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Background/Aim: This study investigated the correlation between vitamin D levels and serological markers of liver diseases in two groups of patients: the control group (CG) and the study group (SG). Materials and Methods: The study analyzed data on vitamin D levels categorized as insufficient, sufficient, and optimal, along with serological markers, such as alpha2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin total, gammaglutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, total cholesterol, and triglycerides. Results: The results indicate significant differences in vitamin D levels between the two groups, particularly in SG, where vitamin D levels varied according to its status and correlated with serological markers. Marker levels, including alpha2-macroglobulin, glucose, and total cholesterol, were notably higher in SG compared to CG, suggesting a potential association with non-alcoholic fatty liver disease (NAFLD). Further analysis using Pearson correlation revealed a strong, inverse relationship between vitamin D levels and FibroTest, NashTest, alpha2-globulin, and glucose. Additionally, increasing FibroTest and NashTest stages, as well as levels of alpha2-macroglobulin and glucose, were associated with lower vitamin D levels in SG. Conclusion: These findings under-score the complex interplay between vitamin D and serological markers in NAFLD, highlighting the potential significance of vitamin D levels in disease progression. Further research is warranted to elucidate the mechanisms underlying this relationship and its clinical implications. [ABSTRACT FROM AUTHOR]

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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. 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. 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. 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. 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. [Display omitted] • In patients with alcohol-related cirrhosis, hepatocyte-derived biomarkers predict outcome. • Keratin-18 predicts outcome in patients without active alcohol consumption. • Hepatocyte large extracellular vesicles predict outcome in patients with active alcohol consumption. • Those hepatocyte-derived biomarkers improve prediction offered by FibroTest or MELD. [ABSTRACT FROM AUTHOR]

The gold standard for assessing liver fibrosis is a liver biopsy. However, the procedure is invasive and is associated with pain and sometimes fatal consequences. The accuracy of liver biopsy results is further harmed by intra- and inter-observer variability. Small samples only. This muddles the two types of observer variability discussed above. Due to these limitations, non-invasive approaches for fibrosis testing have been developed. Various biochemical serum indicators or imaging techniques that provide a physical measure of hepatic stiffness are non-invasive approaches for assessing liver fibrosis.

Liver cirrhosis and fibrosis is an increasing medical problem all over the world. Several decades ago, hepatitis C infection was the main cause of liver cirrhosis and severe liver fibrosis. After the change of antiviral treatment strategy, we have non-alcoholic fatty liver disease as the main origin factor of liver cirrhosis. After effectively eliminating hepatitis C virus, many patients still have residual post-hepatitis fibrosis. In case of accompanying non-alcoholic fatty liver disease, the natural course of liver lesion is the progress of fibrosis. The presented article highlights the main methods of post-hepatitis liver fibrosis diagnostics after curing viral hepatitis type C and in patients with non-alcoholic fatty liver disease affected by overweight and obesity. We have evaluated fibrosis development with serum markers such as FIB-4, FibroTest and transforming growth factor ß1 level. Post-hepatitis liver fibrosis status after elimination of viral hepatitis type C should be observed, especially in patients with non-alcoholic fatty liver disease. FIB-4 and FibroTest correlate with each other and with biochemical liver indices and generally depend on overweight and obesity. TGF-ß blood level significantly increases in case of fibrosis progression with maximum values in the group of patients with NAFLD and BMI level above 30 kg/m2 (p<0.05). In the case of liver fibrosis progression, the concentration of TGF-ß1 in blood increases (r=0.78, p<0.05). It confirms the role of this cytokine in the activation of hepatic stellate cells and stimulation of the synthesis of collagen and other extracellular fibrotic components and can be a marker of NAFLD progression. [ABSTRACT FROM AUTHOR]

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.

