Is there a need for universal double reflex testing of HBsAg-positive individuals for hepatitis D infection?

Hepatitis D virus(HDV)can infect HBsAg-positive individuals,causing rapid fibrosis progression,early decompensation,increased hepatocellular carcinoma risk,and higher mortality than hepatitis B virus(HBV)mono-infection.Most countries lack high-quality HDV prevalence data,and the collection techniques employed often bias published data.In recent meta-analyses,HDV prevalence in HBsAg-positive patients reaches 5%-15%and is even significantly higher in endemic areas.Since HBV vaccination programs were implemented,HDV prevalence has decreased among younger populations.However,owing to immigrant influx,it has increased in some Western countries.The current practice of HDV screening in HBsAg-positive individuals is stepwise,based on physician’s discretion,and limited to at-risk populations and may require numerous visits.Double reflex testing,which includes anti-HDV testing in all HBsAg-positive individuals and then HDV RNA testing for anti-HDV-positive ones,is uncommon.Reflex testing can identify more HDV infection cases and link identified patients to further care and follow-up.Moreover,laboratory-based double reflex screening is less biased than physician-led testing.Therefore,health-care providers should learn about reflex testing,and federal and provincial hepatitis control programs should implement laboratory-based double reflex testing to obtain reliable HDV prevalence estimates.The test’s cost-effectiveness depends on the number of HBV-positive patients screened to identify one HDV-positive patient.Such testing may be viable in areas with low HBsAg but high HDV prevalence.However,its economic impact on areas with low HDV prevalence needs further study.

Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B

AIM To explore the effect of alanine aminotransferase(ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B(CHB) patients. METHODS A total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT(ALT ≤ 40), slightly elevated ALT(40 < ALT ≤ 80) and elevated ALT(ALT > 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis(stages S2-4), including the aspartate aminotransferase(AST)-to-platelet(PLT) ratio index(APRI), fibrosis index based on 4 factors(FIB-4), King's score, Forns index and gamma-glutamyl transpeptidase(GGT)-to-PLT ratio(GPR), were evaluated for each group. RESULTS Higher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher noninvasive test scores. The areas under the receiver operating characteristics curves(AUROCs) of the noninvasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L(range 0.705-0.755) and 40 < ALT ≤ 80 U/L(range 0.726-0.79) than for patients with ALT > 80 U/L(range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L(range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 < ALT ≤ 80 U/L(range 0.732-0.754 for ≥ S3, range 0.626-0.723 for S4) and ALT > 80 U/L(range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in ALT.CONCLUSION ALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these noninvasive tests.

Clinical Analysis of Virological Tests for Patients with Hepatitis B

Objective:Objectives:To discuss the results of virological tests for patience with hepatitis B,improve the correctness and accuracy of virological tests for hepatitis B and accumulate experience in clinical diagnosis and testing work for hepatitis B.Methods:By selecting 206 patients with hepatitis B who underwent virological and serological tests in the laboratory department at our hospital to analyze the materials of virological and clinical laboratory results for their hepatitis B.Results:HBsAg positive takes up 84.0%,HBsAb positive 10.7%,HBeAg positive 45.6%,HBeAb positive 57.8%and HBcAb positive 78.2%.Conclusion:It is of crucial importance to perform virological tests for patients with hepatitis B,examine five markers of hepatitis B virus accurately and take timely and effective preventive and therapeutic measures.

Evaluation of Liver Function tests （AST ＆ ALT） in Patients with Hepatitis B and C in Tabriz-lran （2013）

Viral hepatitis is among the infections that primarily affect the liver and is one of the main causes of death in the world. Every year, more than one million people worldwide die of viral hepatitis. In recent decades, the number of people with hepatitis B and C has declined in Iran. The purpose of this study was to investigate normal and abnormal liver enzymes （AST, ALT） in patients with chronic hepatitis B and C in a number of public and private laboratories in Tabriz. In the study conducted in 2013, of those who had referred to clinical laboratories for various reasons or who had been reported by centers of infectious or dialysis therapy, a sample of 1,000 patients were identified with hepatitis B and C; 693 people had hepatitis B and 307 people had hepatitis C. On a sample of patients, liver enzymes were evaluated using standard methods. The percentage of women and men in this study were inconsistent with global statistics. However this inconsistency could be justified by the alcohol consumption and an increase in the number of addicted people in society as well as women＇s fear due to some social issues.

