Search

Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore, our aim was to compare the effectiveness of two alternate therapies--tenofovir (TDF) monotherapy and combination therapy of ETV+TDF--in CHB patients with ETV partial virological response. We conducted a retrospective study of 68 patients who had partial virological response to ETV, defined as having detectable HBV DNA following at least 12 months of ETV, and were switched to TDF monotherapy (n = 25) or ETV+TDF (n = 43). Patients were seen in seven US liver/community-based clinics and started on ETV between 2005 and 2009. The majority of patients were male; the vast majority were Asian and had positive hepatitis B e antigen (HBeAg). Patients in both groups had similar pretreatment characteristics. Complete viral suppression (CVS) rates with TDF monotherapy and ETV+TDF were similar after 6 months (71% vs 83%, P = 0.23) and 12 months (86% vs 84%, P = 0.85), and there was no statistically significant difference in CVS rates even when only patients with higher HBV DNA levels at switch (>1000 IU/mL) were evaluated. Multivariate analysis indicated that ETV+TDF was not an independent predictor of CVS compared to TDF monotherapy (OR = 1.19, P = 0.63). In conclusion, TDF monotherapy and ETV+TDF are comparable in achieving CVS in CHB patients with partial virological response to ETV. Long-term alternate therapy with one pill (TDF monotherapy) vs two pills (ETV+TDF) could lead to lower nonadherence rates and better treatment outcomes.

To compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) in Asian and non-Asian chronic hepatitis B (CHB) patients.The efficacy and safety of the initial 48 wk of treatment with TDF was compared in a post-hoc analysis of combined data from 217 Asians and 299 non-Asians included in Studies 102 and 103 and a post-approval, open-label trial (Study 123). Patient groups were compared according to baseline hepatitis B e antigen (HBeAg) status and viral load. The main outcome measures included the proportion of patients who achieved a hepatitis B virus (HBV) DNA level400 copies/mL at Week 48 of treatment. Secondary measures included: HBV DNA and alanine aminotransaminase (ALT) levels over time; proportion of patients with normal ALT levels; proportion of patients with HBeAg loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion; changes in liver histology. Safety and tolerability were evaluated by the occurrence of adverse events (AEs), serious AEs, laboratory abnormalities, discontinuation of the study drug due to AEs, or death. The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug.At week 48, similar proportions of Asians and non-Asians reached HBV DNA400 copies/mL (96% of Asian and 97% of non-Asian patients with HBeAg-negative CHB and 83% of Asian and 79% of non-Asian patients with HBeAg-positive CHB had HBV DNA) and normal ALT (78% of Asian and 81% of non-Asian patients with HBeAg-negative CHB and 71% of Asian and 74% of non-Asian patients with HBeAg-positive CHB had normal ALT). On-treatment HBV DNA decline rates were similar between Asians and non-Asians regardless of baseline HBeAg status and viral load. HBV DNA decline during the first four weeks was 2.9 log10 copies/mL in HBeAg-negative Asians and non-Asians, and in HBeAg-positive non-Asians, and 3.1 log10 copies/mL in HBeAg-positive Asians. HBeAg loss and seroconversion was achieved in 14% of Asians vs 26% and 24%, respectively, in non-Asians. Liver histology improved in 77.2% of Asians and 71.5% of non-Asians. No resistance to TDF developed. No renal safety signals were observed.TDF demonstrated similar viral suppression, normalization of ALT, improvements in liver fibrosis, and no detectable resistance in Asian and non-Asian patients regardless of baseline HBeAg status.

