Advanced Stages Of Liver Fibrosis Research Articles

CLINICAL AND DIAGNOSTIC CRITERIALS OF LIVER FIBROSIS FORMATION IN PATIENTS WITH CHRONIC VIRAL HEPATITIS C WITH EXTRAHEPATIVE MANIFESTATIONS

Background: Chronic viral hepatitis C (CVHC) is often associated with various extrahepatic manifestations, which may complicate the disease's progression. Specific Background: Cryoglobulinemia, characterized by the presence of cryoglobulins in the blood, has been implicated in the exacerbation of liver conditions, yet its role in CVHC remains inadequately explored. Knowledge Gap: Despite existing knowledge of the relationship between cryoglobulinemia and liver disease, the specific impact of cryoglobulinemia on the severity of liver fibrosis and associated extrahepatic manifestations in CVHC patients requires further elucidation. Aims: This study aims to investigate the prevalence of extrahepatic manifestations and the extent of liver fibrosis in patients with CVHC who also present with cryoglobulinemia, thereby determining the clinical implications of cryoglobulin presence. Results: Our findings indicate that patients with cryoglobulinemia demonstrate a significantly higher prevalence of extrahepatic manifestations and advanced stages of liver fibrosis compared to those without cryoglobulinemia. Novelty: This research contributes novel insights into the aggravating role of cryoglobulins in the clinical course of CVHC, highlighting their potential as biomarkers for disease severity. Implications: These results underscore the need for enhanced clinical monitoring and tailored therapeutic approaches for CVHC patients with cryoglobulinemia, as their condition may predict a more severe disease trajectory and necessitate more aggressive management strategies.

Extracellular NAD+ response to post-hepatectomy liver failure: bridging preclinical and clinical findings

Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+’s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD+ biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD+ in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD+ treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD+ was upregulated in PHLF, and rate-limiting enzymes of NAD+ biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD+ administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies.

Mechanisms of high cardiovascular risk in patients with nonalcoholic fatty liver disease

Aim. To optimise the curation of patients with a comorbid course of nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) to explore pathogenetically-based targets of high cardiovascular risk (CVR) formation. Materials and methods. An open comparative study was conducted with the formation of a cohort of 126 patients with comorbid course of NAFLD and CVD with different stages of liver fibrosis, who were divided into comparison groups according to SCORE-2 and SCORE-2-OR. Collection of complaints, medical and life history, examination, general laboratory investigations and examination of hormonal status, abdominal ultrasound, EchoCG and liver elastometry to assess the severity of fibrosis were performed. Work with the study data and graphical analysis was performed using Microsoft Office 2019 software package statistical analysis using STATISTICA 12.0. Results. SCORE-2 risk increased with increasing age of patients (z=-5.29; p0.01). The most common non-cardiovascular co-morbidities in the study sample were cholelithiasis in 35 (66.78%) patients. Soluble leptin receptor levels were lower (z=-8.60; p0.01) and leptin resistance index was higher (z=-5.95; p0.01) in the higher cardiovascular group. Corresponding data were also obtained when the changes in insulin resistance index were calculated and analysed (z=-2.15; p0.01). Fibrosis stage was higher, in patients with higher CVR (z=-3.488; p0.01), while no statistically significant difference in steatosis level was recorded. According to transient elastometry, patients taking statins had lower levels of fibrosis (z=-3.747; p0.01) and hepatic steatosis (z=-3.379; p0.01). Conclusions. The most common pathology is arterial hypertension. Gallstone disease and type 2 diabetes mellitus are often found in patients with a comorbid course. The risk of comorbid pathology and CVD increases with age. Formation of advanced stages of liver fibrosis, hyperinsulinaemia and leptin resistance phenomenon are associated with higher CVR according to SCORE-2 and SCORE-2-OR. The syndrome of increased intestinal permeability is a possible mechanism of increased CVD in patients with NAFLD.

