HBV reactivation after kidney transplantation.

Recent studies suggest that reappearance of hepatitis B surface antigen (HBsAg) and loss of anti-HBs antibodies may be common events in bone marrow recipients and patients with chemotherapy. In this study, we reviewed the virologic laboratory records from kidney recipients. Out of 1512 patients, 228 had been diagnosed with resolved HBV infection (anti-HBc positive, HBsAg negative) but normal liver enzyme levels prior to kidney transplantation. Reappearance of HBsAg after kidney transplantation was observed in two (0.9%) of those patients, which may be attributed to reactivation of a latent infection or to a new HBV infection. In both of the patients, HBV infection may have been reactivated although immunosuppression was just on a low level over the whole period. We conclude that natural immunity to HBV may not protect against reactivation in patients with suppression of the immune system. Periodic follow-up of HBV serology for early diagnosis of reactivation is highly recommended in transplant recipients.     

Correlation Between the Prevalence of Serum HBV DNA and Immunoserologic HBV Markers in the Subjects with or without Hepatitis

The prevalence of serum HBV DNA, detected by polymerase chain reaction, and that of immunoserologic HBV markers (HBsAg, HBeAg, anti-HBs, and anti-HBc), determined by immunoassays, were compared among three groups of subjects: (A) chronic active hepatitis B patients, (B) chronic asymptomatic HBV carriers, and (C) normal individuals. Except five of the normal individuals, all of the subjects are positive for anti-HBc while some of them were also positive for other immunoserologic HBV markers, such as anti-HBs, HBsAg, and HBeAg. Serum HBV DNA were detected in 81% in group A, 52% in group B, and 20% in group C. In both group A and B, serum HBV DNA were detected in all the subjects with anti-HBsAg⁺/HBeAg⁺/HBeAg⁺. However, the percentage of seropositive HBV DNA in the subjects with anti-HBc⁺/HBsAg⁺ in Group A was much higher than that in Group B. Interestingly, the percent of serum HBV DNA⁺ in the individuals with anti-HBc⁺ only was markedly higher than that in the subjects with anti-HBc⁺/anti-HBsAg⁺ in both Group A and C, suggesting that anti-HBs may play a role in the inhibition of HBV replication and clearance of HBV virion from blood. Above serological profiles will provide important information concerning the significance of serum HBV DNA detection in judgement of HBV replication in the individuals with or without HBV infection. Cautions should be taken to clarify those so called normal individuals who have no symptoms of hepatitis B, no HBsAg in the sera and normal transaminase, but have HBV replication in their bodies.     

Hepatitis B virus (HBV) infections in turtles

Thirty turtles (15 Clemys mutica and 15 Geoclemys reevesii) which were inoculated with human sera those were positive for hepatitis B surface antigen (HBsAg) and hepatitis B "e" antigen (HBeAg) were found to be infected with hepatitis B virus (HBV). The levels of HBV infection markers, such as HBsAg and antibody to HBsAg (anti-HBsAg), were retinely monitored in the turtles' serum for 46 weeks. Within two weeks of the inoculation, 42% of the turtles tested were positive for HBsAg, and their reciprocal titers as measured by reverse passive hemagglutination (RPHA) and enzyme linked immunoabsorbance assay (ELISA) ranged from 16 to 96. Within 20 weeks, the remaining turtles tested HBsAg positive, as confirmed by ELISA. At 20 weeks, all but one of the turtles exhibited changes in HBV blood marker from HBsAg to anti-HBs; the one exception was positive for both HBsAg and anti-HBs. At the 47th week, 7 animals were killed and their organs were examined for HBV infected cells utilizing an immunofluorescent technique. Numerous fluorescent cells which reacted with human anti-HBs nad anti-HBc were observed in the following organs: pancreas, liver, kidney, and brain. Histopathologically, edematous changes in hepatocytes and minor cellular infiltration attributed to an inflammatory response were noted. Liver and kidney cells from the infected animals were cultured, and HBV antigen positive cells for HBsAg and HBcAg were detected in the cultures. Throughout the experiment, HBsAg was detected in the supernatant by ELISA. Virus particles which were indistinguishable from Dane particles were seen in the cytoplasmic vacuoles of the cultured cells by electron microscopy. Finally, the presence of HBV DNA was established by molecular hybridization techniques in the culture supernatants of kidney cells from the infected turtles.     

Occult hepatitis B virus infection.