Summary The clinical course for chronic hepatitis B (CHB) patients with normal ALT and with or without minimal histologic activity remains unclear. We assessed frequency, amplitude, disease activities, and associated factors of ALT and/or AST flares in this subpopulation. Forty-seven consecutive treatment naive Asian patients with CHB were enrolled from two liver clinics between December 2003 and January 2013, who had normal baseline ALT by routine clinical biochemical testing performed 6 weeks before or after the liver biopsy. We defined a flare as elevation of ALT/AST above the upper limit of normal of ALT/AST. The mean follow-up was 37.6 (CI = 12, 88) months, and the mean age at entry into the study was 43.3 (CI = 19, 65); 22/47 (46.8%) were males; 15/45 (33.3%), HBeAg+; 68.1% had stage 0–1 fibrosis; 63.8% had grade 0–1 inflammation. During follow-up, 13/47 (27.7%) cases developed ALT flare at least once in a mean of 13.5 (CI = 2, 43) months after liver biopsy; ALT flare was not associated with baseline ALT level, fibrosis stage, inflammation grade, hepatitis B virus (HBV) DNA load, HBeAg status, HBV genotype, HBV precore and basal core promoter mutations. 11/13 (84/6%) of ALT flares resolved during follow-up. 13/13 (100%) of ALT flares met AASLD treatment criteria, but only 6/13 (46.2%) were on HBV treatment. Serum ALT and/or AST flares occur frequently in CHB carriers who initially presented with normal ALT during pretreatment period. Thus, regular follow-up is warranted despite status of ALT/AST. No clinical factors were found to be associated with ALT flares.

A PHASE 3 STUDY OF TENOFOVIR ALAFENAMIDE COMPARED WITH TENOFOVIR DISOPROXIL FUMARATE IN PATIENTS WITH HBEAGNEGATIVE, CHRONIC HEPATITIS B: WEEK 48 EFFICACYAND SAFETY RESULTS M. Buti1, E. Gane2, W.K. Seto3, H.L.Y. Chan4, W.-L. Chuang5, T. Stepanova6, A.J. Hui7, Y.-S. Lim8, R. Mehta9, H.L.A. Janssen10,11, S.K. Acharya12, J.F. Flaherty13, B. Massetto13, A. Cathcart13, P. Dinh13, G.M. Subramanian13, J.G. McHutchison13, C. Pan14, M. Brunetto15, N. Izumi16, P. Marcellin17. 1Hospital General Universitari Vall d’Hebron, Barcelona, Spain; 2Auckland Clinical Studies, Auckland, New Zealand; 3Queen Mary Hospital; 4The Chinese University of Hong Kong, Hong Kong, Hong Kong, China; 5Kaoshing Medical University Hospital, Kaoshing, Taiwan; 6Modern Medicine Clinic, Moscow, Russia; 7Alice Ho Miu Ling Nethersole Hospital, Hong Kong, Hong Kong, China; 8Asan Medical Center, Seoul, South Korea; 9Nirmal Hospital Private Limited, Surat, India; 10Toronto Western Hospital, Toronto, Canada; 11Erasmus Medical Center, Rotterdam, Netherlands; 12All India Institute of Medical Sciences, New Delhi, India; 13Gilead Sciences, Foster City; 14New Discovery, LLC, Flushing, United States; 15University Hospital of Pisa, Pisa, Italy; 16Musashino Red Cross Hospital, Tokyo, Japan; 17Hopital Beaujon, Clichy, France E-mail: John.Flaherty@gilead.com

The modified normal alanine aminotransferase (ALT) value (i.e., males

The management of chronic hepatitis B (CHB) during pregnancy remains a challenge and involves various aspects of maternal–fetal care. Despite the standard immunoprophylaxis, a significant portion of infants born to highly viremic mothers remain infected with hepatitis B virus (HBV). Emerging data suggest that antiviral therapy in the third trimester can prevent immunoprophylaxis failure. To minimize fetal exposure to antiviral agents, antiviral therapy during pregnancy should be reserved for mothers with advanced disease or who are at risk for hepatic decompensation. Current safety data suggest that lamivudine, telbivudine, or tenofovir may be used during pregnancy. However, the timing in initiating antiviral therapy requires careful assessment of risks and benefit. The authors provide a systematic review of the features of HBV during pregnancy, risk factors for vertical transmission, and evidence-based data on antiviral use during pregnancy. They propose an algorithm to assess the need of antiviral treatment and monitor mothers with CHB.