Factors Affecting Health-related Quality of Life in Patients with Chronic Viral Hepatitis in Kazakhstan

Abstract Background: Chronic viral hepatitis is one of the main causes leading to lower health-related quality of life (HRQoL) in patients, so its performance is significantly worse than that of patients with other liver diseases. It is common for a significant percentage of patients infected with hepatitis viruses to have low scores that are independent of the degree of disease activity and in the absence of disease progression. There are many studies evaluating HRQoL in patients with chronic viral hepatitis, but studies examining predictors of reduced quality of life in patients are still scarce. Aim: This study aimed to assess factors affecting HRQoL in patients with chronic viral hepatitis in Kazakhstan. Methods: A cross-sectional study was conducted with the participation of 233 patients with chronic viral hepatitis at the Infectious Diseases Hospital of the Shymkent city and the Hepatological Center of the Shymkent Regional Clinical Hospital for the period from September 2020 to March 2022. The EuroQol-five dimensional questionnaire (EQ-5D) and the EuroQol-visual analogue scale EQ-VAS were used to assess the quality of life. Results: A total of 233 patients diagnosed with chronic viral hepatitis were enrolled in the study. The average value of the EQ-5D index scores in the total number of patients with chronic viral hepatitis was low and amounted to 0.63 ± 0.3. The indicator of the visual analog scale EQ-VAS in the total number of patients was 73.1 ± 15.3. Multiple regression analysis also showed that age (P &lt; 0.001), female (P &lt; 0.014), the stage of liver fibrosis (P &lt; 0.008), alanine transaminase (ALT) level (P &lt; 0.027), and high viral load (P &lt; 0.006) were variables significantly correlating with HRQoL in patients with chronic viral hepatitis. Conclusions: The quality of life in patients with chronic viral hepatitis in this study was low. The main factors leading to a decrease in the quality of life are older age, belonging to the female sex, advanced stage of liver fibrosis, elevated ALT levels, and high viral load. Strengthening social and medical support for patients with chronic viral hepatitis, in particular, with a late stage of the disease, can contribute to improving the quality of life in this category of patients, but further research is needed.

Intensive lifestyle intervention positively affects nonalcoholic fatty liver fibrosis score (NFS) and key metabolic parameters: A retrospective study

To date lifestyle intervention is the only proven therapy to treat nonalcoholic fatty liver disease (NAFLD). In this study, we retrospectively analyze the influence of a structured, multimodal 52-week lifestyle intervention program on NAFLD fibrosis score (NFS) as a marker for liver fibrosis. At baseline, 16/47 subjects (34.0%) in our cohort displayed elevated NFS levels suggestive for advanced stages of liver fibrosis. Already after the initial 12-week hypocaloric fasting phase with a formula diet, this number decreased significantly and continued to decrease until the end of the program to 10/47 (21.3%). At baseline, 48.9% of the participants had impaired glucose metabolism, as defined by impaired fasting glucose, elevated HbA1c, or overt type 2 diabetes mellitus. This proportion reduced markedly to 31.9% by the end of the program. The proportion of advanced stages of liver fibrosis was especially high in the subgroup of participants with impaired glucose metabolism. This group particularly benefited from the lifestyle intervention program in terms of their NFS. The present study demonstrates that participants of structured multimodal lifestyle intervention programs with formula diets can significantly improve their metabolic parameters, such as body weight, fasting glucose, HbA1c, and lipids, and substantially reduce their risk of advanced liver fibrosis. Primary care providers must be aware of the close link between impaired glucose metabolism and increased liver-related risk and refer their metabolically ill patients to effective programs.

