High prevalence of occult hepatitis B in Baltimore injection drug users

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in a serum or liver in the absence of hepatitis B surface antigen (HBsAg). The prevalence and clinical correlates of occult hepatitis B remain incompletely defined. A cross-sectional study was performed to determine the prevalence of occult hepatitis B in a high-risk cohort composed of 188 injection drug users in Baltimore, Maryland. All individuals had chronic hepatitis C viral infections confirmed by RNA detection and liver biopsy. Serologic assays for HBsAg and core antibody (HBcAb) were performed. Serum HBV DNA was detected using the COBAS HBV AMPLICOR monitor assay (lower limit of detection, 200 HBV copies per milliliter) and a semi-nested polymerase chain reaction (PCR) assay (lower limit of detection, 15 HBV copies per milliliter). Although almost all individuals (96%) were anti-HBC positive, only 8 of 188 (4%) were HBsAg positive. Occult hepatitis B was not identified using the COBAS assay, but was found in 81 of 180 (45%) of individuals using semi-nested PCR. Of the 8 HBsAg positive individuals, HBV DNA was found in 1/8 using the COBAS assay and 6/8 using the nested PCR assay. Overall, liver disease was mild, with a median serum alanine aminotransferase (ALT) of 38 IU/L, median activity grade of 3/18, and median fibrosis stage of 1/6. No association was found between the serum AST (aspartate aminotransferase), activity grade, or stage of liver disease and the presence of occult hepatitis B. Serum ALT levels were slightly higher in patients without occult hepatitis B (46 vs. 35 IU/L), and the median years since first injection drug use was somewhat longer in those without occult hepatitis B (24 vs. 20 years). In conclusion, although further research is needed to assess its clinical significance, there is a high prevalence of occult HBV infection in this cohort of HCV-infected injection drug users.     

Prevalence and clinical relevance of occult hepatitis B in the fibrosis progression and antiviral response to INF therapy in HIV-HCV-coinfected patients

Occult hepatitis B virus (HBV) infection is diagnosed when HBc antibodies (HBcAb) and HBV DNA are detectable in serum while hepatitis B surface antigen (HBsAg) is not. This situation has been frequently described in patients with chronic hepatitis C virus (HCV) infection. The objective of this study was to evaluate the prevalence of occult hepatitis B in HIV-HCV-coinfected patients and its clinical relevance in liver histology and viral response after interferon therapy for HCV. A total of 238 HIV-HCV-infected patients,negative for HBsAg, were included. Serum samples were analyzed for the presence of HBV DNA and HBcAb.HBV DNA quantification was determined with the Cobas TaqMan HBV Test (detection limit 6 IU/ml). Data from liver biopsy and laboratory tests were also analyzed. HBcAb resulted in 142 (60%) patients, being the independent associated factors: male gender, previous history of intravenous drug use, age, CD4 count,and HAV antibody presence. Among 90 HBcAb patients that we could analyze, HBV DNA was positive in 15 (16.7% of occult hepatitis B infection in this group, and 6.3% in the whole HIV-HCV cohort studied). No baseline factors, liver histology, or HCV therapy response were related to the presence of HBV DNA. We found that occult hepatitis B is a frequent condition present in at least 6.3% of our HCV-HIV patients and in more than 16% of those with HBcAb. Despite the high prevalence, this phenomenon does not seem to affect the clinical evolution of chronic hepatitis C or modify the viral response to interferon-based HCV therapies     

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.     

Preliminary results of HBV DNA testing of Polish haemophilia patients – lack of occult HBV infection

Identification of hepatitis B virus (HBV) infection in the absence of surface antigen (HbsAg) became possible with the introduction of HBV DNA detection methods. Such occult HBV infection was diagnosed recently in about half of the Japanese HBsAg-negative haemophilia patients. The aim of our study was to assess the prevalence of occult HBV infection in Polish severe haemophilia population on the sample of 115 haemophilia A and B patients (mean age 34.9 +/- 10.9) treated with non-virus inactivated clotting factor preparations before 1995. HBV DNA was detected in nine HBsAg-positive patients (7.8%). The mean HBV DNA load was 72,800 IU mL(-1) (250-400,000 IU mL(-1)). Hepatitis C virus (HCV) RNA was found in six out of nine HBV-positive patients. In conclusion, HBV DNA was identified only in HBsAg-positive patients. Unlike in Japan, the frequency of occult HBV infection in Polish haemophilia population seems extremely rare or absent.     