Background & Aims Despite appropriate immunoprophylaxis, HBV vertical transmission (VT) occurs in 5–10% of infants born to HBs-antigen (HBsAg)+ mothers. We investigated whether amniocentesis increases the risk of transmission. Methods We performed a case-control study on infants who were born to HBsAg+ mothers without antiviral exposure and completed appropriate immunization. Infants born to mothers with amniocentesis were compared to those without amniocentesis to assess VT rates, which were defined by the percentage of infants with HBsAg positivity when they were 7–12months old. Results Of the 642 consecutive infants enrolled, 63 infants with amniocentesis were compared with 198 matched infants selected from the remaining 579 infants without amniocentesis. There was a higher VT rate in infants with amniocentesis than in those without amniocentesis (6.35% vs. 2.53%; p =0.226). Maternal HBV DNA levels before amniocentesis were further stratified to 10 copies/ml, and ⩾7log 10 copies/ml for subset analyses. There were no significant differences in the VT rates between the amniocentesis group and the control group if the maternal HBV DNA levels were 10 copies/ml. However, a significantly higher VT rate was observed in the amniocentesis group vs. the control group if the maternal HBV DNA levels were ⩾7log 10 copies/ml (50% vs. 4.5%, respectively, p =0.006). According to baseline value risk analyses, performing amniocentesis on highly viremic mothers was a risk factor for HBV transmission (OR=21.3, 95% CI: 2.960–153.775). Conclusions Amniocentesis performed on HBsAg+ mothers with HBV DNA ⩾7log 10 copies/ml significantly increased the frequency of VT. HBsAg+ women who plan to have amniocentesis should be evaluated for the risk of VT and stratified according to their HBV DNA levels. Further prospective studies are warranted to verify our findings.

Chronic hepatitis B (CHB) virus infection is an epidemic that is associated with cirrhosis and liver cancer.1 Management of CHB during pregnancy remains a challenge, with unique issues that involve prevention of MTCT and safe use of antiviral therapy. Previous studies indicate that mothers with CHB pose a risk of vertical transmission of hepatitis B virus (HBV) to infants.2,3 Without intervention, 80%-90% of infants who are born to hepatitis B e antigen (HBeAg)-positive mothers may develop CHB infection.3,4 Use of HBV vaccine and immunoglobulin G (HBIg) within 12 hours of birth, followed by two additional HBV vaccination inoculations, has been demonstrated to reduce the mother-to-child transmission (MTCT) rate from 90% to approximately 5%-10%.5 However, despite appropriate passive-active immunoprophylaxis, MTCT remains a concern and has been reported in approximately 8%-15% of infants who are born to highly viremic mothers, resulting in a significant incidence of infant chronic infection and adding to the large pool of patients with CHB in Asia.6–8 Previous studies indicate that use of lamivudine (LAM) or telbivudine (LdT) during late pregnancy in highly viremic mothers can reduce MTCT, although long-term fetal and infant safety has not been established.7,9,10 Currently, tenofovir disoproxil fumarate (TDF) is not approved for treatment of hepatitis B in China. A recent U.S. report suggested that TDF might be used in the third trimester of pregnancy in preventing MTCT.11 However, real-life observational data are lacking on the use of antiviral therapy in late pregnancy for preventing MTCT. In addition, the sample size in the currently published prospective trials for antiviral treatment in pregnancy involves only approximately 100 subjects in the treatment arm, which may not be large enough to capture the uncommon adverse events (AEs). We conducted a prospective study with a sample size of 700 patients to assess the safety and efficacy of third-trimester use of LdT or LAM versus no treatment, based on the patient-physician decision in a real-life MTCT prevention setting.

