RESUMO
Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.
Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepacivirus/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir , Resposta Viral Sustentada , Resultado do Tratamento , Uridina Monofosfato/uso terapêutico , Adulto JovemRESUMO
To evaluate the cost-effectiveness of Hepatitis C therapy, robust real-world data are needed to understand the costs and benefits of treatment alternatives. The objective of this study was to evaluate the true direct cost of treatment in an unselected sequential population of patients treated at a tertiary care centre for hepatitis C virus genotype 1. A total of 200 consecutive patients were treated with interferon, ribavirin and a first-generation direct-acting antiviral agent (DAA) between 2011 and 2013. A total of 41% had cirrhosis, 31% were prior relapsers, and 41% were prior partial or null responders. Costs used were wholesale acquisition cost prices for medications, average hospital costs per day for each diagnosis code based on US inpatient hospital charges. All costs were adjusted to 2013 dollars. Sustained virologic response (SVR) was achieved in 97 patients (48.5%). A total of 14% experienced relapse, 19% breakthrough or nonresponse, and 18.5% discontinued secondary to side effects. Twenty per cent of patients had at least one hospitalization attributable to a complication of therapy. Thirty-seven per cent of patients required erythropoietin-stimulating agents, 16% received filgastrim, and 15% needed a red blood cell transfusion. The mean overall cost of treatment was $83,851 per patient. The cost per SVR was $172,889; $266,670 for patients with cirrhosis. The costs per SVR after treatment with first-generation DAAs are dependent on the stage of disease and therapy side effects. These real-world costs significantly exceed those described in prior cost-effectiveness assessments and should be used instead for future studies.
Assuntos
Antivirais/economia , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/economia , Prolina/análogos & derivados , Inibidores de Proteases/economia , Antivirais/uso terapêutico , Análise Custo-Benefício , Quimioterapia Combinada/economia , Feminino , Custos de Cuidados de Saúde , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Humanos , Interferon-alfa/economia , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Prolina/economia , Prolina/uso terapêutico , Inibidores de Proteases/uso terapêutico , Ribavirina/economia , Ribavirina/uso terapêutico , Centros de Atenção Terciária/economia , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND AND AIMS: New therapies for HCV are rapidly emerging and providers are advising select patients to defer treatment and elect 'watchful waiting'. During the watchful waiting period, patients have been shown to have high rates of illness uncertainty and depression. We sought to answer the question of whether reassuring histological data (showing minimal fibrosis or no fibrosis progression over time) is associated with less illness uncertainty and depressive symptoms. METHODS: This was a single-centre outpatient prospective cohort study to determine whether stage of fibrosis, fibrosis progression and reasons for treatment deferral were related to illness uncertainty and depressive symptoms in patients following watchful waiting. RESULTS: Illness uncertainty was significantly related to depressive symptoms (r = 0.49, P < 0.01). More than half of the participants (54%) had moderate levels of uncertainty. About 40% of the participants were at risk for clinical depression (21.7% at mild to moderate risk and 18.5% at high risk). Treatment naïve subjects had lower mean scores on both the CES-D (depressive symptoms measure) and the MUIS-A (illness uncertainty measure) total score, MUIS-A Ambiguity subscale and MUIS-A Inconsistency subscale than subjects who failed treatment or were interferon intolerant or ineligible. Surprisingly, liver fibrosis stage and progression were not significantly associated with overall illness uncertainty or depressive symptoms. CONCLUSION: Patients with chronic hepatitis C on watchful waiting are at high risk for significant illness uncertainty and depressive symptoms. Reassuring histological data does not seem to correlate with less uncertainty or depressive symptoms.
