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Background and Aims: The liver cancer risk test (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein A1, haptoglobin), hepatocellular carcinoma (HCC) risk factors (gender, age, gamma glutamyl transpeptidase), a marker of fibrosis (alpha2-macroglobulin), and alpha-fetoprotein, a specific marker of HCC. The aim was to externally validate LCR1-LCR2 in hepatitis B. Methods: Preincluded patients were from the Hepather cohort, a multicenter, multiethnic prospective study in 6071 patients. The coprimary study outcome was the negative predictive value of LCR1-LCR2 at 5 years for the occurrence of HCC and survival without HCC according to the predetermined LCR1-LCR2 cutoffs, adjusted for risk covariables and for chronic hepatitis B treatment and quantified using time-dependent Cox proportional hazards models. A post hoc analysis compared the number of patients needed to screen one cancer by LCR1-LCR2 and PAGE-B. Results: A total of 3520 patients, 191 (5.4%) with cirrhosis, with at least 1 year of follow-up were included. A total of 76 HCCs occurred over a median (interquartile range) of 6.0 years (4.8–7.3) of follow-up. Among the 3367 patients with low-risk LCR1-LCR2, the 5-year negative predictive value was 99.3% (95% confidence interval = 99.0–99.6), with a significant Cox hazard ratio (6.4, 3.1–13.0; P < .001) obtained after adjustment for exposure to antivirals, age, gender, geographical origin, HBe-Ag status, alcohol consumption, and type-2 diabetes. LCR1-LCR2 outperformed PAGE-B for number of patients needed to screen mean (95% CI), 8.5 (3.2–8.1) vs 26.3 (17.5–38.5; P < .0001), respectively. Conclusion: The performance of LCR1-LCR2 to identify patients with chronic hepatitis B at very low risk of HCC at 5 years was externally validated. ClinicalTrials.gov: NCT01953458.

Background and rationale. Acoustic radiation force impulse (ARFI) is a non-invasive tool used in the evaluation of liver fibrosis in HCV positive immune-competent patients. This study aimed to assess the accuracy of ARFI in discriminating liver transplanted patients with different graft fibrosis severity and to verify whether ARFI, eventually combined with non-invasive biochemical tests, could spare liver biopsies. This prospective study included 51 HCV positive liver transplanted patients who consecutively underwent to annual liver biopsy concomitantly with ARFI and blood chemistry tests measurements needed to calculate several non-invasive liver fibrosis tests.Results. Overall ARFI showed an AUC of 0.885 in discriminating between patients without or with significant fibrosis (Ishak score 0-2 vs. 3-6). Using a cut-off of 1.365 m/s, ARFI possesses a negative predictive value of 100% in identifying patients without significant fibrosis. AUC for Fibrotest was 0.848 in discriminating patients with Ishak fibrosis score 0-2 vs. 3-6. The combined assessment of ARFI and Fibro-test did not improve the results obtained by ARFI alone.Conclusion. ARFI measurement in HCV positive liver transplanted patients can be considered an easy and accurate non-invasive tool in identify patients with a benign course of HCV recurrence.

La cirrosis hepática en México es una de las principales causas de muerte en sujetos entre los 25 y los 50 años de edad. Una de las principales razones del fracaso terapéutico es el desconocimiento de los mecanismos moleculares que producen el trastorno hepático y lo hacen irreversible. Entre sus características anatómicas prevalece un depósito excesivo de tejido fibroso que adopta diferentes formas, dependiendo de la etiología y etapa de la enfermedad. La biopsia hepática, considerada tradicionalmente como la referencia estándar para estadificar la fibrosis, ha sido muy cuestionada en la última década, por lo que se ha propuesto el desarrollo de tecnologías no invasivas basadas en enfoques distintos pero complementarios: uno biológico que considera los niveles séricos de los productos procedentes de la fibrosis y otro físico que evalúa la cicatrización del órgano por métodos tales como, el ultrasonido, la resonancia magnética y la elastografía, algunos de ellos, estudiados y validados inicialmente en pacientes con hepatitis C. Existe la necesidad de establecer marcadores hepatoespecíficos no invasivos para el diagnóstico de fibrosis hepática, ya que actualmente no se cuenta con un parámetro o panel que cumpla con los criterios de eficacia y confiabilidad, requeridos para su uso diagnóstico. En este trabajo se describen los biomarcadores empleados actualmente para el estudio de la fibrosis hepática en humanos, incluyendo sus ventajas y desventajas y la implementación de tecnologías de nueva generación, y la evaluación de las posibilidades de su empleo para el diagnóstico.

