Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.

BACKGROUND: Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. METHODS: We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. RESULTS: All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. CONCLUSIONS: Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.     

Adult Living Donor Liver Transplantation Using Hepatitis B Core Antibody-Positive Grafts in Korea, a Hepatitis B-endemic Region

Background/Aims

The exclusion of hepatitis B core antibody (HBcAb)-positive donors from liver transplants (LTs) due to the risk of transmitting hepatitis B virus (HBV) does not appear to be practical in Korea, where hepatitis B is endemic. This study assessed the risk of de novo HBV infection in hepatitis B surface antigen (HBsAg)-negative LT recipients receiving a liver from HBcAb-positive donors.

Methods

Of 341 adult living donor LTs conducted at our institution between March 2001 and September 2008, 176 donors (51.6%) were HBcAb-positive, and 26 HBcAb-positive grafts were transplanted to HBsAg-negative recipients. The median follow-up time after LT was 41.9 months.

Results

Without anti-HBV prophylaxis, 2 out of 26 (7.7%) HBsAg-negative recipients who received grafts from HBcAb-positive donors developed de novo HBV infection 20 and 85 months after LT. These patients had been negative for all HBV serologic markers before transplantation. In both cases, there were no abnormalities in liver function tests upon diagnosis of de novo HBV infection.

Conclusions

De novo HBV infection from HBcAb-positive donors after LT does not appear to be of great concern in terms of the number of cases in Korea because high risk patients who are HBV-negative comprise only a small proportion of the recipients. However, HBV-naïve LT recipients still carry the risk of developing de novo HBV infection as in non-HBV endemic areas.     

Favorable outcome of de novo hepatitis B infection after liver transplantation with lamivudine and adefovir therapy

Abstract: De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) always progresses to chronic hepatitis because of the patients' immunocompromised status, and only a few then acquire hepatitis B surface antigen (HBsAg) seroconversion even with efficient antiviral therapy. Here we reported the case of a liver transplant recipient with de novo HBV infection who had a favorable outcome after lamivudine (LAM) and adefovir dipivoxil (ADV) antiviral therapy. The patient received OLT because of end‐stage primary biliary cirrhosis and was found to have de novo HBV infection 3 months later. She was treated with LAM, and her serum HBV DNA turned undetectable 2 weeks later. However, serum HBV DNA turned detectable again after 9 months of LAM therapy and a YMDD mutation was detected. The addition of ADV was efficient to treat LAM‐resistant HBV. After 3 months of combination therapy, LAM was stopped and ADV monotherapy was continued. HBsAg seroconversion was achieved after an additional 12 months. The prevention and treatment of de novo HBV infection after OLT is discussed.     

Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region

Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis.     

Efficacy of combined antiviral therapy with lamivudine and tenofovir in a liver transplanted girl with de novo hepatitis B virus infection

The management of de novo hepatitis B (HBV) infection in children after liver transplantation is not well defined. Because this infection may induce severe liver disease in the graft liver, an efficient antiviral therapy is desirable. Here, we describe the favorable viral outcome observed in a liver transplanted girl with de novo HBV infection following combination therapy with lamivudine and tenofovir.     

Markers for hepatitis A, B and C in methadone maintained patients: an unexpectedly high co-infection with silent hepatitis B

AIMS: To determine the prevalence of hepatitis A, B and C viruses in patients attending a methadone maintenance clinic in New York City. DESIGN: Cross-sectional. SETTING: The Adult Services Clinic of Weill Cornell Medical College, an urban hospital-affiliated methadone program. PARTICIPANTS: Former heroin addicted adults (n = 103) on methadone maintenance therapy. MEASUREMENTS: Markers for hepatitis A virus [HAV immunoglobulin M (IgM) and imunoglobulin G (IgG)], hepatitis B [hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb)] and hepatitis C virus (HCVAb). Serum alanine aminotransferase (ALT) and quantitative HCV RNA were also obtained. Qualitative detection of HBV DNA and HCV genotype were obtained in a subset of subjects. FINDINGS: More than 40% of subjects had markers for all three viruses. HCVAb was the most prevalent (83.5%), followed by HBcAb (65.0%), HAV IgG (46.1%) and HBsAb (41.1%). Hepatitis C RNA was detected in 70.6% of HCVAb positive subjects. While no subject had HBsAg, HBV DNA was detected in 26.4% of subjects who underwent this measure; all (n = 20) had HBcAb as their only HBV marker. The presence of HBV DNA did not influence ALT. Subjects with HCV RNA had higher ALTs than those without HCV RNA. CONCLUSIONS: Most methadone-maintained subjects had at least one marker for viral hepatitis, with 41.8% having markers for HAV, HBV and HCV. A quarter of subjects had silent HBV infection, defined as the presence of HBV DNA in the absence of HBsAg. These subjects should be considered infectious and pose a public health risk.     