Significance of Prior Hepatitis B Virus Infection in the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C

To clarify the clinical significance of prior hepatitis B virus (HBV) infection in the development of C-viral hepatocellular carcinoma (HCC), we conducted two studies: (1) Two hundred thirty-four patients with C-viral HCC and 320 patients with C-viral chronic liver disease without HCC admitted to our hospital between 1990 and 1994 were analyzed for the association of hepatitis B core antibody (HBcAb) positivity with HCC by multivariate logistic regression analysis, and this revealed HBcAb positivity as an independent risk factor for development of HCC adjusted for age and sex. (2) Four hundred fifty-nine patients with biopsy-proven hepatitis C virus-related chronic liver disease between 1986 and 1998 were enrolled in the cohort study and followed for the development of HCC. During an average follow-up of 6.6 ± 3.3 years, HCC developed in 63 patients, 37 of 160 patients positive for HBcAb and 26 of 299 patients negative for HBcAb. Multivariate Cox proportional regression analysis showed that the incidence of HCC increased by age, advanced stage of liver fibrosis, mean alanine aminotransferase value of more than 80 IU/liter, and positivity of HBcAb. Sustained virological responders after interferon therapy revealed a reduced risk for HCC development. In conclusion, prior HBV infection was shown to be one of the independent risk factors for development of HCC in C-viral chronic liver disease.     

Telbivudine therapy for chronic hepatitis B: A journey to identify super‐responders and to optimize treatment using the roadmap model

Hepatitis B virus (HBV) infection is one of the most serious health problems worldwide with a high risk for cirrhosis and liver cancer. Several antiviral agents have been approved for the treatment of chronic hepatitis B, leading to a rapid reduction in HBV DNA and normalization of serum alanine aminotransferase levels. Telbivudine, a potent inhibitor of HBV replication, has been shown to be well tolerated. Because of the emergence of drug resistance, optimization strategies for telbivudine therapy have been shown to improve patient responses. Optimal baseline characteristics in so‐called super‐responders have been used to predict the virological response. Baseline HBV DNA levels < 9 log₁₀ copies/mL (2 × 10⁸ IU/mL) or alanine aminotransferase levels of more than or equal to twofold the upper limit of normal in HBeAg‐positive patients and HBV DNA < 7 log₁₀ copies/mL (2 × 10⁶ IU/mL) in HBeAg‐negative patients were strong predictors for virological response. In addition, the roadmap model, based on early virological response at week 24 of therapy, is considered as a powerful tool to identify patients at risk of treatment failure (HBV DNA ≥ 300 copies/mL, i.e. 60 IU/mL) and to reduce the risk of antiviral resistance. When considering pre‐treatment characteristics and on‐treatment responses, telbivudine may provide physicians with a wide choice of options to effectively treat patients with chronic hepatitis B, especially those with or at risk of renal impairment, or women of childbearing age.     

Impact of non-alcoholic fatty liver disease on chronic hepatitis B.

