Serum Hepatitis B Virus Deoxyribonucleic Acid Research Articles

Diagnostic Performance of Precore Protein 22 Kilodalton Levels of HBV DNA in Chronic Hepatitis B Patients

Hepatitis B Virus (HBV) infection causes inflammation of the liver, which has a high prevalence in both Indonesia and the world. Serum HBV deoxyribonucleic acid (DNA) is important in determining the initiation therapy for Chronic Hepatitis B (CHB) patients. However, it has several limitations. Precore protein 22 kilodalton (p22cr) is synthesized from the HBV gene in hepatocytes, representing covalently closed circle (ccc) DNA. This study aimed to analyze the diagnostic performance of p22cr levels on HBV DNA in CHB patients. An observational analytic study with a cross-sectional approach was conducted on 83 CHB patients who were examined at the Clinical Pathology Laboratory of Dr. Moewardi General Academic Hospital in December 2020. Blood plasma samples were taken for HBV DNA and p22cr examination by using Polymerase Chain Reaction (PCR) and Enzyme-Linked Immunosorbent Assay (ELISA), respectively. The cut-off level of p22cr was determined by the Receiver Operating Curve (ROC) with the widest area Under the Curve (AUC). Sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), Positive Likelihood Ratio (PLR), Negative Likelihood Ratio (NLR), and accuracy were calculated for the diagnostic performance of p22cr. The cut-off point of p22cr on HBV DNA > 20,000 IU/mL was 7.440 ng/mL with AUC 0.693 (p=0.003). The diagnostic performance of p22cr levels on HBV DNA obtained 44.44% sensitivity, 82.98% specificity, 66.67% PPV, 66.10% NPV, 2.61 PLR, 0.67 NLR, and 66.27% accuracy. P22cr level has a good specificity so it can be an alternative examination of HBV DNA in making decisions on therapy in patients with chronic hepatitis B. Further research needs to be done using HBcrAg and excluding elderly patients.

Rapid quantification assay of hepatitis B virus DNA in human serum and plasma by Fully Automated Genetic Analyzer μTASWako g1.

Real-time monitoring of serum hepatitis B virus (HBV) levels is essential for the management of patients with chronic HBV infection in clinical practice, including monitoring the resistance of anti-HBV nucleotide analog or the detection of HBV reactivation. In this context, serum HBV deoxyribonucleic acid (DNA) quantification should be rapidly measured. A rapid HBV DNA quantification assay was established on the Fully Automated Genetic Analyzer, μTASWako g1. The assay performs automated sample preparation and DNA extraction, followed by the amplification and detection of quantitative polymerase chain reaction (PCR) combined with capillary electrophoresis (qPCR-CE) on integrated microfluidic chip. This study aimed to evaluate the analytical and clinical performance of HBV DNA assay on the μTASWako g1 platform in human serum and EDTA-plasma. The HBV DNA assay has a linear quantitative range from 20 to 108 IU/mL of HBV DNA with standard deviation (SD) of ≤0.14 log10 IU/mL. The limits of detection of the assay were 4.18 for the serum and 4.35 for EDTA-plasma. The HBV assay demonstrated the equivalent performance in both human serum and EDTA-plasma matrices. The HBV genotypes A to H were detected with an accuracy of ±0.34 log10 IU/mL. In quantification range, the HBV DNA assay was correlated with Roche cobas AmpliPrep/cobas TaqMan Ver2.0 (CAP/CTM v2) (r = 0.964). The mean difference (μTASWako g1-CAP/CTM v2) of the reported HBV DNA was -0.01 log10 IU/mL. Overall, the sensitivity, accuracy, and precision of the μTASWako g1 HBV assay were comparable to the existing commercial HBV DNA assay, and the assay can be completed within 110 min. This evaluation suggests that the HBV DNA assay on the μTASWako g1 is potentially applied for alternative method of the HBV viral load test, in particular with the advantage of the HBV DNA result availability within 2 h, improving the HBV infection management.

Use of serum Golgi protein 73 for screening chronic hepatitis B virus infection patients needing antiviral therapy in the community.

Use of serum Golgi protein 73 for screening chronic hepatitis B virus infection patients needing antiviral therapy in the community.

