Non-invasive Fibrosis Markers Research Articles

Management of Portal Hypertension in the Older Patient.

Aging is a process of physiological slowing, reduced regenerative capacity and inability to maintain cellular homeostasis. World Health Organisation declared the commencement of population aging globally, largely attributed to improvement in the healthcare system with early diagnosis and effective clinical management. Liver ages similar to other organs, with reduction in size and blood flow. In this review we aim to evaluate the effect of aging in liver disease. Aging causes dysregulation of major carbohydrate, fat and protein metabolism in the liver. Age is a major risk factor for liver fibrosis accelerated by sinusoidal endothelial dysfunction and immunological disharmony. Age plays a major role in patients with liver cirrhosis and influence outcomes in patients with portal hypertension. Transient elastography may be an useful tool in the assessment of portal hypertension. Hepatic structural distortion, increased vascular resistance, state of chronic inflammation, associated comorbidities, lack of physiological reserve in the older population may aggravate portal hypertension in patients with liver cirrhosis and may result in pronounced variceal bleed. Cut-offs for other non-invasive markers of fibrosis may differ in the elderly population. Non-selective beta blockers initiated at lower dose followed by escalation are the first line of therapy in elderly patients with cirrhosis and portal hypertension, unless contraindicated. Acute variceal bleed in the elderly cirrhotic patients can be life threatening and may cause rapid exsanguination due to poor reserve and associated comorbidities. Vasoactive drugs may be associated with more adverse reactions. Early endoscopy may be warranted in the elderly patients with acute variceal bleed. Role of TIPS in the elderly cirrhotics discussed. Management of portal hypertension in the older population may pose significant challenges to the treating clinician.

Non-invasive Serological Markers of Hepatic Fibrosis – Mini Review

Aim: This study examines the pathological outcomes of chronic liver injuries, with a focus on liver fibrosis. It emphasizes understanding the structural changes within the liver that may lead to cirrhosis and functional impairments, crucial for developing targeted antifibrotic therapies. Methods: Our approach reviews existing literature detailing the use of traditional diagnostic methods—biochemical and serological tests alongside liver biopsies. Additionally, we evaluate the reliability and efficacy of non-invasive techniques such as serological test panels and imaging examinations. These methods are compared to understand their viability as supplementary or alternative diagnostic tools to liver biopsy. Significance: Liver fibrosis, if unmanaged, can progress to severe conditions such as cirrhosis and hepatocellular carcinoma, making it vital to understand its progression and treatment options. This study underscores the need for precise and non-invasive diagnostic tools in the clinical management of liver fibrosis, providing insight into the progression of chronic liver diseases and potential therapeutic targets. Conclusion and future perspectives: The research confirms that while liver biopsy remains the definitive method for staging liver fibrosis, its risks and limitations necessitate the use of enhanced non-invasive diagnostic techniques. These methods have shown promising results in accuracy and are critical for broadening clinical applications and patient safety. It is recommended that the scientific community continue to develop and validate non-invasive diagnostic tools. Enhancing the accuracy and reliability of these tools can provide a cost-effective, accessible, and safer alternative for large-scale screening and management of liver fibrosis in asymptomatic populations. Additionally, integrating advancements in radiologic and serological markers can further refine these diagnostic methods, improving overall patient outcomes.

Liver Fibrosis Assessed Via Noninvasive Tests is Associated With Incident Heart Failure in a General Population Cohort

To determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. Using UK Biobank data, we prospectively examined the relationship between non-invasive fibrosis markers [NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and AST to platelet ratio index (APRI)] and incident hospitalization/death from heart failure (n=413,860). Cox-regression estimated hazard ratios (HR) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype, and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high risk NFS score HR 1.59 [1.47-1.76], p<0.0001; FIB-4 HR 1.69 [1.55-1.84], p<0.0001; APRI HR 1.85 [1.56-2.19], p<0.0001; combined fibrosis scores HR 1.90 [1.44-2.49], p<0.0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD) and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3 a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score and heart failure. In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Role of Resmetirom, a Liver-Directed, Thyroid Hormone Receptor Beta-Selective Agonist, in Managing Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis

BackgroundResmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This meta-analysis aimed to summarize the efficiency and safety of resmetirom in treating NASH. MethodsElectronic databases were searched for randomized controlled trials (RCTs) of resmetirom vs placebo in patients with NASH. The primary outcomes were the changes from baseline in hepatic fat content, liver histology, including NASH resolution, and noninvasive markers of hepatic fibrosis. ResultsThree randomized controlled trials (n = 2231) met the inclusion criteria. Compared to placebo, resmetirom achieved greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (for resmetirom 80 mg: MD −27.76% [95%CI: −32.84, −22.69]; for resmetirom 100 mg: MD −36.01% [95%CI: −41.54, −30.48]; P < .00001 for both) and FibroScan controlled attenuation parameter (for resmetirom 80 mg: MD −21.45 dBm [95%CI: −29.37, −13.52]; for resmetirom 100 mg: MD −25.51 dBm [95%CI: −33.53, −17.49]; P < .00001 for both). Resmetirom 80 mg outperformed placebo in NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction. Moreover, resmetirom 80 mg and 100 mg were superior to placebo in cytokeratin-18 (M30) reduction. Greater reductions in liver enzymes, lipids, and reverse triiodothyronine were observed in the resmetirom arms with no impact on triiodothyronine. Nausea and diarrhea were more common with resmetirom than with placebo; other adverse events were comparable. ConclusionResmetirom improves hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients. Resmetirom generally does not affect thyroid function and is well-tolerated.

Serum non-invasive liver fibrosis markers in patients with COVID-19

Serum non-invasive liver fibrosis markers in patients with COVID-19

No gender differences in the 24-month course of non-invasive liver fibrosis markers after DAA therapy in HCV-mono and HCV/HIV-coinfected patients

Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.

Non-invasive Fibrosis Markers for Predicting Esophageal Varices: A Potential Alternative to Endoscopic Screening.

Chronic liver infections and diseases lead to chronic liver injury, which results in fibrosis. Due to this continuous scarring and regeneration, cirrhosis occurs, which is also responsible for several adverse sequelae, including but not limited to esophageal varices. Cirrhosis has resulted in patients' increased morbidity and mortality, especially in low socioeconomic settings such as Pakistan. Endoscopy is the gold standard for measuring the presence or absence of esophageal varices, along with their grade. Currently, some non-invasive markers (aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), fibrosis 4 (FIB-4), AAR to platelet ratio index (AARPRI), aspartate aminotransferase-to-platelet ratio index (APRI), S-index, King's score) are being established that make use of laboratory tests, such as a complete blood profile, liver function profile, and coagulation profile, to estimate the extent of hepatic fibrosis. The objective of this study is to establish a correlation between non-invasive markers of fibrosis and the presence of esophageal varices and to assess their potential as a substitute for gastrointestinal endoscopy screening. Additionally, the study aims to compare these six scores, thereby generating data on their individual and relative accuracy. This was a cross-sectional study conducted at the Shalamar Institute of Health Sciences, Lahore, Pakistan. Outpatient (OPD) data were obtained from the Shalamar online portal system from June 2022 to December 2022. Laboratory tests, abdominal ultrasounds, and endoscopy results were accessed and recorded in the questionnaire. The patient's medical records and contact numbers were also noted in case further questions arose. Data were then compiled into a Microsoft Excel spreadsheet (Microsoft Corp., Redmond, WA) and analyzed after computing the non-invasive procedure formulas. It was analyzed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY). P-values were calculated, and conclusions were drawn. Of the sample size of 100 patients with liver damage and injury, 60% were male and 40% were female. Among males, 15% had a milder (grade 1)degree of esophageal varices, and 45% had a moderate to advanced degree (grades 2-3) of esophageal varices. Among females, 19% had mild (grade 1) varices, while 21% had severe (grade 3) varices. The most common cause of varices in patients who had developed fibrosis and/or cirrhosis was hepatitis C, with a wide margin of other causes. The p-values obtained showed that from the selected list of non-invasive markers of fibrosis, only FIB-4 and AARPRI were statistically significant with p-values of 0.036 and 0.022, respectively. Though endoscopy is currently the gold-standard procedure for detecting the presence or absence and grade of esophageal varices, it is invasive, which makes the patients extremely uncomfortable and apprehensive. It can also lead to post-procedure infection, internal hemorrhages, and trauma due to instrument use. Due to its invasive nature, some patients also tend to refuse this procedure. Non-invasive fibrosis markers can help make a diagnosis without undergoing an endoscopy, which in turn will improve patient compliance and satisfaction. It was observed that FIB-4 and AARPRI can be used together as reliable markers to assess the presence or absence of esophageal varices.

