乙型肝炎患者血清中抗HBc-IgM的临床意义

抗HBc-IgM在鉴别急性乙肝、慢性乙肝及慢性乙肝急性发作中的意义。应用亚培试剂盒检测抗HBc-IgM,追溯120例抗体阳性患者的临床诊断和各临床类型的抗体滴度水平分布,同时统计急性乙肝、慢性乙肝和慢性乙肝急性发作共240例患者的抗HBc-IgM检测结果,比较其抗体阳性率和滴度水平之间的差异。抗HBc-IgM阳性率,急乙肝组明显高于慢乙肝组和慢乙肝急性发作组。抗体滴度<2.0者,慢乙肝组和慢乙肝急性发作组的百分率明显高于急肝组。抗体滴度的检测对鉴别急乙肝和慢乙肝急性发作有较大的意义。     

Changes in levels of hepatitis B virus markers in patients positive for low-titer hepatitis B surface antigen

Aim: Recently, patients positive for the low-titer hepatitis B surface antigen (HBsAg) have been found occasionally owing to the increase in the accuracy of detection methods. The aim of this study is to clarify the clinical status of acute hepatitis B virus (HBV) infection in patients positive for low-titer HBsAg. Method: Eight patients, who were positive for HBsAg at low titers and diagnosed as having acute HBV infection, were enrolled in this study. Assays of HBsAg, hepatitis B core antibody (anti-HBc), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), hepatitis B surface antibody (anti-HBs) and HBV DNA, and biochemical tests were basically conducted every 4 weeks for at least 24 weeks. Result: The average cut-off index of HBsAg was 8.7 ± 9.6 (range, 1.0–25.7). All the patients were negative for anti-HBc, HBeAg, anti-HBe and HBV DNA on their initial visit. The genotype of HBV could be determined in four patients: two were infected with genotype B/HBV, one was infected with genotype A/HBV, and the remaining patient was infected with genotype C/HBV. Although HBsAg clearance was observed within 4 months in all the patients, none of the other HBV markers seroconverted during the observation period. Conclusion: HBV infection terminating with seronegativity for HBV markers may occur in transient HBV infection.     

The role of transplacental hepatitis B core antibody in the mother-to-infant transmission of hepatitis B virus

Aims/Methods: To investigate the influence of transplacental hepatitis B core antibody (anti-HBc) on perinatal hepatitis B virus (HBV) transmission, we studied the anti-HBc titers in 294 mother-neonate pairs.Results: The anti-HBc titer was highest (10^5.13±0.80 to 10^4.36±0.97 in mothers, 10^5.13±0.76 to 10^5.52±0.98 in infants) in the 200 hepatitis B e antigen (HBeAg) positive hepatitis B surface antigen (HBsAg) carrier mothers and their infants, second highest (10^4.51±0.76 and 10^4.68±0.76) in the 60 HBeAg-negative HBsAg carrier mothers and their infants, and lowest (10^3.11±0.76 and 10^3.24±0.83) in the 34 non-carrier mothers and their infants (p<0.05). One hundred and ninety-two infants of HBeAg-positive carrier mothers received hepatitis B immunoglobulin as well as hepatitis B vaccines, and were followed prospectively from birth. Ten infants became HBsAg carriers, and their mothers had significantly lower anti-HBc titers than those of the mothers of 182 infants who did not become carriers (p=0.003), while maternal serum hepatitis B virus DNA levels (29.9±23.6 versus 39.9±58.1 pg/10 ml) did not differ in those two gruops (p>0.25). The same trend was observed in the infants' anti-HBc titers in those two groups (p=0.0006).Conclusions: The association of lower anti-HBc titers in HBeAg-positive carrier mother-infant pairs and the development of carrier status in the infants suggests a positive role of anti-HBc in the modulation of mother-to-infant transmission of HBV. A high maternal anti-HBc level in serum may be a negative predictor of immunoprophylaxis failure in high-risk infants.     

Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection

We investigated the frequency of HBsAg clearance and the possible role of viral superinfection in a long-term follow-up of 184 patients with chronic hepatitis B (CHB). Our subjects were 184 patients with chronic hepatitis B and the follow-up was 12–216 months (mean 66.2±53.7 months). The investigative methods used were: immunoenzymatic assays for HBV, HCV, HDV, and HIV markers; polymerase chain reaction (PCR) for HBV DNA; and liver biopsy and immunoperoxidase. During the follow-up, 20 of the 184 patients cleared serum HBsAg. A comparison of patients with persistent HBsAg (group I) and of those who cleared this marker (group II) showed a significant difference in mortality (P=0.002) between the two groups and a tendency to a more severe exacerbation (flare) in group II (P=0.07). Antibodies to hepatitis C and D virus as well as antibodies to HIV were equally distributed in both groups. Thirteen patients (7.9%) from group I, but none from group II, subsequently developed hepatocellular carcinoma. These results suggest that the frequency of spontaneous clearance of HBsAg during chronic HBV infection is low. No determinant factor for the clearance was found, including the presence of liver cirrhosis. Serum HBV DNA was undetectable by PCR after clearance in 16 out of 17 patients. Some of these findings were presented at the Biennial Scientific Meeting of the International Association for the Study of the Liver, held in Brighton, UK, in June 1992.     

Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease

Background and Aim: Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)‐infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV‐infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Methods: Forty‐three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti‐HBc) (?); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow‐up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Results: Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (?) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (?) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8–48]vs 16 [6–36] weeks, P = 0.001). During convalescence, there was no significant difference between histological activity index score (median [range] 8 [4–11]vs 8 [4–16] weeks, P = 0.629) and fibrosis scores (median [range] 3.5 [1–4]vs 2 [1–4] weeks, P = 0.099] on liver biopsy after recovery among patients with acute exacerbation due to superinfection and spontaneous exacerbation. Conclusions: Acute exacerbations in HBeAg (+) patients are most often due to spontaneous viral activation, while in HBeAg (?) patients, superinfection with non‐B hepatitis viruses and spontaneous viral activation are equally common. HEV is an important cause of acute exacerbation in previously asymptomatic and unrecognized patients with HBV‐related CLD.     

Clinical features of HBsAg-negative but anti-HBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area

BACKGROUND: The presence of antibody to the hepatitis B core antigen (anti-HBc) IgG in serum usually means a past infection of the hepatitis B virus (HBV). The clinical characteristics of patients with hepatocellular carcinoma (HCC), who have only a marker for past HBV infection, were investigated. METHODS: A total of 565 HCC patients were classified according to their markers for HBV and the hepatitis C virus (HCV). The clinical features and the survival rate of hepatitis B surface antigen (HBsAg)(-)/anti-HBc(+) patients were compared to those of HBsAg(+) patients. RESULTS: Four hundred and three patients were positive for HBsAg (B group, 71.3%), 64 were positive for anti-HCV (11.3%), and 90 were negative for both HBsAg and anti-HCV (N group, 15.9%). In the N group, 71 were positive for anti-HBc (PB group, 12.6% of total patients). The clinical characteristics of the PB group were different from those of the B group: age at diagnosis (60.6 +/- 9.6 vs 53.3 +/- 10.6 years, P < 0.001), habitual drinking (59.2% vs 23.6%, P < 0.001), family history of liver disease (9.9% vs 38.9%, P < 0.005), detection with periodic screening (28.2% vs 50.4%, P < 0.001), and elevated alpha-fetoprotein (53.5% vs 76.2%, P < 0.001). In both the PB group and the B group, liver cirrhosis was accompanied by a similar high prevalence (74.6% vs 89.1%). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: The prevalence of HBsAg(-)/anti-HBc(+) HCC is not rare or more common than that of anti-HCV(+) HCC in Korea, a high HBV endemic area. Although some differences in clinical characteristics may imply a different pathogenesis, chronic HBV infection or habitual drinking may be major contributing factors in the development of HCC in these patients.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients With Isolated Hepatitis B Core Antibody: A Multicenter Study