The glomerular mesangium is an important site of activity in patients with heroin addiction. We studied the effect of morphine, a metabolite of heroin, on the mesangial immunoglobulin G aggregate uptake in a model of specific mesangial cell injury. Isolated specific mesangial cell injury was developed in Lewis rats by injecting intravenously antithymocyte serum (ATS). Forty-eight hours later, radioiodinated, heat aggregated immunoglobulin G (AHIgG125I) was administered (20 mg/100 g i.v.) by tail vein. At 4 and 24 h, kidneys, liver, and spleen were removed, glomeruli isolated, and the radioactivity measured. Blood levels of AHIgG125I were measured at 0, 4 and 24 h. For ultrastructural studies, IgG-coated gold particles were injected, and the mesangial circulation was studied. At 4 h, ATS-treated rats showed a lower (p0.02) accumulation of AHIgG125I in the mesangium when compared with control rats (controls 511,012 +/- 10,807 vs. ATS 464,614 +/- 7,944 cpm/g glomerular protein). ATS plus morphine treated rats showed a higher (p0.01) accumulation of of AHIgG125I when compared with rats treated with AS alone. Even at 24, h morphine-treated ATS rats showed a higher accumulation of AHIgG125I when compared with those treated with ATS alone. Ultrastructural studies showed aggregation of IgG-coated gold particles in the mesangial cell endolysosomes of control rats. Our results suggest that macromolecules may dwell longer in the mesangium of rats with intact mesangial cells. This increase in transit time may be related to the uptake of these macromolecules by mesangial cells. Morphine seems to enhance the accumulation of macromolecules in the mesangium, independent of its action on mesangial cells.

BACKGROUND: High serum levels of lipopolysaccharide (LPS) with LPS-MD-2/TLR4 complex activated NF-kb and cytokine cause hepatic necrosis in animal models. We investigated the dynamic changes of LPS levels in patients with acute on chronic hepatitis B liver failure (ACHBLF). METHODS: We enrolled ACHBLF patients for a 12-week study. Patients' LPS levels were measured along with 10 healthy controls. Patients on supportive care and recovered without intervention(s) were analyzed. Patients' LPS levels during the disease progression phase, peak phase, and remission phase were compared with healthy controls. RESULTS: Among 30 patients enrolled, 25 who received interventions or expired during the study period were excluded from the analysis, five patients on supportive care who completed the study were analyzed. Significant abnormal distributions of LPS levels were observed in patients in different phases (0.0168±0.0101 in progression phase; 0.0960±0.0680 in peak phase; 0.0249±0.0365 in remission phase; and 0.0201±0.0146 in controls; respectively, p

Despite appropriate passive and active immunization, perinatal transmission of hepatitis B virus (HBV) still occurs in 5%-10% of infants born to women with high levels of viremia who test positive for the hepatitis B e antigen (HBeAg). We evaluated the effects of cesarean section delivery on perinatal transmission of HBV from women who tested positive for the hepatitis B surface antigen (HBsAg).We analyzed data from 1409 infants born to HBsAg-positive mothers through vaginal delivery (VD) (n = 673), elective caesarean section (ECS) (n = 496), or urgent cesarean section (UCS) (n = 240) who completed appropriate immunization against HBV. The prevention was assumed to have failed for infants who were HBsAg positive when they were 7-12 months old; this information was used to assess transmission rates.HBV infection was transmitted to a smaller percentage of infants born by ECS (1.4%) than by VD (3.4%, P.032) or UCS (4.2%, P.020). UCS had no effect on vertical transmission, compared with VD (4.2% vs 3.4%, P = .593). Infants born by ECS had a significantly lower rate of vertical transmission than those born by non-ECS (1.4% vs 3.6%, P = .017). Women with HBV DNA levels1,000,000 copies/mL did not transmit the infection to their infants, regardless of method of delivery. There were no differences in maternal or infant morbidity and mortality among the groups.There is a significantly lower rate of vertical transmission of HBV infection to infants delivered by ECS, compared with those delivered vaginally or by UCS. Elective cesarean sections for HBeAg-positive mothers with pre-delivery levels of HBV DNA ≥1,000,000 copies/mL could reduce vertical transmission.