• A correlation was found between APRI, GPR, and FIB-4; and Fibrotest. • These less expensive diagnosis alternatives could be useful in sub-Saharan Africa. • FIB-4 was the diagnosis method with the strongest correlation with Fibrotest. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

The gold standard for assessing liver fibrosis is a liver biopsy. However, the procedure is invasive and is associated with pain and sometimes fatal consequences. The accuracy of liver biopsy results is further harmed by intra- and inter-observer variability. Small samples only. This muddles the two types of observer variability discussed above. Due to these limitations, non-invasive approaches for fibrosis testing have been developed. Various biochemical serum indicators or imaging techniques that provide a physical measure of hepatic stiffness are non-invasive approaches for assessing liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: Children born with single-ventricle hearts require surgery in order to survive. Liver fibrosis is a known complication of Fontan surgery for univentricular hearts. Methods: In this study on 13 post-Fontan and 21 post-Glenn patients, we used elastography (shearwave and transient elastography) as well as serum biochemical fibrosis markers to evaluate the degree of liver fibrosis in comparison to 32 controls. Results: The mean Emedian and Vmedian values determined by shear wave elastography in the Fontan Group were significantly higher than the controls (4.85 kPa vs. 3.91 kPa and 1.25 m/s vs. 1.12 m/s, respectively). Fontan patients had significantly increased Fibrotest, Actitest, AST-to-Platelet Ratio index, ALT and GammaGT levels compared to controls. For post-Glenn patients, the mean Emedian and Vmedian values were similar to healthy controls, whereas the Fibrotest, Actitest and AST-to-Platelet Ratio index were significantly increased. Using transient elastography, we found significantly higher values for Emedian and Vmedian in Fontan patients compared to Glenn patients. Conclusions: Elastography and biochemical fibrosis markers are valuable non-invasive tools for screening and monitoring liver fibrosis in patients with Fontan and Glenn interventions. [ABSTRACT FROM AUTHOR]

Abstract Background Non-invasive shear wave-based techniques have been developed for estimating liver fibrosis in patients with chronic liver diseases. Two-dimensional shear wave elastography provides in real-time, a tow dimensional quantitative map of tissue stiffness and enables measuring the stiffness by adjustment of a region of interest of tissue. The aim of this study was to highlight the role of tow dimensional shear wave elastography (2D-SWE) in detecting the degree of liver fibrosis in patients with chronic hepatitis C and B, in correlation with liver enzymes level and fibrotest. Results This study included 50 patients with chronic hepatitis C and B whose ages were (range, 30-65 years; mean, 48 years). Shear wave elastography cutoff values were 1.35 m/s, 5.48 KPa for (F>0); 1.66 m/s, 8.29 kPa for (F>1); 1.77 m/s, 9.40 kPa for (F>2); and 1.99 m/s, 11.9 kPa for (F>3). An excellent agreement was found between shear wave elastography and Fibrotest in staging of liver fibrosis in 88% of patients (κ w =0.943, 95% CI, 0.88 to 1.00) achieving a highly statistical significance (P0.05). Conclusions 2D shear wave elastography showed better diagnostic performance than visual assessment by conventional US for detection of chronic liver diseases, as well as for evaluation of their severity and prognosis. Elastograhy—Fibrotest combination gives best diagnostic performance in detecting the degree of fibrosis non-invasively and can be used reliably as a first-line pre-therapeutic evaluation of fibrosis in HCV and HBV-infected patients.

One of the biggest problems of modern medicine is the difficulty in early diagnostic and effective treatment of HCV infection due to its wide distribution, latent form and terrible consequences as a formation of liver cirrhosis (CP) and hepatocellular carcinoma (HCC). It is important to mention, that the rate of progression of liver fibrosis. It is an important medical and social problem that the number of patients with NAFLD, overweight and obesity is constantly increases [9]. Due to the high prevalence of NAFLD and CHC, these two pathologies will progress and contribute to the progression of fibrosis, and depending on the genome of the virus and metabolic syndrome. There is a high risk of developing CP and HCC even after achieving a stable virological response.The main aim of our investigation was to assess the stages of fibrosis by using non-invasive methods for patients with overweight and obesity who being treated for HCV infection (with posthepatic fibrosis).

