Rilpivirine (TMC278) is a non-nucleoside reverse transcriptase inhibitor approved in combination with other antiretrovirals for the treatment of HIV‑1 infection in treatment‑naive adults (Edurant® 25 mg once daily; Complera® [USA]/Eviplera® [EU] once daily single‑tablet regimen). Rilpivirine should be administered with a meal to optimize bioavailability. Its solubility is pH dependent. Rilpivirine is primarily excreted via the feces with negligible renal elimination. Rilpivirine is predominantly metabolized by cytochrome P450 3A4. There is no clinically relevant effect of age, gender, bodyweight, race, estimated glomerular filtration rate, or hepatitis B/C coinfection status on rilpivirine pharmacokinetics in adults. Drug‑drug interactions were investigated with cytochrome P450 3A substrates, inducers and inhibitors, drugs altering intragastric pH, antiretrovirals, and other often coadministered drugs. Rilpivirine 25 mg once daily does not have a clinically relevant effect on exposure of coadministered drugs. Coadministration with cytochrome P450 3A inhibitors (ketoconazole, ritonavir‑boosted protease inhibitors, telaprevir) results in increased rilpivirine plasma concentrations, but these are not considered clinically relevant; no dose adjustments are required. Coadministration of rilpivirine with cytochrome P450 3A inducers (e.g. rifampin, rifabutin) or compounds increasing gastric pH (e.g. omeprazole, famotidine) results in decreased rilpivirine plasma concentrations, which may increase the risk of virologic failure and resistance development. Therefore, strong cytochrome P450 3A inducers and proton‑pump inhibitors are contraindicated. Histamine‑2 receptor antagonists and antacids can be coadministered with rilpivirine, provided doses are temporally separated. No dose adjustments are required when rilpivirine is coadministered with: acetaminophen, phosphodiesterase type 5 inhibitors (sildenafil, etc.), atorvastatin (and other statins), oral contraceptives (ethinyl estradiol, norethindrone), chlorzoxazone (cytochrome P450 2E1 substrate), methadone, digoxin, tenofovir disoproxil fumarate, didanosine and other nuceos(t)ide reverse transcriptase inhibitors, and HIV integrase inhibitors (raltegravir, dolutegravir, GSK1265744).

Introduction Sex workers (SWs) are vulnerable to HIV, hepatitis, and syphilis coinfection. Methods A cross-sectional study was conducted in Tubarão, Laguna, and Imbituba, Southern Brazil. We surveyed 147 SWs using face-to-face interviews and blood sampling for serological evaluation. Results Prevalence of hepatitis B (HBV) was 23.1%, syphilis 19.7%, hepatitis C (HCV) 8.8%, and HIV 8.8%. Of 13 HIV-infected patients, 3 were co-infected with HCV, 4 with syphilis, and 5 with HBV. Conclusions SWs had high HIV infection rates, and coinfection with viral hepatitis and syphilis.

OBJECTIVE:

To determine the factors associated with change in bilirubin concentration 12 weeks after the initiation of an atazanavir (ATV)-containing antiretroviral regimen.

METHODS:

We performed a retrospective case note review of all patients prescribed ATV between January 2004 and October 2007 in a cohort of HIV infected subjects. Data collected included baseline demographics, hepatitis B and C serology, current antiretroviral therapy, baseline and week 12 routine bloods. The primary endpoint was the change in bilirubin concentration at 12 weeks after start of ATV. Multvariable linear regression was performed to assess the relationships between the change in bilirubin and variables of interest.

Results:

Eighty-three ATV-treated patients were included in the analysis of whom 46 (60.5%) were hepatitis C antibody positive. The median (interquartile range) change in bilirubin by week 12 was 16 (4, 22) umol/L; only 1 patient developed grade 4 hyperbilirubinaemia at week 12. After controlling for baseline bilirubin levels, HCV seropositivity and baseline ALP were associated with a smaller change in bilirubin over the 12 weeks with a trend towards lower increases in those receiving tenofovir. Sensitivity analyses reported similar associations with methadone use and injection drug use, when these variables replaced HCV sero-positivity in the model.

Conclusion:

Patients with hepatitis C co-infection experience smaller changes in bilirubin upon exposure to ATV. Although the underlying mechanism for this association remains unclear, these data support the safe use of this drug in this patient setting. Further research into the clinical predictors of ATV-related hyperbilirubinaemia is warranted.