The detection of HBV DNA without HBsAg with or without the presence of HBV antibodies outside the acute phase window period defines occult HBV infection. This condition has been described in hepatocellular carcinoma (HCC), chronic hepatitis B, healthy HBV carriage and recovered infection, chronic hepatitis C and individuals without serological markers of HBV. The frequency of the diagnosis depends on the relative sensitivity of both HBsAg and HBV DNA assays. It also depends on the prevalence of HBV infection in the population. Occult HBV in blood donors has a wide range of potential origins within the natural history of the infection. It may originate from recovered infections with anti-HBs and persistent, low-level, viral replication, escape mutants undetected by the HBsAg assays or healthy chronic carriage. The last situation is mostly found with anti-HBc only. Over time, antibody markers may become undetectable leaving HBV DNA as the only marker of the infection. In all cases, the viral load is low, mostly below 10(4) IU/ml, often below 100 IU/ml. At these levels, nucleic acid testing (NAT) in pools is likely to be largely ineffective. Is occult HBV transmissible by transfusion? Carriers of anti-HBs or anti-HBc only were shown infectious in immunosuppressed organ or bone marrow transplant recipients. In immunocompetent recipients, there is no evidence that anti-HBs-containing components are infectious, even in low titre. Donations carrying anti-HBc only and HBV DNA can be infectious and this is a threat where anti-HBc is not screened. Anti-HBc screening identifies most occult HBV infection but not all. HBV NAT needs either extreme sensitivity or to be performed on individual donations to eliminate HBV DNA-containing units.     

Relationship between T cell subsets and suppressor cell activity in chronic hepatitis B virus (HBV) infection.

The relationship between T cell subset, as defined by monoclonal antibodies, and suppressor cell function, using a short lived suppressor cell assay, was studied in 38 chronic hepatitis B virus (HBV) carriers and in 32 patients with HBsAg negative chronic active hepatitis (CAH). Patients with HBV chronic infection showed an absolute reduction in the OKT4 positive subset and a significantly decreased OKT4/OKT8 ratio, as compared with healthy controls. Patients with anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) positive CAH with or without antibodies to HBV antigens, namely anti-HBs and anti-HBc, demonstrated a significant reduction in cytotoxic/suppressor T cells and an increased helper/suppressor ratio. A negative correlation between suppressor index (SI) and OKT4/OKT8 ratio (P less than 0.01), and a positive correlation between SI and OKT8 positive cells absolute number (P less than 0.01) were also observed.     

Detection of an acute asymptomatic HBsAg negative hepatitis B virus infection in a blood donor by HBV DNA testing.

The issue of HBV DNA screening on blood donations is controversially discussed since the economic impact of post-transfusion hepatitis B is expected to be relatively low. We report on a case of HBsAg negative unapparent acute HBV infection, which was detected by HBV NAT testing on 96-member maxi-pools with a commercially available NAT assay, which has a detection threshold of 3 IU/mL of plasma. The presence of an HBsAg escape mutant could be excluded by sequencing the amplified DNA. Follow-up testing showed the presence of an acute HBV infection (anti-HBc-IgM positive) and finally anti-HBs seroconversion. Although the reduction of the diagnostic window with NAT screening on maxi-pools may be relatively low, it may help to improve the residual risk of blood donation, especially in asymptomatic HBV infection, where the HBsAg positive period may be very short and low levels of circulating surface antigen are present. It would also permit to detect occult HBV infection in chronic carriers who are HBsAg negative. Since the viral load in chronic isolated anti-HBc positive carriers is low, there is a potential risk for failure of HBV DNA detection with pool-PCR in blood donors. Anti-HBc screening would reduce the residual risk.     

Efficacy of hepatitis B virus (HBV) vaccine in long term prevention of HBV infection

