Therapeutic effects of pegylated interferon plus ribavirin in chronic hepatitis C patients with occult hepatitis B virus dual infection

Background and Aim: Occult hepatitis B virus (HBV) infection is defined by the detectable serum HBV–DNA in HBV surface antigen‐negative patients. This retrospective study aims to evaluate the therapeutic effects of combined pegylated interferon (PEG–IFN) plus ribavirin (RBV) in patients with concurrent occult HBV/hepatitis C virus (HCV) dual infection. Methods: In total, 126 consecutive chronic hepatitis C (CHC) patients who received combined PEG–IFN and RBV therapy were included. Patients were divided into the occult HBV/HCV dual infection group or the HCV‐monoinfected group according to whether or not they had the detectable serum HBV–DNA. The biochemical and virological responses to combined therapy were compared between these two groups. Serum HCV‐RNA and HBV–DNA were checked before treatment, at the end of treatment as well as at 6‐ and 12‐months' follow up in the occult HBV/HCV group. Result: Six patients were seropositive for HBV–DNA and were included in the occult HBV/HCV dual infection group. There were no statistical differences in the biochemical and virological responses to combined therapy between these two groups. Undetectable serum HBV–DNA was noted at the end of the treatment and the 6‐ and 12‐months' follow up in patients with occult HBV/HCV dual infection. Conclusion: Occult HBV infection in CHC patients is rare. The biochemical and virological responses to combined PEG–IFN and RBV therapy might be similar in CHC patients with or without occult HBV infection. The serum HBV–DNA level was low in patients with occult HBV/HCV dual infection who responded to combined therapy.     

Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients

Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real‐time PCR. HCV was detected by real‐time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non‐HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV‐positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV‐positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV‐positive paediatric cancer patients especially in endemic areas as Egypt.     

Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study

BACKGROUND/AIMS: This study assess prevalence, risk factors, and clinical and virological features of dual hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. METHODS: We evaluated 837 hepatitis B surface antigen positive patients, prospectively enrolled in 14 Italian units. RESULTS: Anti-HCV was present in 59 cases (7%); age specific prevalences were 4.5% (0-30 years), 4.4% (>30-50) and 14% (>50). Independent predictors of dual infection were age >42 years, history of I.V. drug use (IDU), blood transfusion and residence in the South of the country. The strength of the association with IDU was high, but this exposure accounted for five coinfection cases only. Cirrhosis was present in 107 of the 709 patients with HBV alone (15.1%), in 30 of 69 with hepatitis D virus coinfection (43%) and in 17 of 59 with HCV coinfection (28.8%); a light alcohol use was marginally associated with cirrhosis. Of 36 B/C coinfected patients, 16 (44.4%) had only HBV-DNA in serum, (median age=47.5 years) five (13.9%) had both HBV-DNA and HCV-RNA (age=53), nine (25%) had HCV-RNA alone (age=59) and six (16.7%) tested negative for both. CONCLUSIONS: This study depicts the epidemiological and clinical burden of dual HBV/HCV infection in Italy.     

Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.     

隐匿性乙型肝炎病毒感染者临床特点和肝组织病理学检查

目的了解血清肝炎病毒标志物阴性、肝功能反复异常患者中HBV隐匿性感染的比例及其临床和病理学特点。方法对27例血清肝炎病毒标志物阴性、肝功能反复异常患者采用免疫组化法检测肝组织HBsAg、HBcAg和HCVAg，并进行常规的病理学检查。结果肝组织HBsAg和（或）HBcAg阳性9例（33．3％）；HBsAg和（或）HBcAg及HCVAg阳性10例（37．0％）；全阴性8例（29．6％）。在HBV隐匿性感染的19例患者中，慢性肝炎8例，肝硬化11例。结论HBV和HCV感染为血清肝炎病毒标志物阴性患者肝功能反复异常的主要原因之一，尤其是HBV感染。这种HBV隐匿性感染与慢性肝炎、肝硬化的发生关系密切，应引起重视。     

Occult hepatitis B virus infection as a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C in whom viral eradication fails.