Effects of adjuvant therapy with anluohuaxian capsule on serum inflammatory factors, hepatic fibrosis indexes and immune function in patients with hepatitis B cirrhosis

Objective: To investigate the effect of adjuvant therapy with anluohuaxian capsule on the treatment of hepatitis B cirrhosis, and its influence on serum inflammatory factors, liver fibrosis indexes and immune function. Methods: A total of 112 cases of hepatitis B cirrhosis patients were divided into the control group (n=55) and observation group (n=57) according to the random data table, patients in the two groups were given routine treatment, on this basis, the control group received the treatment of Adefovir Dipivoxil Tablets, and the observation group was treated with Adefovir Dipivoxil Tablets combined with Anluo Huaxian pill treatment, two groups were treated for 48 weeks. The levels of serum inflammatory factors, liver fibrosis indexes and immune function indexes of the two groups were compared before and after treatment. Results: Before treatment, There was no significant difference between the two groups of TNF-α, IL-6, hs-CRP, IVC, HA, PIIIP, LN, CD3+, CD4+, CD8+and CD4+/CD8+ levels. After treatment, TNF-α, IL-6, hs-CRP, IVC, HA, PIIIP, LN, CD3+, CD4+, CD8+and CD4+/CD8+ levels in the observation group and control group were significantly lower than those before treatment in the same group, and levels in the observation group after treatment were significantly lower than the control group;Compared with the group before treatment, the levels of CD3+, CD4+ and CD4+/CD8+ of two groups after treatment were significantly increased, and the observation group was significantly higher than the control group. Conclusion: Adjuvant therapy with anluohuaxian capsule on the treatment of hepatitis B cirrhosis, can effectively reduce the inflammatory stress reaction, reduce the level of serum liver fibrosis index and improve the immune function, and has important clinical value.

Influence of compound glycyrrhizin on liver functions, liver fibrosis indexes and inflammatory factors of patients with chronic hepatitis B

Objective:To investigate influence of Compound Glycyrrhizin on liver functions, liver fibrosis indexes and inflammatory factors of patients with chronic hepatitis B.Methods:A total of 96 cases of patients with chronic hepatitis B treated in our hospital from Jan2015 to Jun2016 were selected as subjects, and randomly divided to be 48 cases of observation group and 48 cases of control group. Patients in both of the two groups were received routine liver protecting drug treatment. For observation group, Compound Glycyrrhizin injection was given on the basis of routine treatment. Variations of liver function indexes, liver fibrosis indexes and inflammatory factors between the two groups before and after treatment were compared and observed.Results:No obvious difference showed on AST, ALT, ALB TBIL levels between two groups of patients before treatment;After treatment, AST, ALT, TBIL in two groups of patients were significantly decreased, ALB were significantly increased. Significant difference showed comparing with prior treatment;After treatment, AST, ALT and TBIL levels in observation group were (29.53±9.44) U/L, (32.36±10.93) U/L and (10.12±3.22) μmol/L, which were significantly lower than in control group. ALB levels in observation group were (43.57±12.42) g/L, which were significantly higher than ALB levels in control group. Before treatment, no statistical difference showed on HA, LN, IV-C and PCIII levels between two groups of patients. After treatment, HA, LN, IV-C and PCIII in two groups of patients were significantly decreased, which showed significant difference comparing with prior treatment;After treatment, HA, LN, IV-C and PCIII levels in observation group were (97.33±31.75) μg/L, (77.52±23.72) μg/L, (82.92±24.55) μg/L, (15.33±5.11) μg/L, which were significantly lower than in control group. Before treatment, no significant difference showed on IL-2, IL-6 and TNF- levels between two groups of patients;After treatment, IL-2 levels in two groups of patients were significantly increased, IL-6 and TNF-α were significantly decreased, the differences showed significance;After treatment, IL-2 levels in observation group were (131.48±30.63) U/mL, which were higher than IL-2 levels in control group. IL-6 and TNF-αlevels in observation group were (45.23±16.45) μg/L, (41.75±17.53) ng/L, which were lower than IL-6 and TNF-α levels in control group, differences showed significance.Conclusion:Compound Glycyrrhizin could effectively release liver fibrosis and inflammatory reactions for patients with chronic hepatitis B, and could further improve liver functions.