Efficacy of HBV vaccine in long term prevention of HBV infection was evaluated at 3 years after vaccination in 38 children and 61 adults. All vaccinees were negative for all HBV markers (HBsAg, anti-HBs and anti-HBc) before vaccination. Vaccines (Hevac B) were given for 3 doses, one month apart, to 38 children aged 1 month - 14 years and 61 adults aged 15-45 years. After 3 years of vaccination, blood specimens were collected for the determination of HBsAg, anti-HBs and anti-HBc. The results revealed that no HBsAg antigenemia was found in all 99 vaccinees. Anti-HBs could not be detected in 4 children and 11 adults and this occurred only in the group of subjects who had initial anti-HBs less than 100 mlU/ml at 2 months after the last dose of vaccination. At three years after the first course of vaccination, 89.4 percent of children and 83.4 percent of adults still have anti-HBs above protective level (more than 10 mlU/ml) with geometric mean titers of 101 and 35 mlU/ml in children and in adult groups, respectively. The anti-HBc was detected in 2 out of 38 children and 10 out of 61 adults, but none of them became chronic hepatitis B carriers or developed clinical disease. It is recommended that everyone with anti-HBs values below 100 mlU/ml two months after the last dose of vaccine should be revaccinated with a booster dose within 6 months. Those with anti-HBs levels higher than 100 mlU/ml, should be checked up at 3 years; if the anti-HBs is less than 10 mlU/ml, they should be revaccinated.     

抗个体型抗体对HBV感染的免疫调节作用——用抗个体型抗体诱生抗—HBs

Jerne~([1])指出,机体对抗原的免疫反应可以通过抗体的个体型(Id)和抗个体型抗体(抗-Id)的相互作用而得到调节。这一理论陆续被许多学者的研究结果所证实。     

Hepatitis B virus (HBV) infection and recombination between HBV genotypes D and E in asymptomatic blood donors from Khartoum, Sudan

Sudan is a highly endemic area for hepatitis B virus (HBV), and >5% of blood donors are chronically infected. To examine potential strategies to improve HBV blood safety, 404 replacement donor samples previously screened for HBV surface antigen (HBsAg) were tested for antibody to HBV core (anti-HBc), anti-surface antigen (anti-HBs), and HBV DNA. Of 145 anti-HBc-containing samples (36%) identified, 16 retested were HBsAg positive (11%). Anti-HBs was detected in 43/77 (56%) anti-HBc-reactive samples. Six samples were HBsAg(-)/anti-HBc(+)/anti-HBs(+) and contained HBV DNA, meeting the definition of occult HBV infection (OBI). OBIs had low HBV DNA loads (<10 IU/ml) and were genotype B (n = 1) or genotype D (n = 5). Pre-S/S and/or whole genome sequences were obtained from 47 randomly selected HBsAg-positive donors added to the previous 16. Genotype E was identified in 27 strains (57.5%), genotype D in 19 strains (40.5%), and genotype A2 in 1 strain (2%). Two outlier strains within genotype D ultimately were identified as recombinants of genotypes D and E with identical recombination points, suggesting circulating, infectious, recombinant strains. Anti-HBc screening does not appear to be a sustainable blood safety strategy because of the cost and the negative impact on the Sudanese blood supply, even when reduced by anti-HBs testing. Being at the junction between two main African HBV genotypes, genetic recombination occurred and became part of the molecular epidemiology of HBV in Sudan.     

抗HBs mAb的研制及其对野生与免疫逃逸变异HBsAg的交叉反应特征

目的:抗HBs G6 mAb制备及其对重组野生与免疫逃逸变异HBsAg结合能力与特点的评价.方法:常规制备并纯化抗HBs mAb,以纯化抗HBs mAb IgG包被,采用ELISA对17种野生及"a"决定簇替代性变异全基因重组表达HBsAg进行检测,并与几种市售HBsAg检测试剂进行比较.结果:该杂交瘤细胞生长与分泌特性稳定,其培养上清与腹水效价分别为2048及4096×103;对野生HBsAg检测(ELISA)敏感性不低于0.125 μg/L.该抗体可与15种变异抗原中12种发生反应(P/N≥2.5),反应信号强度分别为低反应组(2份,与野生株A值比较,下同)平均7.55%;中反应组(1例)为59.40%;高反应组(9种)分别为野生株的92.1%～109.4%,低反应或无反应表达产物的免疫逃逸变异部位集中在HBV"a"决定簇I环的起始部即120～124序列之间.部分表达产物采用市售试剂作同步检测,平均显色强度高于或明显高于几种国内应用最为普遍的HBsAg ELISA(P<0.05).结论:抗HBs G6 mAb对多数免疫逃逸变异HBsAg有很强的结合能力,所针对的变异类型亦表现出某种特殊的规律.     

