stage of liver fibrosis. The stage of hepatic tissue fibrosis was assessed by non-invasive methods, namely, elastography and vibration-controlled transient elastometry using FibriScanCompact 530 (Echosens, France). Liver fibrosis biomarkers (AAR, APRI, Fib-4, Forns index) were calculated; MDA test was conducted.&#x0D; Results. 100 % efficacy of dasabuvir and ombitasvir + paritaprevir + ritonavir was confirmed for both 8- and 12-week therapy in comorbid patients with extrahepatic manifestations, patients who underwent interferon-based therapy, regardless of liver fibrosis stage and disease duration.&#x0D; The article provides a comparative description of non-invasive methods for assessing liver fibrosis in patients with chronic hepatitis C: elastography, elastometry and serum fibrosis indices (APRI, AAR, FIB-4, MDA, Forns index). Indirect fibrosis markers are useful, because they allow to determine the late stages of liver fibrosis (F3-F4 on the METAVIR scale) with a very high degree of confidence.

Liver Fibrosis Scores and Hospitalization, Mechanical Ventilation, Severity, and Death in Patients with COVID-19: A Systematic Review and Dose-Response Meta-Analysis.

Methods We identified relevant cohort studies that assessed the relationship between liver fibrosis scores (e.g., FIB-4, NAFLD fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI)) and associated prognosis outcomes by searching the PubMed, EMBASE, and medRxiv databases. The potential dose-response effect was performed using a stage robust error meta-regression. Results Sixteen studies with 8,736 hospitalized patients with COVID-19 were included. One-point score in FIB-4 increase was significantly associated with increased mechanical ventilation (RR: 2.23, 95% CI: 1.37–3.65, P=0.001), severe COVID-19 (RR: 1.82, 95% CI: 1.53–2.16, P < 0.001), and death (RR: 1.47, 95% CI: 1.31–1.65, P < 0.001), rather than hospitalization (RR: 1.35, 95% CI: 0.72–2.56, P=0.35). Furthermore, there is a significant positive linear relationship between FIB-4 and severe COVID-19 (Pnonlinearity=0.12) and mortality (Pnonlinearity=0.18). Regarding other liver scores, one unit elevation in APRI increased the risk of death by 178% (RR: 2.78, 95% CI: 1.10–6.99, P=0.03). Higher NFS (≥−1.5) and Forns index were associated with increased risk of severe COVID-19 and COVID-19-associated death. Conclusion Our dose-response meta-analysis suggests high liver fibrosis scores are associated with worse prognosis in patients with COVID-19. For patients with COVID-19 at admission, especially for those with coexisting chronic liver diseases, assessment of liver fibrosis scores might be useful for identifying high risk of developing severe COVID-19 cases and worse outcomes.

Fontan-associated liver disease.

Fontan-associated liver disease.

The burden of NAFLD in type 2 diabetic subjects from the general population: A Nationwide population-based follow-up study (NASHCO).

The epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) in diabetes have been mainly investigated in the hospital setting. The goal of this study was to evaluate the characteristics of NAFLD and its impact on morbidity and mortality in type 2 diabetic subjects in a community setting. This study included 199 341 participants in the nationwide Constances cohort. After patients with excessive alcohol consumption, viral hepatitis or other causes of liver disease were excluded, 164 285 were analysed and 8386 (5.3%) were considered to have type 2 diabetes. The non-invasive diagnosis of NAFLD and advanced fibrosis was made using a combination of the fatty liver index and Forns index. Median follow-up was 2.5years. Diabetes increased the risk of NAFLD by sixfold (adjusted OR 6.05, 95% CI 5.68-6.45) and the risk of advanced fibrosis by 3.76-fold (aOR 3.76, 95% CI 2.87-4.91) in NAFLD subjects. After controlling for confounders, the presence of NAFLD in diabetic subjects was associated with an increased risk of severe liver-related events (aHR 2.53, 95% CI 1.36-4.69), cardiovascular disease (CVD, aHR 2.71, 95% CI 1.72-4.26) and overall mortality (aHR 2.91, 95% CI 1.53-5.53). The risk of hepatic and extrahepatic complications in diabetic subjects with NAFLD significantly increased with the severity of fibrosis (P<.05). This prospective, longitudinal study in a large community-based cohort provides real-world evidence of the risk for NAFLD and advanced fibrosis in diabetes, and its impact on liver disease progression, diabetes-related complications such as CVD, and overall mortality. These data could be used to estimate real clinical and economic burden of NAFLD in diabetic subjects.

