scholarly journals A New Glutamine Synthetase Index to Evaluate Hepatic Lobular Restoration in Advanced Fibrosis During Anti-HBV Therapy

2021 ◽  
Author(s):  
Shuyan Chen ◽  
Bingqiong Wang ◽  
Jialing Zhou ◽  
Xiaoning Wu ◽  
Tongtong Meng ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Antiviral Therapy ◽  
Hepatic Veins ◽  
Advanced Fibrosis ◽  
Evaluation Tool ◽  
Therapeutic Benefits ◽  
Lobular Architecture ◽  
Stage 4 ◽  
Advanced Liver Fibrosis ◽  
Fibrosis Regression

Abstract Background Hepatic lobular architecture distortion is a deleterious turning point and crucial histological feature of advanced liver fibrosis in chronic liver diseases. Regression of fibrosis has been documented in chronic hepatitis B (CHB) patients. However, the restoration of lobular architecture after antiviral therapy is still unclear. Here, we propose a new glutamine synthetase (GS) index (GS-index) to evaluate the extent of architectural disruption and restoration. Methods We evaluated 43 pre-and post-treatment liver biopsies of CHB patients with advanced fibrosis (Ishak stage≥4). Glutamine synthetase (GS) is normally expressed by perivenular hepatocytes around hepatic veins (HV). When GS expression is observed in the vicinity of portal tracts (PT), it denotes parenchymal extinction and lobular collapse. We propose the new glutamine synthetase index (GS-index), defined as the percentage of GSHV/(GSHV+ GSPT), to evaluate the extent of architectural disruption and restoration. Results The median GS-index improved from 7% at baseline to 36% at week 78 (P<0.001). When GS-index78w≥50% used to define hepatic lobular restoration, 37% patients (16/43) achieved lobular restoration, with improvement in ALT and AST levels. More importantly, GS-index correlated with fibrosis regression, one stage fibrosis improvement in restored group and no change in non-restored patients (P=0.030). Conclusion In the era of antiviral therapy for CHB, restoration of hepatic lobular architecture is achievable. GS-index gives a new evaluation tool to quantitively assess hepatic lobular status and therapeutic benefits in CHB patients.

Evidence that interaction of hepatocytes with the collecting (hepatic) veins triggers position-specific transcription of the glutamine synthetase and ornithine aminotransferase genes in the mouse liver

1991 ◽  
Vol 11 (12) ◽  
pp. 6050-6058
Author(s):  
F C Kuo ◽  
J E Darnell
Keyword(s):  
Blood Flow ◽  
Carbon Tetrachloride ◽  
Glutamine Synthetase ◽  
Liver Tissue ◽  
Mouse Liver ◽  
Hepatic Veins ◽  
Surgical Removal ◽  
Ornithine Aminotransferase ◽  
Regenerating Liver ◽  
Portal Veins

We previously demonstrated that glutamine synthetase (GS) and ornithine aminotransferase (OAT) mRNAs are expressed in the mouse liver acinus preferentially in pericentral hepatocytes, that is, those immediately surrounding terminal central veins (A.L. Bennett, K.E. Paulson, R.E. Miller, and J.E. Darnell, Jr., J. Cell Biol. 105:1073-1085, 1987, and F.C. Kuo, W.L. Hwu, D. Valle, and J.E. Darnell, Jr., Proc. Natl. Acad. Sci. USA, in press). We now show that hepatocytes surrounding large collecting hepatic veins but not portal veins also express these two mRNAs. The pericentral hepatocytes are the most distal hepatocytes with respect to acinar blood flow, whereas this is not necessarily the case for hepatocytes next to the large collecting hepatic veins. This result implies that it is contact with some hepatic venous element which signals positional expression. In an effort to induce conditions that change relationships between hepatocytes and blood vessels, regenerating liver was studied. After surgical removal of two-thirds or more of the liver, there was no noticeable change in GS or OAT expression in the remaining liver tissue during regeneration. However, treatment with carbon tetrachloride (CCl4), which specifically kills pericentral hepatocytes, completely removed GS- and OAT-containing cells and promptly halted hepatic transcription of GS. Repair of CCl4 damage is associated with invasion of inflammatory and scavenging cells, which remove dead hepatocytes to allow regrowth. Only when hepatocytes resumed contact with pericentral veins were the pretreatment levels of OAT and GS mRNA and high levels of GS transcription restored.

scholarly journals Sex Differences in the Association Between Liver Fibrosis and Clinical Outcomes in Acute Cardioembolic Stroke Population With Nonvalvular Atrial Fibrillation