Aim: Recent studies have suggested that an occult hepatitis B virus (HBV) infection negative for HBsAg but positive for HBV-DNA contributes to hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C. Some follow-up studies have suggested the clinical importance of occult HBV infections in HCC development even after interferon (IFN) therapy, but a recent study denies the significance of the impact of occult HBV infection. Focusing on HCC development in patients in whom hepatitis C virus (HCV) eradication by interferon (IFN) therapy had failed, we conducted this study in order to assess the impact of occult HBV infections on HCC development in these patients. Methods: We enrolled 141 patients with chronic hepatitis C (histological stage F2 or F3) who were seropositive for HCV-RNA even after IFN therapy. Serum HBV-DNA was assayed using the real-time polymerase chain reaction. During follow-up, ultrasonography and/or computed tomography (CT) were performed at least every 6 months to monitor HCC development. Results: The cumulative incidence rates of HCC were 8.9%, 25.7% and 53.7% at 5 years, 10 years and 15 years, respectively, after IFN therapy. Multivariate analysis indicated that low platelet counts (<12 x 10(4)/mm(3)), occult HBV infection, high ALT levels (>/=80 IU/L) after IFN therapy and the staging of liver fibrosis were important independent factors affecting the appearance of HCC. Conclusions: Occult HBV was a risk factor for HCC development in patients with chronic hepatitis C in whom HCV eradication had failed. Therefore, patients with chronic hepatitis C with occult HBV should be monitored carefully for HCC after IFN therapy.     

Combination therapy with interferon-alpha and ribavirin in patients with dual hepatitis B and hepatitis C virus infection

BACKGROUND: Patients with dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infection have responded poorly to interferon (IFN) monotherapy. The purpose of the present paper was to assess the effect of combined IFN-alpha and ribavirin therapy in patients infected with both hepatitis B and C. METHODS: Thirty-six patients received 3 or 5 MU IFN-alpha-2b thrice weekly and oral ribavirin (800-1200 mg/day) for 24 weeks. All patients had positive hepatitis B surface antigen, antibody to HCV, and HCV-RNA. Before treatment, one patient had positive hepatitis B e antigen. Eighteen patients had positive HBV-DNA tested by Amplicor (Cobas Amplicor Monitor, Roche Diagnostics, Branchburg, NJ, USA), with a mean HBV-DNA level of 3.1 +/- 0.9 log copies/mL. Another 72 patients with HCV infection alone served as controls. RESULTS: Adverse events led to withdrawal in three patients receiving 5 MU IFN. Based on an intent-to-treat analysis, the biochemical response and serum HCV clearance rate at the end of 48 weeks follow up was similar in patients with dual infection and HCV infection alone (56% vs 72%; and 69% vs 71%, respectively). There was no significant difference in sustained HCV clearance rate between the 3-MU group (n = 13) and the 5-MU group (n = 23; 85% vs 61%). At the end of 48 weeks follow up, two (11%) of 18 pretreatment viremic patients had negative serum HBV-DNA (<200 copies/mL), while eight of those without pretreatment viremia had re-occurrence of HBV-DNA. CONCLUSIONS: Combination therapy with IFN-alpha and ribavirin was effective in achieving sustained HCV clearance in patients with dual HBV and HCV infection, comparable to those with hepatitis C infection alone. Combination therapy using 3 MU IFN-alpha seemed as effective as 5 MU, and was well tolerated in the study population. However, large-scale control trials are necessary to clarify these findings.     

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.     