Long-Term Hepatocellular Carcinoma Development and Predictive Ability of Non-Invasive Scoring Systems in Patients with HCV-Related Cirrhosis Treated with Direct-Acting Antivirals.

Simple SummaryIn the present study we investigated the ability of different non-invasive scoring systems (i.e., Forns index, APRI, FIB-4, ALBI, and aMAP) to predict hepatocellular carcinoma development in a large cohort of patients with HCV-related cirrhosis treated with direct-acting antivirals followed for a median of 44.9 months. ALBI score showed the best performance for the prediction of hepatocellular carcinoma; this score may be a useful inexpensive tool for risk stratification and the personalization of hepatocellular carcinoma surveillance strategy for patients with cirrhosis and previous history of HCV infection treated with DAA.Patients with hepatitis C virus (HCV)-related cirrhosis treated with direct-acting antivirals (DAA) are still at risk of developing hepatocellular carcinoma (HCC). We investigated the accuracy of non-invasive scoring systems (NSS) for the prediction of de novo HCC development in patients treated with DAA on long-term follow-up (FU). We analyzed data from 575 consecutive patients with cirrhosis and no history of HCC who achieved a sustained virologic response (SVR) to DAA therapy. NSS (i.e., Forns index, APRI, FIB-4, ALBI, and aMAP) were calculated at 3 months after the end of therapy. Performance for de novo HCC prediction was evaluated in terms of area under the curve (AUC) and Harrell’s C-index. During a median FU of 44.9 (27.8–58.6) months, 57 (9.9%) patients developed de novo HCC. All five NSS were associated with the risk of de novo HCC. At multivariate analysis, only the ALBI score resulted in being significantly and independently associated with de novo HCC development (adjusted hazard ratio = 4.91, 95% CI 2.91–8.28, p < 0.001). ALBI showed the highest diagnostic accuracy for the detection of de novo HCC at 1-, 3-, and 5-years of FU, with AUC values of 0.81 (95% CI 0.78–0.85), 0.71 (95% CI 0.66–0.75), and 0.68 (95% CI 0.59–0.76), respectively. Consistently, the best predictive performance assessed by Harrell’s C-statistic was observed for ALBI (C-index = 0.70, 95% CI 0.62–0.77). ALBI score may represent a valuable and inexpensive tool for risk stratification and the personalization of an HCC surveillance strategy for patients with cirrhosis and previous history of HCV infection treated with DAA.

Liver fibrosis indices associated with substantial hematoma expansion in Chinese patients with primary intracerebral hemorrhage

