Total Antioxidant Capacity in HBV Carriers, a Promising Biomarker for Evaluating Hepatic Fibrosis: A Pilot Study

Oxidative stress plays a pivotal role in the progression of chronic hepatitis B; however, it is unclear whether the status of blood oxidative stress and antioxidant components differs depending on the degree of hepatic fibrosis. To explore the relationship between oxidative stress/antioxidant capacity and the extent of hepatic fibrosis, fifty-four subjects with liver fibrosis (5.5 ≤ liver stiffness measurement (LSM) score ≤ 16.0 kPa) by chronic hepatitis B virus (HBV) were analyzed. From the analysis of eight kinds of serum oxidative stress/antioxidant profiles and liver fibrosis degrees, the level of total antioxidant capacity (TAC) reflected a negative correlation with the severity of hepatic fibrosis (Pearson correlation, r = −0.35, p = 0.01). Moreover, TAC showed higher sensitivity (73.91%) than the aspartate transaminase (AST) to platelet ratio index (APRI, 56.52%) in the receiver operating characteristic (ROC) curves. Interestingly, the TAC level finely reflected the fibrosis degree in inactive carriers (HBV DNA < 2000 IU/mL), while the APRI did in active carriers (HBV DNA > 2000 IU/mL). In conclusion, TAC is a promising biomarker for evaluating the progression of liver fibrosis in patients with HBV, and this finding may indicate the involvement of TAC-composing factors in the pathogenesis of hepatic fibrosis in chronic HBV carriers.

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Hepatic necroinflammation and severe liver fibrosis in patients with chronic hepatitis B with undetectable HBV DNA and persistently normal alanine aminotransferase

Bangladesh Medical Research Council Bulletin ◽

10.3329/bmrcb.v40i3.25229 ◽

2015 ◽

Vol 40 (3) ◽

pp. 92-96 ◽

Cited By ~ 6

Author(s):

MM Alam ◽

MA Mahtab ◽

SMF Akbar ◽

M Kamal ◽

S Rahman

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Hepatic Fibrosis ◽

Alanine Aminotransferase ◽

Liver Diseases ◽

Hbv Dna ◽

Treatment Recommendation ◽

Normal Alt

Both consensus and controversy remains regarding surrogacy of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and alanine aminotransferase (ALT), however, these markers are used to ascertain the extent of liver damages and to guide therapeutic options in patients with chronic hepatitis B. However, little is known about liver histology of patients with chronic hepatitis B with undetectable HBV DNA and persistently normal ALT. Thirty-five incidentally-detected patients with chronic HBV infection (assessed by expression of hepatitis B surface antigen for more than 6 months) with undetectable HBV DNA and normal serum ALT were enrolled in this study. Liver biopsy specimens were taken from all patients and the extent of hepatic necroinflammation and liver fibrosis were evaluated. Moderate degree of hepatic necroinflammation was detected in 2 of 35 patients and severe hepatic fibrosis was seen in 6 of 35 patients. Two patients with undetectable HBV DNA and sustained normal ALT had moderate hepatic necroinflammation and severe hepatic fibrosis. In spite of undetectable HBV DNA for prolonged period and persistently normal ALT, some patients with chronic hepatitis B express evidences of progressive liver diseases. Large scale studies in different races and geographical regions should be accomplished to develop insights about management of these patients. Studies about extent of liver diseases in these patients should be accomplished in Treatment recommendation and management strategies should be developed for these patients.Bangladesh Med Res Counc Bull 2014; 40 (3): 92-96

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Decreased Total Antioxidant Capacity and Increased Oxidative Stress and Serum Ferritin Levels in Untreated Chronic Hepatitis C Patients

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.718.15 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Isaias Dichi ◽

Danielle Venturini ◽

Andrea Colado Simão ◽

Décio Sabbatini Barbosa ◽

Edson Lopes Lavado ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Antioxidant Capacity ◽

