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BACKGROUND: Despite subsidised access to direct-acting antivirals (DAAs), hepatitis C (HCV) treatment uptake in Australia is declining. Interventions are needed to link people living with HCV to care and treatment. We implemented and measured effectiveness of a state-wide, health department-led, enhanced case management through the primary care practitioner for all HCV notifications, aiming to encourage and support treatment commencement. METHODS: A randomised controlled trial compared enhanced case management, delivered by the health department to diagnosing clinicians, with standard of care using notifiable disease systems in Tasmania, Australia (2020-21). The intervention involved a nurse specialist contacting and providing support by telephone to primary care practitioners making an HCV notification. The primary outcome was the proportion of cases notified with chronic hepatitis C who commenced treatment within 12 weeks of notification. We allowed a 12-week extended follow-up period at the end of the study for participants with no outcomes. RESULTS: Eighty-five primary care practitioners randomised to the intervention and 86 to standard of care arms notified 111 and 115 HCV cases, respectively. The proportion of cases notified with chronic hepatitis (HCV RNA detected) commencing treatment within 12 weeks was similar between study arms (41% vs 33%; p=0·51) and after extended study follow-up (65% vs 48%; p=0·18). RNA test completion was higher in the intervention than in standard of care arm (89% vs. 78%; p=0·03), while completing pre-treatment workup for chronic patients (65% vs. 64%; p=0·93) was similar. CONCLUSION: This was the first prospective randomised study of the utility of immediate HCV notification follow-up of primary care practitioners to enhance treatment uptake using disease notification surveillance data. We demonstrated improvement in HCV RNA testing and trend toward better engagement in care, but no significant increase in treatment uptake.
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Hepatitis C Crónica , Hepatitis C , Humanos , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/diagnóstico , Manejo de Caso , Estudios Prospectivos , Hepatitis C/epidemiología , Hepacivirus , ARN/uso terapéutico , Atención Primaria de SaludRESUMEN
AIM: To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. METHODS: We performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time. RESULTS: Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBeAg positive status (OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-naïve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of non-compliance. Tenofovir therapy was well tolerated. CONCLUSION: Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials.
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BACKGROUND/AIMS: Endoscopic screening for high-risk gastro-oesophageal varices (GOV) is recommended for compensated cirrhotic patients with transient elastography identifying increasing numbers of patients with cirrhosis without portal hypertension. Using liver stiffness measurement (LSM) ± platelet count, the aim was to develop a simple clinical rule to exclude the presence of high-risk GOV in patients with Child-Pugh A cirrhosis. METHODS: A retrospective analysis of 71 patients with Child-Pugh A cirrhosis diagnosed by transient elastography (LSM >13.6 kPa) who underwent screening gastroscopy was conducted. A predictive model using LSM ± platelet count was assessed to exclude the presence of high-risk GOV (diameter >5 mm and/or the presence of high-risk stigmata) and validated using a second cohort of 200 patients from two independent centres. RESULTS: High-risk GOV were present in 10 (15%) and 16 (8%) of the training and validation cohorts, respectively, which was associated with LSM and Pl count (P < 0.05). A combined model based on LSM and Pl count was more accurate for excluding the presence of high-risk GOV than either alone (training cohort AUROC: 0.87 [0.77-0.96] vs. 0.78 [0.65-0.92] for LSM and 0.71 [0.52-0.90] for platelets) with the combination of LSM ≤25 kPa and Pl ≥100 having a NPV of 100% in both the training and validation cohorts. A total of 107 (39%) patients meet this criterion. CONCLUSION: The combination of LSM ≤25 kPa and Pl ≥100 can be used in clinical practice to exclude the presence of high-risk GOV in patients with Child-Pugh A cirrhosis.