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Occult HBV infection harbors potential risk of HBV transmission through hemodialysis (HD). The aim of this study was to assess the occult HBV infection in hemodialysis patients with isolated hepatitis B core antibody (anti-HBc). A total of 289 HD patients from five dialysis units in Tehran, Iran, were included in this study. Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (anti-HBs), anti-HBc, Hepatitis C antibody (anti-HCV), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of HD patients with isolated anti-HBc (HBsAg negative, anti-HBs negative and anti-HBc positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler. Of 289 patients enrolled in this study, 18 subjects (6.2%, 95% confidence interval (CI), 3.5%–8.9%) had isolated anti-HBc. HBV-DNA was detectable in 9 of 18 patients (50%, 95% CI, 27%–73%) who had isolated anti-HBc. Plasma HBV-DNA load was less than 50 IU/ml in all of these patients. Our study showed that detection of isolated anti-HBc could reflect unrecognized occult HBV infection in HD patients. The majority of these infections are associated with low viral loads.     

Safety and immunogenicity of hepatitis B surface antigen‐pulsed dendritic cells in patients with chronic hepatitis B

Summary. The immune modulator capacity of antigen‐pulsed dendritic cells (DC) has been documented in patients with cancers and in animal models of chronic viral infections. Cancer antigen‐pulsed DC are now used for treating patients with cancer. But viral antigen‐pulsed DC are not used in chronic viral‐infected patients because safety of antigen‐pulsed DC has not been evaluated in these patients. DC were isolated from human peripheral blood mononuclear cells by culturing with human‐grade granulocyte‐macrophage colony stimulating factor and interleukin‐4. Human blood DC were cultured with hepatitis B surface antigen (HBsAg) for 8 h to prepare HBsAg‐pulsed DC. After immunogenicity assessment of HBsAg‐pulsed DC in vitro, five million HBsAg‐pulsed DC were administered intradermally to five patients with chronic hepatitis B (CHB) 1–3 times. HBsAg‐pulsed DC were immunogenic in nature because they produced significantly higher levels of interleukin‐12 and interferon‐γ compared to unpulsed DC (P < 0.05). Also, HBsAg‐pulsed DC induced proliferation of HBsAg‐specific T lymphocytes in vitro. CHB patients injected with HBsAg‐pulsed DC did not exhibit generalized inflammation, exacerbation of liver damage, abnormal kidney function, or features of autoimmunity. Administration of HBsAg‐pulsed DC induced anti‐HBs in two patients and HBsAg‐specific cellular immunity in 1 patient. This is the first study about preparation of antigen‐pulsed DC using human consumable materials for treating patients with CHB. Because HBsAg‐pulsed DC were safe for all patients with CHB and had immune modulation capacity in some patients, phase I and phase II clinical trials with antigen‐pulsed DC in CHB and other chronic infections are warranted.     

Hepatitis B surface antigen levels during natural history of chronic hepatitis B: A Chinese perspective study

AIM: To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China.METHODS: Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immune-tolerant (IT, n = 108), immune-clearance (IC, n = 161), hepatitis B e antigen negative hepatitis (ENH, n = 149), low-replicative (LR, n = 135), and liver cirrhosis (LC, n = 70). HBsAg was quantified (Abbott ARCHITECT assay) and correlated with hepatitis B virus (HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) in each phase of CHB was also determined.RESULTS: Median HBsAg titers were different in each phase of CHB (P < 0.001): IT (4.85 log₁₀ IU/mL), IC (4.36 log₁₀ IU/mL), ENH (2.95 log₁₀ IU/mL), LR (3.18 log₁₀ IU/mL) and LC (2.69 log₁₀ IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase (r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed.CONCLUSION: The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immune-modulator or oral nucleos(t)ide analogue therapy.     

Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance

There is no consensus about factors that increase risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B who have achieved seroclearance of hepatitis B surface antigen (HBsAg). To assess the available evidence about risk factors for HCC after HBsAg seroclearance, Scopus, EMBASE, PubMed and Cochrane Library databases were systematically searched for relevant studies published through 15 September 2017. A total of 28 studies involving more than 105 411 patients with chronic hepatitis B were included. HBsAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HBsAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HBsAg seroclearance than among those who remained HBsAg‐positive (1.86% vs 6.56%, P < .001). Risk factors of HCC occurrence included cirrhosis (incidence with vs without: 9.51% vs 1.66%), male gender (2.34% vs 0.64%) and age ≥ 50 year at HBsAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HBsAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HBsAg seroclearance when at least 50 years old.     

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with anti-HBc

AIM:To investigate the relationship between serumsoluble interleukin-2 receptor(sIL-2R)level and anti-HBcin patients with chronic hepatitis B virus(HBV)infection.METHODS:Sera from 100 patients with chronic HBVinfection and 30 healthy controls were included in thisstudy.The patients were divided into group A[HBsAg( ),HBeAg( )and anti-HBc( ),n=50]and group B[HBsAg( ),HBeAg( )and anti-HBc(-),n=50].sIL-2R levelswere determined using ELISA.HBV DNA and alanineaminotransferase(ALT)were also detected.RESULTS:Serum sIL-2R levels were significantly higherin patients with chronic HBV infection than in healthycontrols.Moreover,serum sIL-2R levels were significantlyhigher in patients with HBsAg( ),HBeAg( )and anti-HBc( )(976.56±213.51×10~3 U/L)than in patients withHBsAg( ),HBeAg( )and anti-HBc(-)(393.41±189.54×10~3 U/L,P<0.01).A significant relationship was foundbetween serum sIL-2R and ALT levels(P<0.01)inpatients with chronic HBV infection,but there was nocorrelation between sIL-2R and HBV DNA levels.Theanti-HBc status was significantly related to the age ofpatients(P<0.01).CONCLUSION:The high sIL-2R level is related topositive anti-HBc in chronic hepatitis B patients.Positiveanti-HBc may be related to T-lymphocyte activation andnegative anti-HBc may imply immune tolerance in thesepatients.     

Differentiation of acute and chronic hepatitis B in IgM antiHBc positive patients

AIM: To identify the factors that differentiate acute hepatitis B(AHB) from chronic hepatitis B with acute exacerbation(CHB-AE).METHODS: From 2004 to 2013, a total of 82 patients(male n = 52, 63.4%; female n = 30, 36.6%) with clinical features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B core antigen(Ig M antiHBc) were retrospectively enrolled and divided into two groups; AHB(n = 53) and CHB-AE(n = 29). The AHB group was defined as patients without a history of hepatitis B virus(HBV) infection before the episode and with loss of hepatitis B surface antigen within 6 mo after onset of acute hepatitis. Biochemical and virological profiles and the sample/cutoff(S/CO) ratio of Ig M anti-HBc were compared to determine the differential diagnostic factors.RESULTS: The multivariate analysis demonstrated that, the S/CO ratio of Ig M anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of Ig M anti-HBc was significantly higher in the AHB group, while the HBV DNA level was significantly higher in the CHB-AE group. The optimal cutoff values of Ig M anti-HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio and 5.5 log10 IU/m L, respectively. The sensitivity and specificity were 96.2% and 89.7% for the S/CO ratio of Ig M anti-HBc and 81.1% and 72.4% for HBV DNA levels, respectively. The area under receiver operating characteristic curves of both the S/CO ratio of Ig M anti-HBc and HBV DNA levels were not significantly different(0.933 vs 0.844, P = 0.105). When combining Ig M anti-HBc and HBV DNA, the diagnostic power significantly improved compared to HBV DNA alone(P = 0.0056). The combination of these factors yielded a sensitivity and specificity of 98.1% and 86.2%, respectively.CONCLUSION: The combination of the S/CO ratio of Ig M anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE in patients with positive Ig M anti-HBc.     