唐山地区献血人群隐匿性乙型肝炎病毒感染分析

目的了解唐山地区无偿献血人群隐匿性乙型肝炎感染情况。方法用ELISA法检测无偿献血者的乙型肝炎血清标志物,对于HBsAg阴性样本,进行HBV核酸检测（NAT）,NAT阳性样本,用罗氏试剂确证HBV DNA载量。结果共检测116 741例血样,证实隐匿性乙型肝炎感染者35例,占总献血人数的0.29‰。其中97.1%隐匿性乙型肝炎感染者样本的HBV DNA滴度低于102IU/ml。在HBV DNA阳性人群中,抗-HBc阳性率较高,占81.5%,抗-HBs阳性或乙型肝炎病毒血清标志物全阴性也可检出HBV DNA分别占55.6%和22.9%。结论唐山地区献血人群中血清HBsAg阴性者存在一定比例的隐匿性HBV感染,其HBV病毒载量均较低,核酸检测能够提高HBV感染的检出率。     

Hepatitis B core antibody‐positive donors in cardiac transplantation: a single‐center experience

Hepatitis B virus (HBV) core antibody (HBcAb)‐positive donors are increasingly utilized in solid organ transplantation. We report a single center's experience in cardiac transplantation with 18 HBcAb‐positive donors. Available follow‐up on recipients of cardiac allografts from HBcAb‐positive donors, including 2 donors with low‐level serum HBV DNA at the time of transplantation, demonstrated no documented donor‐derived HBV transmission.     

Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg‐negative and anti‐HBc antibodies‐positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer

Summary. We studied clinical outcome and clinico‐virological factors associated with hepatitis B virus reactivation (HBV‐R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)‐negative/anti‐hepatitis B core antibodies (anti‐HBcAb)‐positive patients. Between 11/2003 and 12/2005, HBV‐R occurred in 7/84 HBsAg‐negative/anti‐HBcAb‐positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV‐R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV‐R involved non‐A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV‐R is a concern in HBsAg‐negative/anti‐HBcAb‐positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti‐HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV‐R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies.     

Living donor liver transplantation for hepatitis B cirrhosis

BACKGROUND AND AIM: Living donor liver transplantation (LDLT) has particular advantages for Turkey where hepatitis B virus (HBV) infection is the most common cause of cirrhosis, both because LDLT circumvents the difficulties encountered in the emerging world in providing deceased donor organs, and because it allows preemptive antiviral therapy. The aim of this study was to review one institution's experience with LDLT in patients with chronic HBV infection. METHODS: A total of 109 patients with chronic HBV infection underwent LDLT between September 1999 and June 2005, of whom 40 were coinfected with hepatitis D virus and 23 had hepatocellular carcinoma. Antiviral prophylaxis was attempted in all, beginning prior to transplantation with lamivudine or adefovir, and continuing after transplantation with low dose intramuscular hyperimmune B immunoglobulin (HBIg) plus lamivudine or adefovir. RESULTS: In a median follow up of 20 months (range 1-66 months), there was no donor mortality. One-year recipient survival was 90%, and in total 16 recipients died. None of the deaths was related to HBV. Recurrence of HBV infection was detected by reappearance of serum hepatitis B surface antigen in six patients (5.5%) at 5, 8, 12, 17, 34 and 46 months after transplantation, respectively. There was no influence of donor hepatitis B core antibody status on the likelihood of recurrence of HBV in the allograft. CONCLUSION: The results indicate that LDLT with antiviral treatment and low dose HBIg provides excellent results for donors and recipients.     

Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy

With the increasing use of potent immunosuppressive therapy, reactivation of hepatitis B virus (HBV) in endemic regions is becoming a clinical problem requiring special attention. A recent annual nationwide survey clarified that HBV reactivation related to immunosuppressive therapy has been increasing in patients with malignant lymphoma, other hematological malignancies, oncological or rheumatological disease. In the survey, rituximab plus steroid‐containing chemotherapy was identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg) negative patients with malignant lymphoma. In this setting, HBV reactivation resulted in fatal fulminant hepatitis regardless of the treatment of nucleoside analog. The Intractable Hepatobiliary Disease Study Group and the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis jointly developed guidelines for preventing HBV reactivation. The essential features of the guideline are as follows. All patients should be screened for HBsAg by a sensitive method before the start of immunosuppressive therapy. Second, hepatitis B core antigen (HBcAb) and hepatitis B surface antibody (HBsAb) testing should be performed in HBsAg negative patients, especially those receiving intensive immunosuppressive therapy. Prophylaxis with nucleoside analogs is essential for preventing HBV reactivation in HBsAg positive patients. In contrast, HBsAg negative with HBcAb and/or HBsAb positive patients should be monitored monthly for an increase in serum HBV DNA during and 12 months after completion of chemotherapy. Nucleoside analogs should be administrated immediately when HBV DNA becomes positive during this period. This strategy facilitates commencement of nucleoside analogs at an early stage of HBV reactivation and results in prevention of severe hepatitis.     

乙型肝炎患者血清中HBcAg与HBV复制指标的关系

目的探讨乙型肝炎患者血清ＨＢｃＡｇ与ＨＢＶ复制指标的关系及临床意义．方法对３１１例乙型肝炎患者进行了ＨＢｃＡｇ检测，并同时进行酶联法乙肝五项、地高辛法ＨＢＶＤＮＡ检测，其中２３７例进行乙肝ＤＮＡ聚合酶（ＤＮＡＰ）检测．结果ＨＢｃＡｇ阳性组的ＨＢＶＤＮＡ检出率（７７６％），明显高于ＨＢｃＡｇ阴性组（３５５％，Ｐ＜００１）；在ＨＢｃＡｇ阴性组中，抗ＨＢｅ阳性者仍能检出２９９％（４４／１４７）ＨＢＶＤＮＡ者阳性；ＨＢｅＡｇ，ＨＢｃＡｇ均阳性者其ＨＢＶＤＮＡ和ＤＮＡＰ的检出率高达８５９％；其他依次为ＨＢｅＡｇ、抗ＨＢｅ和ＨＢｃＡｇ均阳性者７１４％，抗ＨＢｅ，ＨＢｃＡｇ阳性者６９２％，ＨＢｅＡｇ阳性，ＨＢｃＡｇ阴性者６８４％，抗ＨＢｅ阳性，ＨＢｃＡｇ阴性者２７６％．结论血清ＨＢＶＤＮＡ，ＤＮＡＰ，ＨＢｅＡｇ和ＨＢｃＡｇ均是反映乙肝病毒复制的敏感指标，抗ＨＢｅ的出现并不表示病毒复制停止，应参考其他病毒复制指标情况．各种指标的不同组合可以清楚地反映出患者体内病毒复制状况．     

Hepatitis B virus reactivation during belatacept treatment after kidney transplantation

We report a case of HBV reactivation following belatacept treatment in a patient who underwent kidney transplantation in 2015 for HIV‐associated nephropathy (HIVAN). Human immunodeficiency virus viral load was undetectable prior to transplantation, and CD4+ lymphocyte count was greater than 300/mL. Baseline HBV serology at transplantation was HBsAg negative, anti‐HBcAb positive, anti‐HBsAb 312 UI/L, and HBeAg negative/anti‐HBeAb positive. Liver function tests were normal, and viral DNA was undetectable. Two years later, the patient presented with severe acute hepatitis after a progressive disappearance of anti‐HbsAb, quickly followed by HBV reactivation. Immunosuppressive treatment was drastically reduced, and treatment with entecavir was started. The outcome was favorable, and HBV DNA became undetectable after 9 weeks of treatment. This is the first report of acute hepatitis related to HBV reactivation in a kidney transplant recipient treated with belatacept. The risk for HBV reactivation in patients treated with belatacept should not be underestimated, especially in those with resolved HBV infection.     