Background & Aims Many foreign-born persons in the US are at high risk of chronic hepatitis B (HBV) and C (HCV) infections, yet are not aware of their infection, and lack healthcare coverage or linkage to care. Methods A unique partnership, the Hepatitis Outreach Network, combines the expertise and resources of the Mount Sinai School of Medicine, the NYC Department of Health and Mental Hygiene, and community-based organizations, to provide education, screening and link to care in communities with high prevalence of chronic viral hepatitis. Comprehensive HBV and HCV screening identifies infected patients, who then receive further evaluation from either local or Mount Sinai physicians, combined with patient-navigators who organize follow-up visits. Results Of 1603 persons screened, 76 had HBV and 75 had HCV. Importantly, screening for HCV based on traditional risk factors would have missed 67% of those who tested positive. Of the 76 persons with HCV infection, 49 (64%) received a medical evaluation (26 with local providers and 23 at Mount Sinai). Of the 49 HCV-infected persons evaluated, treatment was recommended in 11 and begun in 8 (73%). Of the 76 persons with HBV infection, 43 (57%) received a medical evaluation (31 with local providers and 12 at Mount Sinai). Of the 43 HBV-infected persons evaluated, treatment was recommended and begun in 5 (100%). Conclusions Hepatitis Outreach Network has successfully established novel proof of concept for identifying HBV and HCV infections in foreign-born persons through use of several unique elements that effectively link them to care.

Aims Hepatitis B virus (HBV) reverse transcriptase (RT) mutants, which have not been well characterized according to different disease stages. This study aimed to characterize the profiles of naturally occurring mutations in the HBV RT region and their associated clinical outcomes. Methods HBV RT region mutations and genotypes were determined by PCR-direct sequencing and compared with p-distance model. Results Among 467 consecutive eligible patients (262 chronic hepatitis B patients, 105 cirrhotic patients and 100 hepatocellular carcinoma patients), the nucleos(t)ide analogues-related mutations (rtI169T, rtV173L, rtL180M, rtA181T, rtS202C, rtM204I/V, rtN236T) were found. The p-distance value reached a peak in the age of 20–30 years in the CHB patients and in the age of 40–45 years in the cirrhotic patients and hepatocellular carcinoma patients. The naturally occurring mutation, rtS106C mutation was higher in chronic hepatitis B patients (14/100, 14.0%) and cirrhotic patients (14/100, 14.0%) than that in hepatocellular carcinoma patients (4/100, 4.0%, P = 0.013). And the rtD134E/G/N/S mutations were also higher in chronic hepatitis B patients (22/100, 22.0%) and cirrhotic patients (21/100, 21.0%) than that in hepatocellular carcinoma patients (10/100, 10.0%, P = 0.021 and P = 0.032 respectively). The mutation frequencies in A–B interdomain were higher in cirrhotic patients (101/1900, 5.3%) than that in hepatocellular carcinoma patients (68/1900, 3.6%) (P = 0.009). Conclusions The nucleos(t)ide analogues-related mutations do exist in treatment naive patients with different disease stages. rtS106C, rtD134E/G/N/S and A–B interdomain mutations may be associated with necro-inflammation, immune response and cirrhosis development at ages older than 40.

Focal glomerulosclerosis is the predominant glomerular lesion in patients with drug addiction. Since mesangial expansion has been considered a precursor of glomerulosclerosis we investigated whether the use of these drugs can cause accumulation of macromolecules into mesangium which may contribute to the expansion of mesangium. The majority of drug addicts at times take drugs in groups and may thus be exposed to a variety of drugs (cocaine, alcohol, and heroin). Therefore, we studied the effect of cocaine, alcohol, and morphine alone or in combination on the accumulation of radiolabeled human immunoglobulin-G (IgG) aggregates (AHIgG125I) into glomeruli/mesangium. Cocaine enhanced accumulation of AHIgG125I at 8 hr. Glomerular levels of AHIgG125I levels were also higher in morphine treated rats when compared with untreated animals. Alcohol did not alter the deposition of AHIgG125I. But at an earlier time (4 hr) alcohol enhanced the effect of cocaine on accumulation of IgG aggregates into the mesangium. The combined effects of morphine and cocaine, or morphine and alcohol were not different than the effect of morphine alone. The enhanced accumulation of phlogogenic macromolecules into the mesangium may not only increase the quantity of mesangial matrix but may also alter the quality of matrix. This may be playing an important role in the development of glomerular injury.