346.1: Hepatitis B virus Suppression Predicts Better Recurrencefree Survivals in Liver Transplant Patients With Hepatocellular Carcinoma

Introduction: High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is known to be a strong risk factor of hepatocellular carcinoma (HCC) development. The aim of study was to investigate the predictive role of HBV DNA levels in recurrence of HCC after liver transplantation (LT). Methods: From June 2006 to May 2020, 729 recipients underwent LT for HBV-related HCC in Seoul National University Hospital. The risk factors for HCC recurrence after LT were analyzed including serum HBV DNA load. Results: Recurrence-free survival at 1, 3, 5, and 10 years were 99.6%, 98%, 95.1%, and 87.8%, respectively. Detectable HBV DNA level (higher than 10 IU/mL) before transplant was significant predictors of HCC recurrence in univariate analysis (P=0.027). Further subgroup analysis was performed to demonstrate the significance of HBV DNA level according to the risk of HCC recurrence. Based on the score of the predicted survival after liver transplantation for HCC (SALT), patients were divided in three groups. In high risk group of recurrence with SALT score more than 2.44, detectable HBV DNA level were significantly associated with recurrence free survival (57.9 % vs. 78.7 %, P<0.0001). Conclusion: There is a close relationship between HBV DNA level and HCC recurrence after transplant. High HBV DNA levels before transplant are associated with HCC recurrence after transplant, especially in high recurrence risk group.

Clinical and Virological Features of Acute Hepatic Exacerbations in Patients With Chronic Hepatitis B Virus Infection.

Background and aim: In this study, we aimed to perform a comprehensive analysis of patients with acute hepatic flares observed during the course of chronic hepatitis B infection in order to provide early diagnosis, management, and best characterization of this unique group of hepatitis B patients.Patients and methods: The study was designed in a retrospective and prospective manner. Chronic hepatitis B patients with acute hepatic flares, admitted to the Department of Gastroenterology and Hepatology were enrolled in the study. Demographic, clinical, biochemical, and virological findings were recorded via pre-prepared forms.Results: The study was conducted on 125 patients. The mean age was 34.08 ± 12.68 and the male to female ratio was determined as 2.28. Over 117 patients (93.6%) had at least one symptom. The most common symptoms and signs were fatigue (81.6%), anorexia (64%), jaundice (60%), and nausea (52%). Anti-HBc immunoglobulin M (IgM) antibody was detected in 24 patients (19.2%) and serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) was positive in 107 (85.6%) patients. The most common cause of exacerbations was spontaneous hepatic flares (80.8%).Conclusion: According to the results of this single-center study, acute hepatic exacerbations are more common in young men. The disease usually presents with non-specific symptoms and jaundice is the most common finding. As a sign of intensive inflammation and hepatocellular injury, serum ferritin levels seem to be high. Serum HBV DNA and anti-HBc IgM positivity with elevated alpha-fetoprotein (AFP) levels are presenting features of acute hepatic exacerbations.

Effect of indigenous interferon - alpha on Hepatitis B virus deoxyribonucleic acid level in hepatitis b e antigen-positive chronic Hepatitis B patients

&lt;p class="ABS"&gt;&lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Background and Objective:&lt;/span&gt; HBeAg-positive chronic hepatitis B patients have high serum HBV DNA level showing high viral replication. Goal of treatment of hepatitis B is to prevent cirrhosis, hepatic failure and hepatocellular carcinoma by serum alanine transaminase (ALT) normalization, decrease in serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and loss in hepatitis B e antigen (HBeAg). Interferons (IFNs) have antiviral, anti-proliferative, and immunomodulatory effects. IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; is effective in suppressing HBV replication and in inducing remission of liver disease. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Materials and Methods:&lt;/span&gt; In this prospective, single treatment arm study, HBeAg-positive chronic hepatitis patients without decompensated liver disease were enrolled to receive indigenous recombinant IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; 2b in the dose of 5 MU daily for 6 days a week subcutaneously for 16 weeks. Quantitative HBV-DNA, HBeAg, and hepatitis B surface antigen (HBsAg) were assessed at baseline and at the end of treatment. ALT level assessment was done at baseline and during therapy at week 1, week 2, week 8, week 12, and week 16. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Res&lt;/span&gt;&lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;ults:&lt;/span&gt; Out of 37 patients enrolled in the study, 8 patients (21.62%) did not complete study due to lost to follow-up (3 patients), discontinuation due to adverse event (3 patients), and consent withdrawal (2 patients). Among 29 patients who completed the study, 10 patients (34.48%) had clearance of HBeAg and 1 patient (3.44%) had lost HBsAg after 16 weeks of therapy. Mean ALT level started decreasing after 4 weeks of therapy but did not come to normal range till 16 weeks of therapy. At least 2 log decreases in HBV DNA was observed in 9 (31.03%) patients and at least 1 log decrease in 18 (62.06%) patients. Overall decline in HBV DNA level was observed in 62% patients after 16 weeks of therapy. &lt;span class="ABS_Bold-Italic" lang="en-GB"&gt;Conclusion:&lt;/span&gt; IFN-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; treatment does result in HBeAg and HBsAg loss and decreases HBV-DNA levels in chronic hepatitis B patients. Most of adverse events were mild to moderate in intensity. So, interferon-&lt;span class="Symbol_Bold"&gt;α&lt;/span&gt; therapy was well tolerated, safe, and efficacious to treat HBeAg-positive chronic hepatitis B patients without decompensated liver disease.&lt;/p&gt;