BackgroundWhether liver fibrosis is associated with increased risk for substantial hematoma expansion (HE) after intracerebral hemorrhage (ICH) is still uncertain. We evaluated the association between various liver fibrosis indices and substantial HE in a Chinese population with primary ICH.MethodsPrimary ICH patients admitted to West China Hospital within 24 h of onset between January 2015 and June 2018 were consecutively enrolled. Six liver fibrosis indices were calculated, including aspartate aminotransferase (AST)-platelet ratio index (APRI), AST/alanine aminotransferase ratio-platelet ratio index (AARPRI), fibrosis-4 (FIB-4), modified fibrosis-4 (mFIB-4), fibrosis quotient (FibroQ) and Forns index. Substantial HE was defined as an increase of more than 33% or 6 mL from baseline ICH volume. The association of each fibrosis index with substantial HE was analyzed using binary logistic regression.ResultsOf 436 patients enrolled, about 85% showed largely normal results on standard hepatic assays and coagulation parameters. Substantial HE occurred in 115 (26.4%) patients. After adjustment, AARPRI (OR 1.26, 95% CI 1.00-1.57) and FIB-4 (OR 1.15, 95% CI 1.02-1.30) were independently associated with substantial HE in ICH patients within 24 h of onset, respectively. In ICH patients within 6 h of onset, each of the following indices was independently associated with substantial HE: APRI (OR 2.64, 95% CI 1.30-5,36), AARPRI (OR 1.55, 95% CI 1.09-2.21), FIB-4 (OR 1.35, 95% CI 1.08-1.68), mFIB-4 (OR 1.09, 95% CI 1.01-1.18), FibroQ (OR 1.08, 95% CI 1.00-1.16) and Forns index (OR 1.37, 95% CI 1.10-1.69).ConclusionsLiver fibrosis indices are independently associated with higher risk of substantial HE in Chinese patients with primary ICH, which suggesting that subclinical liver fibrosis could be routinely assessed in such patients to identify those at high risk of substantial HE.

Development and validation of a non-invasive model for diagnosing HBV-related liver cirrhosis

BackgroundLiver cirrhosis is closely related to the abnormal liver function and occurrence of liver cancer. Accurate non-invasive assessment of liver cirrhosis is of great significance for preventing disease progression and treatment decision-making. We aim to develop and validate a non-invasive diagnostic model for liver cirrhosis in patients with chronic hepatitis B (CHB). MethodsFrom July 2015 to April 2017, seven-hundred fifty-four patients with primary HBV-related liver cancer who underwent hepatectomy were reprospectively recruited. All patients were examined with 2D-SWE and serologic testing preoperatively, which were utilized for measurement of liver stiffness and serum fibrosis models. The stage of liver fibrosis was evaluated using a resected liver specimen. Least absolute shrinkage and selection operator (Lasso) regression was used for feature selection and binary logistic regression analysis was chosen to build a diagnostic model, which was presented as a nomogram and evaluated for calibration, discrimination and clinical usefulness. The performance of noninvasive model was then prospectively validated in an independent cohort (361 patients) by the ROC curve analysis. ResultsThe diagnostic model, which consists of 5 selected clinical characteristics (PIII-NP, IV-C, Hyaluronan, Platelet and Liver stiffness), showed the strongest correlation with liver fibrosis stage (ρ = 0.702, P < 0.05). Compared with APRI, FIB-4, King’s Score, and Forns Index, the model presented the optimal discrimination and the best predictive performance with the highest AUC in the training cohort (0.866, 95%CI 0.840–0.892, P < 0.05) and validation cohorts (0.852, 95%CI 0.813–0.890, P < 0.05). Decision curve analysis demonstrated that nomogram based on the model was extremely useful for diagnosing cirrhosis in patients with chronic hepatitis B. ConclusionThis study proposes a non-invasive diagnostic model that incorporates the clinical predictors which can be conveniently used in the individualized diagnosis of HBV-related liver cirrhosis.

From the Editor’s desk…

From the Editor’s desk…

Prevalence and Risk Factors of Cardiovascular Disease in Patients with Chronic Hepatitis B

The association between chronic hepatitis B (CHB) and cardiovascular disease (CVD) remains unclear. We investigated the prevalence and risk factors of CVD in patients with CHB. Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analyzed. Significant liver fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile, highest Forns index quintile, or fibrosis-4 ≥ 2.67. The CVD risk was calculated using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score from the 2013 ACC/AHA Guidelines. Among the 506 subjects with CHB, 15 (3.0%) and 150 (29.6%) patients had a CVD history and significant liver fibrosis, respectively. Patients with CVD history were significantly older; showed a significantly higher prevalence of hypertension, metabolic syndrome, and significant liver fibrosis; and had a significantly higher platelet count, lower aspartate and alanine aminotransferase levels, higher triglyceride level, lower high-density lipoprotein level, and higher ASCVD risk than those without (all p < 0.05). In multivariate analysis, higher ASCVD risk (odds ratio [OR] = 1.090) and significant liver fibrosis (OR = 4.341) independently predicted the risk of CVD history (p < 0.05). The prevalence of CVD risk (6.7% vs. 1.4%; OR = 5.014) and high ASCVD risk (> 15%) (34.0% vs. 7.3%; OR = 6.538) was significantly higher in patients with significant liver fibrosis than in those without (all p < 0.05). Significant liver fibrosis was independently associated with the risk of CVD history in patients with CHB. Prospective studies are needed to validate the longitudinal association between fibrotic burden and CVD development in patients with CHB.