Assuntos
Depressão/epidemiologia , Progressão da Doença , Hepatite C Crônica/complicações , Hepatite C Crônica/psicologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Incerteza , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos ProspectivosRESUMO
Affecting 2-3% of the world's population, hepatitis C is a common viral infection which is a significant cause of morbidity and mortality. Hepatitis C genotype 1 is the dominant viral genotype among Western patients. For the last 20 years, in the era of interferon-based therapy, it was far more difficult to treat relative to genotypes 2 and 3. Accordingly, a significant focus of research was on new antiviral agents for the dominant genotype 1 patient. Now, as promising specific treatments are being introduced for genotype 1, the attention of clinicians and researchers has turned back to the 50-70 million patients infected with a nongenotype 1 hepatitis C. Furthermore, after recent, larger randomized trials, we have realized that genotype 2 is truly interferon sensitive while genotype 3 patients are far less successful with therapy. In this fundamentally altered landscape, genotype 3 is now potentially the most difficult to treat genotype and an area of intense research for new drug development. Herein we review the virology, natural history and the treatment of genotype 3 hepatitis C.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Genótipo , Hepacivirus/classificação , Humanos , Resultado do TratamentoRESUMO
Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Programas de Rastreamento/métodos , Guias de Prática Clínica como Assunto , Administração Oral , Centers for Disease Control and Prevention, U.S. , Hepatite C Crônica/prevenção & controle , Humanos , Fígado/patologia , Estados UnidosRESUMO
There is increasing interest in developing noninvasive means to evaluate liver fibrosis in patients with chronic liver disease to determine disease severity, prognosis and optimal treatment. Transient elastography (TE) has previously been demonstrated to predict the presence or absence of advanced fibrosis. The current study was conducted to determine whether TE can identify patients with chronic liver disease at risk of clinical decompensation. A total of 667 patients underwent TE and were followed for a median of 861 days and 57 patients achieved the primary outcome, a composite of clinical endpoints including death, ascites, encephalopathy, increased Child Score ≥ 2, variceal bleed, hepatocellular carcinoma or listing for transplant. Overall, TE had an area under the receiver operating characteristic curve of 0.87 for predicting clinical outcome. Using a cut-off of 10.5 kPa, TE has a sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 94.7%, 63.0%, 19.3% and 99.2%, respectively. A predictive model for clinical events was developed using generalized cross-validation for clinical endpoints considering TE, liver biopsy results and multiple other predictors. Individually, TE performed better than biopsy, or any other variable, for predicting clinical outcome [Harrell's C Statistic 0.86 for TE, 0.78 for stage]. Patients with a TE score of >12.5 kPa were found to have a relative hazard for clinical event of 18.99 compared with patients with TE score <10.5. A combined variable model including TE, aspartate aminotransferase/alanine aminotransferase ratio and model for end-stage liver disease (MELD) yielded the highest predictive accuracy with Harrell's C value of 0.93. In the subset of patients with cirrhosis, TE was not found to be independently associated with clinical outcomes in univariate or multivariate analysis although it retained a high sensitivity and NPV of 97.5% and 92.3%, respectively, at a kPa cut-off of 10.5. TE can successfully identify patients with chronic liver disease who are at low risk of clinical decompensation over a time period of 2 years.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite Crônica/complicações , Hepatite Crônica/diagnóstico , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e EspecificidadeRESUMO
The aim of this study is to review clinical trial data on the newly approved protease inhibitors boceprevir and telaprevir to develop consensus recommendations on the optimal use of these agents for the treatment of patients with chronic hepatitis C virus (HCV) infection. An expert panel of seven leading authorities in viral hepatitis was convened to establish and disseminate a practical guide on best practices for incorporating boceprevir and telaprevir into therapy for HCV infection in both treatment-naive and treatment-experienced patients. The topics covered include selecting candidates for boceprevir- or telaprevir-based treatments, predictors of response and early viral kinetics, response-guided therapy approaches, on-treatment management strategies to optimize the likelihood of response and minimize the risk of drug resistance, management of adverse effects during therapy and key considerations for special populations. The expert panel incorporated the best available clinical evidence into recommendations on how boceprevir and telaprevir should be used in the clinical setting. They indicated how treatment regimens may differ according to the baseline factors, such as presence of cirrhosis and when therapy may need to be modified or stopped altogether because of adverse events or poor virologic response. This practical guide will serve as a valuable resource for clinicians embarking on the new treatment paradigm of boceprevir or telaprevir in combination with peginterferon/ribavirin for chronic genotype 1 HCV infection.
