Hepatitis E virus infection in a single center in Japan

Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland.

Diagnosis and Quantitation of Fibrosis

Liver fibrosis markers as assessed by ultrasound elastography and serum samples: A large comparative study in hepatitis virus B and C liver diseases.

Background and Aims: Given the high prevalence of chronic liver diseases, non-invasive assessment of liver fibrosis is critical for screening and management of these conditions. While the FIB-4 index is widely used, its age-dependent nature may reduce specificity in older adults. The FIB-3 index, which excludes age, has been proposed as an alternative. This study aimed to compare the diagnostic performance of FIB-3 and FIB-4 for detecting advanced fibrosis across age groups using magnetic resonance elastography (MRE) as the reference standard. Methods: We retrospectively analyzed 3424 patients aged ≥30 years with chronic liver disease who underwent MRE. Advanced fibrosis was defined as liver stiffness ≥ 3.62 kPa. The cutoff values and diagnostic performance of the FIB-4 and FIB-3 indices for advanced fibrosis were evaluated within subgroups stratified by age quartiles (Q1–Q4), and the areas under the ROC curves (AUROCs) were compared using DeLong’s test. Results: Both FIB-3 and FIB-4 indices demonstrated comparable diagnostic accuracy for advanced fibrosis (AUROC 0.82 (95% CI: 0.81–0.83) for both; p = 0.70). In age-stratified analysis, the cutoff values for the FIB-4 index increased with increasing age (Q1: 1.72, Q2: 2.90, Q3: 3.66, Q4: 4.20), reflecting its age-dependent formula. In contrast, the FIB-3 index exhibited relatively minor variation in cutoff values across quartiles (Q1: 2.32, Q2: 3.52, Q3: 3.74, Q4: 3.14). Conclusions: FIB-3 index offers similar diagnostic accuracy to FIB-4 index while demonstrating more consistent performance across age groups. These findings provide evidence that FIB-3 index may be a useful alternative, particularly in older populations where FIB-4 index interpretation may be confounded by age.

We aimed to elucidate the relationship between serum liver fibrosis markers (Mac-2 binding protein glycosylation isomer (M2BPGi), FIB-4 index, aspartate aminotransferase to platelet ratio index and hyaluronic acid), and skeletal muscle mass and to investigate factors linked to skeletal muscle mass loss (SMML) in patients with chronic hepatitis C (CHC, n = 277, median age = 64 years). We defined patients with psoas muscle index [PMI, sum of bilateral psoas muscle mass calculated by manual trace method at the lumber 3 level on the computed tomography images divided by height squared (cm2/m2)] less than 6.36 cm2/m2 for male and 3.92 cm2/m2 for female as those with SMML based on the recommendations in current guidelines. Receiver operating curve (ROC) analysis was performed for predicting SMML in 4 liver fibrosis markers and parameters linked to SMML were also investigated in the univariate and multivariate analyses. In terms of liver fibrosis stages, F4 was observed in 115 patients, F3 in 67, F2 in 38, F1 in 53, and F0 in 4. The median (range) PMI for male and female were 6.198 (2.999–13.698) and 4.100 (1.691–7.052) cm2/m2, respectively. There were 72 male patients with SMML (55.4%) and 58 female patients with SMML (39.5%) (P = .0112). In both male and female, a significant inverse correlation between PMI and levels of liver fibrosis markers was observed in all liver fibrosis markers. ROC analyses for predicting SMML revealed that FIB-4 index had the highest area under the ROC (AUC = 0.712), followed by M2BPGi (AUC = 0.692). In the multivariate analysis of factors linked to SMML, gender (P = .0003), body mass index (P < .0001), FIB-4 index (P = .0039), and M2BPGi (P = .0121) were found to be significant predictors. In conclusion, liver fibrosis markers, especially FIB-4 index, can be helpful for predicting SMML in CHC patients.