2021 ◽  
Author(s):  
Lei Yang ◽  
Ke Gao ◽  
Xin-Ye Yao ◽  
Yong-lan Tang ◽  
Wan-Ying Yang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Liver Fibrosis ◽  
Clinical Outcomes ◽  
Cardioembolic Stroke ◽  
Advanced Fibrosis ◽  
Short Term ◽  
Nonvalvular Atrial Fibrillation ◽  
Severe Stroke ◽  
Advanced Liver Fibrosis ◽  
The Impact

Abstract Background: Liver cirrhosis is a confirmed risk factor for worse clinical outcomes of stroke, however the contribution of liver fibrosis to cardioembolic stroke (CES) and its short-term outcomes are poorly understood. This study aimed to investigate whether liver fibrosis is associated with more severe stroke, worse short-term clinical outcomes of acute CES, due to nonvalvular atrial fibrillation (NVAF), as well as the impact of sex on the association. Methods: Using data of 522 patients with NVAF admitted within 48 hours after acute symptom of CES onset. We calculated Fibrosis-4 score (FIB-4) and defined liver fibrosis as: likely advanced fibrosis (FIB-4>3.25), indeterminate (FIB-4, 1.45-3.25), unlikely advanced fibrosis (FIB-4<1.45). We invested the impact of liver fibrosis degree on stroke severity on admission, major disability at discharge and all cause death at 90 days stratified by sex. Results: Among 522 acute CES patients with NVAF, the mean FIB-4 on admission reflected intermediate fibrosis, whereas liver enzymes were largely normal. After adjusting for possible confounders, multivariate analyses revealed that likely advanced liver fibrosis was associated with severe stroke (OR=2.21, 95% CI: 1.04-3.54), major disability at discharge (OR=4.59, 95% CI: 1.88-11.18), and 90-days mortality (HR=1.25, 95% CI: 1.10-1.56). Further grouped by sex, these associations were stronger in males but not significant in females.Conclusions: In patients with largely normal liver enzyme, likely advanced liver fibrosis is associated with severe stroke, major disability and all cause death after acute CES due to NVAF; the association unfolded more obvious in males, but not for females.

scholarly journals Sex Differences in the Association between Liver Fibrosis and Clinical Outcomes in Acute Cardioembolic Stroke Patients with Nonvalvular Atrial Fibrillation

2021 ◽  
Author(s):  
Lei Yang ◽  
Ke Gao ◽  
Xin-Ye Yao ◽  
Yong-lan Tang ◽  
Wan-Ying Yang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Liver Fibrosis ◽  
Clinical Outcomes ◽  
Normal Liver ◽  
Advanced Fibrosis ◽  
Stroke Patients ◽  
Short Term ◽  
Nonvalvular Atrial Fibrillation ◽  
Severe Stroke ◽  
Advanced Liver Fibrosis

Abstract Background: Liver cirrhosis is a confirmed risk factor for clinical outcomes of stroke patients. However, the contribution of liver fibrosis to cardioembolic stroke (CES) and its short-term outcomes are poorly understood. This study aimed to investigate the association between liver fibrosis and short-term clinical outcomes of acute CES patients, due to nonvalvular atrial fibrillation (NVAF), as well as the impacts of sex on the association. Methods: Using data of 522 patients with NVAF admitted within 48 hours after acute symptom of CES onset. We calculated Fibrosis-4 score (FIB-4) and defined liver fibrosis as: likely advanced fibrosis (FIB-4>3.25), indeterminate (FIB-4, 1.45-3.25), unlikely advanced fibrosis (FIB-4<1.45). We investigated the impact of liver fibrosis degree on stroke severity, major disability at discharge and all cause death at 90 days stratified by sex. Results: Among 522 acute CES patients with NVAF, the mean FIB-4 on admission reflected intermediate fibrosis with largely normal liver enzymes. After adjusting for all confounders, multivariate analyses revealed that likely advanced liver fibrosis was associated with severe stroke (OR=2.21, 95% CI: 1.04-3.54), major disability at discharge (OR=4.59, 95% CI: 1.88-11.18), and 90-days mortality (HR=1.25, 95% CI: 1.10-1.56). Further grouped by sex, these associations were stronger in males but not significant in females.Conclusions: In patients with largely normal liver enzyme, likely advanced liver fibrosis is associated with severe stroke, major disability and all cause death after acute CES due to NVAF, and the association unfolded more obvious in males, but not for females.

scholarly journals Association between serum and dietary antioxidant micronutrients and advanced liver fibrosis in non-alcoholic fatty liver disease: an observational study

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9838
Author(s):  
Juliana Moraes Coelho ◽  
Katia Cansanção ◽  
Renata de Mello Perez ◽  
Nathalie Carvalho Leite ◽  
Patrícia Padilha ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Dietary Intake ◽  
Hepatic Fibrosis ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Serum Retinol ◽  
Alcoholic Fatty Liver ◽  
Advanced Liver Fibrosis ◽  
Alcoholic Fatty Liver Disease