Previous hepatitis B virus infection is associated with worse disease stage and occult hepatitis B virus infection has low prevalence and pathogenicity in hepatitis C virus‐positive patients

Abstract: Background: Anti‐hepatitis C virus (anti‐HCV) patients with chronic liver disease (CLD) frequently show markers of previous hepatitis B virus (HBV) infection. Moreover, they may carry occult HBV infection. These features might influence clinical and biochemical features as well as stage of disease. Aim: To assess the prevalence and clinical associations of previous (positivity for anti‐HBs and/or anti‐HBc antibodies) and occult HBV infection (positivity for HBV‐DNA by nested‐PCR) in the serum of anti‐HCV‐positive, HCV‐RNA‐positive, HBsAg‐negative patients with various degrees of CLD seen at a tertiary referral centre. Patients: A total of 119 patients fulfilled the inclusion criteria (84 chronic hepatitis and 35 liver cirrhosis). Results: Forty‐eight patients (40.3%) showed markers of previous HBV infection. This feature was more frequent (P = 0.02) among cirrhotics (57%) as compared to chronic hepatitis patients (33%). Chronic hepatitis patients positive for markers of previous HBV infection had worse histology as compared to negative ones (grading: 6.4 ± 2.7 versus 4.6 ± 3.0, P = 0.004; staging: 1.6 ± 1.2 versus 1.0 ± 1.0, P = 0.01). Eight patients were positive for HBV‐DNA in serum (6.7%). No difference in the presence of occult HBV infection was seen between various degrees of liver disease (7.1% of chronic hepatitis, 5.7% of cirrhosis) and among patients who were positive (10.4%) or negative (4.2%) for markers of previous HBV infection. No significant biochemical, virological, or histological difference was observed between age, age at infection, duration of infection, marker patterns of previous HBV infection‐matched HBV‐DNA‐positive and negative chronic hepatitis patients. Conclusions: Our findings suggest that previous HBV infection among anti‐HCV patients is associated with worse disease stage. In these patients, the prevalence of occult HBV infection is low and there is no difference in distribution among patients with or without markers of previous HBV infection. Furthermore, it does not seem to be associated with disease stage. Lastly, at least among patients with chronic hepatitis, it does not seem to affect the severity of disease.     

Occult hepatitis B virus infection in Greek patients with chronic hepatitis C and in patients with diverse nonviral hepatic diseases

Occult hepatitis B virus (HBV) infection has been reported in patients with chronic hepatitis C who are negative for HBV surface antigen (HBsAg). However, the significance of 'silent' HBV in hepatitis C virus (HCV) infection is unknown. We investigated 540 subjects for the presence of occult HBV in Greek HCV patients, patients with nonviral liver diseases and healthy donors in an attempt to determine the frequency and importance of this phenomenon. One hundred and eighty-seven anti-HCV(+)/HBsAg(-) patients' sera were investigated for the presence of HBV-DNA by polymerase chain reaction. Two hundred and eighty-two selected blood donors (positive for antibodies to HBV core antigen) and 71 patients with various nonviral hepatic diseases consisted the control groups [both controls were anti-HCV(-)/HBsAg(-)]. HBV-DNA was detected in 26.2% of HCV-infected patients vs 8.5% of patients with nonviral diseases (P = 0.003) and 0/282 of donors (P = 0.0000). HBV-DNA was neither associated with HBV markers, nor with the clinical status of HCV and nonHCV patients. Neither epidemiological, histologic and virologic data nor the response to therapy were associated with the HBV-DNA detection. Hence one quarter of HCV-infected patients had occult HBV infection. Similar findings were not found in both control groups. Occult HBV infection in Greek patients with chronic hepatitis C does not seem to modify the progression of chronic liver disease. Further studies of longer duration are needed in order to clarify the role of 'silent' HBV infection in HCV-infected patients.     