BackgroundImproved renal function (IRF) observed in acute heart failure (AHF) is associated with poor prognosis. Since IRF is linked to renal congestion resulting from inadequate decongestion, predicting IRF could enhance management strategies. The Fibrosis-4 (Fib-4) index, originally developed as a marker for liver fibrosis, correlates with hepatic congestion, which is associated with renal congestion, making it a potential predictor of IRF. This study aims to investigate whether the Fib-4 index can predict IRF in patients with AHF and preserved ejection fraction (AHFpEF).MethodsWe analyzed 389 patients hospitalized for AHF between April 2004 and March 2022 at Yamanashi University Hospital. All-cause mortality was monitored for 1 year. IRF was defined as a ≥ 20% increase in the estimated glomerular filtration rate (eGFR) compared to admission levels. Preserved ejection fraction was defined as an ejection fraction ≥ 40%.ResultsIRF was observed in approximately 21% of patients with AHFpEF. Kaplan–Meier analysis showed that patients with IRF had higher mortality rates than those without IRF (p = 0.03, log-rank test). Multivariable analysis for IRF revealed that the eGFR, albumin level, and a Fib-4 index ≥ 3.24 (determined by receiver-operating characteristic curve) on admission were independent predictors of IRF in patients with AHFpEF.ConclusionIRF in patients with AHFpEF is associated with poor prognosis. A higher Fib-4 index at admission in AHFpEF can serve as a predictor of IRF.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10157-025-02669-w.

The fibrosis-4 index (FIB-4 index) is a marker of liver fibrosis. It has been reported that the FIB-4 index in compensated phase is associated with estimated right-sided filling pressure and poor prognosis in patients with heart failure. However, the relationship with invasively obtained right-sided cardiac pressures has been unclear. Hemodynamic status was evaluated by right heart catheterization in 189 heart failure patients who were in a clinically compensated phase between January 2015 and September 2017. Patients were assigned to two groups based on a median FIB-4 index of 2.15, then hemodynamic parameters and event rates were compared. Endpoint was defined as a composite of all-cause death, readmission for heart failure, or left ventricular-assist device implantation. Then, we also investigated correlations between the FIB-4 index and clinical factors, including hemodynamic parameters. Patients with a high FIB-4 index were significantly older (76 [IQR, 63-80] vs. 65 [IQR, 56-74] years, P < 0.001) and had higher right atrial pressure (RAP; 7 [IQR, 5-11] vs. 4 [IQR, 1-6] mmHg, P < 0.001) and pulmonary capillary wedge pressure (16 [IQR, 12-22] vs. 12 [IQR, 8-19] mmHg, P = 0.011) than those with a low FIB-4 index. The FIB-4 index correlated more strongly with parameters of right-sided than left-sided HF (RAP, R = 0.41, P < 0.001; inferior vena cava diameter, R = 0.44, P < 0.001; pulmonary capillary wedge pressure, R = 0.15, P = 0.038; brain natriuretic peptide, R = 0.14, P = 0.29). Multiple regression analysis showed that the FIB-4 index independently correlated with RAP. In conclusion, the FIB-4 index can non-invasively reflect right-sided filling pressure, which might explain why it is associated with a poor prognosis, among patients with heart failure.

IntroductionHepatitis E virus (HEV) is enterically transmitted and is endemic in some areas of the world. In the UK it was generally thought to be associated with travel but infection...

Background Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of noninvasive alternatives, galectin-3-binding protein (G3BP) was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics. Aim of the Work to evaluate serum Galectin-3 as a marker of liver fibrosis and correlate it to the stage of fibrosis assessed by FibroScan, FIB-4 index and APRI score Patients and Methods This was prospective study, was carried out on 30 patients with liver fibrosis/cirrhosis due to chronic HCV inthe Hepatic Virology Unit and the gastroenterology department of Ain Shams university hospitals and 30 health controls with normal, non fibrotic and non cirrhotic, liver, from January 2022 to June 2022 Results There were high significant difference between both groups as regard Serum level of Galectin-3 and APRI score. Conclusion Serum level of galectin-3 was highly expressed in chronic HCV Egyptain patients and positively correlated to FIB-4 index, APRI score and fibroscan.so the serum level of galectin-3 beside other modalities, lab investigations and clinical examination may guide us about the progression to fibrosis and cirrhosis in those patients. In these patients, if galectin-3 levels were found to be high, serum alpha-feto protein level and ultrasonographic examination could be repeated at more frequent intervals. This may also guide us in terms of the treatment plan. Measurement of galectin-3 in sera of large number of patients and follow up may pave the way to pick up early fibrosis and showed its prognostic effect.

