BACKGROUND/AIMS: The efficacy of tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B (CHB) patients following prior treatment failure with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in Asian populations. In this study we investigated the efficacy and safety of TDF rescue therapy in CHB patients after multiple NA treatment failure. METHODS: The study retrospectively analyzed 52 CHB patients who experienced failure with two or more NAs and who were switched to regimens containing TDF. The efficacy and safety assessments included hepatitis B virus (HBV) DNA undetectability, hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT) normalization and changes in serum creatinine and phosphorus levels. RESULTS: The mean HBV DNA level at baseline was 5.4 +/- 1.76 log10 IU/mL. At a median duration of 34.5 months of TDF treatment, the cumulative probabilities of achieving complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12, 24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48 patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with elevated ALT at baseline. Lower levels of HBV DNA at baseline were significantly associated with increased CVR rates (p < 0.001). However, CVR rates did not differ between TDF monotherapy or combination therapy with other NAs, and were not affected by mutations associated with resistance to NAs. No significant adverse events were observed. CONCLUSIONS: TDF is an efficient and safe rescue therapy for CHB patients after treatment failure with multiple NAs.
Adenine/adverse effects/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Alanine Transaminase/blood ; Antiviral Agents/adverse effects/*therapeutic use ; Biological Markers/blood ; Creatinine/blood ; DNA, Viral/blood ; Drug Resistance, Viral/genetics ; Drug Substitution ; Female ; Genotype ; Hepatitis B e Antigens/blood ; Hepatitis B virus/*drug effects/genetics/immunology/pathogenicity ; Hepatitis B, Chronic/blood/diagnosis/*drug therapy ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Mutation ; Phosphorous Acids/adverse effects/*therapeutic use ; Phosphorus/blood ; Retrospective Studies ; Time Factors ; Treatment Failure ; Viral Load ; Young Adult

BACKGROUND/AIMS: The aims of the present study were to determine the outcomes of inactive hepatitis B virus (HBV) surface antigen (HBsAg) carriers over a 10-year study period and to elucidate the HBV serological profile of their family members. METHODS: We retrospectively analyzed the medical files of inactive HBsAg carriers followed up at the Department of Infectious Diseases of Kocatepe University Medical Faculty Hospital between March 2001 and January 2011. RESULTS: In total, 438 inactive HBsAg carriers were enrolled in this trial. The follow-up period was 33.7+/-22.5 months (mean+/-SD). Anti-hepatitis-B surface antibody seroconversion occurred in 0.7% of cases, while chronic hepatitis B was found in 0.5%. The anti-hepatitis-D virus (HDV) status was evaluated in 400 patients and anti-hepatitis C virus (HCV) in 430. It was found that 1% and 0.2% were positive for anti-HDV and anti-HCV, respectively. HBV serology was investigated in at least 1 family member of 334/438 (76.3%) patients. The HBsAg positivity rate was 34.6% in 625 family members of 334 patients. A comparison of the HBsAg positivity rates in terms of HBV DNA levels in index cases revealed that HBsAg seropositivity rates were higher in family members of HBV DNA-negative patients than in family members of HBV DNA-positive cases (P=0.0001). CONCLUSIONS: The HBsAg positivity rate was higher in family members of inactive HBsAg carriers than in the general population; these family members therefore have a higher risk of HBV transmission. Furthermore, despite negative HBV DNA levels, transmission risk was not reduced in these patients, and horizontal transmission seems to be independent of the HBV DNA value.
Adult ; Antibodies/blood ; Carrier State ; DNA, Viral/analysis ; Family Health ; Female ; Follow-Up Studies ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/*blood ; Hepatitis B virus/genetics/immunology ; Hepatitis B, Chronic/*diagnosis/transmission/virology ; Hepatitis Delta Virus/immunology ; Humans ; Male ; Middle Aged ; Retrospective Studies

<b>OBJECTIVEb>To investigate the role ofCD4+CD25+ T regulatory (Treg) cells, T helper (Th)17cells and interleukin (IL)-6 in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and determine their value as prognostic markers.

<b>METHODSb>The Chinese National Knowledge Infrastructure (CNKI), WanFang, Chinese Scientific Journals (VIP), PubMed, Embase and Web of Science databases were searched for English language case-control studies on the relationship between regulatory T lymphocytes and ACLF.The quality of included studies was assessed using the Newcastle-Ottawa scale. The meta-analysis was designed according to the PICOS approach recommended by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. RevMan software, version 5.1, was used to perform the meta-analysis.