A final report on safety and immunogenicity of a bivalent aqueous subunit HBV vaccine

The bivalent form of an aqueous formalin-inactivated hepatitis B vaccine was evaluated for safety and immunogenicity in chimpanzees. To evaluate safety five animals were inoculated intravenously with vaccine containing 500 micrograms HBsAg and two animals with 50 micrograms. None of these animals developed hepatitis or any serologic marker indicative of the presence of residual live virus in the vaccine. Twenty-four animals were used to evaluate immunogenicity and protective efficacy. Seven of these immunized animals produced weak or no anti-HBs responses. Two doses of 50 micrograms HBsAg given subcutaneously 1 month apart protected each of four animals that were challenged with 10(3.5) CID50 HBV at 6 and 12 months after immunization and protected three of four animals challenged at 24 months against development of hepatitis or HBsAg. Three of 4 animals in each group immunized with two doses of 20, 10, or 5 micrograms HBsAg were similarly protected when challenged 6 months after immunization. Thirteen of 20 immunized animals that did not develop HBsAg after challenge with HBV developed anamnestic anti-HBs or anti-HBc responses between 2 and 18 months after challenge, indicating minimal replication of challenge virus. The time of onset and frequency of occurrence of these delayed responses was related to the titer of anti-HBs at the time of challenge. False positive Ausab test results were observed in quarantined chimpanzees. These were neither preceded by appearance of HBsAg nor accompanied by development of anti-HBc. In most cases these reactions were due to a reactant having a sedimentation coefficient and an electrophoretic mobility resembling that of IgM. This reactant generally did not appear to confer resistance to challenge with HBV. The humoral immune response was characterized as being entirely of the IgM class 2 weeks after immunization and switched entirely into the IgG class by 10-12 weeks after vaccine administration. At the time of challenge all animals with antibody had anti-HBs of subtype a.     

IgG subclass composition of antibodies to HBsAg in circulating immune complexes from patients with hepatitis B virus infections

The IgG subclass of antibody associated with hepatitis B surface antigen (HBsAg) in circulating immune complexes (CIC) from patients with either acute or chronic hepatitis B virus (HBV) infections was measured using an isotype and antigen-specific ELISA. All patients were HBsAg positive but were negative for free anti-HBs antibody. The subclass of antibody associated with HBsAg in CIC in both groups was predominantly IgG1 and IgG4. This is in contrast to free anti-HBs in convalescent sera from patients recovering from HBV infection, which are highly restricted to IgG1 and IgG3. The finding of high levels of IgG4 antibodies in CIC suggest that CIC containing this subclass may be cleared less efficiently than CIC containing antibodies of other subclasses. Formation of these CIC may be an important factor in the progression of infection to chronicity and may also be involved in the antigen-specific immunosuppression seen in early acute and chronic HBV infections.     

奉贤地区HBsAg阴性的HBV自然感染母亲对新生儿影响的研究

目的　为揭示HBsAg阴性的乙型肝炎病毒 (HBV)自然感染孕妇的宫内感染及其危险因素。方法　采用多聚酶链反应 (PCR)技术结合酶联免疫吸附法 (ELISA) ,对奉贤地区 131例HBsAg阴性的HBV自然感染孕妇外周血 ,及其分娩后的脐带血进行HBV血清学标志物 (HBVM)和HBVDNA检测。结果　HBsAg阴性的HBV自然感染孕妇宫内的感染率 (除外单一抗 -HBs阳性 )为 5 2 6 7% ;脐血中不同HBVM组合的HBVDNA检出率依次为 :抗 -HBe( )、抗 -HBc( ) >抗 -HBs( )、抗 -HBe( )、抗 -HBc( ) >抗 -HBs( )、抗 -HBe( ) >抗 -HBs( )、抗 -HBc( ) >抗 -HBs( ) ;脐血HBVDNA总检出率为 16 79%。结论　HBsAg阴性的HBV自然感染孕妇也可能发生宫内感染。提议HBsAg阴性的HBV自然感染孕妇和新生儿有进行自动和被动免疫接种的必要性     

Anti-idiotypic humoral and cellular responses to antibody to hepatitis B surface antigen in hepatitis B viral infections.