Diagnostic value of FIB-4, aspartate aminotransferaseto-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase

AIM To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index(APRI), and liver stiffness measurement(LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase(PNALT).METHODS We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase(PIALT1) group [alanine transaminase(ALT) within 1-2 × upper limit of normal value(ULN)], and 64 in PIALT2 group(ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed.RESULTS The pathological examination revealed moderate inflammatory necrosis ratios of 16.81%(16/95), 32.56%(28/86), and 45.31%(28/64), and moderate liverfibrosis of 24.2%(23/95), 33.72%(29/86), and 43.75%(28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group(P < 0.05). No significant difference was found in the areas under the curve(AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group(P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference(P > 0.05) was found in AUCs for all comparisons(P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI(P < 0.05).CONCLUSION APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

AIM： To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B （CHB）. METHODS： A total of 137 consecutive patients with CriB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase （ALT） level. The sensitivity, specificity, positive predictive value （PPV）, negative predictive value （NPV）, the likelihood ratio （LR） of aminotransferase/platelet ratio index （APRI） ≥ 1.5 or 〈 1.5 in combination with different hyaluronic acid （HA） cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis （fibrosis stages 2 and 4） and no to mild fibrosis/cirrhosis （fibrosis stages 0 and 1）. RESULTS： The APRI correlated with fibrosis stage in CriB patients. The APRI ≥1.5 in combination with a cut-off HA cut-off point 〉 300 ng/mL could detect moderate to severe fibrosis （stages 2-4） in Crib patients. The PPV was 93.7%, the specificity was 98.9%. The APRI 〈 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION： The APRI ≥ 1.5 in combination with a HA cut-off point 〉 300 ng/mL can detect moderate to severe fibrosis （stages 2-4） in Crib patients.

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse(ARFI), aspartate aminotransferase to platelet ratio index(APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B(CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage(all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI(P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage(Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI(Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

Comparison of real-time polymerase chain reaction with the COBAS Amplicor test for quantitation of hepatitis B virus DNA in serum samples

AIM:To compare the clinical performance of a real-time PCR assay with the COBAS Amplicor Hepatitis B Virus (HBV) Monitor test for quantitation of HBV DNA in serum samples. METHODS: The reference sera of the Chinese National Institute for the Control of Pharmaceutical and Biological Products and the National Center for Clinical Laboratories of China, and 158 clinical serum samples were used in this study. The linearity, accuracy, reproducibility, assay time, and costs of the real-time PCR were evaluated and compared with those of the Cobas Amplicor test. RESULTS: The intra-assay and inter-assay variations of the real-time PCR ranged from 0.3% to 3.8% and 1.4% to 8.1%, respectively. The HBV DNA levels measured by the real-time PCR correlated very well with those obtained with the COBAS Amplicor test (r = 0.948). The real-time PCR HBV DNA kit was much cheaper and had a wider dynamic range. CONCLUSION: The real-time PCR assay is an excellent tool for monitoring of HBV DNA levels in patients with chronic hepatitis B.

Predictive potential of IL-28B genetic testing for interferon based hepatitis C virus therapy in Pakistan: Current scenario and future perspective

In Pakistan which ranked second in terms of hepatitis C virus(HCV) infection, it is highly needed to have an established diagnostic test for antiviral therapy responseprediction. Interleukin 28B(IL-28B) genetic testing is widely used throughout the world for interferon based therapy prediction for HCV patients and is quite helpful not only for health care workers but also for the patients. There is a strong relationship between single nucleotide polymorphisms at or near the IL-28 B gene and the sustained virological response with pegylated interferon plus ribavirin treatment for chronic hepatitis C. Pakistan is a resource limited country, with very low per capita income and there is no proper social security(health insurance) system. The allocated health budget by the government is very low and is used on other health emergencies like polio virus and dengue virus infection. Therefore it is proposed that there should be a well established diagnostic test on the basis of IL-28 B which can predict the antiviral therapy response to strengthen health care set-up of Pakistan. This test once established will help in better management of HCV infected patients.