OBJECTIVES:

The estimation of liver volume (LV) has been widely studied in normal liver, the density of which is considered to be equivalent to 1 kg/l. In cirrhosis, volumetric evaluation and its correlation to liver mass remain unclear. The aim of this study was to evaluate the accuracy of computed tomography (CT) scanning to assess LV in patients with cirrhosis.

METHODS:

Liver volume was evaluated by CT (CTLV) and correlated to the explanted liver weight (LW) in 49 patients. Liver density (LD) and its association with clinical features were analysed. Commonly used formulae for estimating LV were also evaluated. The real density of cirrhotic liver was prospectively measured in explant specimens.

RESULTS:

Wide variations between CTLV (in ml) and LW (in g) were found (range: 3-748). Cirrhotic livers in patients with hepatitis B virus infection presented significantly increased LD (P = 0.001) with lower CTLV (P = 0.005). Liver volume as measured by CT was also decreased in patients with Model for End-stage Liver Disease scores of >15 (P = 0.023). Formulae estimating LV correlated poorly with CTLV and LW. The density of cirrhotic liver measured prospectively in 15 patients was 1.1 kg/l.

CONCLUSIONS:

In cirrhotic liver, LV assessed by CT did not correspond to real LW. Liver density changed according to the aetiology and severity of liver disease. Commonly used formulae did not accurately assess LV.

Background:

This study aimed to better understand the barriers to perinatal hepatitis B prevention and to identify the reasons for poor hepatitis B knowledge and delivery of education to hepatitis B surface-antigen- positive pregnant women among healthcare providers in Santa Clara County, California. Materials and

Methods:

Qualitative interviews were conducted with 16 obstetricians and 17 perinatal nurses in Santa Clara County, California, which has one of the largest populations in the United States at high risk for perinatal hepatitis B transmission.

Results:

Most providers displayed a lack of self-efficacy attributed to insufficient hepatitis B training and education. They felt discouraged from counseling and educating their patients because of a lack of resources and discouraging patient attitudes such as stigma and apathy. Providers called for institutional changes from the government, hospitals, and nonprofit organizations to improve care for patients with chronic hepatitis B.

Conclusions:

Early and continuing provider training, increased public awareness, and development of comprehensive resources and new programs may contribute to reducing the barriers for health care professionals to provide counseling and education to pregnant patients with chronic hepatitis B infection.

BACKGROUND:

About ninety percent of immunocompetent adults recover from hepatitis B virus (HBV) infection within 6 months after transmission. The infection is considered to be terminated if the antibodies (HBsAb) to the hepatitis B surface antigen (HBsAg) become detectable and the HBsAg and Hepatitis B virus DNA (HBV DNA,) are no longer perceptible. After recovery from an acute infection, the detection of HBsAb is assumed to indicate lifelong immunity. However, after initiation of severe immunosuppression, HBV reactivation, as detected by HBsAg seroreversion may be observed in patients with previously resolved HBV infections.

CASE PRESENTATION:

We present an unusual case of a 64-year-old Caucasian woman showing clinically apparent HBV seroreversion more than 45 months after hematopoietic stem cell transplantation (HSCT). Despite living without immunosuppressive agents for more than 40 months, she developed a fulminant HBV infection with detection of a mutated hepatitis B virus carrying two immune escape mutations (D144E/G145R) in the HBsAg (HBsIE mutation).

CONCLUSION:

After HSCT, the absence of risk factors such as strong immunosuppression and graft-versus-host disease decreases the risk of HBV seroreversion but may rearward seroreversion to a later time. Therefore, when monitoring HSCT, patients with serological markers of a resolved HBV infection [HBcAb + (hepatitis B core antibody), HBsAb+, and HBsAg-], the follow up has to be extended over several years to exclude HBV reactivation with HBsAg seroreversion. Furthermore, this case demonstrates the complexity of virus evolution after HBsAg seroreversion as a result of immunosuppression after HSCT.