Cellular immune responses in patients with dual infection of hepatitis B and C viruses: Dominant role of hepatitis C virus

Several lines of evidence have suggested that immune mechanisms are involved in the pathogenesis of hepatitis B virus (HBV)- and hepatitis C virus (HCV) -related hepatitis. Study of patients with dual HBV and HCV infection raises the question of which is etiologically more relevant in determining the liver cell damage. To address this issue, proliferation of peripheral blood mononuclear cells (PBMCs) in response to a panel of HBV and HCV antigens was assayed in 13 patients with chronic dual hepatitis B and C, 7 patients with chronic hepatitis B, 7 patients with chronic hepatitis C, and 6 patients with hepatitis B surface antigen (HBsAg) carrier state. Although HBV or HCV hepatitis patients had a significant response to HBV or HCV antigens, respectively, the patients with dual hepatitis B and C exclusively responded to HCV antigens, but not to HBV antigens. One patient who was seropositive for both HBV-DNA and HCV-RNA showed a low response to HBV antigens initially but lost the response 3 months later and became responsive to more HCV antigens. These findings suggest that HCV has a dominant role in the immune response of the patients with dual HBV and HCV infection.     

Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients

Purpose  The presence of hepatitis B virus (HBV) DNA in liver tissue and/or in serum in the absence of detectable hepatitis B surface antigen (HBsAg) is called occult HBV infection. This pattern was identified in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the role of antibodies to hepatitis B core antigen (anti-HBc) as a screening test for occult HBV infection in Egyptian chronic HCV patients. Methods  One hundred chronic HCV patients negative for HBsAg were included and subdivided into two groups according to anti-HBc-IgG seroreactivity. Group A included 71 patients positive for anti-HBc (53 men and 18 women, mean age ± SD 48.8 ± 9.6 years), and group B included 29 patients negative for anti-HBc (18 men and 11 women, mean age ± SD 46.6 ± 11.7 years). All patients were subjected to full clinical assessment, routine laboratory investigations, abdominal ultrasonography and quantification of HBV-DNA by real-time PCR. Results  Chronic HCV patients positive for anti-HBc have more severe liver disease compared with anti-HBc negative patients. Although HBV-DNA in the serum was detected in 22.5% of anti-HBc-positive chronic HCV patients, it was not detected in any of anti-HBc-negative chronic HCV patients. There was no significant difference in any of the clinical and laboratory data tested between anti-HBc-positive patients with and without HBV-DNA in the serum. Conclusion  A significant number of patients with anti-HBc had detectable levels of HBV-DNA in the serum. Egyptian chronic HCV patients have a high prevalence of occult HBV infection.     

Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection

AIM: To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus (HCV) infection, and its relation to disease severity. METHODS: We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study. RESULTS: Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis (CAH). Of these 169 patients, 85 (50.3%) tested positive for anti-HBc. Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 (64.5%) and 14 (23.7%) respectively (P < 0.001). Twenty-five patients were tested for HBV DNA by qualitative PCR. The test was positive in 3 of them (12%; occult HBV infection). CONCLUSION: Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.     

Analysis of occult hepatitis B virus infection in liver tissue of HIV patients with chronic hepatitis C

OBJECTIVE: Current data on the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals conflict. As occult HBV infection could have an impact on the outcome of liver disease in HIV-positive patients, we investigated a large number of HIV-positive/HBV-surface-antigen (HBsAg) negative subjects with hepatitis C virus (HCV) infection by using the 'gold standard' approach for occult HBV detection--analysis of liver DNA extracts. METHODS: The presence or absence of HBV DNA was determined by PCR testing of four different viral genomic regions in DNA extracts of needle liver biopsy specimens of 101 HBsAg negative individuals with HIV/HCV co-infection. HBV genotyping was performed by sequencing analysis of the preS-S gene in occult HBV isolates from 18 cases. RESULTS: Occult HBV infection was diagnosed in 42 of the 101 cases (41%). No clinically relevant difference was found between occult HBV-positive and -negative patients. HBV genotype D and A were detected, respectively, in 11 (61%) and 7 (39%) of 18 cases analysed. CONCLUSIONS: Occult HBV infection frequently occurs in HIV/HCV co-infected patients indicating the importance of performing prospective studies able to clarify its clinical impact in these patients. HBV genotype A is highly prevalent in HIV-infected subjects with occult HBV infection in a similar way to HBsAg/HIV-positive individuals.     

