The recent outbreak of hepatitis C virus (HCV) at Singapore General Hospital (SGH) has highlighted the dangers of viral hepatitis. In this case, infection control and environmental contamination were the culprits, particularly, a drop of blood containing 5 million IU HCV. From a broader perspective, there has been a revolution in HCV therapy with the recent rapid evolution of short-term (12 weeks) safe, all oral directly- acting antiviral (DAA) therapy leading to cure rates of 90% to 100%, even in previously difficult to treat patients with liver cirrhosis, previous treatment failure and those on immunosuppression. Consequently, treating HCV in risk groups such as renal dialysis and haemophiliacs can eliminate a pool of infected patients to prevent future outbreaks. A seroprevalence study is needed to identify a possible "birth cohort" effect that could aid screening. For HBV, vaccination has reduced prevalence to 3.8%, but these patients are prone to complications such as HBV flares. Since 2014, 13 patients developed liver failure and were listed for liver transplantation at National University Hospital (NUH) but 6 died beforehand. This avoidable catastrophe is due to undiagnosed HBV infection or patients who did not return for follow-up. Good antiviral therapy is available, but the issues are similar to HCV, identification of patients and linkage to care. A cure seems likely in the future as pharmaceutical companies are developing new agents. Singapore has joined in this initiative with a recent award of a national research translational grant to better understand the pathophysiology and the processes needed for a cure of HBV.
Antiviral Agents ; therapeutic use ; Disease Outbreaks ; prevention & control ; Health Services Accessibility ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; epidemiology ; prevention & control ; Hepatitis C, Chronic ; drug therapy ; epidemiology ; Humans ; Patient Selection ; Risk Assessment ; Singapore ; epidemiology

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.
Abdomen/diagnostic imaging ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Esophageal and Gastric Varices/complications/prevention & control ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Ultrasonography

<b>OBJECTIVEb>To 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.

<b>METHODSb>One-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.

<b>RESULTSb>Following 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.

<b>CONCLUSIONb>Pregnant 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

<b>OBJECTIVEb>To observe the long-term efficacy and safety of telbivudine (LdT) for pregnant women with chronic hepatitis B (CHB) and their children born from the treatment period.

<b>METHODSb>A total of 118 pregnant women with CHB were enrolled in the study and provided informed consent for participation. The women opted for participation in the treatment group (7 =73; LdT 600 mg once daily, starting in early pregnancy and continued until after delivery) or in the control group (n =45; no LdT treatment). All newborns were given active and passive immunization upon birth and tested for serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), anti-hepatitis B core antibody (anti-HBc), anti-hepatitis B surface antibody (anti-HBs) and HBV DNA at 0, 1, 7 and 12 months of age. The Paediatrics Neuropsychological Development Scale for Children aged 0 - 6 (5 items) established by the Capital Institute was used to test the children; in addition, the children were evaluated by observation for action ability (fine and gross motor skills), adaptability, language ability and social behaviour. Total IQ was estimated as a developmental quotient (DQ) by using the equation: points from the 5 scale items actual age in months * 100.

<b>RESULTSb>The LdT group included 69 women with successful pregnancies, 1 case of miscarriage and 3 cases that were lost to follow-up. The control group included 34 women with successful pregnancies, 4 cases of miscarriage, 1 case with fatal outcome, and 6 cases of no pregnancy. Compared to the control group, the LdT group had a significantly higher successful pregnancy rate (x² =4.86 in the LdT group, P < 0.05). In addition, the LdT group had a significantly higher rate of term delivery (53 cases vs. 34 cases, x² = 6.38, P < 0.05). The neonates born to the women in the LdT group included 53 cases of weakly-negative HBsAg at birth and 1 case at 1 month old, as well as negativity for HBV DNA, and HBsAg remaining weakly positive at 6 months old; the intrauterine infection rate was 1.8% and no case of deformity occurred.Among the 34 neonates in the control group, 6 showed HBsAg positivity at 1 month old, and the HBsAg positivity remained for all 6 at 6 months old; the intrauterine infection rate was 16.6%, which was significantly higher than that of the LdT group (x² = 5.10, P < 0.05). The neonates in the LdT group had a significantly higher anti-HBs production rate at 1 year old than those in the control group (98.1% (52/53 vs. 82.4% (28/34). X² = 4.87, P < 0.05). The neonates in the LdT group showed normal growth and development for all 53 cases of young children, and IQ levels of excellent for 3 cases, smart for 8 cases, normal for 40 cases, and low for 2 cases. The neonates in the control group showed normal growth and development for all 34 cases of young children, and IQ levels of excellent for 2 cases, smart for 4 cases, normal for 27 cases, and low for 1 case.

<b>CONCLUSIONb>Childbearing chronic HBV patients treated with LdT had higher rates of successful pregnancy, blocking of intrauterine infection and anti-HBs reduction compared to their untreated counterparts. The children bom to LdT-treated women showed no difference in long-term growth and development and total IQ from the children born to the untreated women with chronic HBV.

Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; Thymidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

Although much advancement has been achieved in the treatment of chronic hepatitis B, antiviral resistance is still a challenging issue. Previous generation antiviral agents have already developed resistance in a number of patients, and it is still being used especially in resource limited countries. Once antiviral resistance occurs, it predisposes to subsequent resistance, resulting in multidrug resistance. Therefore, prevention of initial antiviral resistance is the most important strategy, and appropriate choice and modification of therapy would be the cornerstone in avoiding treatment failures. Until now, management of antiviral resistance has been evolving from sequential therapy to combination therapy. In the era of tenofovir, the paradigm shifts again, and we have to decide when to switch and when to combine on the basis of newly emerging clinical data. We expect future eradication of chronic hepatitis B virus infection by proper prevention and optimal management of antiviral resistance.
Adenine/analogs & derivatives/pharmacology/therapeutic use ; Antiviral Agents/pharmacology/*therapeutic use ; Drug Resistance, Viral/drug effects ; Drug Therapy, Combination ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy/prevention & control ; Humans ; Mutation ; Nucleosides/*chemistry/pharmacology/therapeutic use ; Organophosphonates/pharmacology/therapeutic use ; Virus Replication/drug effects

<b>OBJECTIVEb>To study the changes of experimental markers of hepatic fibrosis in patients with chronic hepatitis B treated by Dahuang Zhechong Wan combined with adefovir dipivoxil.

<b>METHODb>Ninty and four cases of chronic viral hepatitis B patients were randomly divided into two groups. The treatment group (50 cases) was orally given 10 mg of adefovir dipivoxil once a day, 1 Wan each time, combined with Dahuang Zhechong Wan, 3 times a day, 1 Wan each time. And the control group (44 cases) was treated with adefovir dipivoxil alone, 6 months as a course.

<b>RESULTb>Both the difference of liver fibrosis indexes between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P < 0.01 or P < 0.05). Both the difference of experimental markers such as ALT, AST, GGT, TBIL between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P < 0.01).

<b>CONCLUSIONb>Dahuang Zhechong Wan combined with adefovir dipivoxil could prevent hepatic fibrosis in patients with chronic hepatitis B, reduce the incidence of liver cirrhosis, improve life quality and prognosis.

Adenine ; administration & dosage ; analogs & derivatives ; Administration, Oral ; Adult ; Aged ; Antiviral Agents ; administration & dosage ; Biomarkers ; analysis ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hepatitis B, Chronic ; complications ; drug therapy ; Humans ; Liver ; metabolism ; Liver Cirrhosis ; prevention & control ; virology ; Male ; Middle Aged ; Organophosphonates ; administration & dosage ; Young Adult

<b>OBJECTIVEb>To evaluate the therapeutic efficacy and safety of lamivudine treatment in late pregnancy by analyzing the maternal-fetal outcomes of chronic hepatitis B (CHB) mothers featuring hepatitis B e antigen (HBeAg)-positivity and highly viremic status.

<b>METHODSb>A total of 256 pregnant women in the second or third trimester with monoinfected CHB, HBeAg-positivity, and HBV DNA more than 6 log10 copies/mL were divided into two groups: lamivudine (lam) treatment (n=164) or no treatment (controls; n=92). All infants were treated with hepatitis B immune globin (HBIg; 200 IU) within 12 hrs of birth and 15 days later, and were given the recombinant HBV vaccine (20 mug) at 0, 1 and 6 months. All infants were followed-up to at least seven months and hepatitis B surface antigen (HBsAg) and HBV DNA levels were used to determine perinatal transmission (PT) rates. The mothers' data from routine blood analysis, tests of hepatic and renal function, detection of HBV markers and HBV DNA were retrospectively analyzed to determine changes associated with the lam treatment. Correlations of lam treatment with HBV PT rate, alanine aminotransferase (ALT) normalization, adverse reactions, pregnancy complications, congenital deformities, and infants' growth/development were determined by statistical analyses.

<b>RESULTSb>Prior to delivery, the lam-treated mothers had significantly lower HBV DNA levels (3.72+/-1.78 vs. controls: 7.83+/-0.67 log10 c/ml; t=-22.359, P less than 0.001). The rate of virological response in the lam-treated group was 97.56% (160/164). The lam-treated group had significantly higher ALT normalization rate (90.20% vs. controls: 55.88%; X2=13.349, P less than 0.001) and significantly lower HBeAg titer (957.73+/-458.42 vs. controls: 1296.35+/-383.14 S/CO; t=-5.410, P less than 0.001). At birth, the infants from lam-treated mothers had significantly lower HBsAg-positivity (15.24% (25/164) vs. controls: 30.43% (28/92); X2=8.284, P=0.004). By 7-12 months after birth, none of the infants born to lam-treated mothers tested positive for HBsAg, compared to 8.70% (8/92) of the infants born to mothers in the control group (X2=14.721, P less than 0.001). None of the lam-treated mothers required treatment discontinuation due to adverse events or lam-resistance. No congenital deformities were observed during the study and follow-up periods. There were no differences between the lam-treated and control groups for postpartum hemorrhage, gestational age, infants' height/weight or Apgar scores.