Objective To compare the effect of the FIB4 index on skeletal muscle mass (SMM) loss (i.e., pre-sarcopenia) with that of three other liver fibrosis markers [FIB3 index, aminotransferase to platelet ratio index (APRI), and platelet count] or sarcopenia-related factors such as age and body mass index (BMI) in patients with metabolic dysfunction associated with steatotic liver disease (MASLD, 2,093 men and 1,280 women; median age, 55 years). Methods An SMM decrease was defined as a fat-free index, as tested by a bioelectrical impedance analysis, <18 kg/m2 in men and <15 kg/m2 in women. We compared the diagnostic ability of the above-mentioned six markers to induce an SMM decrease. Results The median BMI was 25.0 kg/m2. The median FIB4 index, FIB3 index, APRI, and platelet count were 0.99, -0.40, 2.93 and 25.2 × 104/μL. The prevalence of SMM decrease in men and women was 21.7% (455/2,093) and 16.7% (214/1,280), respectively. For all cases, the percentage of a decreased SMM was 15.0% (372/2,479) in cases with FIB4 index <1.3, 32.1% (268/834) in cases with 1.3< FIB4 index <2.67 and 48.3% (29/60) in cases with FIB4 index >2.67 (overall p<0.0001). In almost all subgroup analyses, the cases were well-stratified according to the FIB4 index. In all cases, the area under the receiver operating characteristic curve (AUC) for SMM decrease was highest for BMI (AUC=0.94), followed by the FIB4 index (AUC=0.67). In all subgroup analyses, except for BMI ≥25 kg/m2, the FIB4 index had the second highest AUC for SMM decrease after BMI. Conclusion The FIB4 index may be useful for predicting pre-sarcopenia in patients with MASLD.

Hepatitis E virus (HEV) infection rarely causes icteric hepatitis, yet 10%-40% of adult Americans have serological evidence of previous infection. The aim of this study was to investigate the incidence, presentation, and outcome of acute and previous HEV infection in a large cohort of patients with suspected drug-induced liver injury (DILI). Serum samples from 2012 patients enrolled in the DILI Network were tested for anti-HEV immunoglobulin G (IgG). Those with detectable anti-HEV IgG underwent testing for anti-HEV IgM; those with detectable anti-HEV immunoglobulin m (IgM) were tested for HEV RNA. Anti-HEV IgG was detected in 407 (20%) patients and associated with increasing subject age and earlier year of enrollment. The median age of seropositive subjects was more than a decade higher than seronegative subjects (59.8 vs 48.7 years). The overall prevalence of anti-HEV declined from 22% (2004-2011) to 18% (2012-2019), suggestive of a cohort effect. The frequency of acute hepatitis E (median ALT = 1231 IU/L) also decreased from 3% (2004-2008) to 1.2% (2009-2013) to 0.6% (2014-2019). These results suggest that acute HEV infection is usually subclinical and was much more frequent in this cohort before 2004. Acute HEV infection accounts for less than 1% of suspected American DILI cases and is more frequent in older men. Previous HEV infection is also most commonly seen in older individuals. Clinicians should consider testing for unsuspected acute HEV infection in older adult patients with acute hepatocellular DILI and jaundice.

We evaluated the prognosis of hepatocellular carcinoma (HCC) patients with Child-Pugh (C-P) class A based on FIB-4 index, which is a liver fibrosis marker. A total of 915 HCC patients with C-P class A were investigated. We assessed the prognosis using FIB-4 index, and factors associated with survival rates were analyzed in these patients. When patients were categorized according to FIB-4 index as <2.0 (n = 93), ≥ 2.0 and <4.0 (n = 311), and ≥ 4.0 (n = 511), survival rates at 5 years were 70.5% [95% confidence interval (CI) 59.0-79.9], 56.4% (95% CI 50.1-62.5), and 47.1% (95% CI 42.2-52.1), respectively. Patients with FIB-4 index <2.0 had a higher survival rate than the other groups (≥ 4.0 vs ≥ 2.0 and <4.0, p = 0.010; ≥ 2.0 and <4.0 vs <2.0, p = 0.028). We were able to predict prognosis in patients with C-P score 5 by FIB-4 index, but survival rate did not significantly differ in patients with C-P score 6. Multivariate analysis identified C-P score, FIB-4 index [≥ 2.0 and <4.0; hazard ratios (HRs) 1.638 (95% CI 1.084-2.474); p = 0.019/≥ 4.0; HR 1.828 (95% CI 1.217-2.744); p = 0.004], Lens culinaris agglutinin-reactive α-fetoprotein, tumor size, number, vascular invasion, antiviral therapy, and hepatectomy as independent predictive factors for survival. The FIB-4 index is useful for assessing prognosis in HCC patients with C-P class A, especially those with C-P score 5.