Detection of HBV DNA and antigens in HBsAg-positive patients with primary hepatocellular carcinoma

Hepatitis B virus (HBV) markers include HBV deoxyribonucleic acid (DNA) and HBV antigens. The former involves HBV covalently closed circular DNA (cccDNA) as well as total HBV DNA, whereas the latter involves HBsAg, HBcAg, and HBx. Samples of tumor and adjacent non-tumor liver tissue were collected from 28 HBV-associated HCC patients. Intrahepatic total HBV DNA and cccDNA were measured using the real-time PCR Taqman assay. HBV antigens in hepatocytes were detected using immunohistochemical staining. Intrahepatic levels of total HBV DNA or cccDNA in HCC patients with different intrahepatic HBV antigen expression patterns were compared, and the correlation between serum HBV DNA and intrahepatic HBV DNA was analyzed. No significant differences in intrahepatic cccDNA levels were observed between tumor and non-tumor liver tissue (median -3.00 vs. -2.30 log copies/cell, P=0.298). However, the tumor tissue had significantly higher levels of total HBV DNA (median -0.60 vs. -1.24 log copies/cell, P=0.045) but significantly lower proportion of intrahepatic HBV DNA in the form of cccDNA (median 0.25% vs. 4%, P=0.023) than the corresponding values in the non-tumor tissue. Also, HBV antigen levels were lower in the tumor tissue than in the non-tumor tissue. Analysis of the correlation between serum HBV DNA and intrahepatic HBV DNA indicated that the viral status in the tumor tissue was more complicated in HBV-HCC patients-the detected serum HBV DNA failed to accurately reflect intrahepatic viral load. HBV DNA may play an important role in hepatocarcinogenesis, and cccDNA was not the predominant form of HBV DNA in the tumor tissue.

Role of quantitative hepatitis B surface antigen in predicting inactive carriers and HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients.

To evaluate quantitative hepatitis B surface antigen (qHBsAg) as a diagnostic marker for inactive carriers (ICs) and hepatitis B surface antigen (HBsAg) seroclearance in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. We retrospectively studied 300 HBeAg-negative CHB patients with initial serum hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) levels <2000 IU/mL. Serum HBV DNA and alanine aminotransferase (ALT) levels were monitored every 6 months for 24 months. ICs were identified as having persistent HBV DNA levels <2000 IU/mL and normal ALT levels, whereas active carriers (ACs) were identified as having HBV DNA levels ≥2000 IU/mL, with or without elevated ALT levels. The serum qHBsAg level was defined at baseline and evaluated as a diagnostic predictor using a receiver-operating characteristic curve. The study group comprised 134 men and 166 women with a median age of 41.5 years. At baseline, 200 ICs displayed lower levels of qHBsAg (1492 IU/mL) compared with 100 ACs (2936 IU/mL) (P = 0.005). The qHBsAg level was independently associated with the IC state and HBsAg seroclearance. Baseline qHBsAg levels <1000 IU/mL and HBV DNA levels <2000 IU/mL, when detected simultaneously, allowed for identification of ICs with 41% sensitivity and 72% specificity. Fifteen patients (5%) displayed HBsAg seroclearance after 24 months. A qHBsAg cutoff value of <50 IU/mL provided 100% sensitivity and 92% specificity in predicting HBsAg seroclearance. The qHBsAg level at a single timepoint among HBeAg-negative CHB patients with low HBV DNA levels at baseline was not a predictive marker for ICs; however, it accurately predicted spontaneous HBsAg seroclearance at 24 months.