Poverty, social inequality and marginalization of certain population groups cause the exclusion of these groups from the society and the benefits provided by the social relations of the community.The goal of this study was to evaluate the characteristics of social exclusion of the Roma population in the local community and to determine how this exclusion affects the health status of the population.Included-survey, medical examination and laboratory testing of full blood, blood glucose and markers of hepatitis B on 612 Roma. The data obtained are compared to those of the general population of the local community.The social exclusion of the Roma population in the local community causes its significantly worse health status. Infectious diseases caused by poor hygienic conditions in Roma settlements and chronic diseases caused by stress, inadequate nutrition and poor housing conditions occur 5-20 times more frequently than in the general population.

Primary HepatoCellular Carcinoma (PHCC) has been strongly associated with HBV and HCV infections among other aetiological factors. However; do the patients still spread the viruses? This study involved forty one Nigerian adult patients with PHCC and 45 controls who were tested for HBsAg, HBeAg, Anti-HBe, Anti-HBs, anti-HCV IgM and IgG, anti-HDV and HDV antigen using ELISA. Statistical analysis was carried out with the student - t - test and Mc Nemar test at p < 0.05. The subjects consisted of male:female ratio of 3:1 for both the PHCC patients and controls. Evidence of exposure to hepatitis B, C and D viruses was detected in 95.1%, 44% and 0% of the patients respectively while the respective values of 24%, 11.1% and 0% were obtained for the controls. Indication for high (HBeAg) and low (anti HBe) HBV viral replication, and acute HBV infection were detected in 12.5%, 92.7% and 2.2% respectively among the patients while only 35.6% of the controls had low HBV viral replication. Acute and chronic infections of HCV were also found in 26.8% and 24.4% of the patients respectively compared to the respective values of 2.2% and 11.1% of the controls. Occult HBV infection occurred in equal proportions (11%) of both the patients (31.7%) and controls (35.6%). In conclusion, infectious HBV and HCV particles are present among Nigerian patients with PHCC while HDV infection is uncommon. Hence, safe medical care should be practised for all patients with PHCC while relatives should be screened for these viruses.

Mutations in the core protein (HBc) of hepatitis B virus (HBV) are associated with aggressive hepatitis and advanced liver diseases in chronic hepatitis B (CHB). In this study, we identified the L60V variation in HBc that generates a new HLA-A2-restricted CD8(+) T cell epitope by screening an overlapping 9-mer peptide pool covering HBc and its variants. The nonameric epitope V60 were determined by structural and immunogenic analysis. The HBc L60V variation is correlated with hepatic necroinflammation and higher viral levels, and it may be associated with poor prognosis in CHB patients. Immunization with the defined HBV epitope V60 peptide elicited specific cytotoxic T lymphocyte (CTL)-induced liver injury in HLA-A2(+)/HBV transgenic mice. In addition, in vitro and in vivo experiments both demonstrated that the HBc L60V variation facilitates viral capsid assembly and increases HBV replication. These data suggest that the HBc L60V variation can impact both HBV replication and HBV-specific T cell responses. Therefore, our work provides further dissection of the impact of the HBc L60V variation, which orchestrates HBV replication, viral persistence, and immunopathogenesis during chronic viral infection.

Human hepatitis B virus (HBV) and its satellite virus hepatitis D virus (HDV) primarily infect human, chimpanzee or tree shrew (tupaia belangeri). Viral infections in other species are known to be mainly restricted at entry level as viral replication can be achieved in the cells by transfection of viral genome. Sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for HBV and HDV, and amino acids (aa) 157-165 of NTCP are critical for viral entry and likely limit viral infection of macaque. However the molecular determinants for viral entry restriction in mouse NTCP (mNTCP) remain unclear. In this study, mNTCP was found to be unable to support either HBV or HDV infection though it can bind to pre-S1 of HBV L protein and is functional in transporting substrate taurocholate; comprehensive swapping and point mutations of hNTCP and mNTCP revealed molecular determinants restricting mNTCP for viral entry of HBV and HDV. Remarkably, when mNTCP residues 84-87 were substituted by human counterparts, it can effectively support viral infections. In addition, a number of cell lines, regardless of their species or tissue origin, supported HDV infection when transfected with hNTCP or mouse NTCP with residues 84-87 replaced by human counterparts, highlighting the central role of NTCP for viral infections mediated by HBV envelope proteins. These studies advance our understanding of NTCP-mediated viral entry of HBV and HDV and have important implications for developing mouse model for their infections.