Hepatitis B Virus DNA Values Research Articles

Advances in the Pharmacological Management of Chronic Hepatitis B.

Hepatitis B, a vaccine-preventable liver infection, remains a global public health problem. Dedicated groups of experts and funding are focusing on achieving a functional cure to eradicate this disease by 2030. With more than 40 molecules available or under investigation as new treatments for hepatitis B virus (HBV) infection, none of them is curative so far. Available treatments are effective in suppressing HBV replication and in decreasing the risk of developing cirrhosis, liver failure, hepatocellular carcinoma, and death, but do not eliminate the virus, and the risk of hepatocellular carcinoma remains. Nucleoside/nucleotide analogs are recommended as first-line therapy for patients with chronic hepatitis B infection to inhibit viral replication and lower the HBV DNA values, but long-term therapy is usually needed to maintain suppression. Cessation of the therapy in accordance with clinical guidelines can result in virological and clinical relapse. PubMed, Web of Science, clinicaltrials.gov , and gray literature sources were searched for articles discussing HBV management and new therapies. With current nucleoside/nucleotide analog therapies, fewer than 5% of patients lose hepatitis B surface antigen after 12 months, which underscores the need for new drugs that can achieve a functional cure. New therapies are being developed, including small interfering RNAs. Bepirovirsen, a modified antisense oligonucleotide, shows promising results and a good safety profile, but requires further exploration in larger number of patients to determine whether a functional cure is possible. Eradication of HBV infection with currently available therapies is not yet possible. Experts are developing innovative treatments, such as bepirovirsen, to achieve functional cure for this disease and to reduce morbidity and mortality associated with hepatic cirrhosis and hepatocellular carcinoma.

Prevalence and clinical characteristics of hepatitis B surface antigen-negative/hepatitis B core antibody-positive patients with detectable serum hepatitis B virus DNA

BackgroundTo determine the prevalence of detectable serum hepatitis B virus (HBV) DNA in patients who are hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive. The correlation between HBV DNA viral load and serological markers, as well as liver and coagulation function indicators were investigated. Furthermore, the effects of immunosuppressive therapy on DNA replication were assessed.MethodsA total of 2,013 HBsAg-negative/HBcAb-positive patients admitted to our hospital between January and December 2019 were enrolled in this study. Patient clinical characteristics including serological markers, HBV DNA viral load, liver function and coagulation function indicators, and immune function status were analyzed.ResultsIn the Hunan province in China, the prevalence of detectable HBV DNA was 5.4% in HBsAg-negative/HBcAb-positive patients. However, the prevalence of detectable HBV DNA in HBsAg-negative/HBcAb-positive patients may vary because of different HBV serological markers. In patients with detectable serum HBV DNA, the log10 HBV DNA value was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST) levels, and negatively correlated with antithrombin III (AT III) concentrations. Moreover, in patients receiving immunosuppressive therapy, ALT and AST levels were higher than those of patients who did not receive immunosuppressive therapy. The ALT and AST levels in hepatitis B e antibody (HBeAb)-positive patients were significantly higher than that observed in HBeAb-negative patients.ConclusionsFor HBsAg-negative/HBcAb-positive patients, clinicians should pay attention to the patient's immune function status. In situations where HBV DNA cannot be detected, changes in serum ALT, AST, and AT III concentrations can be used to speculate on viral replication status to reduce the risk of HBV infection and transmission.

Hepatitis B seroconversion revisited: new insights into the natural history of acute hepatitis B virus (HBV) infection from quantitative and highly sensitive assays and novel biomarkers