<b>RESULTSb>Nine case-cohort studies were selected for inclusion in the metaanalysis.The results of the meta-analyses showed that the level of CD4+CD25+ Treg cells was not significantly different between patients with HBV-related ACLF and patients with chronic hepatitis B (CHB) (mean difference (MD)=0.59, 95% confidence interval (CI)-1.68, 2.85, P=0.61) nor between patients with HBVrelated ACLF and healthy controls (MD=1.12, 95% CI:-1.42, 3.66, P=0.39). Thus, it appears that ACLF patients do not have a higher level of CD4+CD25+ Treg cells than CHB patients or healthy controls. However, the ACLF patients did appear to have a significantly higher level of Th17 cells than both the CHB patients (MD=1.73, 95% CI:0.21, 3.26, P=0.03) and the healthy controls (MD=1.62, 95% CI:(0.52, 2.72, P=0.004). In addition, the ACLF patients also had significantly higher level than both the CHB patients (MD=11.69, 95%CI:1.98, 21.40, P=0.02) and the healthy controls (MD=13.17, 95% CI:1.38, 24.95, P=0.03).

<b>CONCLUSIONb>CD4+CD25+ Treg cells may be an important protective factor in the progression and prognosis of HBV-related ACLF, while Thl7 cells and IL-6 may be risk factors for further progression and worsened prognosis.

Acute-On-Chronic Liver Failure ; diagnosis ; immunology ; CD8-Positive T-Lymphocytes ; Case-Control Studies ; Disease Progression ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; Humans ; Interleukin-6 ; immunology ; Prognosis ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

BACKGROUND/AIMS: Programmed death-1 (PD-1) expression was investigated in CD4+ and CD8+ T cells from hepatitis B virus (HBV)-infected patients at the chronic hepatitis B (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) stages. METHODS: PD-1 expression in circulating CD4+ and CD8+ T cells was detected by flow cytometry. The correlations between PD-1 expression and HBV viral load, alanine aminotransaminase (ALT) levels and aspartate aminotransferase (AST) levels were analyzed using GraphPad Prism 5.0. RESULTS: PD-1 expression in CD4+ and CD8+ T cells was significantly increased in both the CHB group and advanced-stage group (LC plus HCC). In the CHB group, PD-1 expression in both CD4+ and CD8+ T cells was positively correlated with the HBV viral load, ALT, and AST levels. However, in the LC plus HCC group, significant correlations between PD-1 expression and the clinical parameters were nearly absent. CONCLUSIONS: PD-1 expression in peripheral CD4+ and CD8+ T cells is dynamic, changes with HBV infection progression, and is related to HBV viral load and liver function, especially in CHB. PD-1 expression could be utilized as a potential clinical indicator to determine the extent of virus replication and liver injury.
Adult ; CD4-Positive T-Lymphocytes/*metabolism ; CD8-Positive T-Lymphocytes/*metabolism ; Carcinoma, Hepatocellular ; Disease Progression ; Female ; Hepatitis B, Chronic/*diagnosis/immunology ; Humans ; Liver Cirrhosis ; Liver Neoplasms ; Male ; Programmed Cell Death 1 Receptor/*metabolism ; Viral Load

BACKGROUND/AIMS: The prevalence of occult HBV infection depends on the prevalence of HBV infection in the general population. Hemodialysis patients are at increased risk for HBV infection. The aim of this study was to determine the prevalence of occult HBV infection in hemodialysis patients. METHODS: Total of 98 patients undergoing hemodialysis in CHA Bundang Medical Center (Seongnam, Korea) were included. Liver function tests and analysis of HBsAg, anti-HBs, anti-HBc and anti-HCV were performed. HBV DNA testing was conducted by using two specific quantitative methods. RESULTS: HBsAg was detected in 4 of 98 patients (4.1%), and they were excluded. Among 94 patients with HBsAg negative and anti-HCV negative, one (1.1%) patient with the TaqMan PCR test and 3 (3.2%) patients with the COBAS Amplicor HBV test were positive for HBV DNA. One patient was positive in both methods. Two patients were positive for both anti-HBs and anti-HBc and one patient was negative for both anti-HBs and anti-HBc. CONCLUSIONS: The present study showed the prevalence of occult HBV infection in HBsAg negative and anti-HCV negative patients on hemodialysis at our center was 3.2%. Because there is possibility of HBV transmission in HBsAg negative patients on hemodialysis, more attention should be given to prevent HBV transmission.
Adult ; Aged ; Aged, 80 and over ; Antibodies/blood ; DNA, Viral/analysis ; Feces/*virology ; Female ; Hepatitis B/complications/*epidemiology/transmission ; Hepatitis B Core Antigens/immunology ; Hepatitis B virus/genetics/immunology ; Hepatitis C Antibodies/blood ; Humans ; Kidney Failure, Chronic/*complications/diagnosis ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prevalence ; Renal Dialysis ; Risk Factors