Frequent delayed spontaneous seroclearance of hepatitis B virus after incident HBV infection among adult high‐risk groups

High rates (~25%) of developing chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen (HBsAg)‐positive for > 6 months following infection) have been observed in people who use drugs (PWUD) and men who have sex with men (MSM). We aimed to estimate the frequency of delayed HBsAg seroclearance, along with its determinants, and time to delayed HBsAg seroclearance. Data were used from MSM and PWUD enrolled in the Amsterdam Cohort Studies (1985‐2002) who had anti‐hepatitis B core antibody seroconversion. Potential determinants for standard HBsAg seroclearance, delayed HBsAg seroclearance and chronic HBV were examined using multinominal logistic regression. Time to HBsAg seroclearance was estimated using Kaplan‐Meier curves. A total of 147 incident HBV infections occurred during follow‐up. On initial HBsAg testing after infection (6‐12 months), 42 (29%) were HBsAg‐positive and 105 (71%) were HBsAg‐negative (‘standard HBsAg seroclearance’). Of the 42 initially HBsAg‐positive individuals, 22 subsequently tested HBsAg‐negative (of whom 7 (31.8%) were HBV DNA positive at last visit, suggesting occult HBV). Overall, 15 became HBsAg‐negative and HBV DNA‐negative (‘delayed HBsAg seroclearance’), while 27 remained HBsAg and/or HBV DNA‐positive (‘chronic HBV’). The 5‐year cumulative probability of delayed HBsAg seroclearance was 41.6% for initially HBsAg‐positive individuals. Delayed HBsAg seroclearance and remaining chronically infected were associated with younger age and HIV/hepatitis C virus (HCV)‐co‐infection. In conclusion, delayed HBsAg seroclearance is common in these key adult populations at‐risk for HBV, while proportion developing HBV chronicity (18%) is still higher compared to the general population (~5%). Given the proportion of individuals with occult HBV infection and that HCV direct‐acting antivirals can lead to HBV reactivation, HBV DNA testing in HCV co‐infected MSM/PWUD are warranted prior to treatment initiation.     

Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area

BACKGROUND/AIMS: The acquisition of hepatitis B virus (HBV) infection following organ transplantation from donors with occult HBV infection is an important cause of morbidity and mortality. The aim of this study is to determine the prevalence of occult HBV in allogeneic hematopoietic stem cell (HSC) transplantation donors. METHODS: We performed a retrospective study on 124 consecutive hepatitis B surface antigen negative HSC donors. Their serum samples were analyzed by PCR for the pre-S/S, pre-core/core and X regions of the virus. Samples reactive by at least two PCR assays were considered HBV-DNA positive. RESULTS: Nineteen of the 124 HSC donors (15.3%) had occult HBV infection. Sixteen of these 19 donors with occult HBV infection (84.2%) tested positive for hepatitis B core antibody while 78 of 105 subjects (74.3%) without occult HBV infection were also positive (P=0.56). Fourteen of the 19 donors (73.7%) with occult HBV infection tested positive for hepatitis B surface antibody while 67 of the 105 subjects without occult HBV infection were also positive (P=0.45). CONCLUSIONS: The prevalence of occult HBV infection among HSC donors in Hong Kong is high. Anti-HBc and anti-HBs status had no significant correlation with the presence of occult HBV infection.     