BackgroundHepatitis B virus (HBV) serum markers during typical acute self-limited infection are usually depicted as a composite of traditional HBV markers. The current study updates and expands our knowledge of acute hepatitis B with quantitative molecular and serological data on longitudinal samples from five plasmapheresis donors with acute HBV.Methods137 longitudinal samples from five plasmapheresis donors with acute HBV were tested, four with self-limited infection and one who developed persistent infection. Testing included quantitative hepatitis B surface antigen (HBsAg), antibodies to HBV antigens, quantitative HBV e antigen (HBeAg), HBV DNA, quantitative HBV core-related antigen (HBcrAg), the highly sensitive ARCHITECT HBsAg NEXT (HBsAgNx) assay, and a quantitative research assay for HBV pregenomic RNA (pg RNA).ResultsPeak levels of HBV DNA and HBsAg differed by several orders of magnitude among the panels (2.2 × 105–2.7 × 109 IU/ml for HBV DNA and 7.9–1.1 × 105 IU/ml for HBsAg). HBsAg levels peaked an average of 2.8 days after the HBV DNA peak. The overall duration of observed HBsAg positivity was increased by the more sensitive HBsAgNx assay compared to the quantitative assay in four panels. Intermittently detectable low-level HBV DNA was observed after HBsAg loss in three panels. Peak HBeAg levels occurred 2–20 days after the DNA peak and ranged from 1.1 to 4.5 × 103 IU/ml. In four panels with resolution of infection, anti-HBs levels indicating immunity (≥ 10 mIU/ml) were detected 19–317 days after the HBV DNA peak. Maximum HBcrAg concentrations ranged from 1 × 105 to > 6.4 × 106 U/ml and correlated with HBeAg values (R2 = 0.9495) and with HBV DNA values (R2 = 0.8828). Peak pgRNA values ranged from 1.6 × 103 to 1.4 × 108 U/ml and correlated with HBV DNA (R2 = 0.9013).ConclusionTraditional and new/novel HBV biomarkers were used to generate molecular and serological profiles for seroconversion panels spanning the early to late phases of acute HBV. Seroconversion profiles were heterogeneous and may be instructive in appreciating the spectrum of acute profiles relative to the typical composite representation.

Risk of HBV reactivation in patients with immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma

BackgroundImmunotherapy with immune checkpoint inhibitor (ICI) is a promising treatment for unresectable hepatocellular carcinoma (HCC). However, whether ICIs would have the risk of hepatitis B virus (HBV) reactivation and the...

Hepatitis B seroprevalence in hematological oncology patients

Objectives: Hepatitis B virus (HBV) infection is still a serious public health problem today. Many factors such as frequent blood transfusion, hemodialysis, sexual contact, sterilization in surgical procedures, etc. are involved in the transmission of hepatitis B virus. In our study, HBV seroprevalence was evaluated retrospectively in order to provide vaccination of anti-HBs negative patients and to determine HBV prophylaxis in patients with hematological malignancy. Methods: A total of 499 patients were included in the study. HBsAg, anti-HBs, anti-HBc IgG, anti-HDV, HBV DNA values were measured by ELISA (enzyme-linked immunosorbent assay, Liason, Diasorin, Italy) with Real-Time PCR (Cobas-Tagman, Roche Switzerland) and recorded. The obtained datas were evaluated by SPSS for Windows 15.00 statistical program. A value of p <0.05 was accepted as a statistical significance value. Results: HBsAg positivity was found to be 3.4% (n = 17) in all patients. Appropriate treatment regimens were started to patients with HBsAg (+). There were 166 (33.3%) patients with anti-HBs (+). One hundred nineteen (23.8%) patients had anti-HBc IgG (+), 40 (33.6%) of them were started a prophylactic treatment regimen. Anti-HBs positivity were reported after vaccination in 48 (16.8%) patients. Occult hepatitis have not been detected in patients with anti-HBc IgG positivity. Conclusions: As a result of this study, anti-HBs negative patients with hematological malignancies were vaccinated. Patients and physicians should be informed about vaccination and hepatitis serology controls of hematological malignancy and other immunosuppressed patients. Sensitivity in this context should be increased in terms of prophylactic treatments.