Skeletal muscle mass increases after viral eradication with direct-acting antivirals in patients with chronic hepatitis C: A longitudinal study.

Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.

Serum biomarkers associated with liver fibrosis in patients with type 2 diabetes

BACKGROUND: The diagnosis of liver fibrosis is an important task in the management of patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The currently used diagnostic methods have a number of disadvantages such as invasiveness and high cost, or insufficient sensitivity and specificity. Therefore, the search for new non-invasive markers of liver fibrosis remains an actual challenge.AIM: To assess a diagnostic value of serum growth differentiation factor-15 (GDF-15), microfibril-associated glycoprotein 4 (MFAP-4), collagen type IV alpha1 (COL4alpha1), Mac-2 binding protein (M2BPGI) and chitinase-3-like protein 1 (YKL-40) as markers of liver fibrosis in patients with type 2 diabetes and NAFLD.MATERIALS AND METHODS: A single center cross-sectional observational study was performed. The study included 74 patients, 23 men and 51 women, aged 18 to 74 years. Liver elastography was used as reference method for the fibrosis evaluation. APRI and fib-4, non-invasive fibrosis indices, were assessed. Serum concentrations of GDF-15, MFAP-4, COL4alpha1, M2BPGI, and YKL-40 were determined by ELISA. ROC analysis was used to evaluate the sensitivity and specificity of serum markers for the diagnosis of the liver fibrosis.RESULTS: Liver fibrosis stage 1 was verified in 16 subjects, stage 2 in 12, stage 3 in 7, and stage 4 in 19. Patients with advanced liver fibrosis (stages 3–4), compared with those without severe fibrosis (stages 0–2), had higher levels of GDF-15 (p=0.003), COL4alpha1 (p=0.007), and YKL-40 (p=0.04). Patients with stage 1-2 liver fibrosis had higher levels of COL4alpha compared to those without any signs of fibrosis (p=0.02). There were no significant differences in the level of MFAP-4 and M2BPGI between patients with different severity of fibrosis. According to the ROC analysis, GDF-15, COL4alpha1 and YKL-40 have diagnostic value in the detection of severe liver fibrosis comparable to that of the APRI and fib-4 indices.CONCLUSION: GDF-15, COL4alpha1 and YKL-40 could be considered as promising non-invasive markers of liver fibrosis in patients with type 2 diabetes and NAFLD.

Shear-wave elastography for monitoring Fontan-associated liver disease: A prospective cohort study.

The spectrum of Fontan-associated liver disease (FALD) varies from abnormal liver function tests to fibrosis and even cirrhosis. In this prospective study, we evaluated the role of shear-wave elastography (SWE) in predicting the presence of advanced FALD. Forty-eight patients (30 males, 13.9 [6-21] years) with a Fontan circulation were evaluated at 8.3 (2.1-18.7) years since the Fontan surgery. The median liver stiffness measurement (LSM) value was higher than values in normal children at 15.4 (9.5-38.7) kPa. The LSMs had a weak but significant correlation with age at the time of LSM (r = 0.25, p = 0.01) and duration post-Fontan surgery (r = 0.31, p = 0.02). It had a poor correlation with the concomitant aspartate transaminase-to-platelet ratio index (r = 0.1, p = 0.39). No difference in the elastography values between children with and without ultrasound evidence of advanced liver disease (17.7 [interquartile range, IQR: 4] vs. 16.1 [IQR: 6], p = 0.62] was observed. Further studies are required to determine the precise role of SWE as a noninvasive marker of liver fibrosis in FALD.

Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study

Background & AimsIn phase 2 studies, efruxifermin, an Fc–FGF21 analog, significantly reduced steatohepatitis and fibrosis in patients with non-alcoholic steatohepatitis (NASH), now called metabolic dysfunction-associated steatohepatitis (MASH), for which there is no approved treatment. Type 2 diabetes (T2D) and obesity are prevalent among patients with MASH and increasingly treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This study evaluated the safety and efficacy of efruxifermin in patients with MASH, fibrosis, and T2D taking a GLP-1RA. MethodsCohort D was a double-blind, placebo-controlled phase 2b study in adults with T2D and MASH with fibrosis (F1–F3) on stable GLP-1RA therapy randomized (2:1) to receive efruxifermin 50 mg or placebo, once weekly for 12 weeks. The primary endpoint was safety and tolerability of efruxifermin added to a stable dose of GLP-1RA. Secondary endpoints included changes in hepatic fat fraction (HFF), markers of liver injury and fibrosis, and metabolic parameters. ResultsAdults (N=31) with T2D and MASH fibrosis (F1–F3) on a stable GLP-1RA (semaglutide, 48.4%; dulaglutide, 45.2%; liraglutide, 6.5%) received efruxifermin 50 mg (N=21) or placebo (N=10) for 12 weeks. The addition of efruxifermin to a GLP-1RA appeared safe and well tolerated. The most frequent efruxifermin-related adverse events were mild–moderate gastrointestinal events. One patient receiving efruxifermin discontinued due to nausea, and another withdrew consent. There were no treatment-related serious adverse events. After 12 weeks, efruxifermin reduced HFF by 65% (P<.0001 vs placebo) compared to a 10% reduction for placebo (GLP-1RA alone). Efruxifermin also improved noninvasive markers of liver injury, fibrosis, glucose, and lipid metabolism while maintaining GLP-1RA–mediated weight loss. ConclusionsThe tolerability profile of efruxifermin added to GLP-1RA appeared comparable to that of either drug alone, while also significantly reducing HFF and noninvasive markers of fibrosis in patients with MASH and T2D. Liver health in patients already on a GLP-1RA may be further improved by addition of efruxifermin. Clinicaltrials.gov no. NCT05039450

Imbalance of mitochondrial fusion in peripheral blood mononuclear cells is associated with liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis

Mitochondrial dysfunction and inflammation contribute to the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH). This study aims to evaluate the potential association between mitochondrial dynamics and cell death markers from peripheral blood mononuclear cells (PBMCs) and the presence of MASH with significant liver fibrosis among metabolic dysfunction-associated steatotic liver disease (MASLD) patients. Consecutive patients undergoing bariatric surgery from January to December 2022 were included. Patients with histologic steatosis were classified into MASH with significant fibrosis (F2-4) group or MASLD/MASH without significant fibrosis group (F0-1). Mitochondrial dynamic proteins and cell death markers were extracted from PBMCs. A total of 23 MASLD/MASH patients were included (significant fibrosis group, n = 7; without significant fibrosis group, n = 16). Of the mitochondrial dynamics and cell death markers evaluated, OPA1 protein, a marker of mitochondrial fusion is higher in MASH patients with significant fibrosis compared to those without (0.861 ± 0.100 vs. 0.560 ± 0.260 proportional to total protein, p = 0.001). Mitochondrial fusion/fission (OPA1/DRP1) ratio is significantly higher in MASH patients with significant fibrosis (1.072 ± 0.307 vs. 0.634 ± 0.313, p = 0.009). OPA1 (per 0.01 proportional to total protein) was associated with the presence of significant liver fibrosis with an OR of 1.08 (95%CI, 1.01–1.15, p = 0.035), and adjusted OR of 1.10 (95%CI, 1.00–1.21, p = 0.042). OPA1 from PBMCs is associated with MASH and substantial fibrosis. Future studies should explore if OPA1 could serve as a novel non-invasive liver fibrosis marker.

Effect of Concurrent Metabolic Dysfunction-Associated Steatotic Liver Disease on Serial Non-invasive Fibrosis Markers in Chronic Hepatitis B.