BACKGROUND: The impact of superimposed non-alcoholic fatty liver disease (NAFLD) is well established in patients with chronic hepatitis C (CH-C), but the impact in patients with chronic hepatitis B (CH-B) is less clear. Aim: This study aims to evaluate the prevalence of NAFLD in patients with CH-B and the association with viral and host factors, particularly in patients with metabolic syndrome (MS). DESIGN: Data from patients with CH-B was obtained from our databases. Patients with excessive alcohol use were excluded. Hepatitis B virus (HBV) genotyping by INNO-LIPA was available for some patients. The presence of MS was defined according to the Adult Treatment Panel III (ATP III). All biopsies were read by two hepatopathologists using Metavir, modified histologic activity index (MHAI), as well as a NAFLD pathologic protocol. Patients were classified as (1) those without NAFLD; (2) those with simple hepatic steatosis; (3) and those with superimposed non-alcoholic steatohepatitis (NASH). Factors associated with superimposed NAFLD, its subtypes, and hepatic fibrosis were also analysed. RESULTS: Subjects included 153 HBV patients [66% male, age 50.5+/-27.5 years, body mass index 24.7+/-3.7 kg/m(2), waist 83.2+/-10.9 cm; 8.5% Caucasian, 67% Asian, aspartate aminotransferase (AST) 63.2+/-88.2 IU/l, alanine aminotransferase (ALT) 98.6+/-164.6 IU/l, glucose 111.6+/-50.5 mg/dl, HBV-DNA 1.8 x 10(8)+/-1.9 x 10(6) copies/ml, 7% with MS, 13% with diabetes, 20% with arterial hypertension and 8.5% with dyslipidaemia]. Liver biopsy was available for 64 subjects [19% had superimposed NAFLD, 13% had superimposed NASH, 86% had some degree of fibrosis, and 39% had advanced fibrosis (Ishak >3)]. Patients with HBV and superimposed NASH were significantly older (55 vs. 42 years, P=0.008), more likely to have hypertension (63% vs. 15%, P=0.006) and dyslipidaemia (50% vs. 8%, P=0.006), and had a larger waist circumference (92 vs. 83 cm, P=0.03). The presence of fibrosis was associated with higher waist circumference (84 vs. 80 cm, P=0.03), higher HBV-DNA (1.9 x 10(8) vs. 5 x 10(6) copies/ml, P=0.005), and elevated ALT >40 IU/l (73.6% vs. 33.3%, P=0.02). CONCLUSIONS: The components of MS (obesity, hypertension, and dyslipidaemia) are associated with the presence of NASH in patients with CH-B. The presence of hepatic fibrosis seems to be associated with known host and viral factors as well as the presence of abdominal obesity.     

Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers

BACKGROUND/AIMS: A recent NIH research workshop on hepatitis B virus (HBV) revisited the definition of healthy HBsAg carriers. The new definition inactive surface antigen (HBsAg) carriers includes an estimated serum HBV DNA level below 105 copies/ml. However, this cut-off value needs to be confirmed. METHODS: Eighty-five consecutive patients, HBsAg-positive/HBeAg-negative with persistently normal alanine aminotransferase (ALT) and undetectable serum HBV DNA with standard assay (Versant HBV DNA Assay (bDNA), Bayer) were prospectively followed for 3.2+/-2.6 (range 0.5-11) years; 58 underwent a liver biopsy. Serum HBV DNA was quantified with a sensitive polymerase chain reaction assay (Cobas Amplicor HBV Monitor, Roche) (sensitivity 200 copies/ml), and liver histology was assessed using the Ishak scoring system. RESULTS: The median serum HBV DNA level was 1300 copies/ml (<200-179 x 10(3) copies/ml), 16% of the subjects had no detectable serum HBV DNA and 98% had levels below 10(5) copies/ml. Histologic lesions were mild (total score <7) in all cases. Loss of HBsAg was observed in three patients, three patients experienced a transient increase in ALT (<2 x upper limit of normal), and serum HBV DNA levels remained stable (1-6 years) in 97% of the 38 patients retested. CONCLUSIONS: In our study of inactive HBsAg carriers, the median serum HBV DNA level was 1300 copies/ml, the serum HBV DNA level was below 10(5) copies/ml in 98% of the patients, and remained stable; histological lesions were mild in all cases.     

Role of hepatitis B virus infection in chronic liver disease of diabetic patients: A case-control study

Summary In the literature there is no agreement on the prevalence of chronic liver disease (CLD) and the role of hepatitis B virus (HBV) infection in diabetics. We undertook an epidemiological case-control study of the prevalence of CLD and HBV infection in 394 diabetics and 265 healthy subjects from Seriate and Como. The results did not show any significant differences between: 1) the prevalence of CLD in the diabetic population and in controls (4.8%vs 4.5%); 2) the prevalence of HBV infection in diabetics (HBsAg+: 8.3%: HBVAb+: 55.8%) and in controls (HBsAg+: 8.6%; HBVAb+: 54.7%); 3) the prevalence of HBV infection in diabetics with CLD (HBsAg+: 21%; HBVAb+: 52.6%) and in controls with CLD (HBsAg+: 16.6%; HBVAb+: 50%); 4) the prevalence of HBV infection in diabetics with and without CLD (HBsAg+: 21%vs 7.7%; HBVAb+: 52.6%vs 56%); 5) the prevalence of HBV infection in diabetics treated by injection and orally (HBsAg+: 6.9%vs 8.6%; HBVAb+: 58.3%vs 55.2%). The relative risk of CLD for the factor HBsAg+ was 3.2 in the diabetic populationvs 1.4 in controls. In view of the presence of antidelta antibodies (HDVAb) in 25% of HBsAg+ diabetics with CLD and the lack of HBV markers in 26.3% of diabetics with CLD, we assume that other viruses (Delta, nonA-nonB) may play roles. Probably the interaction of all possible etiopathogenetic factors (alcohol, viruses, glycometabolic derangement) is determinant for CLD in diabetics.     