Chronic Hepatitis C ◽

Serum Ferritin ◽

Total Antioxidant Capacity ◽

Total Antioxidant ◽

Chronic Hepatitis C Patients

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Increased Oxidative Stress, Decreased Total Antioxidant Capacity, and Iron Overload in Untreated Patients with Chronic Hepatitis C

Digestive Diseases and Sciences ◽

10.1007/s10620-009-0833-1 ◽

2009 ◽

Vol 55 (4) ◽

pp. 1120-1127 ◽

Cited By ~ 24

Author(s):

Danielle Venturini ◽

Andréa Name Colado Simão ◽

Décio Sabbatini Barbosa ◽

Edson Lopes Lavado ◽

Victor Emanuel Soares Narciso ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Iron Overload ◽

Antioxidant Capacity ◽

Chronic Hepatitis C ◽

Total Antioxidant Capacity ◽

Total Antioxidant

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The clinical significance of quantitative HBSAG in patients with HBEAG negative chronic hepatitis B

Acta Medica Saliniana ◽

10.5457/ams.v49i2.517 ◽

2019 ◽

Vol 49 ◽

Author(s):

Marija Dimzova ◽

Mile Bosilkovski ◽

Magdalena Gasheva ◽

Boban Toshevski ◽

Biljana Petreska ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Clinical Significance ◽

Significant Positive Correlation ◽

Serum Levels ◽

Hbv Dna ◽

Positive Correlation ◽

Negative Chronic Hepatitis

Background: The quantification of HBsAg provides different and complementary information that helps in determination of the different phases of chronic hepatitis B viral infection, evaluation and follow-up of liver disease progression as well as in treatment individualization.Aim: To evaluate the clinical significance of quantitative HBsAg (qHBsAg) in patients with HBeAg negative chronic hepatitis (CHB) and its correlation with the serum levels of alanine aminotransferase (ALT), quantitative HBV DNA and liver fibrosis.Subjects and Methods: The study included 53 treatment naïve patients with HBeAg negative chronic hepatitis B. All patients underwent complete laboratory and serology testing, quantification of HBV DNA and HBs antigen. The liver stiffness was measured with elastography. Patients’ demographic characteristics, viral and biochemical markers were recorded at one point of time.Results: Correlation analysis between the qHBsAg and ALT showed an significant, positive correlation between the parameters for R=0.42 and p<0.05; there was statistically non-significant positive correlation for R=0.25 and p>0.05 between qHBsAg and HBV DNA. There was a positive correlation between qHBsAg and liver fibrosis for R=0.08 and p>0.05. The serum levels of HBsAg had greater impact on the serum levels of ALT compared to that of HBV DNA for R=0.15 and p>0.05.Conclusion: Patients with higher ALT values and higher liver fibrosis score have higher qHBsAg; qHBsAg can reflect the serum HBV DNA levels.

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Investigating the Efficiency of APRI, FIB-4, AAR and AARPRI as Noninvasive Markers for Predicting Hepatic Fibrosis in Chronic Hepatitis B Patients in Bangladesh

The Open Microbiology Journal ◽

10.2174/1874285801913010034 ◽

2019 ◽

Vol 13 (1) ◽

pp. 34-40

Author(s):

Fazley R. Sha ◽

Moyen Uddin Pk ◽

Nermeen Z. Abuelezz ◽

Rumana Pervin ◽

Rabiul I. Talukder ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Hepatic Fibrosis ◽