Normalization of circulating plasma levels of miRNAs in HIV-1/HCV co-infected patients following direct-acting antiviral–induced sustained virologic response

In a previous recent work, we recognized three plasma circulating microRNAs (miRNAs)—miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p—that correlate largely with liver fibrosis evolution in human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus (HCV) co-infected patients. Here, we investigated whether levels of these three circulating miRNAs can be associated to liver disease evolution in HIV-1/HCV co-infected patients which have achieved HCV sustained virologic response (SVR) 12 weeks after finishing treatment. Eighty-one chronic HIV-1/HCV co-infected patients were longitudinally recruited at baseline (T0) of DAA therapy and 12 weeks (T12) after finishing therapy. At T0 most of the study patients displayed transient elastography values linked to an advanced stage of liver fibrosis (F0-1 9%, F2 11%, F3 32%, F4 48%). Significant reductions in the levels of circulating miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p were detected at T12 in SVR patients, in the overall cohort (P < 0.0001, P < 0.0001, and P = 0.0008, respectively) and in patients with advanced (F3-4) liver fibrosis (p < 0.0001, p < 0.0001, and P = 0.0011, respectively). Of note, no significant reduction in the study miRNA levels was found at T12 in patients who did not achieve SVR (P = 0.8750, P = 0.1250, and P = 0.1260, respectively). HCV-cured patients, in contrast to non-responders, significantly reduced their liver stiffness after two years of achieving SVR (p < 0.0001). DAA-induced SVR is linked with a significant reduction in circulating levels of miR-100-5p_iso3p:-2, miR-122-5p, and miR-192-5p. Our results indicate that miRNA plasma levels may be a useful biomarker of liver damage progression in HIV-1/HCV co-infected individuals that reach DAA-induced SVR.

Diagnostic markers of hepatic steatosis in patients with chronic viral hepatitis C

Objective was to conduct a comparative analysis of routine clinical and laboratory parameters in two groups of patients with chronic viral hepatitis C (CHC) depending on the presence or absence of hepatic steatosis.Methods and materials. The observational retrospective cross-sectional study included 411 patients with CHC, of which 43.80 % were those with hepatic steatosis. The studied parameters were routine clinical and laboratory parameters, the viral genotype, as well as formalized results of a liver biopsy and ultrasound examination of the abdominal organs. To assess the differences between the two groups, the following were calculated: Pearson’s test, two-tailed Fisher’s test, Wilcoxon rank sum test, Spearman’s correlation coefficient, and partial correlation coefficient.Results. It was found that CHC patients with hepatic steatosis were older and had a higher body mass index (BMI) than patients without hepatic steatosis (p&lt;0.01). Among patients with hepatic steatosis, the 3a genotype of the virus (p&lt;0.001) and advanced stages of liver fibrosis (p&lt;0.01) were more often detected, higher concentrations of hepatic transaminase (p£0.001) and iron (p&lt;0 .01) in blood serum were observed, as well as higher liver (p&lt;0.001) and pancreas (p&lt;0.001) sizes on ultrasound than among patients without hepatic steatosis.Conclusion. Age, BMI, viral genotype, stage of liver fibrosis, ALT, AST, GGT, and iron levels, as well as liver and pancreas size are potential predictors of the presence of hepatic steatosis in CHC patients.

Comorbidity and multimorbidity in patients with chronic hepatitis C

The aim of the study was to analyze comorbidity in patients who underwent a course of antiviral therapy for chronic hepatitis C with direct antiviral drugs.Materials and methods: 288 patients diagnosed with chronic hepatitis C with stages of liver fibrosis from F1 to F4 according to the METAVIR scale, various genotypes, who underwent antiviral therapy with direct antiviral drugs in the period from 2018 to 2021, were under observation, with an analysis of comorbid and multimorbid diseases.Results of the study: most often in these patients, regardless of gender and antiviral therapy regimen, lesions of the gastrointestinal tract were registered in the form of various inflammatory diseases, as well as non-alcoholic fatty liver disease. In second place in terms of frequency of occurrence, diseases of the endocrine system were diagnosed, primarily due to the development of metabolic syndrome, as well as damage to the thyroid gland, as an extrahepatic manifestation of chronic HCV infection. Slightly less marked diseases of the cardiovascular system. A relationship was found between the number of comorbid diseases and the body mass index, with an increase in which the stage of liver fibrosis progresses.Conclusions: The frequency of comorbidity and multimorbidity in patients with chronic HCV infection is significantly higher than in uninfected patients. Patients with chronic hepatitis C with advanced stages of liver fibrosis (F3 and F4 according to the MEVIR scale) with overweight and obesity of varying severity are characterized by the highest incidence of comorbidities. A variety of extrahepatic manifestations of chronic hepatitis C determine the polymorbid profile of the patient.