Perioperative Antiviral Treatment Facilitate the Postoperative Recovery for Patients with HBV Related to Hepatocellular Carcinoma

Objective: This study aimed to determine whether perioperative antiviral treatment is facilitate for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and Child-Pugh grade A cirrhosis in perioperative recovery of liver function and HBV activation. Methods: The study included 115 patients with HBV-related HCC and Child-Pugh grade A cirrhosis who underwent resection. Patients were prospectively assigned to a preoperative antiviral treatment group (n = 51) or postoperative antiviral treatment group (n = 52); twelve patients who had not received antiviral treatment before and after surgery were designated a non-treatment group (n = 12). HBV reactivation during a month after the operation was defined as a HBV DNA value tenfold over preoperative values. Postoperative liver dysfunction was defined as prothrombin activity 50 mmol/L on postoperative day 5. Results: Postoperatively, liver dysfunction was present in 1 of 51 (1.96%) patients who received preoperative antiviral therapy, 1 of 52 (1.92%) who received postoperative therapy, and 3 of 12 (25%) who received no antiviral therapy. HBV reactivation postoperatively occurred at similar rates. Conclusions: Preoperative and postoperative antiviral treatment of patients with Child-Pugh grade A cirrhosis and high levels of HBV DNA undergoing hepatic resection for HCC are both facilitate in preventing perioperative liver dysfunction and reactivation of HBV. Thus, in this population with high levels of HBV DNA, perioperative antiviral treatment is important.

Infección crónica por virus de la hepatitis B antígeno e negativo. Manejo en función de puntos de corte de glutámico-pirúvica transaminasa y ácido desoxirribonucleico del virus de la hepatitis B

ObjectivesTo identify glutamic pyruvic transaminase (GPT) and hepatitis B virus DNA (HBV-DNA) cut-off values at diagnosis in patients with hepatitis B virus e antigen-negative chronic infection (HBeAg(–)), which may be predictors of clinical course, prognosis and/or the need for antiviral therapy. MethodsA retrospective and observational cohort study of patients diagnosed with HBeAg(–) chronic infection (2005-2012). A normal GPT cut-off value at diagnosis that predicts abnormal GPT values in the clinical course of the infection, a baseline HBV-DNA cut-off value that predicts an increase in HBV-DNA above 2,000IU/ml, and GPT and HBV-DNA as predictors of the need for treatment were investigated using ROC curves. Results126 patients were enrolled (follow-up: 42.1±21.5months), 93 of which had normal GPT levels at diagnosis. In the ROC curve analysis, 900IU/ml was found to be the HBV-DNA cut-off value that best predicted this value's increase above 2,000IU/ml (sensitivity: 90%; specificity: 88%; PPV: 79%; NPV: 100%; diagnostic precision: 89%), while 25mU/ml was the normal GPT cut-off value at diagnosis that best predicted subsequently elevated GPT levels (sensitivity: 95.4%; specificity: 81.6%; PPV: 67%; NPV: 96%; diagnostic precision: 80.6%). Patients with GPT 26-40mU/ml at diagnosis presented with more complications or required more treatment than subjects with GPT≤25mU/ml (P<.05). The combined GPT and HBV-DNA values that elicited the highest treatment need were 38mU/ml of GPT and 6,000IU/ml of HBV-DNA (sensitivity: 75%; specificity: 93.4%; PPV: 60%; NPV: 96.6%). ConclusionHBeAg(–) patients with GPT<25mU/ml and HBV-DNA<900IU/ml at diagnosis have positive outcomes and may not require such stringent follow-up in the first years after diagnosis.

Predictors for advanced liver fibrosis in chronic hepatitis B virus infection with persistently normal or mildly elevated alanine aminotransferase.