Lamivudine treatment for acute severe hepatitis B: a pilot study

Abstract: Background: Experience with lamivudine treatment of immunocompetent patients with acute hepatitis B is limited. Aim of study: To evaluate the safety and efficacy of lamivudine for the treatment of acute severe hepatitis B virus (HBV) infection in immunocompetent adults. Patients and Methods: Fifteen patients (10 men, 5 women, mean age 34.3±7.3 years) with severe acute HBV infection were treated with lamivudine 100 mg daily for 3–6 months, starting 3–12 weeks after onset of infection. Prior to treatment, 5 patients had grade 1–4 encephalopathy; all patients had severe coagulopathy (mean INR was 4.5±6.4), and all patients had evidence of severe hepatocyte lysis (mean alanine aminotransferase 3738±1659 U/L, and mean total serum bilirubin 18±6.8 mg/dl). All patients had evidence of highly replicative HBV (mean HBV DNA 13.5 × 10⁶±11 × 10⁶ copies/ml). Results: Thirteen patients (86.6%) responded to treatment. Encephalopathy disappeared within 3 days of treatment and coagulopathy improved within 1 week. Serum HBV DNA was undetectable (by polymerase chain reaction) within 4 weeks, and serum liver enzyme levels normalized within 8 weeks. Two patients in whom lamivudine therapy was delayed developed fulminant hepatitis and underwent urgent liver transplantation. (One died of vascular complications 1 month later). The 11 patients who were serum HBeAg‐positive before treatment seroconverted, and HBeAb developed within 12 weeks in 9 of them; HBsAg was undetectable in all 11 tested patients, and protective titer of HBsAb developed within 12–16 weeks in 9 of them. Therapy was well tolerated in all cases. Conclusions: These data indicate that lamivudine induces a prompt clinical, biochemical, serological and virological response in immunocompetent patients with de novo HBV infection. Lamivudine may prevent the progression of severe acute disease to fulminant or chronic hepatitis and should be considered for use in selected patients. A large randomized controlled, double‐blind prospective study is needed.     

慢性肝病患者乙肝病毒血清学标志物转换规律及其意义

目的探讨乙肝病毒血清学标志物（HBVM）在慢性肝病患者中的转换规律及临床意义。方法选择慢性肝病患者包括慢性病毒性乙型肝炎、慢性重型乙型肝炎、肝炎肝硬化和原发性肝癌患者183例,采用ELISA方法对HBVM（HBsAg、HBsAb、HBeAg、HBeAb和HBcAb）进行检测,采用荧光定量聚酶链反应法进行HBV DNA检测,将HBV DNA检测值进行对数转换行统计学分析。结果慢性肝病患者的HBVM共有3种模式：大三阳（L3PP：HB-sAg、HBeAg和HBcAb）、小三阳（S3PP：HBsAg、HBeAb和HBcAb）和小二阳（S2PP：HBsAg和HBcAb）。L3PP HBVDNA水平高于S3PP和S2PP（P〈0.01）。随着慢性肝病病情发展,L3PP阳性率呈下降趋势,S3PP和S2PP阳性率呈上升趋势（P均〈0.01）;不同临床类型的慢性肝病患者3种HBVM模式的分布存在统计学差异（P〈0.01）。结论 L3PP慢性肝病患者HBV DNA复制水平高于S3PP或S2PP模式。随着慢性肝病病情的进展,HBVM的模式可发生转换,HBeAg阴转,L2PP转为S3PP或S2PP。     

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants

BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic hepatitis B, but resistance to this agent is common after prolonged administration. METHODS: One patient with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 15 months of treatment. The resistance was confirmed by mutation in the HBV DNA polymerase gene. The patient was treated subsequently with adefovir dipivoxil for 7 months. RESULT: HBV DNA and HBsAg were tested negative, but HBeAb and HBsAb were positive. CONCLUSION: This study provides an evidence that adefovir dipivoxil can be effective in the treatment of lamivudine-resistant HBV mutants.     