Background & Aims: In patients with compensated alcohol-related cirrhosis, reliable prognostic biomarkers are lacking. Keratin-18 and hepatocyte-derived large extracellular vesicle (lEV) concentrations reflect disease activity, but their ability to predict liver-related events is unknown., Methods: We measured plasma keratin-18 and hepatocyte lEV concentrations in 500 patients with Child-Pugh class A alcohol-related cirrhosis. The ability of these hepatocyte-derived biomarkers, alone or combined with model for end-stage liver disease (MELD) and FibroTest scores, to predict liver-related events at 2 years was analyzed, taking into account the alcohol consumption at inclusion and during follow-up., Results: Keratin-18 and hepatocyte lEV concentrations increased with alcohol consumption. In patients without active alcohol consumption at enrollment (n = 419), keratin-18 concentration predicted liver-related events at 2 years, independently of FibroTest and MELD. Patients with both keratin-18 concentrations >285 U/L and FibroTest >0.74 had a 24% cumulative incidence of liver-related events at 2 years, vs. 5% to 14% in other groups of patients. Similar results were obtained when combining keratin-18 concentrations >285 U/L with MELD >10. In patients with active alcohol consumption at enrollment (n = 81), hepatocyte lEVs predicted liver-related events at 2 years, independently of FibroTest and MELD. Patients with both hepatocyte lEV concentrations >50 U/L and FibroTest >0.74 had a 62% cumulative incidence of liver-related events at 2 years, vs. 8% to 13% in other groups of patients. Combining hepatocyte lEV concentrations >50 U/L with MELD >10 had a lower discriminative ability. Similar results were obtained when using decompensation of cirrhosis, defined according to Baveno VII criteria, as an endpoint., Conclusion: In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers with FibroTest or MELD scores identifies patients at high risk of liver-related events, and could be used for risk stratification and patient selection in clinical trials., Impact and Implications: In patients with compensated alcohol-related cirrhosis, reliable predictors of outcome are lacking. In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers (keratin-18 and hepatocyte-large extracellular vesicles) with FibroTest or MELD scores identifies those at high risk of liver-related events at 2 years. The identified patients at high risk of liver-related events are the target-of-choice population for intensive surveillance (e.g., referral to tertiary care centers; intensive control of risk factors) and inclusion in clinical trials., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background. The main causes of liver fibrosis in transfusion-dependent thalassemia major are hepatitis C virus (HCV) infection and hepatic iron overload. The study aimed to assess liver fibrosis in Egyptian adolescents and young adult poly-transfused beta thalassemia patients infected with HCV using liver FibroScan in relation to iron overload and Liver iron concentration (LIC).Material and methods. Fifty-one regularly transfused beta thalassemia patients above 12 years old were subjected to measurement of serum alanine transaminase (ALT), serum ferritin (SF), HCV (antibody and RNA), LIC assessed by hepatic R2* and transient elastography (TE) (FibroScan). FibroTest and liver biopsy were done to 25 patients.Results. Eighty two% of studied thalassemia patients were HCV antibody positive; 21(49%) of them were viremic (HCV RNA positive); median LIC was 12 mg/gm dry weight. There were strong positive correlation between the degree of liver stiffness and Ishak fibrosis score assessed in liver biopsy specimens (P = 0.002) and between FibroScan and FibroTest results (P < 0.001). Patients with HCV viremia showed significantly higher ALT, γ-glutamyl transpeptidase (GGT), SF, LIC and increased liver stiffness compared to patients with no viremia (P = 0.0001, 0.001, 0.012, 0.006 and 0.001) respectively. Liver cirrhosis (TE values > 12.5kPa) was encountered in 23.5% and variable degrees of liver fibrosis (TE values > 6–12.5 kPa) in 35% of studied thalassemic patients.Conclusion. Young beta thalassemia patients with active hepatitis C infection may have hepatic cirrhosis or fibrosis at young age when accompanied with hepatic siderosis. Non invasive Liver FibroScan and Fibro-Test were reliable methods to assess liver fibrosis in young thalassemic-patients.

Noninvasive markers of fibrosis have emerged as an alternative to the staging of fibrosis by means of liver biopsy. Apart from being noninvasive and thus lacking the adverse effects of liver biopsy, they offer some advantages such as reduced risk of sampling error, objectiveness in the interpretation of the result, appropriateness for repeated measurements and lower cost. Many studies have validated different panels of blood markers and imaging/transient elastography for the estimation of fibrosis with acceptable accuracy. Clinical scenarios leading to inacurate or failed estimation must be acknowledged, as well as the fact that performance of blood markers and transient elastography, and their diagnostic cut-off values vary among specific liver diseases. The combination of two blood markers or of a blood marker and transient elastography has been shown to increase accuracy of the estimation. Further, unlike liver biopsy the noninvasive markers of fibrosis are not associated with a ceiling effect after cirrhosis is identified, but can discriminate early from advanced stages of cirrhosis. Longitudinal studies have shown their utility as predictors of complications from portal hypertension and mortality, outperforming liver biopsy. In conclusion, noninvasive markers of fibrosis provide major advantages over liver biopsy. The reported performance of some of the available tests-particularly when used in combination-make them a reliable tool, very attractive for daily clinical practice.

Background and Aims: This study aimed at measure the correlation between simple less expensive and noninvasive tests for liver fibrosis and Fibrotest among patients with chronic hepatitis B (HBV) or C (HCV) in resource-limited settings., Materials and Methods: This was a cross-sectional study conducted at the Centre Pasteur of Cameroon among adults with chronic HBV or HCV infection. The correlation between aspartate aminotransferase to platelet ratio index(APRI), the gamma-glutamyl transferase to platelet ratio (GPR), and Fibrosis-4 score (FIB-4); and Fibrotest was assessed using the Spearman rank test providing the rho (ρ) coefficient of correlation., Results: Of the 52 patients (mean age: 49 years, males: 51.9%) included, 52% were infected with HBV (n = 27). The APRI, GPR, FIB-4, and Fibrotest median scores (25th-75th percentiles) were: 0.37 (0.25-0.64), 0.34 (0.20-1.45), 1.49 (0.88-3.12), and 0.43 (0.21-0.80), respectively. The correlation with Fibrotest were: APRI (ρ = 0.678, p value < 0.0001), GPR (ρ = 0.621, p value < 0.0001) and FIB-4 (ρ = 0.772, p value < 0.0001)., Conclusions: This study found a significant correlation between APRI, GPR and FIB-4; and Fibrotest among patients with chronic HBV or HCV infection in Cameroon. FIB-4 appeared as the diagnosis method with the strongest correlation with Fibrotest., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)