The aim of the present study was to evaluate the predictors for advanced liver fibrosis in patients with chronic hepatitis B virus (HBV) infection with persistently normal alanine aminotransferase (PNALT), or persistently or intermittently mildly elevated ALT (PIEALT). A total of 305 patients were included in the present study. Liver biopsies were evaluated using the METAVIR scoring system. Liver stiffness (LS) was measured using Fibroscan. Multivariate logistic regression and the area under the receiver operating characteristic curve (AUROC) were used to examine the diagnostic value of the predictors for advanced liver fibrosis. HBV DNA viral load in the PNALT group was significantly lower compared with the PIEALT group (4.57±1.68 vs. 5.71±1.69 log10 IU/ml; P<0.001). Body mass index and LS were also significantly lower in the PNALT group compared with the PIEALT group (P<0.001). The proportion of patients with liver fibrosis was significantly higher in the PIEALT group compared with the PNATL group (P=0.001). High ALT levels were an independent predictor for liver fibrosis, with an odds ratio (OR) of 2.69 (P=0.002). Male sex (OR=0.34, P=0.007), high ALT levels (OR=2.37, P=0.029) and a high HBV DNA load (OR=1.39, P=0.005) were independent predictors for advanced liver fibrosis. The AUROC was 0.65 (P=0.003) when using ALT levels to predict advanced liver fibrosis. ALT levels at ≥0.88 upper limit of normal (ULN; 35 IU/l) were considered as positive for advanced liver fibrosis, the sensitivity and specificity were 87.8 and 47.4%, respectively. The AUROC was 0.64 (P=0.004) when using the HBV DNA value to predict advanced liver fibrosis. When an HBV DNA value of ≥4.99 log10 IU/ml was considered as positive for advanced liver fibrosis, the sensitivity and specificity were 78.0 and 49.5%, respectively. The AUROC was 0.72 (P<0.001) when combining ALT, HBV DNA load and sex into a formulation to predict advanced liver fibrosis. When the formulation score at >-2.22 was considered as positive for advanced liver fibrosis, the sensitivity and specificity were 61.5 and 70.7%, respectively. Therefore, normal ALT levels do not always indicate the absence of hepatic fibrosis. A combination of ALT levels, sex and serum HBV DNA load may more effectively identify patients with CHB at high risk of developing fibrosis. These patients may benefit from liver biopsy.

A persistently low HBV DNA level is a predictor of spontaneous HBsAg clearance in patients with chronic hepatitis B

The incidence and predictors of spontaneous hepatitis B surface-antigen (HBsAg) seroclearance in patients with chronic hepatitis B virus (HBV) were evaluated. A total of 1427 patients with chronic HBV infection, who were followed between 1994 and 2013, were investigated in this retrospective study. All data were extracted from patient files. Spontaneous HBsAg seroclearance occurred in 84 patients during 8798 person-years of follow-up. The patients were categorized into 3 groups at follow-up based on HBV DNA features as continuously <100 copies/mL (Group A), 0-10,000 copies/mL (Group B), and 0 to >10,000 copies/mL (Group C). Alanine aminotransferase features in the 2 groups were categorized as continuously normal (<40 U/L) and 0 to >40 U/L. Spontaneous HBsAg seroclearance was seen primarily in patients with Group A HBV DNA features, and continuously low HBV DNA values were the main predictor of HBsAg seroclearance (P < 0.001). These results suggest that a continuously low viral load is the most important factor affecting spontaneous HBsAg seroclearance.

Can hepatitis B virus DNA in semen be predicted by serum levels of hepatitis B virus DNA, HBeAg, and HBsAg in chronically infected men from infertile couples?

Hepatitis B virus (HBV) in semen is important for father-to-child transmission of HBV and has adverse effects on sperm quality. However, risk factors associated with HBV in semen remain unclear. Serum HBV DNA and hepatitis B e antigen (HBeAg) levels may pose a risk on HBV in semen. This study aims to examine whether serum HBV DNA, HBeAg, and hepatitis B surface antigen (HBsAg) level were associated with HBV DNA in semen. 151 male patients chronically infected with HBV from infertile couples were included. Serum HBsAg and HBeAg were determined using an electrochemiluminescence immune assay (ECLIA). Serum and seminal plasma HBV DNA were detected by the QIAGEN Real-Time HBV DNA assay. Of 151 patients, 143 (94.7%) were serum HBV DNA-positive and 65 (43.0%) were seminal plasma HBV DNA-positive. Serum HBV DNA and HBeAg level of seminal plasma HBV DNA-positive patients were significantly higher (p < 0.001) as compared with those of seminal plasma HBV DNA-negative patients, HBsAg level of seminal plasma HBV DNA-positive patients was significantly lower (p < 0.001) compared with that of seminal plasma HBV DNA-negative patients. The best serum HBV DNA, HBeAg, and HBsAg value for discriminating between seminal plasma HBV DNA-positive and HBV DNA-negative patients were ≥6.9 log10 IU/mL (sensitivity 100.0%, specificity 90.7%), >14.8 S/CO (sensitivity 96.9%, specificity 81.5%), and <1791.5 S/CO (sensitivity 81.5%, specificity 81.2%), respectively. The combination of serum HBV DNA and HBeAg had high diagnostic sensitivity (100.0%) and specificity (95.4%) for the presence of HBV DNA in semen. As such, these serum markers especially the combination of HBV DNA and HBeAg are useful predictors of the presence of HBV DNA in semen in HBV chronically infected men from infertile couples.