Background Despite clinical trials with antioxidant supplementation, few studies have been conducted to evaluate the nutritional status of antioxidant vitamins and minerals, and none have reported on the status of these serum antioxidants associated with the dietary intake of antioxidants by non-alcoholic fatty liver disease (NAFLD) patients. Objective To evaluate association between serum and dietetics antioxidants with liver fibrosis in patients with NAFLD. Methods Across-section analysis with out with 72 patients diagnosed with NAFLD. Hepatic fibrosis was measured by FibroScan®, and liver stiffness ≥7.9 kPa was considered to indicate advanced fibrosis. Retinol, alpha-tocopherol, ascorbic acid, beta-carotene, serum zinc, and selenium were evaluated, as was the dietary intake of these micronutrients in the previous 24 h (using 24-h dietary recall). The Mann–Whitney test was used to compare the fibrosis groups and, a linear regression analysis was performed to determine associated risk factors between age, sex, BMI, hepatic fibrosis, and serum antioxidants. Results A high proportion of inadequate serum retinol (20.8%), vitamin C (27%), and selenium (73.6%) was observed in the patients with NAFLD, in addition to a significant inadequacy of vitamin A (98.3%) and vitamin E (100%) intake. Patients with advanced liver fibrosis had reduced levels of serum retinol (P = 0.002), with liver fibrosis being the independent risk factor associated with serum retinol lower. Conclusion Hepatic fibrosis was associated with a reduction in serum retinol and was reduced in advanced fibrosis. NAFLD patients showed an important serum deficiency and insufficient dietary intake of the evaluated micronutrients.

scholarly journals Baseline Amino Acid Substitutions in the NS5A ISDR and PKR Binding Domain of Hepatitis C and Different Fibrosis Levels and Levels of Development of Hepatocellular Carcinoma in Patients Treated with DAAs

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 255
Author(s):  
Stefania Paolucci ◽  
Antonio Piralla ◽  
Federica Novazzi ◽  
Alice Fratini ◽  
Renato Maserati ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
High Frequency ◽  
Transient Elastography ◽  
Hcv Rna ◽  
Amino Acid Substitutions ◽  
Advanced Fibrosis ◽  
Ns5a Region ◽  
Advanced Liver Fibrosis

Variations in the interferon sensitivity-determining region (ISDR) within the NS5A region were related to the development of hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV). The aim of the study was to investigate a relationship between ISDR/PKR substitutions and their association with liver fibrosis or HCC development. A total of 316 patients infected with HCV and treated with DAAs were evaluated. HCV RNA was quantified and sequenced before treatment. The liver fibrosis stage was assessed by transient elastography and equalized to METAVIR scores. Multivariate analysis showed that ≥3 substitutions in ISDR and ≥6 in PKR-bd were significantly associated with advanced fibrosis. Advanced fibrosis was observed in patients with higher substitutions in ISDR and PKR-bd. A higher correlation between advanced fibrosis and a high frequency of ≥3 substitutions in ISDR and ≥6 in PKR-bd was observed in patients infected with genotype 2c. In addition, in a higher proportion of HCC patients, advanced fibrosis (40.4% vs. 88.2%; p < 0.001) and ≥6 substitutions in PKR-bd (15.4% vs. 41.2%; p = 0.01) was observed. In conclusion, a higher number of substitutions in ISDR and PKR-bd were associated with advanced liver fibrosis, suggesting a use of like predictors for progression in the liver damage. A significantly higher number of PKR-bd substitutions was observed in HCC patients; in particular, in patients infected with HCV genotype 2c.

scholarly journals Sequential Combination of FIB-4 Followed by M2BPGi Enhanced Diagnostic Performance for Advanced Hepatic Fibrosis in an Average Risk Population

2020 ◽  
Vol 9 (4) ◽  
pp. 1119 ◽  
Author(s):  
Mimi Kim ◽  
Dae Won Jun ◽  
Huiyul Park ◽  
Bo-Kyeong Kang ◽  
Yoshio Sumida
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Predictive Value ◽  
Diagnostic Performance ◽  
Classification Tree ◽  
Intermediate Zone ◽  
Average Risk ◽  
Advanced Fibrosis ◽  
Risk Population ◽  
Advanced Liver Fibrosis