Receiver Operating Curve ◽

Aspartate Transaminase ◽

Training Cohort ◽

Non Invasive ◽

Cohort Groups

Background and Aims:Accurate, affordable non-invasive markers are highly needed for efficient diagnosis and management of liver fibrosis caused by chronic hepatitis B. This is the first study to investigate the diagnostic efficiency of Aspartate Transaminase to Platelet Ratio (APRI), Fibrosis Index (FIB-4), Aspartate transaminase to Alanine Transaminase Ratio (AAR) and AAR/Platelet ratio index (AARPRI) as non-invasive markers to predict hepatic fibrosis caused by Chronic Hepatitis B (CHB) in Bangladesh.Methods:In this study, a training cohort of 1041 CHB patients were recruited, whereas 104 and 109 CHB patients of matched ages were recruited as internal and external validation cohort groups respectively. Histological and hematological data were analyzed. METAVIR scoring system was used to classify liver fibrosis stages. Area Under Receiver Operating Curve (AUROC), correlations and cutoff values for the four diagnostic markers were calculated and assessed.Results:92%, 81% and 84% of the patients had liver fibrosis in the training cohort, internal and external cohort groups respectively. Among the four noninvasive panels, APRI showed the best area under ROC; (0.767, CI: 0.780-0.914; 0.775) for the training cohort, (0.775, CI: 0.693-0.857), and (0.847, CI: 0.780-0.914) for the internal and external cohorts respectively. Cut-off value of APRI was 0.512 with sensitivity/specificity of 84%/67% in training cohort, 81% / 66% in the internal cohort, and 88% / 66% in an external cohort. The odds ratio for APRI was 32.95 (95%CI: 4.746-228.862,p<0.001).Conclusion:Among all the four tested markers, APRI is the most accurate non-invasive test to predict major liver fibrosis (F2-3) in Bangladeshi CHB patients.

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STUDY THE BIOCHEMICAL, VIRAL AND LIVER FIBROSIS RESPONSES IN PATIENTS WITH CHRONIC HEPATITIS B AFTER 12 MONTH-TREATMENT BY ENTECAVIR

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2014.6.5 ◽

2015 ◽

pp. 36-43

Author(s):

Viet Thinh Nguyen ◽

Van Huy Tran

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Liver Biopsy ◽

Key Words ◽

Chronic Hepatitis B ◽

Hbv Dna ◽

Controlled Study ◽

Viral Responses

Introduction: Assessing the histological character liver fibrosis by transient hepatic elastography (TE) by Fibroscan has several advantages when compared with liver biopsy and can indicate repeatedly; therefore it can help us to follow up the treatment of chronic hepatitis B. This study is aimed at assessing the biochemical, viral and liver elasticity responses in patients with chronic hepatitis B after 12 months of entecavir treatment. Methods: Prospective, open, non-controlled study. 75 patients over 16 years old were diagnosed with chronic hepatitis B and treated with Entecavir 0.5 mg orally 2 hours after meal during 12 months. Using Fibroscan to assess the liver fibrosis according to the METAVIR classification. Results: ALT decreased rapidly after 3 months of treatment. There were differences in ALT at baseline, compared with ALT at 3 months, 6 months and 12 months (p < 0.05). HBV-DNA responsed below detection thredsold is 32%, 54.7% and 84% after 3, 6, 12 months of treatment, respectively (p<0.05). The change in the Fibroscan value > 1KPa at 6 months was 53.3% after treatment, and this was lower than this proportion at 12 months (61.3%) (p<0.001). Conclusion: Fibroscan may be used as a mean to monitor the responses to HBV treatment besides the biochemical and viral responses. Key words: Chronic B hepatitis, Entecavir, Elastography, Fibroscan

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Discriminant value of serum HBV DNA levels as predictors of liver fibrosis in chronic hepatitis B

Journal of Viral Hepatitis ◽

10.1111/j.1365-2893.2011.01437.x ◽

2011 ◽

Vol 18 (7) ◽

Cited By ~ 16

Author(s):

F. M. Sanai ◽

A. Helmy ◽

K. I. Bzeizi ◽

M. A. Babatin ◽

A. Al‐Qahtani ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Hbv Dna

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A209 NON-INVASIVE ASSESSMENT OF LIVER FIBROSIS USING APRI, FIB-4, AND TRANSIENT ELASTOGRAPHY IN CHRONIC HEPATITIS B PATIENTS

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.207 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 239-240

Author(s):