Background and Aim: Mortality of alcohol‐related liver disease (ArLD) is increasing, and liver fibrosis stage is the best mortality predictor. Non‐invasive tests (NITs) are increasingly used to detect fibrosis, but their value as prognostic tests in chronic liver disease, and in particular in ArLD, is less well recognized. We aimed to describe the prognostic performance of four widely used NITs (Fibrosis 4 test [FIB4], Enhanced Liver Fibrosis [ELF] test, FibroScan, and FibroTest) in ArLD. Methods: Applying systematic review methodology, we searched four databases from inception to May 2020. Inclusion/exclusion criteria were applied to search using Medical Subject Heading terms and keywords. The first and second reviewers independently screened results, extracted data, and performed risk‐of‐bias assessment using Quality in Prognosis Studies tool. Results: Searches produced 25 088 articles. After initial screening, 1020 articles were reviewed independently by both reviewers. Eleven articles remained after screening for eligibility: one on ELF, four on FibroScan, four on FIB4, one on FIB4 + FibroScan, and one on FibroTest + FIB4. Area under the receiver operating characteristic curves for outcome prediction ranged from 0.65 to 0.76 for FibroScan, 0.64 to 0.83 for FIB4, 0.69 to 0.79 for FibroTest, and 0.72 to 0.85 for ELF. Studies scored low–moderate risk of bias for most domains but high risk in confounding/statistical reporting domains. The results were heterogeneous for outcomes and reporting, making pooling of data unfeasible. Conclusions: This systematic review returned 11 papers, six of which were conference abstracts and one unpublished manuscript. While the heterogeneity of studies precluded direct comparisons of NITs, each NIT performed well in individual studies in predicting prognosis in ArLD (area under the receiver operating characteristic curves >0.7 in each NIT category) and may add value to prognostication in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Non-invasive shear wave-based techniques have been developed for estimating liver fibrosis in patients with chronic liver diseases. Two-dimensional shear wave elastography provides in real-time, a tow dimensional quantitative map of tissue stiffness and enables measuring the stiffness by adjustment of a region of interest of tissue. The aim of this study was to highlight the role of tow dimensional shear wave elastography (2D-SWE) in detecting the degree of liver fibrosis in patients with chronic hepatitis C and B, in correlation with liver enzymes level and fibrotest. Results: This study included 50 patients with chronic hepatitis C and B whose ages were (range, 30-65 years; mean, 48 years). Shear wave elastography cutoff values were 1.35 m/s, 5.48 KPa for (F>0); 1.66 m/s, 8.29 kPa for (F>1); 1.77 m/s, 9.40 kPa for (F>2); and 1.99 m/s, 11.9 kPa for (F>3). An excellent agreement was found between shear wave elastography and Fibrotest in staging of liver fibrosis in 88% of patients (κw=0.943, 95% CI, 0.88 to 1.00) achieving a highly statistical significance (P<0.001). There was a significant moderate positive concordance between US scoring and staging by 2D-SWE and staging by Fibrotest (rs, 0.49; P<0.01) and (rs, 0.48; P<0.01) respectively. However, no significant concordances were noticed between staging by AST and ALT and 2D-SWE and staging by Fibrotest (P>0.05). Conclusions: 2D shear wave elastography showed better diagnostic performance than visual assessment by conventional US for detection of chronic liver diseases, as well as for evaluation of their severity and prognosis. Elastograhy—Fibrotest combination gives best diagnostic performance in detecting the degree of fibrosis non-invasively and can be used reliably as a first-line pre-therapeutic evaluation of fibrosis in HCV and HBV-infected patients. [ABSTRACT FROM AUTHOR]

Hepatic disease accounts for approximately 2 million deaths/year worldwide. Liver fibrosis, as the last stage of numerous chronic liver diseases, is one of the most relevant prognostic factors. The liver biopsy with the histopathological examination is considered to be the "gold standard" for the identification and staging of the hepatic fibrosis. However, liver biopsy is known as an invasive investigation that has multiple limitations. Research studies conducted in the last few years focused on identifying non-invasive type methods for the evaluation of hepatic fibrosis; usually, there are 2 categories of such investigations: serologic tests and imaging techniques. This narrative review presents the non-invasive investigation methods used in the liver fibrosis evaluation. New molecular perspectives on fibrogenesis and fibrosis regression, as well as the appearance of therapeutic antifibrotic agents, justify the necessity of non-invasive tools to detect and grade liver fibrosis. [ABSTRACT FROM AUTHOR]