Evaluation of thyroid hormones in liver cirrhosis patients on the basis of child pugh score

Introduction: Cirrhosis is an advanced stage of liver fibrosis that is accompanied by distortion of the hepatic vasculature. It is the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury. Objectives: The study was intended to assess serum Triiodothyronine (T3), Thyroxine (T4) levels and Thyroid Stimulating Hormone (TSH) on the basis of Child Pugh Score in patients with Liver Cirrhosis. Methodology: 100 clinically diagnosed cases of Liver Cirrhosis patients were enrolled for the study. Estimation of Thyroid Hormones were performed. Statistical evaluation was done for analysis of the results. Result: The study documented a significant decrease in T3 levels (P= &lt;0.0001), a non-significant increase in T4 levels (P=0.997) and a slightly significant increase in TSH levels (P=0.034) on the basis of CP Score. Conclusion: The patients with liver cirrhosis have significantly decreased levels of T3 with increased CP Score. The routine liver enzymes like AST, ALT and ALP may be unable to predict the risk of development of liver cirrhosis specially in the early stages. Therefore, screening of serum T3 levels is strongly recommended in patients with early-stage liver diseases like ALD, NAFLD, NASH and CLD.

Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice

Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings. A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas. There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median= 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of <1.3 (range <1.0 to <1.45) and 21% reported using age-specific cut-offs. For Fibroscan®, 21% of respondents used a single liver stiffness cut-off: 8kPa in 50%, while the rest used 7.2kPa, 7.8kPa and 8.7kPa. Among the 63% of respondents who used lower and upper liver stiffness cut-offs, there were variations in both values (<5 to <10kPa and >7.5 to >20kPa, respectively). The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management. Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.

A comparative study on roles of natural killer T cells in two diet-induced non-alcoholic steatohepatitis-related fibrosis in mice

Background Immune responses are important in the progression of non-alcoholic fatty liver disease (NAFLD). Natural killer T (NKT) cells are main components of the innate immune system that modulate immunity. However, the role of NKT cells in NAFLD remains controversial. Objective We aimed to investigate the role of NKT cells in non-alcoholic steatohepatitis (NASH)-related fibrosis in fast food diet (FFD)- and methionine choline-deficient (MCD) diet-induced mouse models. Methods Hepatic NKT cells were analysed in wild-type (WT) and CD1d-/- mice fed FFD or MCD diets. Hepatic pathology, cytokine profiles and liver fibrosis were evaluated. Furthermore, the effect of chronic administration of α-galactosylceramide (α-GalCer) on liver fibrosis was investigated in both FFD- and MCD-treated mice. Results FFD induced a significant depletion of hepatic NKT cells, thus leading to mild to moderate NASH and early-stage fibrosis, while mice fed MCD diets developed severe liver inflammation and progressive fibrosis without a significant change in hepatic NKT cell abundance. FFD induced a similar liver fibrogenic response in CD1d-/- and WT mice, while MCD induced a higher hepatic mRNA expression of Col1α1 and TIMP1 as well as relative fibrosis density in CD1d-/- mice than WT mice (31.8 vs. 16.3, p = .039; 40.0 vs. 22.6, p = .019; 2.24 vs. 1.59, p = .036). Chronic administration of α-GalCer induced a higher hepatic mRNA expression of TIMP1 in MCD-treated mice than controls (36.7 vs. 14.9, p = .005). Conclusion NKT cells have protective roles in NAFLD as the disease progresses. During diet-induced steatosis, mild to moderate NASH and the early stage of fibrosis, hepatic NKT cells are relatively depleted, leading to a proinflammatory status. In severe NASH and the advanced stage of liver fibrosis, NKT cells play a role in inhibiting the NASH-related fibrogenic response. Chronic administration of α-GalCer induces NKT cell anergy and tolerance, which may play a role in promoting the liver fibrogenic response.