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Diagnóstico por Imagen de Elasticidad/métodos , Várices Esofágicas y Gástricas , Cirrosis Hepática , Hígado/patología , Recuento de Plaquetas/métodos , Anciano , Endoscopía del Sistema Digestivo/métodos , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Medición de Riesgo/métodosRESUMEN
BACKGROUND AND AIM: Reducing the burden of hepatitis C virus (HCV) related liver disease will require treating people who inject drugs (PWID), the group at most risk of infection and transmission. We determine the cost-effectiveness of treating PWID with interferon-free direct-acting antiviral therapy in Australia. METHODS: Using a deterministic model of HCV treatment and liver disease progression, including a fixed rate of re-infection, the expected healthcare costs and quality-adjusted life years (QALYs) of a cohort of newly HCV-infected PWID were calculated for: no treatment; treatment after initial infection ("early-treatment"); and treatment prior to developing compensated cirrhosis ("late-treatment"). Incremental cost-effectiveness ratios (ICERs) were used to compare scenarios. RESULTS: Late-treatment was cost-effective compared to no treatment, with a discounted average gain of 2.98 (95%confidence interval 2.88-5.22) QALYs per person for an additional cost of $15,132 ($11,246-18,922), giving an ICER of $5078 ($2847-5295) per QALY gained. Compared to late-treatment, early-treatment gained a further discounted average of 2.27 (0.58-4.80) QALYs per person for $38,794 ($34,789-41,367), giving an ICER of $17,090 ($2847-63,282), which was cost-effective in approximately 90% of Monte-Carlo uncertainty simulations. For every 100 newly HCV-infected PWID, there were an estimated 40 (39-56) eventual liver-related deaths without treatment, compared to 7 (6-11) and 8 (7-13) with early-treatment and late-treatment available respectively. CONCLUSIONS: Treating HCV-infected PWID with new therapies is cost-effective and could prevent a significant number of liver-related deaths. Although late-treatment was the most cost-effective option, the cost per QALY gained for early-treatment compared to late-treatment is likely to be below unofficial Australian willingness to pay thresholds.
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Antivirales/administración & dosificación , Antivirales/economía , Análisis Costo-Beneficio , Costos de la Atención en Salud , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/economía , Abuso de Sustancias por Vía Intravenosa , Adolescente , Adulto , Australia , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Hepatitis C Crónica/mortalidad , Hepatitis C Crónica/transmisión , Humanos , Modelos Biológicos , Años de Vida Ajustados por Calidad de Vida , Recurrencia , Adulto JovenRESUMEN
BACKGROUND: Although interferon-free regimens are approved for patients co-infected with HIV and genotype-2 or genotype-3 hepatitis C virus (HCV), interferon-based regimens are still an option for those co-infected with HIV and HCV genotypes 1 or 4. These regimens are limited by clinically significant toxic effects and drug interactions with antiretroviral therapy. We aimed to assess the efficacy and safety of an interferon-free, all-oral regimen of sofosbuvir plus ribavirin in patients with HIV and HCV co-infection. METHODS: We did this open-label, non-randomised, uncontrolled, phase 3 study at 45 sites in seven European countries and Australia. We enrolled patients (aged ≥18 years) co-infected with stable HIV and chronic HCV genotypes 1-4, including those with compensated cirrhosis. Once-daily sofosbuvir (400 mg) plus twice-daily ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg) was given for 24 weeks to all patients except treatment-naive patients with genotype-2 HCV, who received a 12-week regimen. The primary efficacy endpoint was sustained virological response 12 weeks after treatment. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01783678. FINDINGS: Between Feb 7, 2013, and July 29, 2013, we enrolled 275 eligible patients, of whom 262 (95%) completed treatment; 274 patients were included in the final analysis. Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77-91) in patients with genotype-1 HCV, 88% (69-98) in patients with genotype-2 HCV, 89% (81-94) in patients with genotype-3 HCV, and 84% (66-95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67-99] and 91% [81-97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36-100] and 86% [73-94], respectively). There was no emergence of sofosbuvir-resistance mutations in patients with HCV viral relapse. Six (2%) patients discontinued treatment because of adverse events. The most common adverse events were fatigue, insomnia, asthenia, and headache. Four (1%) patients had serious adverse events regarded as related to study treatment. Additionally, four (1%) patients receiving antiretroviral treatment had a transient HIV viral breakthrough; however, none required changes in antiretroviral regimen. INTERPRETATION: Sofosbuvir and ribavirin provided high rates of sustained virological response after 12 weeks of treatment in treatment-naive and treatment-experienced patients co-infected with HIV and HCV genotypes 1-4. The characteristics of this interferon-free combination regimen make sofosbuvir plus ribavirin a useful treatment option for this patient population. FUNDING: Gilead Sciences.