Background and aims: Pirfenidone (PFD), an oral antifibrotic drug, has been authorized by the EMA and FDA for treatment of idiopathic pulmonary fibrosis. Few studies have addressed its use in advanced liver fibrosis (ALF). We evaluated a prolonged-release formulation (PR-PFD) plus standard of care on disease progression in ALF. Methods: 281 ALF patients from 12 centers receiving PR-PFD (600 mg bid) were screened; 122 completed 1 year of treatment. Additionally, 74 patients received only standard of care regimen. Average age was 64 ± 12 years, 58% female. 43.5% had fatty liver disease (NAFLD), 22.5% viral hepatitis C (VHC), 17% autoimmune hepatitis (AIH), and 17% alcoholic liver disease (ALD). Baseline fibrosis was F4 in 74% and F3 in 26%. Antifibrotic effects were assessed by transient elastography (Fibroscan®) and Fibro Test® (FT); Cytokines and PFD plasma levels were tracked and quality of life evaluated. Results: We found a significant reduction in fibrosis in 35% of PR-PFD patients and only in 4.1% in non PR-PFD patients. Child–Pugh score improved in 29.7%. Biochemical values remained stable; 40.6% and 43.3% decreased ALT or AST, respectively. TGFβ1 (pg/mL) levels were lower in PFD-treated patients. PFD serum concentration (µg/mL) was higher (8.2 ± 1.7) in fibrosis regression profile (FRP) patients compared to fibrosis progression profile (FPP) patients (4.7 ± 0.3 µg/mL, p < 0.01). 12% reported transient burning or nausea and 7% photosensitivity. Quality of life (Euro-Qol scale) improved from 62 ± 5 to 84 ± 3 (p < 0.001) and from 32 ± 3 to 42 ± 2 (p < 0.008) (FACIT scale). Conclusions: PR-PFD is efficacious and safe in ALF and associated with promising antifibrotic effects. Trial registration: Clinical trial number: NCT04099407. [ABSTRACT FROM AUTHOR]

Background/aims: Non‐invasive fibrosis tests (NITs) can be used to triage non‐alcoholic fatty liver disease (NAFLD) patients at risk of advanced fibrosis (AF). We modelled and investigated the diagnostic accuracy and costs of a two‐tier NIT approach in primary care (PC) to inform secondary care referrals (SCRs). Methods: A hypothetical cohort of 1,000 NAFLD patients with a 5% prevalence of AF was examined. Three referral strategies were modelled: refer all patients (Scenario 1), refer only patients with AF on NITs performed in PC (Scenario 2) and refer those with AF after biopsy (Scenario 3). Patients in Scenarios 1 and 2 would undergo sequential NITs if their initial NIT was indeterminate (FIB‐4 followed by Fibroscan®, enhanced liver fibrosis (ELF)® or FibroTest®). The outcomes considered were true/false positives and true/false negatives with associated mortality, complications, treatment and follow‐up depending on the care setting. Decision curve analysis was performed, which expressed the net benefit of different scenarios over a range of threshold probabilities (Pt). Results: Sequential use of NITs provided lower SCR rates and greater cost savings compared to other scenarios over 5 years, with 90% of patients managed in PC and cost savings of over 40%. On decision curve analysis, FIB‐4 plus ELF was marginally superior to FIB‐4 plus Fibroscan at Pt ≥8% (1/12.5 referrals). Below this Pt, FIB‐4 plus Fibroscan had greater net benefit. The net reduction in SCRs was similar for both sequential combinations. Conclusions: The sequential use of NITs in PC is an effective way to rationalize SCRs and is associated with significant cost savings. [ABSTRACT FROM AUTHOR]

Introduction: Infection with hepatitis B virus (HBV) genotype G has been associated with increased liver fibrosis levels compared with other genotypes in cross‐sectional studies, yet its role in fibrosis evolution remains to be established. Methods: In this prospective cohort study, 158 human immunodeficiency virus (HIV)‐HBV coinfected patients had available HBV genotyping at baseline. Liver fibrosis was assessed at baseline and every 6 to 12 months by the FibroTest (BioPredictive, Paris, France). Risk factors for fibrosis regression (F3‐F4 to F0‐F1‐F2) and progression (F0‐F1‐F2 to F3‐F4) between baseline and end of follow‐up were evaluated. Results: Most patients were male (88.6%) with a median age of 39 years. HBV genotype A was more prevalent compared with other HBV genotypes (62.7% vs D = 10.8%, E = 10.8%, and G = 15.8%). Patients were followed up for a median of 83 months (IQR = 37‐97). In the 43 (27.2%) patients with F3‐F4 baseline liver fibrosis, 7 (16.2%) regressed to F0‐F1‐F2 fibrosis at the last follow‐up visit. In the 115 (72.8%) with F0‐F1‐F2 fibrosis at baseline, 19 (16.5%) progressed to F3‐F4 fibrosis at last visit. In multivariable analysis, fibrosis progression was independently associated with older age (P <0.005), baseline CD4+ cell count less than 350/mm 3 (P <0.01), longer antiretroviral therapy duration (P <0.03), and HBV genotype G infection (vs non‐G, P <0.01). When examining averages over time, the rate of FibroTest increase was faster in genotype G vs non‐G–infected patients with baseline F0‐F1‐F2 fibrosis (P for interaction = 0.002). Conclusion: In HIV‐HBV coinfected patients, HBV genotype G is an independent risk factor for liver fibrosis progression as determined by noninvasive markers. HBV genotype G–infected patients with low initial liver fibrosis levels may require more careful monitoring. [ABSTRACT FROM AUTHOR]