Non-Invasive Indirect Markers of Liver Fibrosis after Interferon-Free Treatment for Hepatitis C.

The effectiveness of interferon-free therapy during the course of HCV infection has already been confirmed. Liver fibrosis can be assessed in several ways, from biopsies to imaging tests. The present study evaluates the usefulness of non-invasive indirect biomarkers of liver fibrosis (APRI, GAPRI, FORNS, FIB-4, the AP index and HUI score) as markers of the effective treatment of HCV with the 3D regimen. Blood samples were collected from 70 patients suffering from chronic hepatitis C. Patients received the 3D AbbVie regimen for hepatitis C. All patients had HCV genotype 1b. The APRI, GAPRI, FIB-4, FORNS, HUI and AP index (age–platelet score) values were calculated with their respective algorithms. The stage of fibrosis was evaluated on the basis of a liver biopsy and confirmed by FibroScan-based transient elastography. An undetectable level of HCV RNA after 12 weeks of treatment with the 3D regimen indicates 100% eradication of hepatitis C virus. After the treatment, non-invasive indirect markers of liver fibrosis achieved levels below the limit for significant fibrosis, Thus, non-invasive indirect biomarkers of hepatic fibrosis failed to detect the presence of significant fibrosis, which was proved in histopathological examination. However, the eradication of hepatitis C virus by means of the 3D regimen treatment does not mean that patients were completely cured.

Noninvasive Evaluation of Liver Fibrosis in a Sample of Putative Inactive HBV Carriers in Rome, Italy.

Background Noninvasive methods are useful for investigating patients with chronic HBV infection. The severity of liver disease in inactive HBsAg carriers can be noninvasively assessed by transient elastography (TE) alone or in association with biochemical markers of fibrosis. Objectives The study evaluates the effectiveness of the TE compared to common fibrosis scores (FSs), APRI, Forns Index, and FIB4, for identifying significant fibrosis in Italian and foreigner HBsAg carriers. To investigate the risk of progression of the liver disease, liver stiffness (LS) and HBV-DNA were monitored over time. Methods Viral load, biochemical parameters, and LS have been retrospectively evaluated in 125 putative inactive HBV carriers, who visited two outpatient departments (Colleferro Hospital and INMP) from 01/03/2014 to 31/12/2019. Differences in clinical, biochemical, and demographic variables between Italians and foreigners were analyzed. 66 of 125 patients were followed up for 24 months by monitoring liver stiffness and HBV-DNA. Results Mean overall LS was 5.55 ± 1.92 kPa; 18 (14.4%) patients had a LS ≥7.5 kPa. Mean of APRI, Forns, and FIB4 was 0.29 ± 0.11, 4.15 ± 1.63, and 1.16 ± 0.59, respectively. FS did not differ between the patients with LS <7.5 kPa and those with LS ≥7.5 kPa. Italians displayed a significant lower ALT (0.53 ± 0.18 vs. 0.67 ± 0.33, p < 0.05) and AST (0.59 ± 0.16 vs. 0.70 ± 0.21, p < 0.01) value than foreigners. No differences in LS and HBV-DNA levels were observed. In 66 patients followed up for 24 months, HBV-DNA increased by ≥2000 UI/ml after 12 months in 15 individuals and remained ≥2000 UI/ml after 24 months in 10/15 individuals. 7/10 patients showed LS ≥ 7.5 kPa after 24 months, and 4 of them underwent antiviral therapy for HBV. Patients with HBV-DNA <2000 IU/ml had a significantly lower LS than those with HBV-DNA ≥2000 IU/ml (5.30 ± 1.43 vs. 7.69 ± 1.07, p < 0.0001). Conclusions Analysis shows lower effectiveness of FS vs. TE in the assessment of putative inactive HBV carriers. Furthermore, using FibroScan® and HBV-DNA can identify “false” inactive carriers.