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Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/etiología , ARN Viral/sangre , Ribavirina/uso terapéutico , Uridina Monofosfato/análogos & derivados , Adolescente , Adulto , Anciano , Coinfección/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Sofosbuvir , Resultado del Tratamiento , Uridina Monofosfato/uso terapéutico , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Liver disease frequently complicates cystic fibrosis (CF), with CF liver disease (CFLD) a leading cause of death. Liver biopsy is rarely performed because of the patchy nature of the disease. Transient elastography can reliably stage liver fibrosis via liver stiffness measurement (LSM). AIMS: To evaluate LSM as a diagnostic tool in adults with CFLD. METHODS: Fifty adult patients with CF were prospectively studied: 25 with CFLD and 25 without CFLD. The presence of CFLD and portal hypertension (PHT) was assessed according to strict established criteria based on serial biochemistry and imaging. All patients underwent LSM; APRI, Hepascore(®) and Forns score were calculated. RESULTS: Median LSM was higher in those with CFLD [8.1 kPa (IQR 6.8-9.5) vs. 5.0 kPa (IQR 4.1-5.6); P < 0.001]. On multivariate analysis, LSM was the only variable associated with CFLD (OR 2.74, 95% CI 1.53-4.89; P = 0.001). AUROC for LSM predicting CFLD was 0.87 (95% CI 0.77-0.98) and an LSM ≥ 6.8 kPa predicted CFLD with 76.0% sensitivity and 92.0% specificity. Median LSM was higher in those with PHT [15.7 kPa (IQR 9.2-17.2) vs. 5.4 kPa (IQR 4.3-6.8); P < 0.001]. The AUROC for LSM predicting the presence of PHT was 0.96 (95% CI 0.92-1.00). An LSM cut-off of ≥ 8.9 kPa predicted the presence of PHT with 87.5% sensitivity, 90.5% specificity, 63.6% positive predictive value and 92.9% negative predictive value. CONCLUSIONS: LSM is an accurate and reliable non-invasive tool in assessing CFLD and PHT. An LSM ≥ 6.8 kPa is highly suggestive of CFLD and an LSM <8.9 kPa reliably excludes PHT.
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Fibrosis Quística/complicaciones , Diagnóstico por Imagen de Elasticidad/métodos , Hipertensión Portal/diagnóstico , Hepatopatías/diagnóstico , Hepatopatías/patología , Adulto , Área Bajo la Curva , Estudios de Casos y Controles , Femenino , Humanos , Hepatopatías/etiología , Masculino , Análisis Multivariante , Estudios Prospectivos , Curva ROC , VictoriaRESUMEN
BACKGROUND AND AIM: Unexplained liver injury including fibrosis and portal hypertension has rarely been reported among patients with HIV in the absence of co-infection with hepatitis B (HBV) or hepatitis C (HCV). We describe a series of HIV mono-infected patients with evidence of non-cirrhotic portal hypertension. METHODS: HIV-infected patients with evidence of portal hypertension who were anti-HBV and anti-HCV negative and HBV and HCV RNA polymerase chain reaction (PCR) negative were identified from patients managed by the Victorian statewide HIV referral service located at The Alfred Hospital, Melbourne. Portal hypertension was defined as either radiological or endoscopic evidence of varices, portal vein flow obstruction, or elevated hepatic venous pressure gradient (HPVG). RESULTS: Five patients were found to have portal hypertension. These patients were male, aged 41 to 65 years, with known duration of HIV infection between 11 to 25 years. All had been treated with antiretroviral therapy, including didanosine. Tests for metabolic, autoimmune, and hereditary causes of liver disease failed to establish an etiology for the liver injury. All had radiological or endoscopic findings of varices, and four patients had radiological features of portal vein obstruction or flow reversal. Only one patient underwent HPVG measurement, which was elevated. Non-invasive fibrosis assessment revealed increased liver stiffness in three (out of four) patients, and no cirrhotic features were found on those who underwent liver biopsy. CONCLUSIONS: To our knowledge, this is the largest published series of non-cirrhotic portal hypertension in HIV mono-infected patients in Australia. Further research is needed to understand what relationship, if any, HIV or its treatments might have on liver injury over time.