Amaç: Bu çalışmada kronik hepatit B KHB ’de karaciğer biyopsisinde saptanan fibrozis ve inflamasyon derecesi referans alınarak fibrotestin FT fibrozisi ve actitestin AT nekroinflamatuar aktiviteyi belirlemedeki duyarlılığının araştırılması amaçlandı.Gereç ve Yöntem: Bu prospektif çalışmaya 2013 yılı içerisinde takip edilen 53 KHB hastası dahil edildi. Biyopsiler modifiye Knodell skorlama sistemine gore değerlendirildi. Karaciğer biyopsisi yapıldığı gün hastalardan FT ve AT için kan örneği alındı.Bulgular: Çalışmaya alınan hastaların 22’si kadın, 31’i erkekti. KHB hastalarında karaciğer biyopsisi ve FT karşılaştırılmasında ciddi fibrozisi tespit etmek için FT’nin duyarlılığı %93.5, seçiciliği ise %54.5 olarak tespit edildi. FT’nin pozitif prediktif değeri PPD %74.3, negatif prediktif değeri NPD ise %85.7 olarak hesaplandı. FT için ROC analizi sonucu eğri altında kalan alan %75.1’ti p=0.003 . KHB hastalarında karaciğer biyopsisi ve AT karşılaştırılmasında ise ciddi nekroinflamasyonun tespiti için AT’nin duyarlılığı %89.2, seçiciliği %64’tü. PPD %73.5 ve NPD ise %84.2 olarak hesaplandı. AT için ROC analizi sonucu eğri altında kalan alan % 65’ti p=0.001 . Sonuç: KHB’de FT ve AT’nin ciddi fibrozis ve nekroinflamasyonu göstermedeki duyarlılıkları yüksekti. Bununla birlikte FT ve AT biyopsi yapılmaksızın tek başına kullanılabilecek bir belirteç olarak görülmemektedir

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.

Owing to the high prevalence of various chronic liver diseases, cirrhosis is one of the leading causes of morbidity and mortality worldwide. In recent years, the development of non-invasive tests of fibrosis allows accurate diagnosis of cirrhosis and reduces the need for liver biopsy. In this review, we discuss the application of these non-invasive tests beyond the diagnosis of cirrhosis. In particular, their role in the selection of patients for hepatocellular carcinoma surveillance and varices screening is highlighted.

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. 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.

Background. Liver cirrhosis is the most often cause of the portal hypertension syndrome development, though structural and morphological liver remodeling usually begins on the stage of chronic hepatitis. Morphologic patterns of the development of portal hypertension syndrome on the pre-clinical stage are still poorly investigated. Objective. To determine the histological and necroinflammatory activity of the liver in patients with portal hypertension. Methods. Patients were divided into four groups: I group (n=38) – chronic hepatitis without clinical signs of portal hypertension; II group (n=42) - chronic hepatitis transforming to cirrhosis with clinical signs of portal hypertension (varicose veins of the esophagus and/or the cardia, splenomegaly, ascitis); III group (n=34) – complicated portal hypertension on the background of liver cirrhosis (bleeding from the varices of the esophagus and/or the cardia, hypersplenism); control group (n=30) - physically healthy individuals aged 23-37 years. An integrated evaluation of the liver histological and necroinflammatory activity through the set of laboratory tests was performed (the method of “FibroTest-ActiTest”; immunofermental analysis of L-FABP concentration). Results. It is found that the patients with pre-clinical stage of portal hypertension syndrome show portal and periportal fibrosis with single septa, and the patients with clinical stages of portal hypertension show portal and periportal cirrhosis with multiple septa. Patients with the complications of portal hypertension show cirrhosis of the liver. With the increase of the necroinflammatory activity the portal pressure increases directly. This fact was confirmed with the increase of L-FABP protein level in the plasma, along with the increase of the actitest results. Conclusion. The diagnostic methodic of “FibroTest-ActiTest” and the plasma level of L-FABP are the modern models for chronic liver disease histological and necroinflammatory activity evaluation, though there is still the need to determine the correlation with the direct histological picture of liver biopsy.