Is Serum Angiotensin-Converting Enzyme Level Useful For Determining Necroinflammatory Activity In Chronic Hepatitis B Infection?

The purpose of this study was to investigate the relationship between the findings from liver biopsy and the serum angiotensin-converting enzyme (ACE) level to determine whether ACE might serve as a potential noninvasive sign of necroinflammatory activity in patients with Chronic Hepatitis B (CHB) infection. A total of 54 CHB patients referred for liver biopsy were enrolled in the study. Serum ACE levels were determined photometrically with a kinetic test. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatitis B virus-deoxyribonucleic acid (HBV-DNA), histological activity index (HAI), and white blood cell counts were higher in patients with severe fibrosis, while albumin levels were low. The serum ACE levels showed a statistically significant correlation with HBV-DNA, HAI score, and ALT-AST levels. In this study, a statistically significant relation between serum ACE levels and HAI scores was observed. This represents the first analysis to compare necroinflammation of the liver and serum ACE levels. There may be some explanations that the suppression of hepatocyte growth factor (HGF) by Angiotensin II and increased inflammatory damage might be a reason for the correlation between HAI and ACE. Serum ACE levels, HBV-DNA levels, and serum transaminase levels might be used together as noninvasive markers for the prediction of necroinflammation in CHB patients.

Hepatitis B Virus Reactivation in Patients Receiving Interferon-Free Direct-Acting Antiviral Agents for Chronic Hepatitis C Virus Infection.

BackgroundLittle is known about the risk of hepatitis B virus (HBV) reactivation in patients receiving interferon (IFN)-free direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV).MethodsPatients who were seropositive for HBV core antibody and who received IFN-free DAAs for HCV were enrolled. Hepatitis B virus reactivation was defined as reappearance of serum HBV deoxyribonucleic acid (DNA) ≥100 IU/mL in patients with baseline undetectable viral load, or ≥2 log10 IU/mL increase of HBV DNA in patients with baseline detectable viral load. Hepatitis B virus-related alanine aminotransferase (ALT) flare was defined as ALT ≥5 times upper limit of normal or ≥2 times of the baseline level. Hepatitis B virus-related hepatic decompensation was defined as presence of jaundice, coagulopathy, hepatic encephalopathy, or ascites.ResultsCompared with no HBV reactivation in 81 HBV surface antigen (HBsAg)-negative patients, 2 of 12 HBsAg-positive patients had HBV reactivation (0% [confidence interval {95% CI}, 0%–4.5%] vs 16.7% [95% CI, 4.7%–44.8%], P = .015). No patients had ALT flare or hepatic decompensation. Baseline HBsAg level at a cutoff value of 500 IU/mL was associated with HBV reactivation in HBsAg-positive patients. There was no HBsAg seroreversion in HBsAg-negative patients.ConclusionsHepatitis B virus reactivation is limited to HBsAg-positive patients receiving IFN-free DAAs for HCV. Higher baseline HBsAg levels are associated with HBV reactivation. The risk of ALT flares or hepatic decompensation is low in these patients.

Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh.

ABSTRACTBackground and aim Assessment of therapeutic response is important for monitoring the prognosis and to take decision for cessation of nucleoside analogues therapy in chronic hepatitis B patients. In addition to serum alanine aminotransferase (ALT), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load and HBeAg status, identification of molecular markers associated with host immune response would be essential to assess therapeutic response. In this regard the current study was performed with the aim to detect expression of platelet endothelial cell adhesion molecule (PECAM)-I gene in peripheral blood monocytes (PBMCs) of treated chronic hepatitis B patients and also to correlate expression of this gene with serum HBV DNA load and serum ALT levels.Materials and methods The study analyzed 60 chronic hepatitis B (CHB) patients, including 30 untreated and 30 nucleoside analogs treated and 10 healthy controls. PECAM-1 gene expression/ transcripts were detected by conventional RT-PCR.Results The expression PECAM-1 mRNA in the PBMCs of CHB patients was significantly higher in untreated (3.17 ± 0.75) than the treated patients (1.64 ± 0.29) (p < 0.01). Expression of PECAM-1 was positively correlated with serum ALT levels of both untreated (r = 0.580) and treated (r = 0.566) CHB patients. Moreover, in both untreated and treated groups, these gene expressions were positively correlated to serum HBV DNA load with the correlation coefficient r = 0.545 and r = 0.591 respectively.Conclusion PECAM-1 may be used as a biomarker for assessment of inflammatory activity as well as therapeutic response in CHB patients.How to cite this article: Sultana N, Tabassum S, Munshi SU, Hossain M, Imam A. Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(2):87-91.