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Antirretrovirales/uso terapéutico , Infecciones por VIH/complicaciones , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Adulto , Anciano , Antirretrovirales/efectos adversos , Australia , Diagnóstico por Imagen de Elasticidad , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Hipertensión Portal/patología , Hígado/diagnóstico por imagen , Hígado/patología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: to determine if intrahepatic immune activation is increased in HIV-hepatitis B virus (HBV) co-infected patients compared to HBV mono-infected patients and whether this reduced following HBV-active antiretroviral therapy (ART) in HIV-HBV co-infected patients. DESIGN: : Case-control observational study. METHODS: we examined liver biopsies for markers of T-cell and monocyte infiltration and activation, natural killer cells, hepatic stellate cell (HSC) activation (staining for alpha smooth muscle actin) and apoptosis [using terminal dUTP nick-end labelling (TUNEL)] in treatment-naive Asian HIV-HBV co-infected (n = 16) and HBV mono-infected patients matched for age and HBV e-antigen status (n = 16). Liver biopsies from a subset of co-infected patients (n = 15) were also compared prior to and following 48 weeks of HBV-active ART. RESULTS: HIV-HBV co-infected patients had a median CD4 T-cell count of 25 cells/microl and lower alanine aminotransferase levels than HBV mono-infected patients (P = 0.03). In HIV-HBV co-infected patients, hepatocyte apoptosis was increased (P = 0.04) but there were fewer intrahepatic CD4 and CD8 T cells (P < 0.001), lower activation of intrahepatic T cells, Kupffer cells and HSC (P = 0.002, 0.008 and < 0.001, respectively). Following ART, there was a significant decrease in intrahepatic HBsAg staining (P = 0.04) and Kupffer cell activation (P = 0.003). CONCLUSIONS: we found no evidence of increased intrahepatic mononuclear and HSC activation in this cohort of HIV-HBV co-infected individuals with advanced immune suppression. An increase in intra-hepatic apoptosis in HIV-HBV co-infected individuals may potentially contribute to accelerated fibrosis in this setting.
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Infecciones Oportunistas Relacionadas con el SIDA/patología , Apoptosis/fisiología , Infecciones por VIH/patología , VIH-1/fisiología , Hepatitis B Crónica/patología , Células Asesinas Naturales/inmunología , Hígado/patología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Adulto , Terapia Antirretroviral Altamente Activa , ADN Viral , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/inmunología , Humanos , Inmunohistoquímica , Terapia de Inmunosupresión , Hígado/virología , Masculino , Reacción en Cadena de la Polimerasa , Carga ViralRESUMEN
Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV) coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a vesicular stomatitis virus (VSV)-pseudotyped HIV expressing enhanced green fluorescent protein (EGFP). Following HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8 infection of AD38 cells was inhibited by maraviroc and NL4-3 was inhibited by AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV. Coinfection of the AD38 cell line with HIV did not alter the HBV DNA amount or species as determined by Southern blotting or nucleic acid signal amplification. However, coinfection with HIV was associated with a significant increase in intracellular HBsAg when measured by Western blotting, quantitative HBsAg, and fluorescence microscopy. We conclude that HIV infection of HBV-infected hepatic cell lines significantly increased intracellular HBsAg but not HBV DNA synthesis and that increased intrahepatic HBsAg secondary to direct infection by HIV may contribute to accelerated liver disease in HIV-HBV-coinfected individuals.
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Infecciones por VIH/virología , VIH-1/fisiología , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/fisiología , Hepatitis B/virología , Hepatocitos/virología , Línea Celular , VIH-1/genética , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , HumanosRESUMEN
There are many potential reasons for increased liver-related mortality in HIV-hepatitis B virus (HBV) coinfection compared with either infection alone. HIV infects multiple cells in the liver and might potentially alter the life cycle of HBV, although evidence to date is limited. Unique mutations in HBV have been defined in HIV-HBV-coinfected individuals and might directly alter pathogenesis. In addition, an impaired HBV-specific T-cell immune response is likely to be important. The roles of microbial translocation, immune activation and increased hepatic stellate cell activation will be important areas for future study.
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Infecciones por VIH/complicaciones , Hepatitis B Crónica/complicaciones , Terapia Antirretroviral Altamente Activa , VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/crecimiento & desarrollo , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/mortalidad , Hepatitis B Crónica/virología , Humanos , Inmunidad Celular , Inmunidad Innata , Hígado/inmunología , Hígado/virología , Mutación/efectos de los fármacosRESUMEN
Liver disease is a major cause of mortality in individuals with HIV-HBV coinfection. The pathogenesis of liver disease in this setting is unknown, but is likely to involve drug toxicity, infection of hepatic cells with both HIV and HBV, and an altered immune response to HBV. The availability of therapeutic agents that target both HIV and HBV replication enable dual viral suppression, and assessment of chronic hepatitis B is important prior to commencement of antiretroviral therapy. Greater importance is now placed on HBV DNA levels and staging of liver fibrosis, either by liver biopsy or noninvasive measurement, such as transient elastography, since significant liver fibrosis may exist in the presence of normal liver function tests. Earlier treatment of both HIV and HBV is now generally advocated and treatment is usually lifelong.