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.

The article presents current data on the diagnosis methods of liver diseases. Recommendations on the management of patients with pathology of the hepatic system on the detection of disease are given. The possibility of using different diagnostic techniques, including ultrasound, serum markers, and histological studies are investigated. The choice of diagnosis method is discussed.

Aims: FibroTest and ActiTest are noninvasive tests used in determining the level of fibrosis and the degree of necroinflammatory activity in the liver. In our study, we aimed to investigate whether these tests could be alternative to liver biopsy. Materials and Methods: Fifty patients were included in the study. Serum samples were obtained and liver needle biopsy was performed on the same day. Levels of fibrosis in FibroTest and levels of activity in ActiTest, both determined via serum biochemical markers, were compared with levels of fibrosis and activity in histopathological examination. For statistical analyses, Mc Nemar chi square test and Spearman′s correlation tests were used. Results: There was a significant positive correlation between fibrosis in biopsy and the level of fibrosis in FibroTest in patients with hepatitis B virus (HBV) (rho: 0.67, P < 0.0001). However, no significant correlation was determined between the activity in biopsy and the degree of activity in ActiTest (rho: 0.29, P < 0.05). No significant correlation was determined between both fibrosis and activity established in biopsy and the results of FibroTest and ActiTest in the group of patients with hepatitis C virus (HCV) (rho: 0.22, P < 0.05 and rho: 0.15, P < 0.05, respectively). Conclusion: Our results suggest that novel and safer noninvasive biochemical tests are needed as an alternative to histopathology in patients infected with HBV and HCV. Consequently, we believe that liver biopsy maintains its place as a gold standard in determining the histopathological condition of the liver.

Percutaneous liver biopsy (LB) remains an important tool in the diagnosis and management of parenchymal liver diseases. In current practice, it is most frequently performed to assess the inflammatory grade and fibrotic stage of commonly encountered liver diseases, with the diagnostic role relegated to secondary importance. The role of LB remains a vastly controversial and debated subject, with an ever-increasing burden of evidence that questions its routine application in all patients with liver dysfunction. It remains, essentially, an invasive procedure with certain unavoidable risks and complications. It also suffers shortcomings in diagnostic accuracy since a large liver sample is required for an ideal assessment, which in clinical practice is not feasible. LB is also open to observer interpretation and prone to sampling errors. In recent years, a number of noninvasive biomarkers have evolved, each with an impressive range of diagnostic certainty approaching that achieved with LB. These noninvasive tests represent a lower-cost option, are easily reproducible, and serve as suitable alternatives to assess hepatic inflammation and fibrosis. This article aims to debate the shortcomings of LB while simultaneously demonstrating the diagnostic accuracy, reliability and usefulness of noninvasive markers of liver disease thereby making the case for their utilization as suitable alternatives to LB in many, although not all, circumstances.

Liver biopsy (LB) is the gold standard method for assessment of liver histology. It provides valuable, otherwise unobtainable information, regarding the degree of fibrosis, parenchymal integrity, degree and pattern of inflammation, bile duct status and deposition of materials and minerals in the liver. This information provides immense help in the diagnosis and prognostication of a variety of liver diseases. With careful selection of patients, and performance of the procedure appropriately, the complications become exceptionally rare in current clinical practice. Furthermore, the limitations of sampling error and inter-/intra-observer variability may be avoided by obtaining adequate tissue specimen and having it reviewed by an experienced liver pathologist. Current noninvasive tools are unqualified to replace LB in clinical practice in the face of specific limitations for each tool, compounded by a poorer performance towards the assessment of the degree of liver fibrosis, particularly for intermediate stages.