Assuntos
Antivirais/uso terapêutico , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Prolina/análogos & derivados , Inibidores de Proteases/uso terapêutico , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Feminino , Hepatite C Crônica/virologia , Humanos , Masculino , Guias de Prática Clínica como Assunto , Prolina/uso terapêutico , Viremia/tratamento farmacológico , Viremia/virologiaRESUMO
The diagnosis of cirrhosis requires screening for oesophageal varices by upper gastrointestinal endoscopy. In many countries, serological tests and elastography are replacing liver biopsy for diagnosing cirrhosis. The aims of this study were to see whether there was an optimal cut-off of liver stiffness that could predict the presence of large (>F2) oesophageal varices and whether this was disease specific. A total of two hundred and twenty-two patients with all cause cirrhosis (Child class A) were screened, and 211 had successful elastography and are included in the analysis. Of the patients studied, one hundred and thirty-two patients had no or small F1 varices and 79 had large varices. Liver stiffness of 19.8 kPa had a negative predictive value of 91% and a positive predictive value of 55% with an area under the curve (AUC) on receiver operating characteristics (ROC) of 0.73 in differentiating between small and large varices. Seven patients with large varices would have been incorrectly classified. In the 157 patients with hepatitis C as the aetiology of cirrhosis, the negative predictive value was 98% and only one patient was misclassified. Liver stiffness was superior in diagnostic accuracy to platelet count in all patients. A liver stiffness of >19.8 kPa could be utilized as a cut-off for endoscopy and beta blocker utilization, particularly in patients with hepatitis C.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Varizes Esofágicas e Gástricas/diagnóstico , Hepatite C/complicações , Hepatite C/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Thrombocytopenia is a common hematologic toxicity among patients with chronic liver disease. AIM: To give a brief overview of thrombocytopenia and its effects on patients with chronic liver disease. RESULTS: Thrombocytopenia is generally mild to moderate in severity and can thus be managed relatively easily. Severe thrombocytopenia (platelet count <50,000 /microL), however, may present significant challenges to patient management. Thrombocytopenia can increase the risk of bleeding associated with invasive or surgical procedures. Therefore, while perhaps less widely appreciated than the impact of anemia or neutropenia, effective prevention and management of thrombocytopenia is also critical for patients with liver disease. CONCLUSIONS: This supplement to Alimentary Pharmacology & Therapeutics provides a comprehensive review of the significance of thrombocytopenia in patients with chronic liver disease, its pathophysiology and relationship to coagulation disorders, impact on clinical care and resource utilization, and novel therapies that may be able to supplant platelet transfusions.
Assuntos
Hepatopatias/complicações , Trombocitopenia/etiologia , Transtornos da Coagulação Sanguínea , Doença Crônica , Humanos , Administração dos Cuidados ao Paciente , Contagem de Plaquetas , Transfusão de Plaquetas , Trombocitopenia/terapiaRESUMO
BACKGROUND: Patients with chronic liver disease and hepatitis C virus (HCV) frequently experience thrombocytopenia that complicates the management of their disease. Traditional therapy for thrombocytopenia consists of platelet transfusion, which can be associated with significant safety and economic issues. Consequently, efforts have been directed toward developing novel approaches for the treatment of thrombocytopenia. AIM: To summarize the available data on the limitations of traditional therapies and the effects of novel therapies currently in clinical development for the treatment of thrombocytopenia. RESULTS: Recent research has begun to reveal the complex mechanisms that regulate thrombopoiesis. Cytokines and growth factors, such as interleukin-11 and thrombopoietin (TPO), play a key role in the production of platelets. A number of recent clinical studies have provided evidence that pharmacologic agents that target megakaryocyte precursors and stimulate thrombopoiesis can effectively reverse thrombocytopenia. Here, we review the regulation of thrombopoiesis, the role of TPO, and a number of novel compounds that stimulate platelet production by acting through the TPO receptor. Agents that stimulate TPO include the orally available nonpeptidic agonists eltrombopag and AKR-501, peptidic agonists AMG-531 and Peg-TPOmp, and small engineered antibodies. CONCLUSION: Results from clinical trials with these agents in healthy subjects confirm that activation of thrombopoiesis via the TPO pathway is an effective method of stimulating platelet production. This approach may provide safer, more effective treatment for thrombocytopenia in patients with chronic liver disease. Several of these agents are currently being tested in large scale trials.
Assuntos
Antivirais/uso terapêutico , Hematínicos/uso terapêutico , Hepatite C/complicações , Hepatopatias/complicações , Trombocitopenia/tratamento farmacológico , Doença Crônica , Citocinas/uso terapêutico , Humanos , Administração dos Cuidados ao Paciente , Receptores de Trombopoetina/agonistas , Receptores de Trombopoetina/uso terapêutico , Trombocitopenia/etiologiaRESUMO
BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. METHODS: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. RESULTS: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. CONCLUSIONS: In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.
Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/administração & dosagem , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Feminino , Genótipo , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do TratamentoRESUMO
The aim was to assess the validity of a digitally computed fibrosis ratio as a measure of fibrosis stage in liver biopsy specimens. We scored 230 liver biopsy specimens from patients with chronic hepatitis C for fibrosis using modified Knodell criteria; fibrosis ratios were computed from digital images that encompassed the complete trichrome-stained section of each case. Although an overall correlation between fibrosis ratio and ordinal score was present, subset analysis showed that this correlation existed only among biopsy specimens with high scores (3-6, early bridging fibrosis to established cirrhosis). There was no correlation or difference between category means found among biopsy specimens with low scores (0-3, normal to early bridging fibrosis). Furthermore, concordance by both estimates in direction of fibrosis change among serial liver biopsy specimens was found in only 11 (30%) of 37 pairs compared. The findings suggest that a qualitative assessment of the computerized fibrosis pattern is necessary for the interpretation of computerized fibrosis ratio measurements, particularly in patients with early stage fibrosis.
Assuntos
Biópsia , Hepatite C Crônica/patologia , Processamento de Imagem Assistida por Computador , Cirrose Hepática/patologia , Humanos , Cirrose Hepática/classificação , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
Liver support using extracorporeal devices and hepatocyte transplantation has received renewed interest for the management of acute and chronic liver failure. The aim of this study was to determine whether xenogeneic porcine hepatocytes could integrate into the liver parenchyma of cirrhotic Lewis rats when administered by an intrasplenic route. Cirrhosis was induced by carbon tetrachloride (CCl4) inhalation and confirmed histologically. Freshly isolated porcine hepatocytes were infused directly into the splenic pulp at laparotomy over a 5-15-min interval. Using (111)In-labeled hepatocytes, the degree of localization of porcine hepatocytes to the spleen and liver was found to be greater than 60% in both control and cirrhotic rats. Integration of porcine hepatocytes into the rat liver parenchyma was determined by immunohistochemical staining for porcine albumin in rat liver sections. Further confirmation was provided by in situ hybridization using a porcine-specific probe that binds to a distinct repetitive element (PRE) in porcine DNA. Evidence of integrated porcine hepatocytes was seen for over 50 days in animals under cyclosporine immunosuppression. These data demonstrate the integration of xenogeneic porcine hepatocytes into the liver of the cirrhotic rat and their ability to produce porcine albumin for up to 50 days.
Assuntos
Transplante de Células , Cirrose Hepática Experimental/terapia , Fígado/citologia , Albuminas/metabolismo , Animais , Tetracloreto de Carbono/toxicidade , Imuno-Histoquímica , Hibridização In Situ , Fígado/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , Masculino , Ratos , Ratos Endogâmicos Lew , Especificidade da Espécie , Baço , Suínos , Transplante HeterólogoRESUMO
BACKGROUND/AIMS: A double-blinded trial evaluating silymarin, an herbal supplement for liver disease, to prevent complications of chronic hepatitis C virus infection has not been done. SUBJECTS: One hundred and seventy-seven consenting residents of an Egyptian village with chronic hepatitis C virus were randomly assigned to receive either silymarin or multivitamin supplements. METHODS: Participants had baseline and follow-up clinical, ultrasound, blood tests and quality-of-life assessments. Community nurses visited weekly to ascertain compliance, distribute supplements and record adverse effects. RESULTS: At 12 months almost all of 141 remaining subjects reported feeling better, although symptoms and quality-of-life scores did not differ between the silymarin and multivitamin groups. Both the silymarin and vitamins were tolerated equally well; and >95% of supplements were taken by >95% of subjects. One in each group had no detectable hepatitis C virus antibodies while two in the silymarin group and three receiving multivitamins had undetectable hepatitis C virus RNA. Serum alanine aminotransferase elevations did not differ between groups. Serum hepatic fibrosis marker, hyaluronic acid and YKL-40, and abdominal ultrasound results were similar in both groups and may have progressed slightly at 12 months. CONCLUSIONS: The recommended dose of silymarin can be safely taken for 1 year and improves symptoms and general well-being, but has no effect upon hepatitis C virus viremia, serum ALT, or serum and ultrasound markers for hepatic fibrosis. More prolonged evaluation and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus.