Simple SummaryThis retrospective study analyzed 237 consecutive patients with coexisting nonalcoholic fatty liver disease and chronic hepatitis B (NAFLD-CHB) with long observation period (median follow-up duration, 13 years). The optimal cutoff for the FIB-4 index of 1.77 was calculated based on the maximum Youden index value, and the value was 1.77 with an AUC of 0.70. The significant higher risk of developing hepatocellular carcinoma (HCC) in patients with a high FIB-4 index (≥1.77) than the patients with a low FIB-4 index (<1.77) (adjusted hazard ratio, 4.35; 95% CI, 1.42–13.24; log-rank test, p = 0.006) were found among the NAFLD-CHB patients whose baseline characteristics were balanced by propensity score matching. The FIB-4 index might be a useful predictor of the development of HCC among NAFLD–CHB patients.Background: The FIB-4 index, a noninvasive tool (FIB-4 index = age × aspartate transaminase (AST)/(platelet count × √alanine aminotransferase (ALT)), is a useful assessment for liver fibrosis. Patients with a high FIB-4 index were reported to have a high risk of developing hepatocellular carcinoma (HCC). This study analyzed the clinical association of the FIB-4 index with HCC development in patients with coexisting nonalcoholic fatty liver disease and chronic hepatitis B (NAFLD–CHB). Methods: This retrospective study analyzed 237 consecutive patients with NAFLD–CHB between January 2006 and December 2010 at the National Police Hospital in Korea. Patients with HCC at baseline and those diagnosed with HCC within 6 months from baseline were excluded. Propensity score matching analysis (PSM) was adopted to balance the baseline characteristics between patients with low and high FIB-4 index values. The cumulative rates of HCC development were compared between the two groups using the Kaplan–Meier method in the matched population. Results: The median follow-up duration was 13 years (interquartile range, 8.2–15.7). The optimal cutoff for the FIB-4 index of 1.77 was calculated based on the maximum Youden index value, with an AUC of 0.70. Among a total of 237 patients with NAFLD–CHB, HCC developed in 20 patients (8.4%) (14 of the 90 patients with a high FIB-4 index vs. 6 of the 147 patients (4.1%) with a low FIB-4 index; log-rank p = 0.003). Patients with a high FIB-4 index had a significantly and independently higher risk of HCC than those with a low FIB-4 index (adjusted hazard ratio, 4.35; 95%; confidence interval, 1.42–13.24; log-rank test, p = 0.006). Conclusion: A high FIB-4 index (≥1.77) might be a useful marker for predicting the development of HCC in patients with NAFLD–CHB.

Prognostic value of liver fibrosis assessed by the FIB-4 index in patients with acute coronary syndrome

The association between serum testosterone level and liver fibrosis in patients with non-alcoholic fatty liver disease is unclear. To clarify this association, we investigated the relationship between serum free testosterone concentration and markers of liver fibrosis in men with type 2 diabetes mellitus but no obvious features of alcohol consumption. This retrospective observational cross-sectional study enrolled 248 men with type 2 diabetes mellitus. The FIB-4 index was measured as a marker of liver fibrosis, and multiple linear regression analysis was performed to examine its association with serum free testosterone concentration. In addition, the 7S domain of type IV collagen (IV-7S) was examined in 140 of the 248 patients. The mean free testosterone concentration was 10.6 ± 6.8 pg/mL and the means of the FIB-4 index and IV-7S were 1.64 ± 1.19 and 4.02 ± 1.11 ng/mL, respectively. After adjusting for all relevant variables, serum free testosterone concentrations were inversely associated with both the FIB-4 index and IV-7S (β; -0.28, P < 0.0001, and β; -0.28, P = 0.002, respectively). Measuring serum free testosterone concentrations in men with type 2 diabetes mellitus may help to predict progression to advanced liver disease. Identifying patients at risk may help to prevent the development of cirrhosis and hepatocellular carcinoma.