Correlation Between Quantitative HBsAg and HBV-DNA in Chronic Hepatitis B Infection

Background : Methods used to diagnose and monitor chronic hepatitis B (CHB) by quantitation of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) levels is expensive. Cheaper laboratory test as an additional marker is needed, thus we studied serum quantitative HBsAg to be used as surrogate marker in CHB patients. This study was aimed to investigate correlation between serum quantitative HBsAg and HBV-DNA in CHB patients. Method : In this cross-sectional study, we enrolled 62 CHB patients between January 2010 and December 2012 who had quantitative HBsAg and HBV-DNA assays in a private laboratory at Denpasar. HBV-DNA was measured by real-time polymerase chain reaction and quantitative serum HBsAg was measured by chemiluminescent microparticle immunoassay (CMIA). Stastistical analysis was performed by Mann-Whitney and Spearman’s correlation. Results : Of 62 patients, most subjects were males (82.26%). Mean HBsAg titer of CHB in HBeAg positive and negative patients were 281,000 and 4,900 IU/mL, respectively; while mean HBV-DNA in HBeAg positive and negative patients were 59,000,000 and 7,530,000 IU/mL, respectively. We found that quantitative HBsAg and HBV-DNA in HBeAg positive and HBeAg negative patients were statistically signi cant (p = 0.0001, p = 0.0001, respectively). Signi cant correlation was found between serum quantitative HBsAg and HBV-DNA (r = 0.737; p= 0.000). Quantitative HBsAg was signi cantly correlated with HBV-DNA in HBeAg-positive subgroup (r = 0.717; p = 0.0001); and signi cant correlation was also found in HBeAg-negative subgroup (r = 0.443; p = 0.006) although the correlation was weak. Conclusion : Quantitative HBsAg has signi cant correlation with HBV-DNA in CHB patients. Keywords : quantitative HBsAg Assay, HBV-DNA, HBeAg, chronic hepatitis B infection

Liver Function Tests in Viremic and Nonviremic Chronic Hepatitis B Virus–Infected Pregnant Women

The major risk factor of perinatal transmission of Hepatitis B virus (HBV) infection is the level of maternal HBV-deoxyribonucleic acid (DNA) during the third trimester of pregnancy. The primary aim of this study was to evaluate the hematological and biochemical status in Hepatitis B e-antigen (HBeAg)-negative chronic HBV-infected pregnant women and to correlate the findings with the presence or absence of viremia. Ninety-five consecutive chronic HBV-infected pregnant women were evaluated between the 28th and 32nd week of gestation. Viral load was determined by using the COBAS TaqMan HBV test. Sixty-nine women were evaluated and 14 of them exhibited HBV-DNA levels higher than 2000 IU·ml. In this study, viremic women exhibited significantly higher alanine aminotransferase (ALT), creatinine, and uric acid values as well as significantly lower white blood cell count compared with nonviremic women. There was also a significant statistical difference concerning ALT/sodium ratio between viremic and nonviremic women (0.20 ± 0.22 vs. 0.10 ± 0.09, respectively, p= .024). The optimal cutoff points discriminating those women with a high probability to have detectable serum HBV-DNA were 0.092 for ALT/sodium ratio (sensitivity = 73.0%, specificity = 61.5%, area under the receiver operating characteristic curve [AUC] = 71.05%) and 12.8 IU/L for ALT (sensitivity = 73.0%, specificity = 63.0%, AUC = 72.2%). Chronic HBV-infected pregnant women with ALT/sodium ratio ≥ 0.11 had the higher probability of having serum HBV-DNA levels higher than 2000 IU/ml (sensitivity = 76.92%, specificity = 58%, AUC = 62.38%). Presence of HBV-DNA in maternal blood during the third trimester of pregnancy is significantly associated with maternal serum ALT levels in HBeAg-negative chronic HBV-infected pregnant women. Women with an ALT/sodium ratio greater than 0.092 have the higher probability of HBV-DNA presence in maternal blood whereas an ALT/sodium ratio greater than 0.11 could discriminate those women with HBV-DNA levels higher than 2000 IU/ml.