D H Little ◽

S Fischer ◽

S K Fung

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Liver Biopsy ◽

Chronic Hepatitis B ◽

Transient Elastography ◽

Hbv Dna ◽

Advanced Fibrosis ◽

Predictive Values ◽

Non Invasive

Abstract Background Accurate assessment of liver fibrosis is important to identify patients with chronic hepatitis B (CHB) who require antiviral therapy. As liver biopsy is invasive and costly, non-invasive tests of liver fibrosis are increasingly being used. Aims We aimed to evaluate the performance of the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis 4 index (FIB-4), and transient elastography (TE) in predicting fibrosis in patients with CHB. Methods We retrospectively analyzed a prospectively enrolled cohort of consecutive adults with CHB who underwent liver biopsy for routine clinical indications (ALT > ULN and HBV DNA > 2,000 IU/ml) from January 2018 to December 2019. Demographic information, routine biochemistry, HBV serology including HBV DNA, abdominal ultrasound, fibrosis stage by liver biopsy and TE data were collected. Positive predictive values (PPV) and negative predictive values (NPV) were calculated using published cut-off values with liver biopsy as the reference standard. Results Fifty-five patients of Asian ethnicity (mean age 46 years, 65% male) were included. Most patients were HBeAg-negative (67%) and treatment-naïve (80%). Eleven (20%) patients had advanced fibrosis (F3-F4 METAVIR) and 4 (7%) patients had cirrhosis (F4). APRI <0.50 had a NPV of 73% for significant fibrosis (F2-F4) and APRI >1.50 had a PPV of 33% for significant. All 4 patients with cirrhosis were misclassified as having no cirrhosis with an APRI <1. FIB-4 <1.45 had a NPV of 90% for advanced fibrosis (F3-F4). No patient, including 11 patients with advanced fibrosis, had a FIB-4 above the cut-off value to detect advanced fibrosis (>3.25). TE data was available for 38 patients. TE <7.25 kPa had a NPV of 78% for significant fibrosis and TE >12.4 kPa had a PPV of 50% for cirrhosis. Conclusions In Asian patients with CHB and a low prevalence of advanced fibrosis or cirrhosis, APRI, FIB-4, and TE performed well in excluding those with advanced fibrosis but were unable to accurately identify those with significant/advanced fibrosis and cirrhosis. Further studies with larger numbers of CHB patients are needed to confirm our results. Funding Agencies None

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Novel biomarkers for the management of chronic hepatitis B

Clinical and Molecular Hepatology ◽

10.3350/cmh.2020.0032 ◽

2020 ◽

Vol 26 (3) ◽

pp. 261-279 ◽

Cited By ~ 3

Author(s):

Takako Inoue ◽

Yasuhito Tanaka

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Early Stage ◽

Hbv Dna ◽

Alpha Fetoprotein ◽

Protein Glycosylation ◽

Undetectable Serum ◽

Risk Patients

Hepatitis B virus (HBV) cannot be eliminated completely from infected hepatocytes because of the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), it is important to manage CHB to prevent HCC development in high-risk patients with high viral replicative activity or advanced fibrosis. Serum biomarkers are noninvasive and valuable for the management of CHB. Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with hopeful outcomes. Therefore, HBcrAg can predict HCC occurrence or recurrence. Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. Because elevated M2BPGi in CHB is related to liver fibrosis and the prediction of HCC development, monitoring its progression is essential. Because alpha fetoprotein (AFP) has insufficient sensitivity and specificity for early-stage HCC, a combination of AFP plus protein induced by vitamin K absence factor II, or AFP plus <i>Lens culinaris</i> agglutinin-reactive fraction of alpha-fetoprotein might improve the diagnosis of HCC development. Additionally, Dickkopf-1 and circulating immunoglobulin G antibodies are the novel markers to diagnose HCC or assess HCC prognosis. This review provides an overview of novel HBV biomarkers used for the management of intrahepatic viral replicative activity, liver fibrosis, and HCC development.

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