Concurrent hepatic steatosis has diverse effects on chronic hepatitis B (CHB), however the combined effects of metabolic dysfunction-associated steatotic liver disease (MASLD) and CHB on liver fibrosis progression remains unclear. The primary aim of this study was to utilize serial fibrosis measurements to compare the dynamic change in fibrosis in CHB patients with/without concurrent MASLD. The secondary aim was to investigate factors associated with steatosis development and regression in CHB patients. This was a retrospective cohort study of all non-cirrhotic CHB patients identified from 1/1/2011 to 31/12/2016. Hepatic steatosis was diagnosed by ultrasound. Fibrosis markers included liver stiffness (LSM) by transient elastography, APRI and FIB-4. General linear mixed effects modelling was used to fit polynomial and linear estimates. Of 810 CHB patients (n = 2,373 LSM measurements; median age 44.4y; 48% male; 24% HBeAg positive), 14% had concurrent MASLD. LSM was higher at baseline but decreased in MASLD patients over time, while LSM remained stable in non-MASLD patients, such that all patients had similar LSM beyond 4-5 years. MASLD patients had lower APRI compared to non-MASLD patients, which was predominately due to a higher platelet count and higher ALT over time. There was substantial discordance between LSM, APRI and FIB-4. Baseline BMI was the only factor that predicted steatosis development and regression. We found no evidence of an association between concurrent MASLD and fibrosis progression amongst CHB patients without baseline advanced liver disease. APRI and FIB-4 may have reduced accuracy in MASLD patients.

Noninvasive markers of hepatic fibrosis and their clinical application in coronary artery disease.

Noninvasive markers of hepatic fibrosis and their clinical application in coronary artery disease.

Liver fibrosis index is associated with functional outcome among acute ischemic stroke patients

IntroductionThe fibrosis-4 (FIB-4) index and the fibrosis-5 (FIB-5) index are noninvasive markers of liver fibrosis in patients with nonalcoholic fatty liver disease. Although liver fibrosis a potential risk factor for stroke development, it is uncertain whether liver fibrosis influences stroke outcomes. We investigated the associations between these two indices and stroke patient outcomes and compared their predictive accuracy. MethodsWe conducted a double-center, hospital-based, retrospective study. Consecutive acute ischemic stroke patients (n=2399) were analyzed. We calculated the FIB-4 index and the FIB-5 index and evaluated their relationships with poor stroke outcome, which was defined as a modified Rankin Scale score of 3–6 at three months after stroke. We evaluated the ability of each index to predict stroke outcome according to cutoff values calculated from receiver operating characteristic (ROC) curves. ResultsOf 2399 recruited patients, 1549 patients (mean age, 73 years) were analyzed. The FIB-4 index and FIB-5 index had similar areas under their ROC curves for predicting stroke outcome (FIB-4 index, 0.675 and FIB-5 index, 0.683, P=0.334). The cutoff points of the FIB-4 index and FIB-5 index according to the ROC analysis were associated with poor stroke outcome in the multivariable analyses (odds ratio [OR] 2.23, 95 % confidence interval [CI] 1.72–2.89, OR 1.93, 95 % CI 1.47–2.54, respectively). ConclusionsLiver fibrosis scores may be useful for predicting outcomes in patients with acute stroke. The FIB-4 and FIB-5 indices should be considered comprehensive tools for assessing the outcome risk after ischemic stroke.

The Diagnostic Value of FibroTest and Hepascore as Non-Invasive Markers of Liver Fibrosis in Primary Sclerosing Cholangitis (PSC).

The aim of this study was to evaluate the diagnostic usefulness of two non-invasive, validated, and patented markers of liver fibrosis, the Hepascore and FibroTest, in patients with primary sclerosing cholangitis (PSC). The study group consisted of 74 PSC patients and 38 healthy subjects. All patients had a liver biopsy. The Hepascore and FibroTest were calculated using specific algorithms. The ANOVA rank Kruskal-Wallis test revealed differences in the Hepascore and FibroTest between patients divided according to histological stage (p < 0.001 for both comparisons). The Hepascore and FibroTest had significantly higher results in patients with significant fibrosis (F ≥ 2) in comparison to those with no significant fibrosis (F1) (p < 0.001 for both tests) and higher values in patients with cirrhosis (F4) when compared to those without cirrhosis (F1-F3) (p < 0.001 for both comparisons). The Hepascore test showed a diagnostic sensitivity of 96.8%, a specificity of 100% for fibrosis (at cut-off 0.52) and a diagnostic sensitivity of 95.2%, and a specificity also of 100% for cirrhosis (at 0.80). The FibroTest in point 0.51 for the diagnosis of fibrosis obtained the following values: 58.6%, 90%, 89.5%, and 60%, respectively, and in point 0.73 for the diagnosis of cirrhosis: 42.9%, 100%, 100%, and 45.5, respectively. The Hepascore test reached an excellent diagnostic power in identifying both fibrosis and cirrhosis (AUC = 1.0). The FibroTest and Hepascore are highly valuable for the evaluation of the severity of liver fibrosis and cirrhosis in PSC patients and can be used as a primary screening method, allowing for a significant reduction in the need for liver biopsy. Both markers have the required sensitivity and specificity to detect liver fibrosis and cirrhosis and can be equally used in clinical practice, although the Hepascore seems to be a better test because it is more specific.

