OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Medicine, Chinese Traditional ; Organophosphonates ; therapeutic use ; Young Adult

BACKGROUND/AIMS: To analyze the effects of preexisting lamivudine (LAM) resistance and applying antiviral treatment (adefovir [ADV] add-on LAM combination treatment) on long-term treatment outcomes, and comparing the clinical outcomes of antiviral-naïve chronic hepatitis B patients receiving entecavir (ETV) monotherapy. METHODS: This study enrolled 73 antiviral-naïve patients who received 0.5-mg ETV as an initial therapy and 54 patients who received ADV add-on LAM combination treatment as a rescue therapy from July 2006 to July 2010. RESULTS: During 24-month treatments, the decreases in serum log10HBV-DNA values (copies/mL) were significantly greater in the antiviral-naïve patients treated with ETV than the patients receiving ADV add-on LAM combination treatment. The biochemical response rates for alanine aminotransferase normalization at 6 months (ETV) and 12 months (ADV add-on LAM) were 90.4% (66/73) and 77.8% (42/54), respectively (P=0.048). A Kaplan-Meier analysis indicated that the rates of serologic response, viral breakthrough, and emergence of genotypic resistance did not differ significantly between the two patient groups. There were also no significant intergroup differences in the rates of disease progression (PD) and new development of hepatocellular carcinoma (HCC). CONCLUSION: The long-term clinical outcomes of antiviral-naïve patients treated with ETV and LAM-resistant patients receiving ADV add-on LAM combination treatment were comparable in terms of the emergence of HCC and disease progression.
Adenine/*analogs & derivatives/pharmacology/therapeutic use ; Adult ; Alanine Transaminase/blood ; Antibodies, Viral/blood ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Disease Progression ; Drug Resistance, Viral/drug effects ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Genotype ; Guanine/analogs & derivatives/pharmacology/therapeutic use ; Hepatitis B e Antigens/blood ; Hepatitis B virus/drug effects/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/pharmacology/therapeutic use ; Male ; Middle Aged ; Organophosphonates/pharmacology/*therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: It remains to be determined whether switching from adefovir (ADV) to tenofovir (TDF) provides better virological outcomes in patients exhibiting suboptimal responses to ADV plus nucleoside analogue (ADV+NA) therapy for NA-resistant chronic hepatitis B (CHB). METHODS: In this prospective trial, patients who showed partial responses (defined as serum hepatitis B virus [HBV] DNA >60 IU/mL) to ADV+NA therapy for NA resistance were randomly allocated to receive TDF plus NA (TDF+NA group, n=16) or to continue their current therapy (ADV+NA group, n=16). The primary end point was the proportion of patients with complete virological response (CVR, defined as serum HBV DNA <60 IU/mL) at 48 weeks. RESULTS: The median age was 52 years (16 men), and 28 were positive for hepatitis B e antigen (HBeAg). The baseline characteristics did not differ significantly between the two groups. The proportion with CVR was significantly higher in the TDF+NA group than in the ADV+NA group at 24 weeks (81.3% vs. 25.0%, P=0.001) and 48 weeks (87.5% vs. 37.5%, P=0.002). Furthermore, a decrease in the serum HBV DNA level of >2log10 IU/mL was more likely in the TDF+NA group at both 24 and 48 weeks (68.8% vs. 56.3%, P=0.014 vs. 81.3% vs. 56.3%, P=0.001, respectively). During the follow-up, the rate of HBeAg seroconversion was higher in the TDF+NA group than the ADV+NA group (12.5% vs. 6.25%, P=0.640), as was that for the hepatitis B surface antigen (6.25% vs. 0%, P=0.080). No serious adverse events due to antiviral agents occurred. CONCLUSIONS: In patients exhibiting suboptimal responses to ADV+NA therapy for NA-resistant CHB, switching from ADV to TDF might provide better virological outcomes.
Adenine/*analogs & derivatives/therapeutic use ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/therapeutic use ; Male ; Middle Aged ; Organophosphonates/*therapeutic use ; Prospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome

OBJECTIVETo explore clinical efficacy of Yiguanjian Decoction (YD) combined Adefovir Dipivoxil Tablet (ADT) in treating HBeAg negative chronic viral hepatitis B (CVHB) active compensated liver cirrhosis (LC) patients.