Sweet's syndrome (SS), also known as acute febrile neutrophilic dermatosis, is characterized by the sudden onset of painful erythematous skin lesions together with fever and neutrophilia. SS can be associated with several disorders, such as malignancy, autoimmune disease, and infections. However, SS associated with liver cirrhosis is uncommon. We report a case of SS in a patient who was diagnosed with liver cirrhosis caused by chronic hepatitis B.
Hepatitis B, Chronic/complications/*diagnosis ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Male ; Middle Aged ; Neutrophils/immunology/pathology ; Skin Diseases/*diagnosis/pathology ; Sweet Syndrome/*diagnosis/pathology ; Tomography Scanners, X-Ray Computed

BACKGROUND/AIMS: We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease. METHODS: Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR. RESULTS: Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity. CONCLUSIONS: Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.
Adult ; Aged ; Cohort Studies ; DNA, Viral/analysis ; Female ; Genotype ; Hepatitis B/*complications/*diagnosis ; Hepatitis B Core Antigens/blood/immunology ; Hepatitis B Surface Antigens/blood/immunology ; Hepatitis B virus/*genetics ; Hepatitis C, Chronic/*complications/genetics/*pathology ; Humans ; Liver/virology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Severity of Illness Index

<b>OBJECTIVEb>To observe the functions of peripheral dendritic cells (DCs) in chronic hepatitis B virus (HBV) infection patients of Gan-depression Pi-deficiency syndrome (GPS) and Gan-Dan damp-heat syndrome (GDS) under different immune states, thus to study the features of the immune expressions of the two syndromes in chronic HBV infection, providing objective evidence for Chinese medicine syndrome typing.

<b>METHODSb>The 40 chronic HBV patients were randomly assigned to two groups according to the immune state. Of them, there were 20 chronic HBV patients (under the condition of immune clearance; consisting of 10 patients of GPS and 10 of GDS) and 20 chronic HBV carriers (under the condition of immune tolerance; consisting of 10 patients of GPS and 10 of GDS). Besides, 10 healthy graduate volunteers of Hunan University of Traditional Chinese Medicine were recruited as the healthy control group. Their peripheral blood mononuclear cells (PBMCs) were cultured in vitro. The exterior morphological features and ultrastructure were observed by inverted microscope and electron microscope. The expressions of HLA-DR, CD80, CD86, and CDIa of the DCs surface were detected. The secretory levels of IL-12 in the supernate of DCs were detected by ELISA reagent kit. The proliferation capacities of allogeneic mixed lymphocyte were detected using MTT. The function features of DCs in the chronic HBV patients of two syndrome types under different immune states were compared, thus analyzing the difference of each index between the two syndrome types.

<b>RESULTSb>Compared with the healthy control group, the expression rates of CD86, CD80, and HLA-DR decreased in the HBV carriers group (of the two syndrome types), showing statistical difference (P < 0.05). The expression rate of CD80 decreased in the HBV group (of the two syndrome types), showing statistical difference (P < 0.05). The expression rates of CD86 and HLA-DR were lower in the GPS group than in the GDS group. The expression rate of CD80 was lower in the GPS group than in the GDS group, showing statistical difference (P < 0.05). The proliferation capacities of IL-12 and T lymphocytes were lower in the HBV patients group than in the healthy control group (P < 0.05). The proliferation capacities of IL-12 and T lymphocytes were lower in the GPS group than in the GDS group, showing statistical difference (P < 0.05).

<b>CONCLUSIONSb>The functions of peripheral DCs in chronic HBV infection of patients of the GPS and the GDS under different immune states were different. The phenotype and function tests of DCs provided objective evidence for Chinese syndrome typing of chronic hepatitis B, thus reflecting the features of immune expressions of the two syndrome types and the immunology connotation.