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.

The Diagnostic Performance of Serum Hyaluronic Acid and Collagen III in Differentiating Liver Fibrosis in HCV-Induced Patients

Abstract Introduction/Objective Chronic liver diseases may lead to inflammation and progressive scarring, causing irreversible hepatic damage (cirrhosis). To avoid the complications of liver puncture biopsy, Collagen III and Hyaluronic acid are studied as non-invasive markers of liver fibrosis in chronic liver diseases. Aim of the work: Discovering the diagnostic role of serum Hyaluronic acid and Collagen III in liver fibrosis associated with chronic HCV patients. Methods/Case Report The study was performed on 118 patients with liver fibrosis associated with chronic HCV (60 males and 58 females) and 50 age-matched healthy subjects (27 males and 23 females). Liver function tests were measured, including ALT, AST, [AST/ ALT] ratio, albumin, total bilirubin, and platelets counts. APRI was also calculated as [AST/ (upper limits of normal)/ platelets count 109/L]×100. Serum levels of Collagen III (ng/ml) and hyaluronic acid (µg/L) were determined. Plotted receiver-operating characteristic (ROC) curves were used to assess and compare the diagnostic accuracy of biomarkers. Results (if a Case Study enter NA) The area under ROC curve of collagen III in discriminating liver fibrosis in patients associated with chronic HCV infection and healthy ones was 0.805; P&amp;lt; 0.0001. The Sensitivity and Specificity were 62% and 96%, respectively. While the area under ROC curve of hyaluronic acid in discriminating liver fibrosis patients associated with chronic HCV infection from healthy volunteers was 0.832; P &amp;lt; 0.0001. The Sensitivity and Specificity were 72% and 94%, respectively. Also, there was no significant correlation between levels of collagen III and hyaluronic acid; (r=0.01 &amp; P=0.714). Conclusion Collagen III and Hyaluronic acid can identify patients with liver fibrosis with a detection rate of 62% and 72%, respectively. So, both biomarkers are considered powerful non-invasive methods in discriminating and diagnosing liver fibrosis in chronic HCV patients.

Budd-Chiari syndrome in children: Challenges and outcome

Budd-Chiari syndrome (BCS) is an uncommon disease of the liver, characterised by obstruction of the hepatic venous outflow tract. The etiological spectrum of BCS as well as venous obstruction pattern show wide geographical and demographic variations across the globe. Compared to adults with BCS, children have primary BCS as the predominant etiology, earlier clinical presentation, and hence better treatment outcome. Underlying prothrombotic conditions play a key role in the etiopathogenesis of BCS, though work-up for the same is often unyielding in children. Use of next-generation sequencing in addition to conventional tests for thrombophilia leads to better diagnostic yield. In recent years, advances in radiological endovascular intervention techniques have revolutionized the treatment and outcome of BCS. Various non-invasive markers of fibrosis like liver and splenic stiffness measurement are being increasingly used to assess treatment response. Elastography techniques provide a novel non-invasive tool for measuring liver and splenic stiffness. This article reviews the diagnostic and therapeutic advances and challenges in children with BCS.

Usefulness of the Fibrosis-4 index and alanine aminotransferase at 1year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitisB patients.

Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitisB virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development. Among a total of 882 chronically hepatitisB virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1year of treatment was obtained were evaluated for the incidence of HCC. The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1year (P<0.001), but the reduction was small at 2years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5years, the area under the curve of FIB-4 at 1year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10years, P<0.001). Additionally, an abnormal alanine aminotransferase (≥31U/L) at 1year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1)score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10years, P<0.001). FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.