Caracterización de los pacientes con infección crónica por virus de la hepatitis B sin indicación de tratamiento

Chronic infection by the hepatitis B virus (HBV) is a dynamic process that results from the interaction between HBV replication and the host's immune response. In accordance with the consensus document of the European Association for the Study of the Liver, treatment is not indicated for the immune tolerant and inactive carrier phases. However, there are situations in the 2 phases (which we could call gray areas of chronic HBV infection) in which the correct categorization of patients is not easy and in which the start of treatment can be proposed. In the immune tolerant phase, treatment could be indicated for health professionals whose responsibilities require their participation in invasive procedures. Treatment could also be indicated for pregnant women who are HBeAg-positive, ALT normal and have high HBV DNA values and for whom oral antiviral treatment is indicated during the last trimester of pregnancy to reduce the risk of vertical HBV transmission from mother to child. For patients in the inactive carrier phase who are HBeAg-negative with persistent normal ALT levels and HBV DNA ≥2000IU/mL, the intensity of the hepatic lesion will determine the indication for treatment. If these patients already have established cirrhosis then treatment is indicated if the HBV DNA is detectable, regardless of the ALT level.

Association between CISH polymorphisms and spontaneous clearance of hepatitis B virus in hepatitis B extracellular antigen–positive patients during immune active phase

Background Some hepatitis B extracellular antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in their immune active phase can clear the virus spontaneously and enter into an inactive hepatitis B virus (HBV) carrier state, indicating a benign prognosis. In this study, the association between cytokine-inducible SRC homology 2 domain protein (CISH) gene polymorphisms at -292 (rs414171) and the spontaneous clearance of HBV in HBeAg-positive CHB patients in immune the active phase was investigated. Methods Seventy HBeAg-positive CHB patients in the immune active phase were followed up for 76 weeks without antiviral therapy. The alanine transaminase, aspartate transaminase, HBV DNA, HBeAg and hepatitis B extracellular antibody levels were tested regularly. At week 76, 27 patients were classified into group A (HBV DNA level below 2 104 IU/ml and the value of HBeAg declined below 10% of the baseline at week 76), and 43 patients were classified into group B (HBV DNA level higher than 2×104 IU/ml or the value of HBeAg did not decline substantially at week 76). CISH (rs414171) polymorphisms were also tested using the iPLEX system. Results The HBV DNA levels at week 12 were significantly greater in group B compared with group A (group A: (6.87±1.40) log10IU/ml; group B: (7.61±1.38) log10IU/ml, P=0.034) and the HBeAg values were greater in group B at week 28 compared with group A (P=0.001). The differences in HBV DNA and HBeAg values increased between the groups over time. Sixteen patients in group A and 11 in group B were genotype AA. Those with genotype AT or TT included 11 in group A and 31 in group B (AA vs. AT and TT, odds ratio 4.10 (95% confidence interval: 1.462-11.491), P=0.006). Conclusion CISH gene polymorphisms at -292 (rs414171) are associated with HBV clearance in HBeAg-positive CHB patients in the immune active phase, and AA is a favorable genotype for this effect.

Inactıve hepatitis B surface antigen carriers and intrafamilial tramsmission: results of a 10-year study.