METHODSTotally 68 HBeAg negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group using random digit table, 34 in each group. Patients in the control group took ADT alone, 10 mg each time, once per day. Those in the treatment group additionally took YD, one dose per day. The therapeutic course for all was 48 weeks. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) were detected once in every two weeks. Hepatitis B virus (HBV)-DNA and four items of serum liver fibrosis [procollagen type I (PCN), hyaluronidase (HA), procollagen III peptide (PCIII), laminin (LN)] were detected once per every 4 weeks. Abdominal ultrasound B was performed before and after treatment. The inner diameter of the portal vein and the size of spleen were recorded. The fibrosis degree of liver was evaluated using Fibroscan. Efficacy of Chinese medicine (CM) was evaluated between the two groups before and after treatment using CM syndrome integrals. Efficacy of Western medicine (WM) was also evaluated between the two groups using Child-Pugh grading. Results Compared with before treatment in the same group, ALT and AST levels restored to normal levels, HBV-DNA turned negative (HBV-DNA < or = 1 x 10(2)) in the two groups after 48-week treatment. Besides, levels of TBil, ALB, PCIV, HA, PCIII, and LN obviously decreased (P < 0.05, P < 0.01). Results of ultrasound B showed the inner diameter of the portal vein and the size of spleen decreased. Fibroscan results showed that the elasticity value of the liver obviously decreased (P < 0.05). Besides, post-treatment levels of PCIV, HA, PCEJ, and LN, and the elasticity value of the liver decreased more obviously in the treatment group than in the control group (P < 0.01). There was no statistical difference in post-treatment levels of ALT, AST, TBil, ALB, inner diameter of the portal vein, or the size of spleen between the two groups (P > 0.05). Compared with before treatment in the same group, scores of Chinese medical syndrome and Child-Pugh scores decreased in the two groups after treatment (P < 0.05, P < 0.01). Besides, scores of Chinese medical syndrome decreased more obviously in the treatment group than in the control group (P < 0.05). The effective rate was 8824% (30/34) in the treatment group, higher than that of the control group [67.65% (23/34)] with statistical difference (P <0.05). Conclusion Combined treatment of YD and ADT could significantly improve symptoms of CM and fibrosis degree of liver of HBeAg negative CVHB active compensated LC patients.

Adenine ; analogs & derivatives ; therapeutic use ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; DNA, Viral ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; virology ; Organophosphonates ; therapeutic use ; Tablets

BACKGROUND/AIMS: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. METHODS: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. RESULTS: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. CONCLUSIONS: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis/metabolism ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Male ; Middle Aged ; Organophosphonates/*therapeutic use ; Polymerase Chain Reaction ; Republic of Korea ; Retrospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. METHODS: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. RESULTS: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. CONCLUSIONS: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis/metabolism ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Male ; Middle Aged ; Organophosphonates/*therapeutic use ; Polymerase Chain Reaction ; Republic of Korea ; Retrospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome

OBJECTIVETo observe the clinical efficacy of combination therapy with peg-IFNalpha and adefovir (CPIA) in women who were hepatfis B virus (HBV) carriers and had just given birth and received telbivudine (LdT) during pregnancy for prevention of mother-to-child transmission.

METHODSOne-hundred-and-fifty third trimester-pregnant women who were HBV carriers with highly-viremic were treated with LdT until time of birth. After delivery, those women with alanine aminotransferase (ALT) level exceeding two times the upper limit of normal and HBV DNA level that had decreased more than 31 gIU/mL or hepatitis B e antigen (HBeAg) titer that had decreased more than 50% were switched to CPIA for 96 weeks.

RESULTSFollowing delivery, 45 of the women were switched to the CPIA treatment, of which 91.1% (41/45) achieved virological response, 55.6% (25/45) achieved HBeAg clearance or seroconversion, and 26.7% (12/45) achieved hepatitis B surface antigen (HBsAg) clearance or seroconversion.The immediate post-delivery (and pre-CPIA) levels of HBeAg and HBV DNA were negatively associated with HBeAg clearance. Ninety-eight of the total study participants stopped the LdT treatment and there were no cases of significant deterioration of liver function.

CONCLUSIONPregnant women who are HBV carriers and receive LdT for protection against mother-to-child transmission, and who show significant ALT elevation and decreased HBeAg titer and/or reduced HBV DNA after delivery, may be good candidates for the CPIA therapy following delivery.

Adenine ; analogs & derivatives ; therapeutic use ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; Carrier State ; virology ; DNA, Viral ; blood ; Drug Therapy, Combination ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Infectious Disease Transmission, Vertical ; prevention & control ; Interferon-alpha ; therapeutic use ; Organophosphonates ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; virology ; Pregnancy Trimester, Third ; Recombinant Proteins ; therapeutic use ; Thymidine ; analogs & derivatives ; therapeutic use

OBJECTIVETo explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN.