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Coinfection with HIV and hepatitis B virus (HBV) has become a significant global health problem. Liver disease is now one of the leading causes of morbidity and mortality in individuals with HIV, particularly those with viral hepatitis. There are a number of agents available with dual activity against HIV and HBV, and effective treatment depends on understanding the potential advantages and pitfalls in using these agents. There are a number of unresolved issues in the management of HIV/HBV coinfection. These include the role of liver biopsy, the significance of normal aminotransferase levels, serum HBV DNA threshold for treatment, treatment end-points, and the treatment of HBV when HIV does not yet require treatment. Treatment of HBV should be considered in individuals with HIV/HBV coinfection with evidence of significant fibrosis (>/=F2), or with elevated serum HBV DNA levels (>2000 IU/mL). Sustained suppression of serum HBV DNA to below the level of detection by the most sensitive available assay should be the goal of therapy, and, at present, treatment of HBV in HIV/HBV coinfection is lifelong. If antiretroviral therapy is required, then two agents with anti-HBV activity should be incorporated into the regimen. If antiretroviral therapy is not required, then the options are pegylated interferon, adefovir or the early introduction of antiretroviral therapy. Close monitoring is necessary to detect treatment failure or hepatic flares, such as immune reconstitution disease. Further studies of newer anti-HBV agents in individuals HIV/HBV coinfection may advance treatment of this important condition.
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Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Antivirales/uso terapéutico , Quimioterapia Combinada , HumanosRESUMEN
BACKGROUND AND AIM: The rate of cardiac injury in upper gastrointestinal hemorrhage is unclear. The aims of this study were to determine prospectively the risk of cardiac troponin I release and associated adverse cardiac events in patients with acute upper gastrointestinal hemorrhage. METHODS: From January to September 2003, we prospectively studied patients with documented hematemesis and melena referred to the gastroenterology unit in a tertiary teaching hospital in Melbourne, Australia. Serial assays for cardiac troponin I were performed at 0, 12 and 24 h. Serial creatine kinase levels and electrocardiographs were also performed. Clinical and biochemical data were collected. The primary endpoint was a troponin level >0.5 microg/L within 24 h of recruitment. Various clinical variables were then compared between the groups of patients with or without troponin rise. RESULTS: A total of 156 patients were included in the study. The mean age was 67 years (range 19-96). There were 104 (67%) male patients. A troponin level of greater than 0.5 microg/L was found in 30/156 (19%); 126 (81%) patients had normal troponin levels. Age greater than 65 years, signs of hemodynamic instability at presentation, a recent history of cardiac disease, cardiovascular compromise following endoscopy, and re-bleeding were associated with troponin release. CONCLUSION: Upper gastrointestinal bleeding is associated with a risk of cardiac injury of up to 19%. Troponin assay could be used to screen for cardiac damage, especially in elderly patients who present with hemodynamic instability.
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Hemorragia Gastrointestinal/complicaciones , Cardiopatías/sangre , Cardiopatías/etiología , Troponina I/sangre , Adulto , Anciano , Anciano de 80 o más Años , Australia , Biomarcadores/sangre , Creatina Quinasa/sangre , Electrocardiografía , Femenino , Cardiopatías/diagnóstico , Hospitales de Enseñanza , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Lamivudine resistance is associated with long-term monotherapy for chronic hepatitis B and can lead to potentially serious clinical consequences. Scant information exists regarding the influence of hepatitis B virus variants in the development of resistance. The present study was designed to identify factors predictive of lamivudine resistance, with a particular focus on the role of precore and basal core promoter variants in the setting of hepatitis B e antigen-negative disease. METHODS: Eighty-five patients, representing four major genotypes, were followed prospectively on lamivudine therapy. Resistance was defined as an increase in viral load, with polymerase gene sequencing confirming a lamivudine resistance mutation. Median follow up was 19 months (6-54 months). The Cox proportional hazards model was used to determine variables independently predicting for the early onset of lamivudine resistance. RESULTS: The rate of lamivudine resistance was 6%, 31% and 51% at 12, 24 and 48 months, respectively. Multivariate analysis identified the precore variant, high baseline alanine aminotransferase (ALT), and persistent viremia (at 6 months) as independent predictors of the early development of lamivudine resistance, with rate ratios of 4.93 (95% confidence interval [CI]: 1.32-18.5), 1.22 (95%CI: 1.08-1.49), and 4.73 (95%CI: 1.49-15.0), respectively (P < 0.05). Female sex predicted early resistance (rate ratio 5.27 [95%CI: 1.23-22.5, P < 0.05]) although numbers were small (n = 12). Genotype did not influence treatment response nor time to onset of resistance. CONCLUSION: Patients with precore variant hepatitis B virus are likely to develop lamivudine resistance early and should be considered for alternate first-line monotherapy. In the future, combination antiviral therapy may limit the development of resistance.