Novel hepatitis B virus surface antigen mutations associated with occult genotype B hepatitis B virus infection affect HBsAg detection

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty‐seven hepatitis B surface antigen (HBsAg)‐positive/HBV DNA‐positive blood donors served as control group for comparison. Occult HBV‐related mutations with a high incidence (P < .05) in the S gene were identified. To further verify these occult infection‐related mutations, a conservative full‐gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection‐related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P < .05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P < .05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P < .05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P < .0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion.     

Hepatitis B Surface Antigen Quantification across Different Phases of Chronic Hepatitis B Virus Infection Using an Immunoradiometric Assay

Background/AimsQuantification of hepatitis B surface antigen (HBsAg) is an emerging serologic test and may be useful for identifying treatment strategies for chronic hepatitis B (CHB). This study aimed to evaluate HBsAg titers during the natural course of CHB and identify correlations between HBsAg titers and hepatitis B virus (HBV) DNA concentrations across different CHB phases measured using an immunoradiometric assay (IRMA).MethodsCHB phases were defined on the basis of HBV DNA concentrations, the presence of hepatitis B e antigen/antibody (HBeAg/Ab) and serum alanine aminotransferase levels. Serum HBsAg titers and paired HBV DNA concentrations in the different phases of CHB were compared using 627 serum samples.ResultsMean HBsAg titers were significantly higher in the immunotolerant (IT) phase and immunoreactive (IR) HBeAg-positive phase than in the low-replicative (LR) and HBeAg-negative CHB (ENH) states. The correlation between HBsAg titers and HBV DNA concentrations was modest in the IT (n=36, r=0.804, p<0.001) and IR (n=48, r=0.773, p<0.001) phases, and it was poor in the LR state (n=116, r=0.289, p=0.002); however, no significant correlation was observed in the ENH state (n=67, r=0.146, p=0.237) or in the oral nucleos(t)ide analogue-treated group (n=267).ConclusionsHBsAg quantification using IRMA might be useful for discriminating different CHB phases and different stages of chronic liver disease.     

Hepatitis B seroprevalence in Thailand: 12 years after hepatitis B vaccine integration into the national expanded programme on immunization

OBJECTIVES: To evaluate the impact of the universal hepatitis B (HB) vaccination programme on the prevalence of hepatitis B surface antigen (HBsAg) carriers and immunity to HB virus infection among children <18 years and to determine the HB seroprevalence in the Thai population. METHODS: We enrolled people in four provinces, including Chiangrai, Udon Thani, Chonburi and Nakhon Si Thammarat to geographically represent populations in the North, Northeast, Center and South of the country respectively. Serology for HBsAg, anti-hepatitis B surface (anti-HBs), and anti-hepatitis B core (anti-HBc) was tested using ELISA commercial kits. In total, 6213 subjects aged 6 months to 60 years from the four provincial hospitals and two to three district hospitals of each participating province participated. RESULTS: Overall HBsAg, anti-HBs, and anti-HBc seropositive rates amounted to 4%, 41.6% and 26.5% respectively. Of 2887 participants aged 6 months to 18 years, 2303 were born after (group I) and 584 prior to (group II) HB vaccine integration into the expanded programme on immunization of each participating province. The HBsAg seropositive rate was 0.7% among group I children and 4.3% among group II children. The prevalence rate of anti-HBc was 2.9% in group I and 15.8% in group II. In children under 18 years, the HBsAg carrier rate was 0.98% among complete vaccinees and 1.36% among participants without vaccination. CONCLUSIONS: This finding supports the efficacy of universal HB immunization in reducing the prevalence of HB infection in Thailand which is a highly endemic country.     

Four-year follow up of hepatitis C patients vaccinated against hepatitis B virus

AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C. METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6 mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series. RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P<0.05). Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P<0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity. CONCLUSION: We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provide protection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.     