Liver biopsy, owing to its limitations and risks, is an imperfect gold standard for assessing the severity of the most frequent chronic liver diseases chronic hepatitis C (HCV), B (HBV) non alcoholic (NAFLD) and alcoholic (ALD) fatty liver diseases. This review summarizes the advantages and the limits of the available biomarkers of liver fibrosis. Among a total of 2,237 references, a total of 14 validated serum biomarkers have been identified between 1991 and 2008. Nine were not patented and five were patented. Two alternatives to liver biopsy were the most evaluated FibroTest and Fibroscan. For FibroTest, there was a total of 38 different populations including 7,985 subjects with both FibroTest and biopsy (4,600 HCV, 1,580 HBV, 267 NAFLD, 524 ALD, and 1014 mixed). For Fibroscan, there was a total of 11 published studies including 2,260 subjects (1,466 HCV, 95 cholestatic liver disease, and 699 mixed). For FibroTest, the mean diagnostic value for the diagnosis of advanced fibrosis assessed using standardized area under the ROC curves was 0.84 (95% confidence interval 0.83-0.86), without a significant difference between the causes of liver disease, hepatitis C, hepatitis B, and alcoholic or non alcoholic fatty liver disease. High-risk profiles of false negative/false positive of FibroTest, mainly Gilbert syndrome, hemolysis and acute inflammation, are present in 3% of the populations. In case of discordance between biopsy and FibroTest, half of the failures can be due to biopsy; the prognostic value of FibroTest is at least similar to that of biopsy in HCV, HBV and ALD. In conclusion this overview of evidence-based data suggests that biomarkers could be used as an alternative to liver biopsy for the first line assessment of fibrosis stage in the four most common chronic liver diseases, namely HCV, HBV, NAFLD and ALD. Neither biomarkers nor biopsy alone is sufficient for taking a definite decision in a given patient; all the clinical and biological data must be taken into account. There is no evidence based data justifying biopsy as a first line estimate of liver fibrosis. Health authorities in some countries have already approved validated biomarkers as the first line procedure for the staging of liver fibrosis.

Objectives: In this study, we aimed at investigating the accuracy of fibrotest (FT) in measuring fibrosis and actitest (AT) in measuring necroinflammatory activity by taking the fibrosis and inflammation level found in liver biopsy as reference in chronic hepatitis B (CHB). Material and Methods: This prospective study included 53 CHB patients who were being monitored in 2013. The biopsies were assessed in line with the modified Knodell scoring system Blood samples were drawn from the patients for FT and AT on the day when their liver biopsies were performed. Results: Twenty two of the patients included in the study were female and 31 male. FT sensitivity of 93.5% and selectivity of 54.5% was detected to identify severe fibrosis in CHB patients as a result of comparison of liver biopsy with FT. Positive predictive value (PPV) of FT was calculated as 74.3% and negative predictive value (NPV) as 85.7%. ROC curves analysis showed an AUC value of 75.1% for FT (p=0.003). In comparison of the liver biopsy with AT, on the other hand, an AT sensitivity of 89.2% and selectivity of 64% was detected to identify severe necroinflammation in CHB patients. PPV was calculated as 73.5% and NPV as 84.2%. ROC curves analysis showed an AUC value of 65% for AT (p=0.001). Conclusion: The accuracy of FT and AT in showing fibrosis and necroinflammation in CHB was quite high. However FT and AT does not seem to be a marker to be used alone without performing a liver biopsy. [ABSTRACT FROM AUTHOR]

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 0-2vs. 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. [ABSTRACT FROM AUTHOR]

This review summarized the diagnostic value of fibrosis biomarkers and the efficacy of anti-viral treatments on fibrosis progression. Non-invasive biomarkers can facilitate the screening and management of chronic hepatitis C and B. Screening for significant fibrosis is-mandatory as very effective anti-viral treatments are available, permitting to stop or to reduce the fibrosis progression. The reduction of fibrosis progression will decrease the mortality due to complications of cirrhosis. In patients with chronic hepatitis C, pegylated interferons combined with ribavirin are effective in reducing fibrosis progression. In patients with chronic hepatitis B, lamivudine, adefovir and pegylated interferon are also effective in reducing fibrosis progression. In patients with chronic hepatitis Delta, pegylated interferon is also effective in reducing fibrosis progression