PRO-C3 and ADAPT algorithm accurately identify patients with advanced fibrosis due to alcohol-related liver disease.

SummaryBackgroundAlcohol is a main cause of preventable deaths and frequently leads to the development of alcohol‐related liver disease. Due to the lack of diagnostics, patients are commonly diagnosed after developing clinical manifestations. Recently, the biomarker PRO‐C3 was shown to accurately identify fibrosis due to non‐alcoholic fatty liver disease.AimTo assess the diagnostic accuracy of PRO‐C3, the ADAPT score and best‐performing non‐patented serological test to detect advanced alcohol‐related liver fibrosis.MethodsWe enrolled 426 patients with alcohol overuse in a prospective biopsy‐controlled study. We evaluated the accuracy of PRO‐C3 and the PRO‐C3‐based algorithm ADAPT to detect advanced liver fibrosis.ResultsThe accuracy of PRO‐C3 was good with an AUROC of 0.85 (95% CI 0.79‐0.90). The best‐performing non‐patented test was the Forns index with an AUROC of 0.83 (95% CI 0.78‐0.89). The ADAPT algorithm performed better as compared to both the Forns index and PRO‐C3 alone with an AUROC = 0.88 (95% CI 0.83‐0.93).ConclusionPRO‐C3 is a new marker with high accuracy to detect advanced alcohol‐related liver fibrosis. The diagnostic accuracy of PRO‐C3 can be further improved by using the ADAPT algorithm in which the test outperforms currently available non‐patented serological fibrosis markers. The study is registered in the Odense Patient Data Exploratory Network (OPEN) under study identification numbers OP_040 (https://open.rsyd.dk/OpenProjects/da/openProject.jsp?openNo=40) and OP_239 (https://open.rsyd.dk/OpenProjects/openProject.jsp?openNo=239&lang=da).

Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease

Background & AimsAlcohol is the most common cause of liver-related mortality and morbidity. We therefore aimed to assess and compare the prognostic performance of elastography and blood-based markers to predict time to the first liver-related event, severe infection, and all-cause mortality in patients with a history of excess drinking.MethodsWe performed a prospective cohort study in patients with early, compensated alcohol-related liver disease. At baseline, we obtained a liver biopsy, transient elastography (TE), 2-dimensional shear-wave elastography (2D-SWE), enhanced liver fibrosis test (ELF), FibroTest, fibrosis-4 index (FIB-4), non-alcoholic fatty liver fibrosis score (NFS) and Forns index. We compared C-statistics and time-dependent AUC for prognostication. We used validated cut-off points to create 3 risk groups for each test: low, intermediate and high risk.ResultsWe followed 462 patients for a median of 49 months (IQR 31–70). Median age was 57 years, 76% were males, 20% had advanced fibrosis. Eighty-four patients (18%) developed a liver-related event after a median of 18 months (7-34). TE had the highest prognostic accuracy, with a C-statistic of 0.876, and time-dependent AUC at 5 years of 0.889, comparable to 2D-SWE and ELF. TE, ELF and 2D-SWE outperformed FibroTest, FIB4, NFS, Forns index and biopsy-verified fibrosis stage. Compared to patients with TE <10 kPa, the hazard ratios for liver-related events for TE 10–15 kPa were 8.1 (3.2–20.4), and 27.9 (13.8–56.8) for TE >15 kPa. Periods of excessive drinking during follow-up increased the risk of progressing to liver-related events, except for patients in the low-risk groups.ConclusionTE, ELF and 2D-SWE are highly accurate prognostic markers in patients with alcohol-related liver disease. Easy-to-use cut-offs can distinguish between substantially different risk profiles.Lay summaryAlcohol is the leading cause of death and illness due to liver disease. In this study, we assessed the ability of biomarkers to predict the risk of developing symptomatic liver disease in patients with early stages of alcohol-related liver disease. We found that several tests accurately predicted the risk of liver-related events such as ascites, esophageal varices and hepatic encephalopathy during an average follow-up of 4.1 years. Liver stiffness measurements by ultrasound elastography and the enhanced liver fibrosis test performed best. By using them, we were able to stratify patients into 3 groups with significantly different risks.