Seroconversion of hepatitis B envelope antigen (HBeAg) by entecavir in a child with chronic hepatitis B

Hepatitis B virus (HBV) infection is a worldwide health problem. Consensus guidelines for the treatment of chronic HBV in children have not been established, and indications for antiviral therapy in adults with chronic HBV infection may not be applicable to children. The medications that are Food and Drug Administration approved for the treatment of children with HBV include interferon (IFN)-alpha and lamivudine. Nondetectable serum HBV deoxyribonucleic acid, Hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion following 1 year duration of entecavir treatment. A review of the literature of entecavir treatment of chronic hepatitis B in children is also provided.

Four‐year follow‐up of two chronic hepatitis B recipients of hepatitis B surface antigen‐positive cadaveric liver grafts from asymptomatic carriers

Only seven cases of liver transplantation (OLT) with positive serum hepatitis B surface antigen (HBsAg) grafts have been reported in the world till now. Here we report the 4-year follow-up results and clinical pathologic characteristics of two recipients of chronic hepatitis B transplanted with HBsAg-positive cadaveric liver grafts from asymptomatic carriers. Lamivudine combined with hepatitis B immune globulin were used for the control of hepatitis B virus (HBV) infection in both of the recipients post-OLT. The liver functions, virus status and pathologic characteristics of two recipients were followed up according to the rounte protocol of Liver Transplantation Center of West China Hospital. The serum HBV deoxyribonucleic acid (DNA) turned negative within 30 days post-OLT, but HBsAg remained positive for both of the recipients during follow up. HBV breakthrough occurred in one recipient at the month 12 post-OLT, with detectable serum HBV-DNA (740 copies/mL) and tyrosine-methionine-aspartate-aspartate motif mutation (rtM204I and rtM204V). After the replacement of lamivudine by adefovir dipivoxil 10 mg daily for 2 months, serum HBV-DNA of this recipient became undetectable again and maintained undetectable during follow up. Both of the recipients have survived for more than 4 years post-OLT, with stable liver function and mild hepatitis. Due to extreme scarcity of liver graft, we think that HBsAg-positive liver graft without active HBV-DNA replication and severe pathological manifestation from asymptomatic carriers may deserve consideration when no other graft is available in a bearable waiting time.

Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation

High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is a strong risk factor of hepatocellular carcinoma (HCC) development, independent of hepatitis B e antigen, serum alanine aminotransferase level, and liver cirrhosis. We evaluated whether serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC treated with radiofrequency ablation (RFA). The study population was 69 consecutive patients with HBV-related HCC treated locally completely with RFA between January 2000 and September 2007. The risk factors for HCC recurrence were analyzed based on laboratory data, including serum HBV DNA load, together with tumor size and number using univariate and multivariate proportional hazard regression analyses. HCC recurrence was observed in 42 of 69 patients during the median observation period of 1.5years. Cumulative recurrence rates at 1, 3, and 5years were 26.5, 57.8, and 74.3%, respectively. In univariate analysis, albumin (<3.5g/dl), platelet count (<150×10(3)/mm(3)), prothrombin activity (PT) (<70%), Child-Pugh class B, serum HBV DNA load (>4.0log10copies/ml), and tumor number (>3) were associated with the recurrence at p≤0.15. Multivariate Cox regression analysis with stepwise variable selection showed that the tumor number (risk ratio, 4.63; 95% CI, 1.50-14.25, P=0.0076), low PT (3.39, 1.52-5.78, P=0.0029), and high HBV DNA load (2.67, 1.16-6.14, P=0.021) were independent risk factors for HCC recurrence. Serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC after RFA.