Adult ; B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; Case-Control Studies ; Cells, Cultured ; Dendritic Cells ; immunology ; Female ; HLA-DR Antigens ; metabolism ; Hepatitis B, Chronic ; blood ; diagnosis ; immunology ; Humans ; Interleukin-12 ; immunology ; Male ; Medicine, Chinese Traditional ; T-Lymphocytes ; immunology ; Young Adult

<b>OBJECTIVEb>To study the effect of Yidu Recipe (YDR) in treating patients of chronic hepatitis B (CHB) with positive hepatitis B e-antigen (HBeAg) and its influence on the quantity and function of T-cell subsets.

<b>METHODSb>Fifty-seven CHB patients measured up the inclusive criteria were randomly assigned to the control group and the treated group, treated respectively by entecavir alone and entecavir + YDR for 6 months. Changes of alanine a minotransferase (ALT), aspartate a minotransferase (AST), HBV-DNA, HBV-M, interleukin-4 (IL-4) and Chinese medicine syndrome score, as well as amounts of natural killer (NK) T cell, gamma-interferon (gamma-IFN), Th1, Th2, Tc1 and Tc2 cells in peripheral blood (detected by flow cytometry) before and after treatment were observed. And the liver function normalization rate, negative inversion rates of HBV-DNA and HBeAg were estimated at terminal of the trial.

<b>RESULTSb>Seven cases were dropped out in the observation period. Compared with the control group, levels of ALT, AST, HBV-DNA and Chinese medicine syndrome score were lower after treatment (P < 0.05), and liver function normalization rate was higher in the treated group, while the difference between groups in negative inversion rates HBV-DNA and HBeAg were insignificant (P > 0.05). Amount of IFN-gamma increased, IL-4 reduced, and Tc1 cell raised after treatment, which led to the rise of Tcl/Tc2 ratio in both groups; while in the treated group, in addition to the above-mentioned changes, the Th1 cell was increased also, and thus to make elevation of Th1/Th2 ratio (P < 0.05).

<b>CONCLUSIONb>The efficacy of entecavir + YDR in treating HBeAg positive CHB patients is better than that of entecavir alone. YDR can effectively improve patients' liver function, inhibit HBV-DNA replication and improve clinical symptoms, its action may be realized by way of increasing the amount of NKT cells, inducing increase of IFN-gamma and decrease of IL-4 secretions, and regulating the balance between Th1/Th2 and Tc1/Tc2.

Adult ; Antiviral Agents ; therapeutic use ; Diagnosis, Differential ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; T-Lymphocyte Subsets ; immunology ; Th1-Th2 Balance ; Yin Deficiency ; drug therapy ; immunology ; Young Adult

<b>OBJECTIVEb>To investigate the immunoregulation mechanism of Bushen Recipe (BSR) in patients with chronic hepatitis B (CHB) of Gan-Shen yin-deficiency and lingering damp-heat syndrome (GSS).

<b>METHODSb>Thirty-five patients with positive HBV DNA and abnormal alanine transaminase (ALT) level were assigned to the treatment group (22 patients) and the control group (13 patients), they were treated with BSR and alpha-2b interferon for 6 months respectively. Blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and HBV DNA were measured before and after treatment. And the expressions of immune effector molecules of nature killer (NK) cell, including perforin (PF), granzyme B (GrB), granulysin (GNLY), tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (gamma-IFN), were detected using flow cytometry.

<b>RESULTSb>Levels of ALT and AST declined significantly in both groups after treatment (P < 0.05 or P < 0.01), showing insignificant difference between them. And the expressions (%) of PF and GNLY in the treatment group reduced significantly after treatment, from 69.62 +/- 27.58 to 34.86 +/- 31.60 for PF and from 64.54 +/- 25.96 to 25.72 +/- 24.98 for GNLY (both P < 0.05). In the treatment group and the control group, as compared with before treatment, the total scores of Chinese medicine symptoms were significantly declined after treatment (P < 0.01), and the total scores of Chinese medicine symtoms in the treatment group was significantly lower than that of the control group (P < 0.05). As compared with the total effective rate of Chinese medicine syndromes in the control group after treatment, that in the treatment group was significantly increased (P < 0.05).

<b>CONCLUSIONb>The mechanism of BSR in immuneregulating on patients with CHB of GSS is by way of declining the expressions of relative immune effector molecules to promote the recovery of the damaged liver.

Adjuvants, Immunologic ; therapeutic use ; Adolescent ; Adult ; Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Young Adult