Is Hepatitis C Virus Positivity a Contributing Factor to Occult Hepatitis B Virus Infection in Hemodialysis Patients?

Hepatitis B (HBV) infections continue to occur in adult hemodialysis units. Occult HBV infection (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive) may be a contributing factor in these patients. This study was designed to (1) investigate the prevalence of occult HBV infection in hemodialysis patients and (2) compare the prevalence of occult HBV infection among hepatitis C (HCV)-positive and HCV-negative hemodialysis patients. The study included 138 patients on chronic hemodialysis. Eighty-four patients were HCV positive and 54 were HCV negative. HBV DNA testing was performed by polymerase chain reaction. We also recorded general characteristics of the patients, duration of hemodialysis, and serum alanine aminotransferase and aspartate aminotransferase levels. Twenty-one (15.2%) of the 138 hemodialysis patients were HBV DNA positive. Nine (16.6%) of the 54 anti-HCV antibody negative hemodialysis patients were HBV DNA positive. Twelve (14.2%) of the 84 anti-HCV antibody positive patients were HBV DNA positive. The prevalence in anti-HCV Ab positive and negative hemodialysis patients were same (P > .05). Hemodialysis duration, demographic features, and biochemical parameters were not significantly different in patients with and without occult HBV infection in both HCV-positive and -negative hemodialysis patients (P > .05). HCV positivity is not a contributing factor to occult HBV infection in hemodialysis patients. None of the parameters tested help to distinguish patients with occult HBV infection from those who are HBV DNA negative.     

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.
METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.
RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.
CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA mor     

Viremia profiles in children with chronic hepatitis B virus infection and spontaneous e antigen seroconversion

BACKGROUND & AIMS: This study investigated the viremia profiles in children with chronic hepatitis B virus (HBV) infection and spontaneous hepatitis B e antigen (HBeAg) seroconversion. METHODS: Fifty-eight children with chronic HBV infection met the following criteria: normal alanine aminotransferase (ALT) level at enrollment, followed up for more than 10 years, no antiviral treatment, and having undergone spontaneous HBeAg seroconversion during follow-up evaluation. They were grouped according to the post-HBeAg seroconversion HBV-DNA levels: (1) low viremia: transient or never 10(4) copies/mL or greater (n=35) (2) fluctuating high viremia: 10(4) copies/mL or greater at least twice at intervals more than 1 year apart (n=23). Abdominal sonography, ALT, and HBV-DNA levels were assessed annually. Another 14 nonseroconverted children served as controls. The precore mutant (nt1896) and genotypes were examined. RESULTS: The initial HBV-DNA level of the 58 seroconverters was 10(8.4+/-1.0) copies/mL and decreased to 10(2.9+/-2.0) copies/mL at the end of follow-up period. Their mean ages at enrollment, at peak HBV-DNA, at peak ALT, at HBeAg seroconversion, and at final follow-up were 7.0 +/- 3.7, 13.4 +/- 5.8, 16.3 +/- 6.0, 17.2 +/- 5.8, and 23.7 +/- 4.1 years, respectively. The precore mutant appeared more often in the fluctuating-high-viremia group than in the low-viremia group (60.9% vs 22.9%, P=.004). HBV genotypes had no effect on the viremia profiles. After HBeAg seroconversion, none had persistent abnormal ALT levels. CONCLUSIONS: Generally, these young seroconverters had decreased viral loads, normal ALT levels, and uneventful courses after HBeAg seroconversion. A longer follow-up period is necessary to elucidate the significance of HBeAg seroconversion occurring in childhood and young adulthood.     