The Glycodiversity of HCV E2 Glycoprotein-Specific Antibodies as a Signature of Hepatic Damage and Virotherapy Efficacy

The HCV E2 glycoprotein-specific Abs (E2-Ab) is an important factor in the host resistance to hepatitis C virus (HCV) infection. There is evidence that the E2-Ab sialylation is associated with liver damage and virotherapy efficacy. The aim of this study was to further profile the E2-Ab glycosylation. The fucosylation and sialylation of E2-Ab in one hundred six (HCV)-infected patients were tested using the lectin-based ELISA platform. Data were analyzed by the stage of hepatic fibrosis, HCV genotype and the response to IF-RBV virotherapy. The changes in the E2–Ab glycosylation were also evaluated by the receiver operator characteristic curve (ROC) and multiple regression analysis. The E2-Ab reactivity to fucose-specific Aleuria aurantia lectin (AAL) and sialo-specific Sambucus nigra agglutinin (SNA) was decreased in the advanced stages of liver fibrosis. The SNA binding analysis was more informative in the discrimination of patients with advanced fibrosis compared to those with earlier fibrosis stages or no fibrosis group. No significant correlation between the reactivities of SNA and AAL lectins was established irrespective of HCV genotype. The patients infected with HCV 3a genotype showed an increased E2-Ab fucosylation, a lower E2-SNA/E2-AAL ratio and a better response to virotherapy. The association of the E2-SNA/E2-AAL ratio with virotherapy outcome was observed in patients infected with HCV 1b genotype. A better response to IF-RBV therapy was found in patients with a higher fucosylated E2 Abs and a lower E2-SNA/E2-AAL ratio. Thus the significance of E2 antibodies in the course of HCV hepatitis was demonstrated to be dependent on their glycosylation, the sialylation/fucosylation ratio, as well as on HCV genotype.

N6-Methyladenosine Modification Participates in the Progression of Hepatitis B Virus-Related Liver Fibrosis by Regulating Immune Cell Infiltration.

AimN6-methyladenosine (m6A) modification has been demonstrated to play an important part in hepatitis B virus (HBV) infection and immune response. This study aims to further investigate whether m6A modification plays an important role in the progression of HBV-related liver fibrosis through the regulation of immune cell infiltration.MethodsIn this study, 124 chronically HBV infected cases were obtained from the Gene Expression Omnibus database. In total, 489 m6A-and-stage related genes were selected to be associated with the m6A modification and the stage of liver fibrosis. Based on these genes, we identified two distinct gene clusters, gene clusterA and gene clusterB. The immune characteristics of the two clusters were comprehensively compared. The m6A-S score was constructed as quantification of individual m6A status. The correlations between m6A regulators and infiltrating immune cells were examined and compared in different pairs of groups with various m6A traits.ResultsBiological functions, immune cell infiltration, and cytokines expression were compared between the two gene clusters proving that the gene clusterB was more immune active and had a more advanced liver fibrosis stage. The m6A-S score was associated with immune infiltration and the progression of liver fibrosis. Five different grouping conditions with different m6A traits were set up. According to the intersection of significant genes and cells, ALKBH5 interacting with macrophage and WTAP interacting with nature killer T cells may be key points in the progress of liver fibrosis.ConclusionsN6-methyladenosine modification is closely related to the immune cell infiltration and the fibrosis stage of chronic HBV-infected liver tissue. It provides us a better understanding of the progression of liver cirrhosis via evaluating the m6A modification pattern and immune infiltration characteristics.