Background/AimsThe aims of the present study were to determine the outcomes of inactive hepatitis B virus (HBV) surface antigen (HBsAg) carriers over a 10-year study period and to elucidate the HBV serological profile of their family members.MethodsWe retrospectively analyzed the medical files of inactive HBsAg carriers followed up at the Department of Infectious Diseases of Kocatepe University Medical Faculty Hospital between March 2001 and January 2011.ResultsIn total, 438 inactive HBsAg carriers were enrolled in this trial. The follow-up period was 33.7±22.5 months (mean±SD). Anti-hepatitis-B surface antibody seroconversion occurred in 0.7% of cases, while chronic hepatitis B was found in 0.5%. The anti-hepatitis-D virus (HDV) status was evaluated in 400 patients and anti-hepatitis C virus (HCV) in 430. It was found that 1% and 0.2% were positive for anti-HDV and anti-HCV, respectively. HBV serology was investigated in at least 1 family member of 334/438 (76.3%) patients. The HBsAg positivity rate was 34.6% in 625 family members of 334 patients. A comparison of the HBsAg positivity rates in terms of HBV DNA levels in index cases revealed that HBsAg seropositivity rates were higher in family members of HBV DNA-negative patients than in family members of HBV DNA-positive cases (P=0.0001).ConclusionsThe HBsAg positivity rate was higher in family members of inactive HBsAg carriers than in the general population; these family members therefore have a higher risk of HBV transmission. Furthermore, despite negative HBV DNA levels, transmission risk was not reduced in these patients, and horizontal transmission seems to be independent of the HBV DNA value.

Evaluation of 48-week response of treatment-naive chronic hepatitis B patients to 0.5 mg/day entecavir

The hepatitis B virus (HBV) is an important healthcare problem. Chronic hepatitis B infection may present with a wide range of manifestations from inactive carrier state to cirrhosis and hepatocellular cancer. Therefore, treatment is very important in chronic hepatitis B. In this study, the treatment results of 199 chronic hepatitis B patients taking entecavir 0.5 mg/day for 48 weeks were evaluated. This study retrospectively evaluated data of 199 treatment-naive chronic hepatitis B patients who were treated with entecavir. Of the 199 treatment-naive chronic hepatitis B patients, 141 (70.9%) were males and 58 (29.1%) were females, and mean age of the whole group was 37.5 ± 12.1 years. HBeAg was positive in 91 (45.7%) and antiHBe was positive in 108 (54.3%) patients. Mean HBV DNA value was 666,449,365.5 ± 2,759,013,996.9 IU/mL, mean ALT value was 112.1 ± 95.7 U/L, and mean AST value was 95.3 _ 71.2 U/L. At week 24 of the treatment, HBV DNA levels were below 50 IU/mL in 56% of the HBeAg-positive and 76% of the HBeAg-negative patients. At week 48 of the treatment, HBV DNA levels were below 50 IU/mL in 79% of the HBeAg-positive and 87% of the HBeAg- negative patients. At week 24, ALT had normalized in 72% of the HBeAg-positive and 79% of the HBeAg-negative patients. At week 48, ALT had normalized in 89% of the HBeAg-positive and 88% of the HBeAg-negative patients. AntiHBe seroconversion was seen in 2 of 91 patients (2.2%), but the loss of HBsAg was never observed. The 48-week entecavir treatment at a dose of 0.5 mg/day was shown to be effective both for HBeAg-positive and negative patients.

Hepatitis B inactive carriers: Clinical course and outcomes

Hepatitis B virus (HBV) inactive carriers are HBV e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) levels and HBV DNA of ≤ 10000 copies/mL. We aimed to determine the clinical impact of ALT and HBV DNA elevations during the course of HBV infection. From January 1989 to January 2012, 146 inactive carriers were prospectively followed every 6-12 months with ALT and HBV DNA measurements and with hepatocellular carcinoma (HCC) surveillance. During the follow-up of 8 ± 6.3 years, 56 of the 146 patients maintained ALT ≤ 40 U/L and HBV DNA ≤ 10000 copies/mL. However, 39 had rises of ALT > 40-80 U/L and 4 had ALT > 80 U/L; all except one reverted to baseline values. Also, during follow up, 69 (47.3%) inactive carriers had increases in HBV DNA of > 10000-999999 copies/mL; 38 of these patients' HBV DNA returned to baseline levels, while the remaining 31 patients maintained elevated HBV DNA values but had corresponding ALT of ≤ 40 U/L. There were four liver-related outcomes: 129 (88.4%) remained "inactive carriers", 13 (8.9%) had loss of hepatitis B surface antigen (HBsAg), one (0.7%) had a spontaneous reactivation to HBeAg-negative chronic hepatitis, and two (1.4%) developed HCC. Although the prognosis of inactive carrier is favorable, transient ALT and HBV DNA elevations may be observed but have minimal clinical significance. Moreover, continuous HCC surveillance remains necessary since the risk of development still exists.