Hepatitis B virus reactivation and alemtuzumab therapy

Reactivation of hepatitis B virus infection in subjects receiving cytotoxic treatment for heamatological malignancies occurs in 21-53% of chronic HBsAg carriers and in an unknown number of HBsAg negative subjects harbouring occult HBV infection. Immunotherapy with alemtuzumab, a humanized monoclonal antibody against CD52 epitopes on lymphocytes cells produces deep immunosuppression. We describe two subjects with chronic lymphocytic leukaemia and occult HBV infection who developed a virological and biochemical flare of hepatitis B following immunotherapy with alemtuzumab. One of them developed full blown hepatitis with seroreversion from anti-HBs to HBsAg after four weeks of alemtuzumab therapy. Lamivudine (100 mg die) achieved a complete clinical recovery and HBV-DNA clearance from blood within 8 weeks. The second patient (HBsAg and HBV-DNA seronegative, anti-HBs and anti-HBc positive before treatment) was kept under prophylaxis with lamivudine up to three months after alemtuzumab. Two months after withdrawal of lamivudine, clinical and laboratory features of acute hepatitis B developed. Lamivudine therapy was restarted and a prompt recovery was obtained with HBsAg and HBV-DNA clearance.     

Influence of GB virus-C/hepatitis G virus infection on the long-term course of chronic hepatitis B

Abstract: Aims/Background: The clinical significance of GB virus-C/hepatitis G virus (GBV-C/HGV) infection in chronic hepatitis B is not well known and its role in the outcome of liver disease was investigated. Methods: HGV-RNA and antibody to HGV (anti-E2) were studied in 125 patients with chronic hepatitis B (41 with multiple hepatitis virus exposure), 82 asymptomatic HBsAg carriers and 103 healthy adults. Results: In chronic hepatitis B, HGV-RNA was more frequent in patients with HDV infection and/or anti-HCV positivity than in those without (29% vs 6%, p<0.0001), mainly in drug addicts (38%). At diagnosis the overall prevalence of any marker (HGV-RNA plus anti-E2) was similar in chronic hepatitis due to HBV alone (17%), in HBsAg carriers (16%) and in healthy adults (17%) and increased to 58% in those exposed to HDV and/or HCV. During 1–11 years of follow-up, HGV infection persisted in 70% of patients with chronic hepatitis B. About 40% of HGV persistently coinfected patients underwent sustained biochemical remission, whereas continuing disease activity was observed in 80% of patients who cleared HGV-RNA. Conclusions: In chronic HBV infection the rate of exposure to HGV is similar to that in healthy adults, except for high risk patients. Long lasting HGV coinfection or anti-E2 seroconversion did not modify the course of chronic hepatitis B.     

Long‐term entecavir therapy results in falls in serum hepatitis B surface antigen levels and seroclearance in nucleos(t)ide‐naïve chronic hepatitis B patients

Entecavir (ETV) is reported to result in suppression of hepatitis B virus DNA (HBV DNA) replication with minimal drug resistance. However, information on the long‐term effect of such therapy on serum hepatitis B surface antigen (HBsAg) level and elimination of HBsAg is not available. ETV therapy was started in 553 nucleos(t)ide‐naïve patients with chronic hepatitis B infection (HBeAg positive: 45%) in our hospital. Serum HBsAg levels were measured serially by the Architect assay. The median baseline HBsAg was 2180 IU/mL (0.12–243 000 IU/mL), and median follow‐up period was 3.0 years, with 529, 475, 355, 247 and 163 patients followed‐up for 1, 2, 3, 4 and 5 years, respectively. At year 5, the mean log HBsAg decline from baseline was −0.48 log IU/mL, and the cumulative HBsAg clearance rate was 3.5%. Multivariate analysis identified HBV DNA level at baseline (<3.0 log copies IU/mL, odd ratio = 10.2; 95% confidence interval = 1.87–55.5, P = 0.007) and HBsAg level (<500 IU/mL, odd ratio = 29.4; 95% confidence interval = 2.80–333, P = 0.005) as independent predictors of HBsAg seroclearance. These results indicate that although serum HBsAg level declines gradually during ETV therapy, HBsAg seroclearance remains a rare event.