<b>CONCLUSIONb>In highly viremic HBsAg+ mothers with CHB, lam treatment in the second or third trimester of pregnancy is safe and effective for reducing HBV maternal-neonatal transmission.

Adult ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B, Chronic ; drug therapy ; transmission ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; prevention & control ; Lamivudine ; therapeutic use ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; virology ; Pregnancy Outcome ; Pregnancy Trimester, Third ; Treatment Outcome ; Young Adult

No abstract available.
Antiviral Agents/therapeutic use ; Ascites/diagnosis/prevention & control/therapy ; Cholagogues and Choleretics/therapeutic use ; Fatty Liver/diagnosis/diet therapy ; Fatty Liver, Alcoholic/diagnosis/drug therapy ; Hemorrhage/prevention & control/therapy ; Hepatic Encephalopathy/diagnosis/prevention & control/therapy ; Hepatitis B, Chronic/diagnosis/drug therapy ; Hepatitis C, Chronic/diagnosis/drug therapy ; Humans ; Liver Cirrhosis/*diagnosis/drug therapy/pathology/*therapy ; Liver Cirrhosis, Biliary/drug therapy ; Vasodilator Agents/therapeutic use

<b>OBJECTIVEb>To explore the mechanism of oxymatrine in preventing hepatic fibrosis formation in patients with chronic hepatitis B (CHB).

<b>METHODSb>A total of 80 CHB patients receiving routine therapies for liver protection and support were divided into two groups. Oxymatrine at the daily dose of 150 mg was injected intravenously in the therapeutic group (n=40), and gluthion (1.2 g daily) was injected in the control group (n=40) for 8 weeks. The liver functions, indexes of hepatic fibrosis and the levels of transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in these patients before and after the therapy.

<b>RESULTSb>Liver functions was obviously improved after therapy in both groups, showing no significant difference between them (P>0.05). The indexes of hepatic fibrosis such as HA, LN, PCIII and C-IV were significantly lower in the therapeutic group than in the control group (P<0.01). The serum levels of TGF-beta1 and TNF-alpha decreased while IL-10 increased significantly after the treatment in the therapeutic group (P<0.05).

<b>CONCLUSIONb>The effect of oxymatrine against hepatic fibrosis is mediated by lowering the levels of TGF-beta1 and TNF-alpha and increasing the level of IL-10 in CHB patients.

Adult ; Alkaloids ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; pathology ; Humans ; Interleukin-10 ; blood ; Liver Cirrhosis ; drug therapy ; pathology ; prevention & control ; Male ; Middle Aged ; Quinolizines ; therapeutic use ; Transforming Growth Factor beta1 ; blood ; Tumor Necrosis Factor-alpha ; blood

<b>OBJECTIVEb>To observe the effect of Chinese medicine therapy for strengthening-Pi and nourishing-Shen (SPNS) in preventing lamivudine induced YMDD mutation and its immunological mechanism.

<b>METHODSb>One hundred and sixty chronic hepatitis B (CHB) patients with positive HBeAg were equally assigned to two groups at random: the observation group and the control group. Patients in the observation group were treated with lamivudine combined with SPNS, and those in the control group were treated with lamivudine only, with the treatment lasting for 52 weeks in total. Changes in indexes, including liver function, HbeAg, HBV-DNA, YMDD variation, CD(4), CD(4)/CD(8) ratio, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), blood routine, renal function, as well as any adverse reactions that occurred in patients, were observed at different time points.

<b>RESULTSb>The ALT, AST recovery rate and HBV-DNA negatively inversing rate at the 24th week, the 36th week and the 52nd week were all higher (P<0.05); meanwhile, the YMDD mutation rate at the 36th week and the 52nd week was lower (P<0.05) in the observation group than in the control group. The posttreatment levels of CD(4), CD(4)/CD(8) ratio, IFN-gamma, and IL-4 as well as the pre-post treatment difference of these indexes in the observation group were significantly different from those in the control group (P<0.05).

<b>CONCLUSIONb>Chinese medicine SPNS therapy can significantly reduce the YMDD variation of HBV, and the mechanism may be related to its regulation of the CD(4) level, CD(4)/CD(8) ratio and Th1/Th2 balance.

Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; DNA, Viral ; genetics ; Drug Resistance, Viral ; drug effects ; genetics ; immunology ; Female ; Genes, Viral ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; prevention & control ; virology ; Humans ; Immune Evasion ; genetics ; Lamivudine ; adverse effects ; therapeutic use ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Mutation ; physiology ; Palliative Care ; methods ; Secondary Prevention ; Young Adult