Comparison of Sound Touch Elastography, Sound Touch Quantify, and 4 Serum Fibrosis Indexes for the Diagnosis of Liver Fibrosis in Patients With Chronic Hepatitis B.

The aim of this research was to compare the use of shear wave elastography (sound touch elastography [STE] and sound touch quantify [STQ]) and serum liver fibrosis indexes in the evaluation and staging of chronic hepatitis B (CHB) liver fibrosis. Sound touch elastography is a form of 2-dimensional shear wave elastography, and STQ is a form of point shear wave elastography. Between June 2018 and March 2019, 122 patients with CHB were assessed using STE and STQ. Serum liver biomarkers tests were undertaken, and liver biopsy was performed, and these were used to assign a pathological stage based on the Scheuer scoring system. A receiver operating characteristic curve was used to analyze the diagnostic value of noninvasive methods for evaluating and staging liver fibrosis. The cutoff values of STE for liver fibrosis stages S2 to S4 were 8.85, 9.97, and 10.29 kPa, respectively, and the areas under the receiver operating characteristic (AUCs) curve were 0.703, 0.821, and 0.900, respectively. The cutoff values of STQ for liver fibrosis stages S2 to S4 were 11.31, 13.81, and 20.60 kPa, respectively, and the AUCs were 0.674, 0.807, and 0.893, respectively. The AUCs of STE and STQ in diagnosing fibrosis stage were significantly higher than those of liver serum biomarkers (P < 0.05). The AUCs for the ability of the aspartate transaminase-to-platelet ratio index, the fibrosis index based on the 4 factors, the King score, and the Forns index to diagnose S2 fibrosis were 0.502, 0.624, 0.542, and 0.616, respectively, and the AUCs for their ability to diagnose S4 fibrosis were 0.856, 0.861, 0.883, and 0.823, respectively. Both STE and STQ are noninvasive methods for the assessment of liver fibrosis in CHB patients, with better diagnostic performances than those of 4 serum fibrosis indexes.

Comorbidities Are Associated with Fibrosis in NAFLD Subjects: A Nationwide Study (NASH-CO Study).

The relationship between the severity of NAFLD and extra-hepatic events such as cardiovascular disease (CVD), extra-hepatic cancer (EHC) or chronic kidney diseases (CKD) has not been clearly investigated in the general population. The aim of this study was to assess whether the severity of fibrosis in NAFLD subjects was associated with extra-hepatic diseases based on noninvasive markers in a large population-based cohort. The study population included a cohort of 118,664 participants from the nationwide CONSTANCES cohort. After excluding individuals with excessive alcohol consumption and other causes of liver disease, 102,344 were included. The noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The history of CVD or EHC was recorded by a physician, and CKD was defined by a glomerular filtration rate < 60ml/mn. The prevalence of NAFLD (FLI > 60) was 18.2%, 10% with mild fibrosis (Forns Index < 4.2), 7.7% with intermediate fibrosis (Forns Index 4.2-6.9), and 0.4% with advanced fibrosis (Forns Index > 6.9). The prevalence of CVD, EHC, or CKD increased significantly with the severity of fibrosis (p < 0.0001). When adjusted for demographic, metabolic risk factors, and smoking, NAFLD with intermediate or advanced fibrosis remained associated with CVD (OR 1.36, p < 0.0001 and OR 3.07, p < 0.0001, respectively), EHC (OR 1.24, p = 0.001 and OR 1.64, p = 0.004, respectively), and CKD (OR 1.18, p = 0.03 and OR 2.09, p < 0.0001, respectively). In a large adult population-based cohort, there is a dose-dependent relationship between the severity of fibrosis and CVD, EHC, or CKD in NAFLD subjects.