De Novo Superinfection of Hepatitis B Virus in an Anti-HBs Positive Patient with Recurrent Hepatitis C Following Liver Transplantation

A 60-year-old woman with end stage liver cirrhosis caused by genotype 2 hepatitis C virus (HCV) infection received an orthotopic liver transplantation (OLT). The patient was negative for the hepatitis B surface antigen (HBsAg) and positive for the anti-hepatitis B surface antibody (anti-HBs) prior to and one and a half months following the OLT. Due to reactivation of hepatitis C, treatment with interferon-alpha and Ribavirin started two months following the OLT and resulted in a sustained virological response. We performed a liver biopsy because a biochemical response was not achieved. Surprisingly, liver pathology showed HBsAg-positive hepatocytes with a lobular hepatitis feature, which had been negative in the liver biopsy specimen obtained one and a half months post-OLT. High titers of both HBsAg and HBeAg were detected, while anti-HBs antibodies were not found. Tests for IgM anti-hepatitis B core antibody and anti-delta virus antibodies were negative. The serum HBV DNA titer was over 1×10(7) copies/mL. A sequencing analysis showed no mutation in the "a" determinant region, but revealed a mixture of wild and mutant strains at an overlapping region of the S and P genes (S codon 213 (Leu/Ile); P codons 221 (Phe/Tyr) and 222 (Ala/Thr)). These findings suggest that de novo hepatitis B can develop in patients with HCV infection during the post-OLT period despite the presence of protective anti-HBs.     

Utilization of hepatitis B core antibody-positive donor liver grafts

Background

The inclusion of hepatitis B core antibody-positive (HBcAb+) liver donors is a strategy utilized to increase organ availability. This study examined HBcAb+ transplantation practices to identify specific factors influencing outcomes.

Methods

Twenty-five HBcAb+ liver transplants were identified retrospectively among 868 adult transplants performed between 1 January 1997 and 31 December 2009. Twelve (48%) recipients had hepatitis C and five (20%) had hepatitis B. Patient and donor demographics, preoperative morbidity, transplant data and outcomes were examined. Statistical analysis was completed using Student''s t-test or the Kaplan–Meier method. A P-value of <0.05 was considered significant.

Results

There was no difference in age, body mass index or comorbidities between HBcAb+ liver recipients and control subjects. Model for End-stage Liver Disease (MELD) scores of >30 were significantly more frequent in HBcAb+ liver recipients (32% vs. 15%; P = 0.04). All patients received immunoglobulin and longterm antiviral therapy as prophylaxis against graft hepatitis B resurgence. No patients who received HBcAb+ livers developed hepatitis B infection on follow-up. Overall survival at 30 days, 1 year and 5 years in HBcAb+ liver recipients was 92%, 74% and 74%, respectively, compared with 96%, 89% and 76%, respectively, in the control group (P = not significant, log-rank test). All except one of the deaths in the HBcAb+ liver recipient group occurred within 90 days postoperatively and in patients with MELD scores >30.

Conclusions

The practice of transplanting HBcAb+ grafts incurs low risk for infection using current methods of prophylaxis. The highest mortality risk was in the early postoperative period, specifically in patients with very high MELD scores. This probably reflects the practice of using positive serology grafts in emergent situations.     

Analysis of serum hepatitis B virus RNA levels among HBsAg and HBsAb copositive patients and its correlation with HBV DNA

There are approximately 2 billion HBV-infected individuals worldwide, and approximately 1.87% to 7% of these individuals are copositive for HBsAg and HBsAb.Our study detected hepatitis B virus pgRNA (HBV RNA) levels in HBsAg and HBsAb copositive patients and then analyzed the correlation with HBV DNA, HBsAg, ALT, and AST levels. A total of 149 HBsAg and HBsAb copositive patients were identified from 66,617 outpatients.HBV RNA, HBV DNA, HBsAg, ALT, and AST serum levels were significantly different in different natural phases of HBV infection (immune tolerance phase, immune clearance phase, low replication phase, and reactivation phase) with statistical significance (P < .01). HBV RNA levels were positively correlated with HBV DNA, HBsAg, ALT, and AST levels. HBV RNA and HBV DNA levels were significantly increased in the HBeAg-positive group (66 patients) compared with the HBeAg-negative group (83 patients) (P < .01). In the HBeAg-positive group, HBV RNA levels were positively correlated with HBV DNA and HBsAg levels. In the HBeAg-negative group, HBV RNA levels were positively correlated with HBV DNA. Serum HBV RNA levels were positively correlated with HBV DNA, HBsAg, ALT, and AST levels.HBV RNA could be used as a virological indicator for antiviral therapy in HBsAg and HBsAb copositive hepatitis B patients.