May Previous Hepatitis B Virus Infection Be Involved in Etiology and Pathogenesis of Autoimmune Liver Diseases?

Viral infections, especially with hepatotropic viruses, may trigger autoimmune liver diseases (AILDs) and deteriorate their course. However, association of previous hepatitis B virus (HBV) infection (presence of anti-HBc with or without anti-HBs or HBV DNA in serum) with AILDs is poorly studied so far. The aim of the study was to assess the prevalence of previous hepatitis B virus infection markers and its clinical significance in patients with autoimmune liver diseases. The study was based on the data obtained from 234 consecutive HBsAg-negative patients with AILDs [81 with autoimmune hepatitis (AIH), 122 with primary biliary cholangitis (PBC) and 31 with primary sclerosing cholangitis (PSC)] and 131 subjects of the control group without liver diseases. Blood samples of the enrolled patients were tested for anti-HBc and HBV DNA. Samples of liver tissue were examined by standard morphologic protocol and, in anti-HBc positive subjects, for HBV DNA. We assessed estimated risks of AILDs according to anti-HBc positivity and association of anti-HBc positivity with stage of liver fibrosis. Anti-HBc was detected in 14.5% participants in the control group vs 26.1% (p = 0.016) in patients with AILDs (including 27.1% subjects with PBC (p = 0.021 vs control group), in 29% of PSC and 23.5% in AIH. HBV DNA was detected in three patients with PBC and in one with AIH. Positive anti-HBc test result was associated with higher risk of AILDs-odds ratio (OR) = 2.078 [95% confidence interval (CI) 1.179-3.665], especially in PBC: OR (95% CI) 2.186 (1.165-4.101). Odds of advanced stage of liver fibrosis (F3-F4 by METAVIR) in anti-HBc-positive subjects with PBC were also higher compared to those who had no previous HBV infection: OR (95% CI) 2.614 (1.153-5.926). Significant proportions of patients with AILDs are anti-HBc positive, and some of them have OBI. Among patients with AILDs, anti-HBc-positivity is most widespread in the PBC group and in subjects with advanced stage of liver fibrosis. Our data may support the idea of an important role of previous HBV infection in the etiology and pathogenesis of AILDs (namely PBC).

Role of serum M2BPGi levels in diagnosing significant liver fibrosis and cirrhosis in patients with chronic hepatitis B

Abstract Background and aim Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum diagnostic marker for liver fibrosis in various liver diseases. We aimed to evaluate its role in assessment of liver fibrosis in chronic hepatitis B infection (CHB) with reference to liver stiffness measurement (LSM) by transient elastography (Fibroscan). Design and Methods A case control study. 50 CHB patients with LSM by transient elastography technology and retrievable serum samples and 20 normal volunteers as a control group were recruited. Results 50 CHB patients (M: F = 30:20; mean age 43years ± 10.58) and 20 normal control volunteers (M: F = 12:8; mean age 37years ± 14.5) were recruited. The mean M2BPGi values for control group, F0-F1, F2, F3 and F4 progressively increased with more advanced stages of liver fibrosis: 0.282, 0.719, 1.322, 1.65 and 1.904 COI, respectively (p &amp;lt; 0.001). M2BPGi levels correlated well with liver stiffness (r = 0.911) and moderately with FIB-4 (r = 0.682), and with APRI (r = 0.536) (all p &amp;lt; 0.001). Using cut-off values of 0.455, 1.02, 1.16, 1.66 and 1.71COI for control, F0-F1, F2, F3 and F4 groups, respectively, the AUROCs were 0.996, 0.996, 0.691, 0.794 and 1.00 for control, F0-F1, F2, F3 and F4 groups, respectively. There was a statistically significant but with weak positive correlation between M2BPGi serum level and INR (r = 0.333, p = 0.018). And there was a statistically significant but with weak negative correlation between M2BPGi serum level and platelet count (r = -0.41, p = 0.003) and HBV DNA (r = -0.373, p = 0.008).There was a statistically significance between M2BPGi serum level and the history of varices (p = 0.023) Conclusions WFA+-M2BP is an accurate serum indicator for assessing different stages of liver fibrosis. WFA+-M2BP provides a simple and reliable alternative or complementary method to liver biopsy and FibroScan.