Background & Aims Despite immunoprophylaxis, mother to child transmission (MTCT) of hepatitis B virus (HBV) still occurs in infants born to hepatitis B surface antigen (HBsAg)–positive mothers. We analyzed methods of risk assessment and interventions for MTCT. Methods We reviewed 63 articles and abstracts published from 1975–2011 that were relevant to MTCT; articles were identified using the PubMed bibliographic database. Results Administration of HB immunoglobulin and HB vaccine to infants at birth (within 12 hours), followed by 2 additional doses of vaccines within 6–12 months, prevented approximately 95% of HBV transmission from HBsAg-positive mothers to their infants. However, HBV was still transmitted from 8%–30% of mothers with high levels of viremia. It is important to assess the risk for MTCT and identify mothers who are the best candidates for intervention. The most important risk factor is maternal level of HBV DNA >200,000 IU (10 6 copies)/mL; other factors include a positive test result for the HB e antigen, pregnancy complications such as threatened preterm labor or prolonged labor, and failure of immunoprophylaxis in prior children. Antiviral therapy during late stages of pregnancy is the most effective method to reduce transmission from mothers with high levels of viremia, but elective cesarean section might also be effective. Antepartum administration of HB immunoglobulin, giving infants a double dose of HB vaccine, or avoiding breastfeeding had no impact on MTCT. Conclusions HBsAg-positive mothers should be assessed for risk of MTCT, and infants should receive immunoprophylaxis. Pregnant women with levels of HBV DNA >200,000 IU/mL should be considered for strategies to reduce the risk for MTCT. We propose an algorithm for risk assessment and patient management that is based on a review of the literature and the opinion of a panel of physicians with expertise in preventing MTCT.

Routine screening for hepatitis B virus (HBV) infection can identify individuals who need vaccination or treatment, as vaccination can prevent HBV infection. Although the overall prevalence of HBV infection in the United States is low (1%), it is high (~10%) in Asian Americans. However, HBV screening rates in this population have been reported to be low.This article systemically reviews the reported prevalence of HBV infection, the rate of HBV screening and access to HBV care, barriers for HBV screening and care, and a possible approach for improving HBV screening in Asian Americans.Articles published from 1999 to 2011 on HBV screening and disparity in Asian Americans were identified by searching electronic databases (PubMed and Cochrane Library), and reviewed.Published studies, including a recent report from the Institute of Medicine of the National Academies, revealed HBV screening rates are low in Asian Americans. This review addresses the need for HBV screening in Asian Americans. Barriers to HBV screening are related to patients, providers, and/or the healthcare system. Screening programs that incorporate culturally sensitive interventions and include educational outreach, vaccination, and a link to healthcare services improve rates of HBV screening and vaccination in this at-risk community.A strategy that integrates efforts from the healthcare profession, federal agencies, and the community will be needed to improve HBV screening and access to HBV care for Asian Americans.

* Department of Gastroenterology and Hepatology, AZ Groeninge Hospital, Kortrijk, Belgium. † Pole Hepato-digestif, Unite Inserm U.1110, Universite de Strasbourg, Laboratoire d’Excellence HepSys, Strasbourg, France. ‡ Southlake Regional Health Centre, Newmarket, ON, Canada. § Division of Gastroenterology, .Department of Medicine, NYU Langone Medical Center, New York University School of Medicine, New York, NY, USA. || Orlando Infectious Disease Center, Orlando, FL, USA. ¶ IST GmbH, Mannheim, Germany. ** F. Hoffmann-La Roche Ltd, Basel, Switzerland.