In order to investigate regulatory significance of humoral and cellular responses to the idiotypic (Id) determinants on the antibody to hepatitis B surface antigen (anti-HBs), they were studied in acute hepatitis B and in chronic HBV infection. The results were compared with humoral and cellular responses of the same patients to hepatitis B surface antigen (HBsAg). In acute hepatitis B, the responses to HBsAg, were delayed until 3-4 weeks after the onset of clinical symptoms. However, the leucocyte migration inhibition (LMI) and the lymphocyte transformation (LTT) responses to affinity purified anti-HBs were found to be evolved very early in the course of acute hepatitis B, though anti-Id antibodies were absent. The majority of chronic HBV carriers showed a poor humoral and cellular response to HBsAg. Ten out of 38 chronic carriers showed anti-Id antibodies which recognized a major cross-reactive idiotype (CRI) on the anti-HBs molecule. Twenty-five out of 38 chronic carriers also showed LMI response to the Id determinants on the anti-HBs. LMI response induced by anti-HBs could be blocked by a specific Balb/c anti-Id antibody which also recognized the CRI. Thus, in both acute and chronic HBV infections, the anti-Id humoral and cellular responses correlated with poor humoral and cellular responses to HBsAg, indicating regulatory significance.     

Reactivation of an occult hepatitis B virus escape mutant in an anti-HBs positive, anti-HBc negative lymphoma patient.

BACKGROUND: Hepatitis B virus (HBV) often persists after resolution, but its replication is suppressed by antiviral T cells. Immunosuppressive treatment may lead to viral reactivation and severe hepatitis. Early antiviral therapy prevents reactivation but some occult HBV infections are not easily detectable. RESULTS: Here we describe a patient with a progressive non-Hodgkin lymphoma who had probably not been vaccinated against HBV and, before immunosuppression, showed antibodies (anti-HBs) against the viral surface antigen (HBsAg) as the only possible marker of occult HBV infection. Under immunosuppression he developed viremia (>10(8)copies/mL). The virus exhibited three S gene mutations (L109R, C137W, G145R) which led to false negative HBsAg results and diminished binding of vaccine-induced anti-HBs. CONCLUSIONS: Reliable screening and monitoring of severely immunosuppressed patients for HBV should include, in addition to anti-HBc and HBsAg, anti-HBs and sensitive HBV DNA assays. Furthermore, active vaccination or hepatitis B immune globulin may not protect against such mutants.     

Antibody detection and kinetics of antibody production during early stages of immunization with hepatitis B virus vaccine

Antibodies to influenza virus and human immunodeficiency virus are detectable in B cells during the early stages of the immune response, prior to their occurrence in plasma. To investigate similar phenomena in a model of immunization against hepatitis B virus (HBV) infection, medical students in Ghana were screened for HBV markers, HBV surface (HBs) antigen (HBsAg), and HBV core antibodies (anti-HBc). Consenting volunteers, 24 of whom were seronegative (susceptible) and 2 of whom were positive for anti-HBc (prior infection), were vaccinated on day 0, day 40, and 6 months. Two sets of 10 blood samples, sequentially collected at intervals of 2 days following each immunization on days 0 and 40, were processed into B-cell lysates and plasma. Solid-phase HBsAg coated on microtiter plates for enzyme immunoassay or nitrocellulose membranes for dot blot assay was used to detect anti-HBs activity by an indirect antiglobulin assay. A commercially procured sandwich immunoassay was used, along with an enzyme-linked immunosorbent assay and a dot blot assay, for the detection of anti-HBs in B-cell lysates and plasma. Following the first injection of vaccine, a single sample of B-cell lysate collected between 5 and 21 days revealed anti-HBs in 18/21 subjects with no plasma antibodies detectable by sandwich immunoassay. After the booster dose was injected on day 40, a single sample of B-cell lysate collected between 44 and 49 days showed anti-HBs in 16/19 subjects, and this was accompanied by plasma antibodies in 8 subjects. In contrast, between 8 and 13 days, both subjects with prior HBV infection showed anti-HBs in B-cell lysates and plasma. Thus, primary immunization with the HBV vaccine appears to transiently elicit low-affinity anti-HBs in B-cell lysates into plasma.     