Prevalence and significance of occult hepatitis B in a liver transplant population with chronic hepatitis C

Occult hepatitis B virus (HBV) infection is defined as the detection of HBV deoxyribonucleic acid (DNA) in the serum or liver tissue of individuals who test negative for hepatitis B surface antigen (HBsAg). We undertook a prospective study to evaluate the significance and course of occult HBV in patients with hepatitis C virus (HCV) cirrhosis undergoing orthotopic liver transplantation (OLT). A sensitive real-time polymerase chain reaction assay was utilized to test for serum HBV DNA at enrollment and for hepatic HBV DNA within the explant liver. Patients were followed with serum HBsAg and HBV DNA post-OLT. A total of 56 patients with HCV cirrhosis were enrolled between October 2002 and July 2004; of these, 44 underwent OLT. The overall prevalence of occult HBV based on positive serum HBV DNA was 16 of 56 (28%), and based on positive hepatic HBV DNA ("occult HBV liver") was 22 of 44 (50%). The presence of serum hepatitis B core antibody (anti-HBc) and a past history of injection drug use correlated with occult HBV.Explant-proven hepatocellular carcinoma (HCC) was found in 13 of 22 (59%) patients with occult HBV liver compared to 8 of 22 (36%) patients without occult HBV liver (P ¼ 0.36, odds ratio 2.5; confidence interval 0.76–8.54 [corrected]. Post-OLT, no cases of HBV reactivation were noted, and there was no significant association between occult HBV and recurrent HCV. In conclusion, occult HBV is far more prevalent in patients with end-stage HCV than would be expected from its prevalence in the general population. Occult HBV infection is strongly associated with the presence of anti-HBc, history of injection drug use, and explant-proven HCC.

Presence of intrahepatic (total and ccc) HBV DNA is not predictive of HBV recurrence after liver transplantation

Previous studies reported that hepatitis B virus (HBV) deoxyribonucleic acid (DNA) can be detected in livers of patients who received transplants for hepatitis B despite the absence of serological markers of HBV recurrence. Quantification of HBV DNA was not performed and presence of covalently closed circular (ccc) DNA was not analyzed in most studies. We aimed to quantify total and ccc HBV DNA in explant liver and post-orthotopic liver transplantation (OLT) biopsies and to correlate the values with HBV recurrence post-OLT. Frozen liver tissue from 34 patients (9 with explant liver only, 9 with explant liver and post-OLT liver biopsies, and 16 with post-OLT biopsies only) in the National Institutes of Health HBV-OLT study was examined using real-time polymerase chain reaction (PCR). Among the 18 patients with explant liver, 7 were hepatitis B e antigen (HBeAg)-positive, 8 had detectable serum HBV DNA, and 10 received antiviral therapy prior to OLT. Total and ccc HBV DNA was detected in explant livers of 17 and 16 patients, respectively. Of the 10 patients who received antiviral therapy pre-OLT, serum HBV DNA was undetectable in 8 at transplantation but 7 had detectable total and ccc HBV DNA in their explant liver. Of the 25 patients with post-OLT biopsies, total HBV DNA was detected in 83% and ccc DNA in 17% of 47 biopsies, although only 2 patients had HBV recurrence. In conclusion, total and ccc HBV DNA could be detected in explant livers of most patients despite antiviral therapy pre-OLT. Total but not ccc HBV DNA could be detected in post-OLT liver biopsies of most patients despite undetectable serum HBV DNA and hepatitis B surface antigen (HBsAg). Our findings suggest that occult HBV reinfection occurs in most HBV patients after OLT and continued administration of appropriate prophylactic therapy is important in preventing overt HBV recurrence.

Antiviral therapy for pre- and post-liver transplantation patients with hepatitis B