Viral level is an indicator of long-term outcome of hepatitis B virus e antigen-negative carriers with persistently normal serum alanine aminotransferase levels

Summary. The association between viral level and the long‐term outcomes of hepatitis B virus (HBV) carriers who test negative for hepatitis B virus e antigen (HBeAg) but have persistently normal serum alanine aminotransferase levels (PNALT) remains unclear. We examined hepatocarcinogenesis, hepatitis reactivation, predictive factors and the time course of HBV DNA levels during follow‐up in 104 HBeAg‐negative Japanese carriers with PNALT. During a mean follow‐up period of 6.4 ± 3.4 years, 5 patients (4.8%) had hepatocarcinogenesis and 14 (13.5%) had hepatitis reactivation. At 5 and 10 years, the cumulative rates of hepatocarcinogenesis were 2.4% and 9.9%, while those of hepatitis activation were 13.7% and 15.5%, respectively. An HBV DNA level of ≥5 log₁₀ copies/mL was the sole predictor of hepatocarcinogenesis with a univariate analysis. An HBV DNA level of ≥5 log₁₀ copies/mL and an alanine aminotransferase (ALT) level of >20 to ≤40 IU/L were independent predictors of hepatitis reactivation in a Cox model. Because there was no association between hepatocarcinogenesis and ALT activity, the HBV DNA level was considered an essential predictor. In addition, the baseline HBV DNA level was related to the future level and was not subject to wide fluctuations. Our results showed that an HBV DNA level of ≥5 log₁₀ copies/mL predicts subsequent hepatocarcinogenesis and hepatitis reactivation in HBeAg‐negative carriers with PNALT. As the baseline HBV DNA level reflects the future level, appropriate clinical management according to the viral level is expected to decrease future risk.     

Occult HBV infection and YMDD variants in hemodialysis patients with chronic HCV infection

BACKGROUND/AIMS: End-stage renal disease patients on chronic hemodialysis are at risk for both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Although the prevalence is unknown in hemodialysis patients, occult HBV infection is frequent in subjects with chronic HCV infection. We aimed to investigate (1) the prevalence and clinical impact of occult HBV infection in hemodialysis patients with chronic HCV infection, and (2) the frequency of YMDD variants (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) in this setting. METHODS: Thirty-three anti-HCV and HCV-RNA-positive, HBsAg-negative hemodialysis patients (mean age 36.9+/-10.4 years, 22 male) were admitted to this study. HBV-DNA (Innogenetics kit) and HCV-RNA (Cobas Amplicor HCV kit) were investigated by polymerase chain reaction technique (PCR). YMDD mutation was studied in all HBV-DNA-positive patients by the BOOM method. RESULTS: HBV-DNA was detected in 12 of 33 patients (36.4%) by PCR. Their mean age was 33.0+/-9.0 years. Age, dialysis period (years) and biochemical parameters were not significantly different in patients with and without occult HBV infection. YMDD variants were identified in six of 12 (50%) patients with occult HBV infection. CONCLUSIONS: Occult HBV infection is frequent in hemodialysis patients with chronic HCV infection. YMDD variants are common in this setting.     

Effects of bezafibrate in patients with chronic hepatitis C virus infection: combination with interferon and ribavirin

An association of hepatitis C virus (HCV) with low-density lipoproteins (LDL) in serum of patients with chronic hepatitis C (CHC) has been suggested. We conducted a prospective study in CHC patients complicated with hyperlipidaemia, to examine whether bezafibrate, which is commonly used for treatment of hyperlipidaemia, reduces serum HCV-RNA titre and improves liver dysfunction. Fifteen patients received daily oral bezafibrate treatment (400 mg/day) for 8 weeks, and its effects on serum lipids, transaminases, HCV-RNA titres, and HCV-RNA titres bound to LDL were evaluated. Fifteen untreated patients with CHC and hyperlipidaemia were used as controls. The mean serum alanine aminotransferase levels and HCV-RNA titres significantly decreased at the end of bezafibrate therapy in the treated group (105 +/- 34 to 80 +/- 32 IU/L, P = 0.02 and 2.23 +/- 2.71 to 1.78 +/- 2.38 x 10(7) copies/mL, P < 0.01 respectively), but no changes were observed in the control group. Serum HCV-RNA titres bound to LDL, as quantified by immunoprecipitation using anti-LDL antibody, also decreased in all 15 treated patients [5.55 +/- 6.59 to 1.07 +/- 1.58 x 10(6) copies/ml, P < 0.01 (mean reduction rate was -78.5 +/- 17.0%)]. Sucrose density-gradient ultracentrifugation study revealed that HCV-RNA-decreased density fractions after the bezafibrate were identical to LDL-density fractions (1.015-1.062 g/mL). Eight CHC patients were treated with bezafibrate, interferon, and ribavirin triple therapy for 32 weeks, and four patients achieved sustained virological response to therapy. This pilot study provides further evidence of an association between HCV and LDL in serum and suggests the potential usefulness of bezafibrate as an anti-HCV reagent for the treatment of CHC patients.     