Comparison of the diagnostic performance of 2D and 3D MR elastography in staging liver fibrosis.

To compare the diagnostic performance and image quality of state-of-the-art 2D MR elastography (MRE) and 3D MRE in the basic application of liver fibrosis staging. This retrospective study assessed data from 293 patients who underwent 2D and 3D MRE examinations. MRE image quality was assessed with a qualitative 2-point grading system by evaluating artifacts. Two experienced analysts independently measured mean liver stiffness values. The interobserver agreement of liver stiffness measurement was assessed by the intraclass correlation coefficient (ICC). The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of 2D and 3D MRE and blood-based markers for fibrosis staging using the pathology-proven liver fibrosis stage as the gold standard. The image quality provided by 3D MRE was graded as significantly higher than that obtained with the 2D MRE method (p < 0.01). Interobserver agreement in liver stiffness measurements was higher for 3D MRE (ICC: 3D 0.979 vs 2D 0.955). The AUC values for discriminating ≥ F1, ≥ F2, ≥ F3, and F4 fibrosis for 3D MRE (0.89, 0.92, 0.95, and 0.93) were similar to those for 2D MRE (0.89, 0.91, 0.94, and 0.92). Both the 2D and 3D MRE methods provided superior accuracy to the blood-based biomarkers, including APRI, FIB-4, and Forns index, especially for ≥ F2, ≥ F3, and F4 fibrosis stages (all p < 0.01). While 3D MRE offers certain advantages and opportunities for new applications of MRE, current widely deployed 2D MRE technology has comparable performance in the basic application of detecting and staging liver fibrosis. • 2D MRE and 3D MRE have comparable diagnostic performance in detecting and staging liver fibrosis. • 3D MRE has superior image quality and interobserver agreement compared to 2D MRE.

Absence of differences in the recurrence rates of hepatitis C virus‑associated hepatocellular carcinoma between direct‑acting antivirals and interferon‑based treatments: A multicenter study

Direct‑acting antivirals (DAAs) have a high rate of achieving a sustained virological response (SVR) to hepatitis C virus (HCV). However, there is a possibility that the rapid elimination of HCV by DAAs can decrease internal interferon (IFN) secretion, resulting in an increased rate of hepatocellular carcinoma (HCC) recurrence than that observed with the current IFN‑based treatment. The present study aimed to retrospectively confirm the absence of differences in the recurrence rates of HCC between patients receiving DAAs and IFN‑based treatment, and to investigate the possible risk factors for recurrence. The HCC recurrence rate following treatment was compared between patients who underwent DAA therapy (DAA group, n=257) and those who received an IFN‑based regimen (IFN group, n=47). Kaplan‑Meier analysis and the log‑rank test were used to compare the groups, and baseline confounds were adjusted by Cox proportional methods. Further comparison of the HCC recurrence rate between the DAA and IFN groups was performed after adjusting these potential confounding variables using propensity score matching. Kaplan‑Meier analysis revealed no significant differences in the HCC recurrence rate between the two groups, as well as no significant difference following the adjustment of the confounding variables. In addition, significant independent risk factors were identified for recurrence in the DAA group, including proteins induced by vitamin K absence or antagonist‑II, the number of previous HCC treatments and the Forns index. Following the adjustment for risk factors for HCC recurrence among the patients in the DAA group, no significant differences in the rate were observed between the DAA and IFN groups. On the whole, these results suggested that HCC recurrence following curative treatment was equivalent in patients treated with DAAs and those treated with IFN. The Forns index was identified as a novel risk factor for HCC recurrence following DAA treatment.