Spectrum of hepatitis B infection in Southern India: A cross-sectional analysis

Background and Aim: Hepatitis B virus (HBV)-related liver disease is not an uncommon problem in India. There are very few reports on pattern of chronic HBV infection from South India. The aim of the present study was to determine the spectrum of chronic HBV infection among patients attending the liver clinic in a tertiary referral center. Materials and Methods: Hepatitis B surface antigen (HBsAg) positive patients registered in the liver clinic between July 2010 and March 2011 were included in the study. All patients had baseline liver function tests, serological markers for HBV infection (hepatitis B e antigen [HBeAg], anti-HBe, anti-HBc total, and anti-HBc IgG, and HBV DNA quantification), serum alpha-fetoprotein, and ultrasound. Based on the viral profile and transaminase levels and ultrasound findings, patients were categorized as immunotolerant, inactive carriers, immune clearance and reactivation phase, and chronic liver disease with or without hepatocellular carcinoma. Results: Majority of the patients were asymptomatic and incidentally detected during blood donation camps, master health checkup (MHC), or during initial screening. Almost 40% of patients were either in immune inactive phase or had features of chronic liver disease. In the immunotolerant phase (24 patients), women were a decade younger than their male counterparts. Alanine aminotransferase (ALT) levels were similar in both HBeAg-positive and negative patients. The mean HBV DNA values were significantly high in HBeAg-positive men and women. In the immune inactive phase (58 patients), there were only three patients who were HBeAg positive. The ALT levels were in the normal range. HBV DNA values were low or not detectable. Among patients with elevated ALT and HBV DNA levels (immune clearance/immune reactive) (fifty patients), the mean ALT levels were higher in HBeAg-negative patients. HBV DNA quantity was significantly high in patients who were HBeAg positive. Conclusion: A significant proportion of HBsAg-positive patients is in inactive or in immunotolerant phase and do not require treatment. Patients with elevated ALT and HBV DNA levels need further evaluation to categorize them into immune clearance or immune reactive phase.

Efficacy of peripartum antiviral treatment for hepatic failure due to hepatitis B virus

Objective To investigate the efficacy of oral nucleosides in preventing hepatic failure during pregnancy (HFP) caused by hepatitis B virus (HBV) infection. Methods Besides receiving standard treatment, 70 women with HFP caused by HBV infection joined a study group (n = 40) or a control group (n = 30) according to their preference. In the study group, 14 women were given lamivudine in the third trimester and an antiviral treatment was continued postpartum. The 26 remaining patients were treated postpartum only, with lamivudine (n = 16) or entecavir (n = 10). Results In the study group, the values for serum HBV DNA and hepatitis B envelope antigen were markedly lower at 1 and 2 months than they were at baseline ( P < 0.001 and P < 0.001, respectively). Moreover, the HBV DNA values at 1 and 2 months were significantly lower in the study than in the control group ( P < 0.05). Overall mortality and incidence of intrauterine infection were also significantly lower in the study group ( P < 0.05). No newborns had any apparent abnormalities in either group. Conclusion Treatment with nucleosides suppressed the replication of HBV DNA and led to biochemical improvement. It also reduced maternal mortality and safely decreased mother-to-child HBV transmission.

PVI-15 Developing a real-time PCR assay to determine the hepatitis B virus DNA in serum

HBV DNA quantitation is used extensively for the monitoring of treatment of hepatitis B virus (HBV) infection. The aim of this study was to develop a highly sensitive and reproducible real-time PCR (RTD-PCR) assay for the quantitation of HBV DNA using the LightCycler system. The performance of this assay was assessed by analyzing serial dilutions of HBV genomic DNA of known concentration and the lower limit of detection was found to be 1 DNA copy/reaction. By using serial dilutions of plasmid standard, RTD-PCR was determined to quantify HBV DNA in a 10–log10 dynamic range. RTD-PCR was found to be more sensitive than the commercially available tests such as the Quantiplex™ HBV DNA and the AMPLICOR HBV MONITOR™ assays. The median coefficient of variation of interexperimental variability was 3.2%. The HBV DNA values obtained with RTD-PCR were highly correlated with assays available commercially. These findings suggest that our RTD-PCR assay combines high sensitivity and reproducibility for HBV DNA quantitation in an incomparable high dynamic range of quantitation.