Assuntos
Hepatite C Crônica/tratamento farmacológico , Silimarina/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Egito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Fatores de TempoRESUMO
Eleven patients with severe refractory Crohns disease were treated with a high calorie, whole diet. Eight patients achieved remission with a drop in DAS from 13 to 4 (t = 6.31, p less than 0.001) and reversal of subacute obstruction in all cases. Nutritional parameters including weight, triceps skinfold thickness, arm muscle area, and serum albumin increased in all patients. The diet was well tolerated with a mean treatment period of 20 days. Clinical relapse of disease occurred in all cases within 9 months (mean 6 +/- 2 months). The mechanism of action of a high calorie diet (HCD) is unclear and warrants further study but antigen or specific food exclusion does not appear to be required as judged by this study.
Assuntos
Doença de Crohn/dietoterapia , Ingestão de Energia , Adulto , Feminino , Humanos , Masculino , Estado Nutricional , Indução de RemissãoRESUMO
BACKGROUND: The treatment of HBeAg-negative chronic hepatitis B (CHB) is considered to be open-ended, with no guidelines for treatment cessation. AIM: To evaluate biochemical and virological relapse requiring retreatment in noncirrhotic HBeAg-negative CHB in patients who stopped treatment following a period of prolonged viral suppression with nucleotides/nucleosides. METHODS: We performed a single-centre retrospective chart review of patients with HBeAg-negative CHB who maintained viral suppression for 4-5 years on anti-viral treatment, and thus subsequently stopped treatment. The primary end point of composite relapse was defined by an increase in HBV DNA >2000 IU/mL, ALT elevation above 1.25 × normal or doubling of ALT from cessation, and re-initiation of anti-viral therapy. RESULTS: We identified 33 patients with HBeAg-negative CHB who stopped treatment following viral suppression. Mean treatment duration was 5.28 ± 2.73 years. Patients were treated with lamivudine (3), adefovir (14), entecavir (4), and tenofovir (12). Eleven (33%) patients met the primary end point of composite relapse. For individual end points, 21 (63%) patients had a viral relapse, 16 (48%) had a biochemical relapse, and 16 (48%) restarted treatment, leaving 17 (52%) patients who remained treatment-free over a median 36 months of follow-up. Lower pre-treatment ALT and detectable HBV DNA within the first month after treatment discontinuation were associated with increased rates of composite relapse (HR 1.01; P = 0.022 for ALT and HR 1.01; P = 0.038 for HBV DNA). CONCLUSION: Patients with noncirrhotic HBeAg-negative CHB can stop treatment after greater than 4-5 years of suppressive therapy with nucleosides/nucleotides with more than 50% remaining treatment-free.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Antígenos E da Hepatite B , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Recidiva , Tenofovir , Suspensão de Tratamento , Adulto JovemRESUMO
BACKGROUND: Primary sclerosing cholangitis (PSC) is characterised by progressive inflammatory and fibrotic destruction of the biliary ducts. There are no effective medical therapies and presently high dose ursodeoxycholic acid is no longer recommended due to significant adverse events in a recent clinical trial. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with PSC in both children and adults. Since CFTR dysfunction leads to altered fatty acid metabolism, specifically reduced docosahexaenoic acid (DHA), we hypothesised that DHA supplementation might be an effective therapy for patients with PSC. AIM: To determine the safety and efficacy of oral DHA supplementation for the treatment of PSC. METHODS: We conducted a 12 month open-label pilot study to evaluate safety of oral DHA and its effects on serum alkaline phosphatase as a primary outcome measure in 23 patients with PSC. DHA was administered orally at 800 mg twice per day. Secondary outcomes included changes in other liver function tests and fibrosis biomarkers. RESULTS: A 1.7-fold increase in serum DHA levels was observed with supplementation. The mean alkaline phosphatase level (±S.E.) at baseline was 357.8 ± 37.1 IU compared to 297.1 ± 23.7 IU (P < 0.05) after 12 months of treatment. There were no changes in other liver function tests and fibrosis biomarkers. No adverse events were reported. CONCLUSIONS: Oral DHA supplementation is associated with an increase in serum DHA levels and a significant decline in alkaline phosphatase levels in patients with PSC. These data support the need for a rigorous trial of DHA therapy in PSC.