Evaluation of Rabbits Liver Fibrosis Using Gd-DTPA-BMA of Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

Objective To evaluate the different pharmacokinetic parameters of the DCE-MRI method on diagnosing and staging of rabbits' liver fibrosis. Methods We had performed DCE-MRI for rabbits that had been divided into the experiment group and the control group. Then, rabbits' images were transferred to a work station to get three parameters such as Ktrans, Kep, and Ve, which had been measured to calculate. After data were analyzed, ROC analyses were performed to assess the diagnostic performance of Ktrans, Kep, and Ve to judge liver fibrosis. Results The distribution of the different liver fibrosis group was as follows: F1, n = 8; F2, n = 9; F3, n = 6; F4, n = 5. No fibrosis was deemed as F0, n = 6. Kep is statistically significant (P < 0.05) for F0 and mild liver fibrosis stage, and the Kep shows AUC of 0.814. Three parameters are statistically significant for F0 and advanced liver fibrosis stage (Ktrans and Kep, P < 0.01; Ve, P < 0.05), and the Ktrans shows AUC of 0.924; the Kep shows AUC of 0.909; the Ve shows AUC of 0.848; Ktrans and Kep are statistically significant for mild and advanced liver fibrosis stages (Ktrans, P < 0.01; Kep, P < 0.05), and the Ktrans shows AUC of 0.840; the Kep shows AUC of 0.765. Both Ktrans and Kep are negatively correlated with the liver fibrosis stage. Ve is positively correlated with the liver fibrosis stage. ConclusionKtrans is shown to be the best DCE parameter to distinguish the fibrotic liver from the normal liver and mild and advanced fibrosis. On the contrary, Kep is moderate and Ve is worst. And Kep is a good DCE parameter to differentiate mild fibrosis from the normal liver.

The complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments.

Nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions worldwide. NAFLD and type 2 diabetes mellitus (T2DM) are known to frequently coexist and act synergistically to increase the risk of adverse (hepatic and extra-hepatic) clinical outcomes. T2DM is also one of the strongest risk factors for the faster progression of NAFLD to nonalcoholic steatohepatitis, advanced fibrosis or cirrhosis. However, the link between NAFLD and T2DM is more complex than previously believed. Strong evidence indicates that NAFLD is associated with an approximate twofold higher risk of developing T2DM, irrespective of obesity and other common metabolic risk factors. This risk parallels the severity of NAFLD, such that patients with more advanced stages of liver fibrosis are at increased risk of incident T2DM. In addition, the improvement or resolution of NAFLD (on ultrasonography) is associated with a reduction of T2DM risk, adding weight to causality and suggesting that liver-focused treatments might reduce the risk of developing T2DM. This Review describes the evidence of an association and causal link between NAFLD and T2DM, discusses the putative pathophysiological mechanisms linking NAFLD to T2DM and summarizes the current pharmacological treatments for NAFLD or T2DM that might benefit or adversely affectthe risk of T2DM or NAFLD progression.