HIV and HBV infection in intravenous drug addicts from northeastern Italy

Three hundred and two intravenous drug addicts (IVDA) from five towns in Northeastern Italy were studied. Of the males, 37/249 (14.8%) were homosexuals and of the females, 29/53 (54.7%) were prostitutes; 118 (39.0%) were alcoholics. AST levels were abnormal in 31.8%, ALT in 45.7%, GTP in 36.4%, and bilirubin in 14.6%. The prevalence of HBsAg (13.9%) and HBeAg (21.4% of HBsAg positive) was significantly higher than in 2,983 controls (4.2% and 6.3%, p less than .001 and p less than .02, respectively). Of the HBsAg positive subjects, 51.7% had anti-HDV antibodies. Among 260 HBsAg negative cases, 146 (56.2%) were anti-HBs and anti-HBc positive, 76 (29.2%) were anti-HBc positive and anti-HBs negative (25 anti-HBe positive and 51 anti-HBe negative), and 38 had no HBV markers. Anti-HIV ELISA positive subjects came to 70.5% (triplicate determination with absolute concordance) and Western blot analysis confirmed the results in 99.1% of ELISA positive and 100% of ELISA negative subjects. The prevalence of anti-HIV was significantly higher in anti-HBc positive than negative cases (p less than .02), even excluding HBsAg positive subjects. Cases negative for HIV and HBV had a significantly lower median duration of drug abuse than those with past or present infection (36 vs 60 months, p less than .001). HIV-related diseases were present in 56.3% of the cases (120/213; PGL in 94, ARC in 24, and AIDS in two).(ABSTRACT TRUNCATED AT 250 WORDS)     

HBV and HCV infection in Japanese dental care workers

Protective measures against occupational exposure to the hepatitis B virus (HBV) and hepatitis C virus (HCV) must be taken in order to prevent infection in dental care workers. To determine the best way to protect these workers, our study examined viral hepatitis infection in dental care workers in regions with a high prevalence of HCV infections in Japan. In total, 141 dental care workers (including dentists, dental hygienists and dental assistants) were enrolled. After a questionnaire to elicit demographic information was administered by an oral surgeon, hepatitis B surface antigen (HBsAg), antibody to HBs (anti-HBs), antibody to hepatitis B core antigen (anti-HBc) and antibody to HCV (anti-HCV) were measured. When necessary, HBeAg, anti-HBe, levels of HBV DNA, anti-HBc IgM and HCV RNA in serum were measured. Of the dental care workers included, 68 (48.2%) had been immunized with a HBV vaccine. Only 9 wore a new pair of gloves for each new patient being treated, 36 changed to a new pair only after the old gloves were torn and 24 did not wear any gloves at all. No one was positive for HBsAg or anti-HCV, though 73 (51.8%) and 17 (12.1%) workers were respectively positive for anti-HBs and anti-HBc. The positive rate of anti-HBc varied directly with worker age and experience. Of the 68 workers immunized with HBV vaccine, 51 (75%) were positive for anti-HBs. Of the 63 workers who were not so immunized, 17 (27%) were positive for anti-HBs and 15 of these were also positive for anti-HBc. Immunized workers were more protected against HBV infection than non-immunized workers, indicating that HBV vaccine was a useful measure for protection against the infection. The anti-HBc positive rate was significantly higher among dental care workers than general blood donors, suggesting that frequency of exposure to HBV was greater in dental care workers. HBV vaccination should be made compulsory for all dental care workers who handle sharp instruments.     

Management of HBV Infection in Liver Transplantation Patients

In the absence of preventative therapy, reinfection of allografts with hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) resulted in dismal allograft and patient survival. Major advances in the management of HBV-infected recipients of OLT during the past 15 years have steadily reduced the rate of reinfection, resulting in improved outcomes. Initially, long-term use of hepatitis B immune globulin (HBIG) as a source of anti-HBs antibodies was effective in preventing or delaying reinfection. Lamivudine monotherapy made it possible to suppress HBV replication prior to OLT, markedly decreasing the risk of reinfection. Although lamivudine monotherapy used before and after OLT could prevent reinfection, its effectiveness was limited by progressive development of lamivudine-resistant mutant infections. Combination therapy with HBIG and lamivudine after OLT reduced both HBV recurrence and the risk of lamivudine resistance even in patients with active HBV replication. Introduction of adefovir provided a safe, alternative oral antiviral able to treat effectively lamivudine-resistant mutants HBV. Available strategies to prevent reinfection have resulted in OLT outcomes for HBV-infected patients comparable to those for patients transplanted for non-HBV indications. In the future, combination therapies of HBIG and both nucleoside and/or nucleotide agents will undoubtedly be optimized. Development of new drugs to treat HBV will increase opportunities to combine agents to enhance safety, efficacy and prevent emergence of HBV escape mutants. New vaccines and adjuvants may make it possible to generate anti-HBs in immunosuppressed patients, eliminating the need for HBIG.