P0646 LOWER RISK OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B PATIENTS TREATED WITH ENTECAVIR: A REACH-B ANALYSIS OF THE ENUMERATE STUDY J. Ahn, M. Nguyen, H. Lee, J. Lim, C. Pan, H. Te, T. Tran, H.N. Trinh, D. Lau, D. Chu, A. Min, T.-S. Leduc, A. Pillai, H. Bae, S. Do, A. Mannalithara, A.S. Lok, W.R. Kim, on behalf of the ENUMERATE Investigators and Asian Health Foundation. Oregon Health & Science University, Portland, Stanford University, Stanford, Tufts University, Boston, Yale University, New Haven, NYU Langone, New York City, University of Chicago, Chicago, Cedars Sinai, Los Angeles, San Jose Gastroenterology, San Jose, Beth Israel Medical Center, Boston, Albert Einstein College of Medicine, Mount Sinai Beth Israel, New York City, Leduc Medical Group Inc, Fountain Valley, Emory University, Atlanta, St. Vincent Medical Center, Los Angeles, Digestive Health Associates of Texas, Plano, University of Michigan, Ann Arbor, United States E-mail: ahnj@ohsu.edu

Since increased mesangial accumulation of matrix has been considered to be an important event in the development of focal glomerulosclerosis, we investigated whether morphine, an active metabolite of heroin, can modulate mesangial accumulation of immune complexes. Control or morphine-dependent rats were administered intraperitoneal ferritin (8 mg/l00 g body weight) daily for 6 weeks. Body weight, blood pressure, serum creatinine, 24-hour urinary protein and creatinine excretion rates were measured at 3-week intervals. Rats were sacrificed at the end of 6 weeks and kidney tissue was studied by light, immunofluorescence and electron microscopy. Serum creatinine levels and urinary protein excretion rates were not different between control and morphine-dependent rats. All morphine-dependent rats developed hematuria, whereas only 1 control rat developed hematuria. Light microscopy revealed no proliferation of mesangial cells and only a minimal increase in the mesangial matrix. Electron-microscopic studies showed deposition of immune complexes in the mesangial region. Mesangial cells showed aggregation of ferritin in lysosomes. Immunofluorescence studies revealed the presence of IgG staining predominantly in the mesangial region. The majority (60%) of morphine-dependent rats showed a diffuse mesangial deposition of IgG when compared to control rats (83%) who showed only focal deposition. These results indicate that morphine enhances deposition of immune complexes in the mesangium. Morphine-induced enhanced deposition of macromolecules may not only alter the quantity of mesangial matrix but may also change its quality. This may play a pathogenic role in the development of glomerular lesions in patients who abuse opiates.

There are limited data on the effects of long-term entecavir therapy in Asian patients with chronic hepatitis B (CHB). We performed a post hoc analysis of 94 Asian hepatitis B e antigen-positive (HBeAg+), nucleos(t)ide analogue-naive patients who received 5 years of therapy with entecavir (up to 2 years in study ETV-022 and the remainder in study ETV-901). Among patients completing week 240, 95% (63 of 66) had levels of hepatitis B virus DNA300 copies/mL, and 76% (50 of 66) had normalized levels of alanine aminotransferase. In addition to patients who achieved a serologic response during ETV-022, a further 40% (26 of 65) achieved HBeAg loss, and 18% (12 of 65) underwent HBeAg seroconversion through year 5 of entecavir therapy. No resistance to entecavir was detected, and the safety profile was consistent with previous reports. The long-term efficacy and safety of entecavir are therefore comparable between Asians and the overall population of HBeAg+ patients with CHB.

A case study of a 45-year-old Chinese woman with chronic hepatitis B (CHB) diagnosed in 1999 …...