The goals of antiviral therapy for hepatitis B patients on the liver transplantation (LT) waiting list are 2-fold: 1) to achieve clinical stabilization, thereby delaying/preventing the need for LT; and 2) to attain low hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels prior to transplant, thereby reducing the risk of recurrent HBV postLT. Lamivudine was the first nucleoside analog to be approved for use in HBV treatment, and has been shown to be safe for long-term use. The combination of hepatitis B immune globulin and lamivudine has been the most common prophylactic therapy to prevent recurrent HBV infection post-LT since the late 1990s, and lamivudine monotherapy was the mainstay of treatment of recurrent HBV in the late 1990s and early 2000. The initial enthusiasm of lamivudine was tempered by the realization that lamivudine does not eradicate HBV, thus most preand post-LT patients require lifelong treatment to maintain viral suppression. Unfortunately, long-term use of lamivudine is associated with increasing rates of drug resistance, from 15 to 30% of patients after 1 yr of treatment to 70% of patients after 4 to 5 yr. Virologic breakthrough due to antiviral resistance has been reported to cause hepatitis flares and in rare instances hepatic decompensation. In the transplant setting, where patients already have decompensated cirrhosis or are receiving immunosuppressive therapy, the risk of severe hepatitis flare and worsening liver failure is higher, and for patients whomanage to receive a timely transplant, the risk of HBV recurrence post-LT is increased. With the approval of 2 nucleoside/tide analogs: adefovir and entecavir, and others in development, the management of preand post-LT hepatitis B patients is continuously evolving. There is an urgent need for safe and effective rescue therapy for patients with lamivudine-resistant HBV, and alternative first-line antiviral therapy with a lower rate of resistance for treatmentnaive patients. These therapies must have rapid and potent antiviral activity, long-term safety, and very low rates of resistance. In this issue of the Journal, Schiff et al. report the final results of a large open-label, multicenter study with 226 waitlisted and 241 post-LT patients with lamivudine-resistant HBV treated with adefovir dipivoxil 10 mg once daily for a median duration of 39 and 99 weeks, respectively. Almost all patients continued lamivudine at some time, but the exact duration of overlapping treatment is not certain. Adefovir resulted in a mean decrease in serum HBV DNA level of 3.5 to 4.0 log10 copies/mL after 48 weeks of treatment, and an increasing proportion of patients had undetectable serum HBV DNA over time. The high proportion of patients with substantial viral suppression may be related to the concomitant use of lamivudine in all patients. In 1 small study of patients with compensated liver disease and lamivudine-resistant HBV, serum HBV DNA decreased at a similar rate in patients randomized to adefovir monotherapy or a combination of lamivudine and adefovir. However, several recent studies have showed that combination of lamivudine and adefovir results in more marked viral suppression and lower risk of adefovir resistance than adefovir monotherapy. Despite the use of combination therapy, 35% of waitlisted patients and 22% of post-LT patients in the current study still had detectable serum

Transplantation of hepatitis B surface antigen-positive livers into hepatitis B virus-positive recipients and the role of hepatitis delta coinfection

The scarcity of liver donors requires consideration of grafts from sources not previously used. Allografts from hepatitis B surface antigen (HBsAg)-carriers without a significant liver disease have been proposed for liver transplant recipients with hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC). Combination prophylaxis schemes against HBV post-liver transplantation (LT) recurrence are currently available; the efficacy of those schemes in HBV-related cirrhosis and HCC must be assessed. This report describes the allocation of HBsAg-positive grafts in three HBsAg-positive recipients, with HBV-related cirrhosis and evolving HCC lesions, two of them with hepatitis Delta virus (HDV) coinfection. Patients were administered anti-hepatitis B immunoglobulins (HBIGs) and lamivudine in order to prevent HBV recurrence. In spite of anti-HBV prophylaxis, HBV infection did persist after LT in all patients (no serum clearance of HBsAg). HBV replication assessed by serum HBV deoxyribonucleic acid (DNA) presence was detected in the first month after LT in the 3 recipients. A prompt HDV reinfection with a clinical and histological pattern of hepatitis was observed in the 2 HBV / HDV coinfected recipients. In 1 of them, an evolving chronic hepatitis required a second LT. The non-HDV-infected patient showed an uneventful follow-up, but the lack of the neutralizing effect of HBIGs and the high risk of escape mutants forced the addition of adefovir-dipivoxil to lamivudine, in order to prevent viral variants and hepatitis recurrence. In conclusion, allografts from HBsAg-positive donors in HBsAg-positive recipients are associated with the persistence of the HBsAg after LT due to the failure of HBIG prophylaxis, even if lamivudine does inhibit virion production. This condition favors HDV replication and HDV hepatitis recurrence in coinfected patients. The allocation of HBsAg-positive grafts in HBsAg-positive recipients could be justified only in recipients without HDV coinfection and a combined prophylaxis with lamivudine and adefovir-dipivoxil is currently the best way to manage escape mutants in these recipients.