Comparison of Clinical Application of the Abbott HBV PCR Kit and the Versant HBV DNA 3.0 Test to Measure Serum Hepatitis B Virus DNA in Taiwanese Patients

With an estimated 350-400 million people worldwide chronically infected with hepatitis B virus (HBV), and the subsequent serious complications caused by liver damage including cirrhosis, liver failure, and hepatocellular carcinoma, HBV infection remains a global health issue, particularly in Taiwan, an HBV-hyperendemic area. Sensitive and accurate quantification of HBV DNA is necessary to monitor patients with chronic hepatitis B who are receiving antiviral therapy to determine treatment response and adapt therapy. We evaluated and compared the clinical performance of two HBV DNA assays based on different technologies: the RealArt HBV PCR Kit (Abbott HBV DNA PCR kit, real-time polymerase chain reaction assay, detection limit: 27 IU/mL) and the VERSANT bDNA 3.0 assay (Bayer, branched DNA signal amplification assay, detection limit: 357 IU/mL). Serum levels of HBV DNA in 173 chronic HBV carriers were determined using both the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 test. Of the 173 samples analyzed for baseline viral load detection, HBV DNA was quantifiable in 147 patients (82.1%) by the RealArt HBV PCR Kit, which was significantly higher than the 92 (53.2%) samples quantified by the VERSANT bDNA 3.0 assay. A total of 86 (49.7%) samples were quantifiable by both assays, whereas 25 (14.5%) were below the detection limit of both assays. The HBV DNA quantification values measured by the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 assay were positively correlated (Spearman's rank correlation coefficient r = 0.932, p < 0.001). On average, the results derived from the RealArt HBV PCR Kit were 0.67 log lower than those of the VERSANT bDNA 3.0 assay. HBV DNA concentrations were significantly higher in 63 HBV e antigen (HBeAg)-seropositive patients than in 110 HBeAg-seronegative patients (5.42 +/- 2.34 logs vs. 3.21 +/- 2.27 logs, p < 0.001). The RealArt HBV PCR Kit is more sensitive and has a wider dynamic range than the VERSANT bDNA 3.0 assay in the clinical setting of chronic hepatitis B patients. The sensitivity and wide dynamic range of the PCR assay allow optimal monitoring and timely adaptation of antiviral therapy. Nevertheless, the HBV DNA values measured by the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 assay were significantly correlated.

Indications for therapy in hepatitis B #

Increased treatment options that are more efficacious and safe and new knowledge on the natural history of chronic hepatitis B virus (HBV) infection have expanded the indications for therapy in hepatitis B. The question is no longer "Who should be treated?" but "When should treatment be initiated?" Treatment is clearly indicated in patients with life-threatening liver disease (acute liver failure, decompensated cirrhosis, or severe hepatitis flare) and in those with compensated cirrhosis and high levels of serum HBV DNA. For patients with precirrhotic liver disease, treatment indications should be based on clinical, biochemical, or histological evidence of liver disease, such as elevated alanine aminotransferase (ALT) levels, abnormal histology, and high levels of serum HBV DNA. The cutoff for ALT and HBV DNA values are constantly being revised and should be set at a lower level for older patients who may have been infected for a longer period of time. High serum HBV DNA levels persisting for a few decades are associated with increased risk of clinical outcomes, but there is insufficient data to support the initiation of treatment based on high serum HBV DNA alone, particularly in young patients, those with persistently normal ALT levels, and those with a single high HBV DNA level. The decision to initiate treatment at the time of assessment or to defer treatment should take into consideration other factors such as desire to start a family, occupational requirement, family history of hepatocellular carcinoma, access to care and insurance coverage, and commitment to long-term treatment and medication compliance. All patients who are not initiated on treatment should continue to be monitored so treatment can be started if and when the indication arises.