Testing for hepatitis B virus alone does not increase vaccine coverage in non-immunized persons

AIM To determine whether hepatitis B virus(HBV)-testing could serve as a gateway to vaccinate non-immunized individuals in a low-prevalent country.METHODS Non-immunized subjects participating in a multi-center, HBV-testing campaign in Paris, France were identified and contacted via telephone 3-9 mo after testing in order to determine vaccination status. Vaccination coverage was evaluated in per-protocol(for all respondents) and intent-to-treat analysis(assuming all non-responders did not vaccinate).RESULTS In total, 1215/4924(24.7%) enrolled subjects with complete HBV serology were identified as nonimmunized and eligible for analysis. There were 99/902 successfully contacted subjects who had initiated HBV vaccination after screening: per-protocol, 11.0%(95%CI: 9.0-13.2); intent-to-treat, 8.2%(95%CI: 6.7-9.8). In multivariable analysis, vaccination was more likely to be initiated in individuals originating from moderate or high HBV-endemic countries(P < 0.001), patients with limited healthcare coverage(P = 0.01) and men who have sex with men(P = 0.02). When asked about the reasons for not initiating HBV vaccination, the most frequent response was "will be vaccinated later"(33.4%), followed by "did not want to vaccinate"(29.8%), and "vaccination was not proposed by the physician"(21.5%). Sub-group analysis indicated a stark contrast in vaccination coverage across centers, ranging from 0%-56%.CONCLUSION HBV-vaccination after HBV screening was very low in this study, which appeared largely attributed to physician-patient motivation towards vaccination. Increased vaccination coverage might be achieved by emphasizing its need at the organizational level.

Low Level of Hepatitis B Surface Antigen Screening in a Tertiary Health Facility in Nigeria 2000-2014: Imperative for Provider Initiated Testing and Counselling for Hepatitis B Virus?

Introduction: Viral hepatitis is a major public health challenge that requires an urgent response. Reducing mortality requires major scale-up in prevention, testing and treatment access;coverage in HBV vaccination, testing and treatment is low and must accelerate massively to achieve the 2030 targets. Less than 1% of HBV-infected individuals are diagnosed in Sub-Sahara Africa, despite the availability of rapid tests with good diagnostic accuracy. Materials and Methods: This was retrospective cross sectional study conducted in Federal Teaching Hospital Gombe, in North East Nigeria. All children and adults who presented to the out-patient departments, and those that were admitted irrespective of their HIV and or Hepatitis C virus status and had Hepatitis B and/or Hepatitis B envelope antigen test were conducted between 2000 to 2015. All children and adults were tested using the Hospital standard for Hepatitis B surface antigen test strip. Results: Between 2000 and 2014, 739,456 children and adults were admitted and reviewed in the outpatient units of the Federal Teaching Hospital Gombe;there were 685,552 adults and 53,904 children. Children constituted 7.3% (53,904/739,456) of admissions and outpatient consultations. 2.8% (210/7570), 3.3% (773/23,783), 3.6% (1145/32,142), 5.2% (1694/33,043), 3.3% (986/29,216), 1.9% (661/3321), 0.1% (53/41,626), 0.2% (113/46,634), 2.6% (1418/54,423), 5.4% (3717/69,696), 3.7% (2332/62,086), 3.5% (3241/90,623), 3.2% (2881/89,398), 3.8% (2428/62,687), 2.8% (1835/63,208) of children and adults were tested for HBsAg in 2000, 2001, 20002, 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013 and 2014 respectively. 23,487 children and adults were tested for HBsAg with a cumulative testing rate of 3%. Overall 4465/23,487 children and adults were seropositive for HBsAg giving a cumulative prevalence of 19%. Conclusion: HBV screening in our health facility is very low. Massive scale up in awareness and HBV vaccination are required. Provider initiated testing and counseling for HBV in health facilities needs support for implementation in Health Facilities in Sub Saharan Africa.