慢性乙型肝炎病毒感染者家族隐匿性乙型肝炎病毒感染的调查

目的 了解慢性HBV感染者家族隐匿性HBV感染的发生率及其与HBV标志物、年龄和性别等的关系.方法 ELISA方法检测慢性HBV感染者家族成员的HBV血清学标志物,套式PCR法检测136例HBsAg阴性家族成员的血清HBV DNA,并将隐匿性HBV感染者和HBsAg、HBV DNA均阴性者分别作为试验组和对照组进行HBV标志物、年龄、性别和生物化学检测结果的比较.两组均数比较采用t检验.率的比较采用χ~2检验或Fisher确切概率法检验.结果 在52个慢性HBV感染者家族中共检测到92例HBsAg阳性者和136例HBsAg阴性者,其中15例为隐匿性HBV感染者,慢性HBV感染者家族HBsAg阳性率和隐匿性HBV感染的发生率分别为40.4%和11.0%,15例隐匿性HBV感染者中有7例抗-HBc阳性(χ~2=5.341,P=0.02),但隐匿性HBV感染的存在与年龄、性别等无关.结论 HBV感染存在家庭聚集现象,且在其家族中存在隐匿性HBV感染,并在抗-HBc阳性者中发生率较高.     

Lack of association between occult hepatitis B virus DNA viral load and aminotransferase levels in patients with hepatitis C virus-related chronic liver disease

BACKGROUND AND AIM: Occult hepatitis B virus (HBV) infection in hepatitis C virus (HCV)-infected patients might enhance the severity of chronic liver disease (CLD). To elucidate the correlation between occult HBV infection and the clinical course of HCV-related CLD, we evaluated whether the fluctuation of occult HBV-DNA directly affects the serum alanine aminotransferase (ALT) level. METHODS: Forty-one patients with HCV-related CLD who received regular outpatient treatment and 42 age-, sex-, and antibody to hepatitis B core antigen positivity-matched healthy volunteers were enrolled. Serum HBV-DNA was quantitatively detected using real-time detection polymerase chain reaction (RTD-PCR). Serial serum samples in three patients were measured for HBV-DNA, ALT and HCV core antigen. RESULTS: Hepatitis B virus DNA was amplified in eight of the HCV-related CLD patients (19.5%), which was significantly higher than that of healthy volunteers (2.4%). No significant difference between the genotype 1 HCV-related CLD group and the genotype 2 group was found. Based on the analyses using serial serum samples, the elevation of HBV-DNA did not occur before the ALT flares, but occurred at the same time or after the ALT flares. CONCLUSIONS: The prevalence of occult HBV infection of HCV-related CLD is significantly higher than that of control. Occult HBV infection has no influence on ALT flares among patients with HCV-related CLD.     

Occult hepatitis B virus infection and lamivudine-resistant mutations in isolates from renal patients undergoing hemodialysis

Background and Aims:  Patients undergoing hemodialysis are at risk of infection with both hepatitis B virus (HBV) and hepatitis C virus (HCV). Occult HBV infection is usually associated with low levels of HBV and is frequently detected in HCV-infected patients. The aims of the present study were to compare the prevalence of occult HBV infection among anti-HCV-positive and anti-HCV-negative patients undergoing hemodialysis, and characterize the molecular patterns of HBV isolates from patients with occult infection.
Methods:  Serum samples from 100 patients negative for hepatitis B surface antigen undergoing hemodialysis, half of whom were positive for anti-HCV antibodies, were tested for the presence of HBV-DNA using semi-nested polymerase chain reaction (PCR). PCR products of the S gene were directly sequenced.
Results:  HBV-DNA was detected in 15 samples. There were no significant differences in HCV status, sex, age, time of dialysis, alanine aminotransferase levels or HBV serological markers between patients with or without occult HBV infection, with the exception of antibody to hepatitis B core antigen (anti-HBc)-only serological marker ( P  = 0.003). All six HBV isolates that could be sequenced were of genotype A/subgenotype A1. Four of these six HBV isolates contained mutations associated with lamivudine resistance in the DNA polymerase (two with L180M/M204V and two with rt173V/180M/204V) and a specific substitution (Y100C) in the HBV small surface protein.
Conclusions:  HBV isolates with the identified substitutions have the potential to spread silently by nosocomial transmission within the hemodialysis unit. These results have potential implications for the management of patients with occult HBV infection undergoing hemodialysis.