The fibrosis-4 (FIB-4) index is the most widely used estimated formula to screen for advanced hepatic fibrosis; however, it has a considerable intermediate zone. Here, we propose an algorithm to reduce the intermediate zone and improve the diagnostic performance of screening for advanced liver fibrosis by incorporating Mac-2-binding protein glycan isomer (M2BPGi) into a FIB-4 based screening strategy in an average risk group. Four-hundred eighty-eight healthy and chronic liver disease subjects were analyzed using a 1:1 propensity score matched for age and sex. Advanced liver fibrosis (≥F3) was defined by magnetic resonance elastography (MRE, ≥3.6 kPa). Classification tree analysis was employed to improve diagnostic performance using a combination of the FIB-4 index and M2BPGi. The median serum M2BPGi levels of healthy subjects, patients without advanced fibrosis, and those with the condition were 0.48, 0.94, and 2.93, respectively. The area under the receiver operating characteristic (AUROC) curve of M2BPGi (0.918) for advanced fibrosis was the highest compared to those of the FIB-4 index (0.887), APRI (0.873), and AST/ALT ratio (0.794). When M2BPGi was incorporated following the FIB-4 index, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 87.1%, 82.5%, 54.0%, and 96.4%, respectively. Moreover, 74.3% (133/179) of cases in the intermediate zone of the FIB-4 index avoided unnecessary referrals. Two-step pathway (FIB-4 followed by M2BPGi) could reduce unnecessary referrals and/or liver biopsies in an average-risk population.

scholarly journals Association of Hepatitis B Core-Related Antigen and Antihepatitis B Core Antibody With Liver Fibrosis Evolution in Human Immunodeficiency Virus-Hepatitis B Virus Coinfected Patients During Treatment With Tenofovir

2020 ◽  
Vol 7 (7) ◽  
Author(s):  
Romuald Cruchet ◽  
Lorenza N C Dezanet ◽  
Sarah Maylin ◽  
Audrey Gabassi ◽  
Hayette Rougier ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis B Virus ◽  
Antiretroviral Therapy ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Advanced Fibrosis ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Fibrosis Regression

Abstract Background Quantitative hepatitis B core-related antigen (qHBcrAg) or antihepatitis B core antibody (qAnti-HBc) could be useful in monitoring liver fibrosis evolution during chronic hepatitis B virus (HBV) infection, yet it has not been assessed in human immunodeficiency virus (HIV)-HBV-coinfected patients undergoing treatment with tenofovir (TDF). Methods One hundred fifty-four HIV-HBV-infected patients initiating a TDF-containing antiretroviral regimen were prospectively followed. The qHBcrAg and qAnti-HBc and liver fibrosis assessment were collected every 6–12 months during TDF. Hazard ratios (HRs) assessing the association between qHBcrAg/qAnti-HBc and transitions from none/mild/significant fibrosis to advanced fibrosis/cirrhosis (progression) and from advanced fibrosis/cirrhosis to none/mild/significant fibrosis (regression) were estimated using a time-homogeneous Markov model. Results At baseline, advanced liver fibrosis/cirrhosis was observed in 40 (26%) patients. During a median follow-up of 48 months (interquartile range, 31–90), 38 transitions of progression (IR = 7/100 person-years) and 34 transitions of regression (IR = 6/100 person-years) were observed. Baseline levels of qHBcrAg and qAnti-HBc were not associated with liver fibrosis progression (adjusted-HR per log10 U/mL = 1.07, 95% confidence interval [CI] = 0.93–1.24; adjusted-HR per log10 Paul-Ehrlich-Institute [PEI] U/mL = 0.85, 95% CI = 0.70–1.04, respectively) or regression (adjusted-HR per log10 U/mL = 1.17, 95% CI = 0.95–1.46; adjusted-HR per log10 PEI U/mL = 0.97, 95% CI = 0.78–1.22, respectively) after adjusting for age, gender, duration of antiretroviral therapy, protease inhibitor-containing antiretroviral therapy, and CD4+/CD8+ ratio. Nevertheless, changes from the previous visit of qAnti-HBc levels were associated with liver fibrosis regression (adjusted-HR per log10 PEIU/mL change = 5.46, 95% CI = 1.56–19.16). Conclusions Baseline qHBcrAg and qAnti-HBc levels are not associated with liver fibrosis evolution in TDF-treated HIV-HBV coinfected patients. The link between changes in qAnti-HBc levels during follow-up and liver fibrosis regression merits further study.

scholarly journals Diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis 4 scores in predicting advanced liver fibrosis in patients with end-stage renal disease and chronic viral hepatitis: Experience from Pakistan

2018 ◽  
Vol 6 (1) ◽  
pp. 38-42 ◽  
Author(s):  
Rajesh Kumar Wadhva ◽  
Muhammad Manzoorul Haque ◽  
Nasir Hassan Luck ◽  
Abbas Ali Tasneem ◽  
Zaigham Abbas ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Chronic Viral Hepatitis ◽  
Advanced Fibrosis ◽  
Advanced Liver Fibrosis ◽  
Apri Score ◽  
Stage Renal Disease ◽  
End Stage ◽  
Sensitivity Specificity ◽  
Esrd Patients

Abstract Objectives The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. Material and Methods The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Results Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. Conclusion APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.

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