Chronic hepatitis B and metabolic risk factors:A call for rigorous longitudinal studies

Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity,including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide,longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.

Performance of common imaging techniques vs serum biomarkers in assessing fibrosis in patients with chronic hepatitis B: A systematic review and meta-analysis

BACKGROUND Noninvasive biomarkers have been developed to predict hepatitis B virus(HBV)related fibrosis owing to the significant limitations of liver biopsy.Both serum biomarkers and imaging techniques have shown promising results and may improve the evaluation of liver fibrosis.However,most of the previous studies focused on the diagnostic effects of various imaging techniques on fibrosis in all chronic liver diseases.AIM To compare the performance of common imaging methods and serum biomarkers for prediction of significant fibrosis caused only by HBV infection.METHODS A systematic review was conducted on the records available in PubMed,EMBASE,and the Cochrane Library electronic databases until December 2018.We systematically assessed the effectiveness of two serum biomarkers and three imagine techniques in predicting significant fibrosis solely caused by HBV infection.The serum biomarkers included aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis index based on the 4 factors(FIB-4).The three imaging techniques included acoustic radiation force impulse(ARFI),FibroScan,and magnetic resonance elastography(MRE).Three parameters,the area under the summary receiver operating characteristic curve(AUSROC),the summary diagnostic odds ratio,and the summary sensitivity and specificity,were used to examine the accuracy of all tests for liver fibrosis.RESULTS Out of 2831 articles evaluated for eligibility,204 satisfied the predetermined inclusion criteria for this current meta-analysis.Eventually,our final data contained 81 studies.The AUSROCs of serum biomarkers of APRI and FIB-4 were both 0.75.For imaging techniques(ARFI,FibroScan,and MRE),the areas were 0.89,0.83,and 0.97,respectively.The heterogeneities of ARFI and FibroScan were statistically significant(I2>50%).The publication bias was not observed in any of the serum biomarkers or imaging methods.CONCLUSION These five methods have attained an acceptable level of diagnostic accuracy.Imaging techniques,MRE in particular,demonstrate significant advantages in accurately predicting HBV-related significant fibrosis,while serum biomarkers are admissible methods.

Occult hepatitis B virus infection and blood transfusion

Transfusion-transmitted infections including hepatitis B virus(HBV) have been a major concern in transfusion medicine. Implementation of HBV nucleic acid testing(NAT) has revealed occult HBV infection(OBI) in blood donors. In the mid-1980 s, hepatitis B core antibody(HBc) testing was introduced to screen blood donors in HBV non-endemic countries to prevent transmission of non-A and non-B hepatitis. That test remains in use for preventing of potential transmission of HBV from hepatitis B surface antigen(HBs Ag)-negative blood donors, even though anti-hepatitis C virus testshave been introduced. Studies of anti-HBc-positive donors have revealed an HBV DNA positivity rate of 0%-15%. As of 2012, 30 countries have implemented HBV NAT. The prevalence of OBI in blood donors was estimated to be 8.55 per 1 million donations, according to a 2008 international survey. OBI is transmissible by blood transfusion. The clinical outcome of occult HBV transmission primarily depends on recipient immune status and the number of HBV DNA copies present in the blood products. The presence of donor anti-HBs reduces the risk of HBV infection by approximately five-fold. The risk of HBV transmission may be lower in endemic areas than in non-endemic areas, because most recipients have already been exposed to HBV. Blood safety for HBV, including OBI, has substantially improved, but the possibility for OBI transmission remains.