Occult hepatitis B virus infection: A major concern in HIV-infected patients: Occult HBV in HIV

Human immunodeficiency virus (HIV)- infected patients are at risk of acquiring viral hepatitis, due to common routes of transmission. As the introduction of highly active antiretroviral therapy (HAART) reduced the frequency of opportunistic infections and improved survival, viral hepatitis emerged as an important cause of morbidity and mortality in HIV-infected cases. Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg). There are conflicting reports on the impact of occult HBV infection on the natural history of HIV disease. In this review, we described the findings of studies on HIV and hepatitis B co-infection with focus on the prevalence of occult HBV infection. The results of this review demonstrated the importance of prevention, diagnosis and treatment of occult HBV infection in HIV-positive patients.     

Occult hepatitis B virus infection and its clinical implications

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Serum HBV level is usually less than 10⁴ copies/mL in these patients. Diagnosis of occult HBV infection requires sensitive HBV-DNA PCR assay. Several possibilities have been hypothesized as the mechanisms of occult HBV infection. These include: (i) mutations of HBV-DNA sequence; (ii) integration of HBV-DNA into host's chromosomes; (iii) infection of peripheral blood mononuclear cells by HBV; (iv) formation of HBV-containing immune complex; (v) altered host immune response; and (vi) interference of HBV by other viruses. The precise prevalence of occult HBV infection remains to be defined. The clinical implications of occult HBV infection involve different clinical aspects. First of all, occult HBV infection harbours potential risk of HBV transmission through blood transfusion, haemodialysis, and organ transplantation. Second, it may serve as the cause of cryptogenic liver disease, contribute to acute exacerbation of chronic hepatitis B, or even fulminant hepatitis. Third, it is associated with development of hepatocellular carcinoma. Fourth, it may affect disease progression and treatment response of chronic hepatitis C. Most of the previous studies utilized retrospective observation without control groups, and lacked direct association of occult HBV infection with specific pathological changes and disease progression. Highly sensitive, quantitative, and functional molecular analyses of HBV, combined with a well-designed prospective clinical assessment will provide the best approach for the future study of occult HBV infection.     

Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B

Aim: The factors associated with hepatitis recurrence after discontinuation of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B were analyzed to predict the risk of relapse more accurately. Methods: A total of 126 patients who discontinued NA therapy were recruited retrospectively. The clinical conditions of a successful discontinuation were set as alanine aminotransferase (ALT) below 30 IU/L and serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL. Results: Relapse of hepatitis B were judged to occur when maximal serum ALT became higher than 79 IU/L or when maximal serum HBV DNA surpassed 5.7 log copies/mL following NA discontinuation since these values corresponded with mean values of ALT (30 IU/L) and HBV DNA (4.0 log copies/mL), respectively. At least 90% of patients with either detectable hepatitis B e antigen or serum HBV DNA higher than 3.0 log copies/mL at the time of NA discontinuation relapsed within one year. In the remaining patients, higher levels of both hepatitis B surface and core‐related antigens at the time of discontinuation, as well as a shorter course of NA treatment, were significantly associated with relapse by multivariate analysis. Conclusions: It appears that negative results for hepatitis B e antigen and serum HBV DNA lower than 3.0 log copies/mL are essential for successful NA discontinuation, which may be attained by a longer treatment period. Levels of hepatitis B surface and core‐related antigens are also significant factors independently associated with relapse of hepatitis.     

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.