Because mesangial expansion is considered a precursor of focal glomerulosclerosis, we studied whether morphine can cause mesangial expansion. We used radiolabeled human immunoglobulin G aggregates (125I-ahIgG) to study mesangial kinetics in control and experimental (morphine-treated) rats. Control and experimental rats were administered 125I-ahIgG by tail vein. Serum levels of 125I-ahIgG and uptake of 125I-ahIgG by liver, spleen, and mesangium were determined at 4, 8, 12, 24, and 36 h after 125I-ahIgG administration. Mesangial 125I-ahIgG levels were higher (P < 0.05) at 4 h and at later periods in morphine-treated vs. control rats. Naloxone, an opioid antagonist, did not attenuate the morphine-induced mesangial accumulation of 125I-ahIgG. The mean uptake of IgG aggregates was lower in the liver and spleen of morphine-treated rats at 36 h (P < 0.05). In both in vivo and in vitro experiments, ultrastructural studies showed accumulation of IgG-coated gold particles in vesicles, endosomes, and lysosomes. Morphine may have increased the accumulation of 125I-ahIgG in the glomeruli either by increasing the delivery of macromolecules into the mesangium or by altering the exit of macromolecules from the mesangium.

Focal glomerular sclerosis is the predominant renal lesion in heroin addicts. We studied whether morphine, a metabolite of heroin, could directly affect the uptake of immunoglobulin G (IgG) complexes by cultured mesangial cells (MC) and macrophages (MP). Pre-incubation of morphine (10(-6) M) decreased uptake of IgG complexes [morphine, 66,577 +/- 6,248 vs. control, 95,735 +/- 5,227 counts.min-1 (cpm).mg protein-1; P < 0.02] by MC. Morphine (10(-4)-10(-6) M) also inhibited (P < 0.01) uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate-labeled low-density lipoprotein by MC. MP pretreated with morphine (10(-6) M) also showed significantly (P < 0.02) lower uptake of IgG complexes (control 94,959 +/- 4,980 vs. morphine, 58,360 +/- 11,608 cpm/mg protein). Binding studies carried out at 4 degrees C on MC and MP indicated that morphine did not modulate surface binding of IgG complexes. Naloxone, a morphine antagonist, also produced a rather decreased (P < 0.05) uptake of IgG complexes by both MP and MC and did not inhibit the effect of morphine on the uptake of IgG complexes. In vivo studies indicated that morphine-treated rats had a higher (P < 0.05) accumulation of aggregated human IgG complexes (125I-labeled ahIgG) in their glomeruli when compared with untreated rats (control rats, 256,929 +/- 40,008 cpm/g protein vs. experimental rats, 398,317 + 51,512 cpm/g). Increased accumulation of 125I-ahIgG in the glomeruli from morphine-treated rats may either be related to increased delivery of 125I-ahIgG into the mesangium or be a result of decreased drainage of 125I-ahIgG from the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)

Worldwide, there are estimated to be 400 million people chronically infected with hepatitis B virus (HBV). In Asia, perinatal transmission of HBV from mother to newborn accounts for the high incidence of CHB infection Perinatally acquired CHB patients have unique features in their natural history, characterized by a long duration of immunotolerance phase, unpredictable patterns of disease reactivation and inactivation, and high risk for cirrhosis or HCC. Asian Americans, 60% of whom are foreign born, thus have similar patterns in the natural history of their disease. This article is a systemic review on the natural history of CHB in the Asian and Asian American population. Future research directions in this special population will also be explored. [N A J Med Sci. 2009;2(3):111-117.] Abbreviations:hepatitis B virus; HBIG, hepatitis B immunoglobulin; CHB, chronic hepatitis B; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBsAb, anti-HBsAg antibody; HBcAb, anti-hepatitis B core antibody; HBeAb, anti-HBeAg antibody; HCC, hepatocellular carcinoma; ALT, alanine aminotransferase ; AST aspartate aminotransferase.