METHODS102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed.

RESULTSSeveral findings were demonstrated with the increase of serum HBV DNA: 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly (P%lt;0.05), while the plasma level of albumin decreased significantly (P%lt;0.05); The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group (P%lt;0.01).

CONCLUSIONWith the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; DNA Replication ; DNA, Viral ; blood ; Drug Therapy, Combination ; Female ; Glomerulonephritis ; etiology ; Hepatitis B ; complications ; drug therapy ; Hepatitis B virus ; genetics ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Prognosis ; Proteinuria ; etiology ; Young Adult

Besides 36 (28 single-tablets and 8 fixed-dose combinations) used antiretroviral drugs clinically, there are a number of investigational antiretroviral agents currently in phase 2-3 clinical trial. Tenofoviralafenamidefumarate (TAF) is a novel nucleoside analogue reverse transcriptase inhibitor that is potent and less toxicity than tenofovir (TDF). Doravirine is a non-nucleoside analogue reverse transcriptase inhibitor that demonstrates activity against NNRTI-resistant viral strains. GSK744 is an integrase inhibitor with a long acting preparation. In addition, several drugs with new mechanisms are also noted, for example, BMS-663 068 is a small molecule CD4 attachment inhibitors and cenicriviroc is a novel CCR5/CCR2 antagonist with antiretroviral activity and anti-inflammatory effects. Several drug classes that target known pathways in HIV latency have being developed, and leading the list are histone deacetylase inhibitors. Other agents include protein kinase C activators, positive transcription elongation factor activators, DNA methyl-transferase inhibitors and histone methyl-transferase inhibitors and so on. This review is focused on the above-mentioned drug candidates that may be used in clinical in next couple of years and those compounds that can reverse latent HIV infections.
Adenine ; analogs & derivatives ; therapeutic use ; Anti-HIV Agents ; therapeutic use ; HIV Infections ; drug therapy ; Humans ; Organophosphates ; therapeutic use ; Organophosphonates ; therapeutic use ; Piperazines ; therapeutic use ; Pyridones ; therapeutic use ; Reverse Transcriptase Inhibitors ; therapeutic use ; Tenofovir

OBJECTIVETo evaluate the efficacy and safety of 4 treatment options for HBeAg-positive chronic hepatitis B (CHB) patients following a suboptimal response to 24-week interferon monotherapy.

METHODSThe data of 193 HBeAg-positive CHB patients with suboptimal response to 24-week interferon monotherapy were collected from Nanfang Hospital between September, 2010 and January, 2013. According to the subsequent treatments, the patients were divided into group A with additional entecavir or adefovir, group B with further interferon monotherapy, group C with conversion to NAs therapy, and group D with direct therapy withdrawal, and the biochemical and virological results at weeks 24, 48 and 72 were analyzed in the 4 groups.

RESULTSAt week 48, the HBV DNA negative rates and serum alanine aminotransferase (ALT) normalization rates were both significantly higher in group A and C than in group B (P<0.05); in group A, ETV therapy subgroup had a significantly higher HBV DNA negative rate than ADV therapy subgroup at week 48 (90.3% vs 59.5%, Χ=8.255, P=0.004). At week 72, 39.7%(27/68) of the patients in group A achieved HBeAg seroconversion, a rate significantly higher than those in groups B (Χ=4.238, P=0.040) and C (Χ=7.681, P=0.006); the HBV DNA negative rate and ALT normalization rate in group A were 85.3%(58/68) and 86.8%(59/68), respectively, both significantly higher than those in group B (Χ=23.018, P<0.001; Χ=5.987, P=0.014) but comparable to those in group C (P>0.05). In the two subgroups in group A, the HBV DNA negative rate and HBeAg seroconversion rate were both significantly higher in ETV subgroup (Χ=9.823, P=0.002; Χ=5.450, P=0.020). In group D, all the patients remained HBeAg-positive with abnormal ALT levels and high level of HBV DNA.

CONCLUSIONFor HBeAg-positive CHB patients with suboptimal response to 24-week interferon monotherapy, combined treatment with NAs (especially ETV) and extension of the treatment course can significantly improve the HBeAg seroconversion rates, HBV DNA negative rates, and ALT normalization rates.

Adenine ; analogs & derivatives ; therapeutic use ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Drug Therapy, Combination ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferons ; therapeutic use ; Organophosphonates ; therapeutic use