Baseline elevated serum angiopoietin-2 predicts long-term non-regression of liver fibrosis after direct-acting antiviral therapy for hepatitis C

We previously revealed that Angiopoietin-2 (Ang2) predicts non-regression of liver fibrosis based on liver stiffness measurement (LSM) at 24 weeks after anti-hepatitis C virus (HCV) treatment. In this study, we extended the observational period to 96 weeks to investigate the factors associated with non-regression after treatment with direct-acting-antivirals (DAAs). Patients treated with DAAs who underwent transient elastography at baseline and 24 and 96 weeks after DAA therapy were included. Baseline and post-treatment serum Ang2 levels were measured. Liver fibrosis stages were defined based on LSM. Multivariate regression was used to evaluate factors associated with non-regression of liver fibrosis between various time points. In total, 110 patients were included. Of these, 11% showed non-regression of LSM-based fibrosis stage at 96 weeks after DAA therapy. In multivariate analysis, advanced liver fibrosis stage and high baseline Ang2 levels were significantly associated with non-regression at 96 weeks. In patients with advanced liver fibrosis (F3/4), baseline Ang2 levels were associated with non-regression of liver fibrosis stage. Between SVR24 and SVR96, post-treatment Ang2 levels and controlled attenuation parameter values at SVR24 were significantly associated with non-regression of liver fibrosis stage in patients with F3/4. Thus, serum Ang2 levels are an important target for monitoring and therapy.

Characteristics of patients aged over 75years with hepatitis C virus infection treated with direct-acting antivirals in Japan: Evidence based on the nationwide, real-world database in Japan.

Direct-acting antivirals (DAAs) have dramatically changed the treatment of chronic hepatitis C. Their high efficacy helps in eradicating hepatitis C virus with few adverse events. Information on real-world use of DAAs therapy in patients aged 75years and older is inadequate. The Japanese DAAs database was constructed in 2014 as a cooperative system between 18 prefectures. The medical reports filled in by doctors and anonymized at the local government office were collected. The patients' demographic features, viral factors, and treatment characteristics were compared among three groups stratified by age when therapy was initiated: Group A (<60years old), Group B (60-74years old), and Group C (≥75years old). Out of the 22,454 patients whose age upon starting therapy could be identified, 24.8% (n=5597) belonged to Group C, which was ten times the number in the Japanese Interferon Database. Female patients, advanced stages of liver fibrosis, and past history of hepatocellular carcinoma treatment were significantly higher in the older age groups (Group A<B<C), whereas sustained virologic response (SVR) rates were not different (91%-93%). In Group C, multivariate logistic regression analysis revealed that predicting factors for virologic response varied among DAAs regimens. However, the completion of DAAs therapy commonly contributed to SVR, regardless of DAAs regimen. DAAs therapy is associated with high SVR rates, even in the oldest age group, and therapy should not be withheld on the basis of old age.

Association between noninvasive assessment of liver fibrosis and coronary artery calcification progression in patients with nonalcoholic fatty liver disease

Advanced liver fibrosis and coronary artery calcification (CAC) progression has been reported to correlate with cardiovascular disease. This study investigated the association between noninvasive liver fibrosis score and CAC progression in patients with nonalcoholic fatty liver disease (NAFLD). We included 1173 asymptomatic adults with CAC scores from 2007–2013. CAC progression was defined as newly incident CAC or a ≥ 2.5-unit increase in the final CAC score square root. Liver fibrosis was assessed using fibrosis-4 index (FIB-4) score and NAFLD fibrosis score (NFS). A total of 293 (25.0%) subjects developed CAC. Mean baseline FIB-4 score was significantly higher in subjects with CAC. CAC progressed in 20.5% of subjects without NAFLD, 27.5% of those with NAFLD and low FIB-4 scores, and 35.9% of those with NAFLD and intermediate/high FIB-4 scores. On multivariate logistic regression analysis, the odds ratio for CAC progression was 1.70 (95% confidence interval, 1.12–2.58) for subjects with NAFLD plus intermediate/high FIB-4 scores versus those without NAFLD. In the sensitivity analysis, the odds ratio for CAC progression was 1.57 (95% confidence interval, 1.02–2.44) for subjects with NAFLD plus an intermediate/high NFS versus those without NAFLD. Advanced liver fibrosis stage assessed using noninvasive markers is associated with a higher risk of CAC progression in subjects with NAFLD.