Serum angiotensin-converting enzyme level for evaluating significant fibrosis in chronic hepatitis B

AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy in our hospital were enrolled,and 70 patients except for 30 patients with hypertension,fatty liver or habitual alcoholic consumption were analyzed.We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase(AST)-to-platelet ratio index(APRI),the fibrosis index based on four factors(FIB-4),the Mac-2 binding protein glycosylation isomer(M2BPGi)level and the number of platelets(Plt). RESULTS Serum ACE levels showed moderately positive correlation with liver fibrotic stages(R2=0.181).Patients with significant,advanced fibrosis and cirrhosis(F2-4)had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis(F0-1).For significant fibrosis(≥F2),the 12.8 U/L cut-off value of ACE showed 91.7%sensitivity and 75.0%specificity.The receiver-operating characteristic(ROC)curves analysis revealed that the area under the curve(AUC)value of ACE was 0.871,which was higher than that of APRI,FIB-4,M2BPGi and Plt. CONCLUSION The serum ACE level could be a novel noninvasive,easy,accurate,and inexpensive marker of significant fibrosis stage in patients with CHB.

Non-invasive diagnosis of hepatitis B virus-related cirrhosis

Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which was earlier thought to be irreversible.However,it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs.Thus,early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB.Liver biopsy is the reference standard for assessment of liver fibrosis.However,the method is invasive,and is associated with pain and complications that can be fatal.In addition,intra-and inter-observer variability compromises the accuracy of liver biopsy data.Only small tissue samples are obtained and fibrosis is heterogeneous in such samples.This confounds the two types of observer variability mentioned above.Such limitations have encouraged development of non-invasive methods for assessment of fibrosis.These include measurements of serum biomarkers of fibrosis;and assessment of liver stiffness via transient elastography,acoustic radiation force impulse imaging,real-time elastography,or magnetic resonance elastography.Although significant advances have been made,most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection.In the present review,we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice.

Update on hepatitis B and C virus diagnosis

Viral hepatitis B and C virus(HBV and HCV) are responsible for the most of chronic liver disease worldwide and are transmitted by parenteral route, sexual and vertical transmission. One important measure to reduce the burden of these infections is the diagnosis of acute and chronic cases of HBV and HCV. In order to provide an effective diagnosis and monitoring of antiviral treatment, it is important to choose sensitive, rapid, inexpensive, and robust analytical methods. Primary diagnosis of HBV and HCV infection is made by using serological tests for detecting antigens and antibodies against these viruses. In order to confirm primary diagnosis, to quantify viral load, to determine genotypes and resistance mutants for antiviral treatment, qualitative and quantitative molecular tests are used. In this manuscript, we review the current serological and molecular methods for the diagnosis of hepatitis B and C.

Assessment of correlation between serum titers of hepatitis c virus and severity of liver disease

AIM:The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral therapy compared to those with higher levels.Moreover,a direct association has been observed between serum titers of HCV and transmission rates of the virus.The aim of the present study was to determine if there was any correlation between HCV viral load and the severity of liver disease. METHODS:Fifty patients with HCV infection were included in the study.These comprised of 34 subjects with a history of alcohol use and 16 non-alcoholics.Quantitative serum HCV RNA assay was carried out using the branched DNA (bDNA) technique.Linear regression analysis was performed between serum viral titers and liver tests.In addition,for the purpose of comparison,the subjects were divided into two groups:those with low viral liters (≤50 genome mEq/mL) and high titers (>50 mEq/mL). RESULTS:All subjects were men,with a mean±SD age of 47±7.8 years.The mean HCV RNA level in the blood was 76.3×10~5±109.1 genome equivalents/mL.There was no correlation between HCV RNA levels and age of the patients (r=0.181),and the history or amount (g/d) of alcohol consumption (r=0.07).Furthermore,no correlation was observed between serum HCV RNA levels and the severity of liver disease as judged by the values of serum albumin (r=0.175),bilirubin (r=0.217),ALT (r=0.06) and AST (r=0.004) levels.Similarly,no significant difference was observed between patients with low viral titers and high liters with respect to any of the parameters. CONCLUSION:Our results indicate that the severity of liver disease is independent of serum levels of hepatitis C virus.These findings are important since they have a direct impact on the current debate regarding the role of direct cytopathic effect of hepatitis C virus versus immune-mediated injury in the pathogenesis of HCV-related liver damage.