Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually

Efficacy of telbivudine with conditional tenofovir intensification in patients with chronic hepatitis B: results from the 2-year roadmap strategy

Background: A 2-year roadmap study was conducted to evaluate the efficacy and safety of tenofovir intensification at Week 24 in patients with chronic hepatitis B (CHB) receiving telbivudine. Scope: A prospective multicenter study was conducted in treatment-naive patients with hepatitis B e antigen (HBeAg)- positive CHB. All patients received telbivudine (600 mg/day) until Week 24. Thereafter, patients with detectable hepatitis B virus (HBV) DNA (≥300 copies/mL) were administered tenofovir (300 mg/day) plus telbivudine, and patients with undetectable HBV DNA continued telbivudine monotherapy until Week 104. The primary endpoint was the proportion of patients with undetectable HBV DNA (<300 copies/mL) at Weeks 52 and 104. Findings: A total of 105 patients were enrolled in the trial, of which 100 were eligible for efficacy analysis. Undetectable HBV DNA levels were observed at Week 24 in 55 patients who continued on with telbivudine monotherapy. The remaining 45 patients with detectable HBV DNA received tenofovir add-on therapy. With monotherapy, 100% (55/55) and 94.5% (52/55) of patients achieved HBV DNA <300 copies/mL at Weeks 52 and 104, respectively; the corresponding values for patients with add-on therapy were 84.4% (38/45) and 93.3% (42/45). Overall, undetectable HBV DNA (<300 copies/mL) was found in 93% (93/100) and 94% (94/100) of patients at Weeks 52 and 104, respectively. HBeAg seroconversion rate was 44.4% (44/99) at Week 104 for the overall patient population. One patient in the monotherapy group and six in the intensification group demonstrated HBsAg clearance at Week 104. HBsAg seroconversion was observed in four patients at Week 104, all belonged to the tenofovir intensification group. Eight patients sustained HBsAg loss during a posttreatment follow-up period of 16 weeks. Alanine aminotransferase (ALT) normalization was constant in the telbivudine monotherapy group, whereas a progressive improvement was observed in the tenofovir intensification group. Two patients in the monotherapy and none in the intensification group experienced viral breakthrough by Week 104. There were no reports of myopathy in either group. The mean changes in estimated glomerular filtration rate (eGFR), estimated using the Modification of Diet in Renal Disease (MDRD) formula, from baseline to Week 104 were +6.145 mL/min/1.73 m2 (p=0.0230) and +7.954 mL/min/1.73 m2 (p=0.0154) in the telbivudine monotherapy and tenofovir intensification groups, respectively. The incidence of serious AEs was four in the telbivudine monotherapy and two in the tenofovir intensification group. The main limitation of this study was limited sample size, which made the power of the observation low, and the absence of a comparative subgroup to assess the progression of patients with detectable HBV DNA without treatment intensification. Conclusions: Data from this 2-year roadmap study confirmed that telbivudine with add-on tenofovir was effective and well tolerated in patients with CHB. Telbivudine was associated with an improvement in eGFR from baseline in both the groups

Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin for HCV in Brazilian Adults with Advanced Fibrosis

Introduction and aim. Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an open-label multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection.Material and methods. All patients received coformulated OBV/ PTV/r daily + DSV twice daily (3-DAA). GTIa-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/ RBV nonresponders with cirrhosis who were treated for 24 weeks. GTIb-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12).Results. The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event.Discussion. The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4)

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 3. Reação celular nos tecidos

Os A.A. analisam as alterações histopatológicas observadas em 378 casos de Leishmaniose Tegumentar da localidade de Três Braços Estado da Bahia, dos quais 307 eram de portadores de lesões exclusivamente cutâneas, 54 de portadores de lesões exclusivamnte mucosas e 17 de portadores de lesões cutâneo-mucosas. A infiltração histiolinfoplasmocitária, na maioria dos casos, parece desempenhar o papel de resposta celular inespecífica à presença de um irritante tecidual, porém, nos casos de forma mucosa, não se pode afastar a possibilidade de que esse infiltrado esteja participando de uma reação de tipo autoagressivo. O plasmócito constitui um elemento quase constante nas lesões desenvolvidas, mas não tem sido observado nas lesões residuais, quer em via de cura ou já cicatrizadas; sua presença nestes casos denota, quase sempre, tendência à recidiva. Os mastdcitos foram observados em lesões tanto da forma cutânea como da forma mucosa, mas predominavam nas primeiras. Seu número foi significantemente maior no padrão de Reação Exsudativa e Neerótico Granulomatosa, onde os fenômenos necróticos são bem desenvolvidos. Os eosinófilos apresentaram associação significativa com os mastócitos, confirmando a existência de um eixo bidirecional entre estás duas células, o qual deve participar da modulação inflamatória, na Leishmaniose Tegumentar. Dois tipos de reação granulomatosa foram observados: um desorganizado, em relação, muitas vezes, com a necrose tissular, e outro organizado, mais raro, do tipo tuberculóide. O primeiro foi interpretado como de origem pós-necrótica, surgindo com a redução da carga parasitária, propiciada pelos fenômenos necróticos: eliminado o antígeno e mantidos os níveis de anticorpos, surgem as condições necessárias ao estabelecimento do granuloma, semelhante àquele observado nas lesões por imunocomplexo em excesso de anticorpos. O outro tipo de reação foi o granuloma de células epiteliódes, que surgiu em dois grupos de pacientes. Nos pacientes jovens, com doença de curto tempo de evolução e intradermorreação não exacerbada, este tipo de granuloma talvez seja a expressão da Hipersensibilidade Granulomatosa Específica, descrita por EPSTEIN (1977). No outro grupo de pacientes, havia em todos intradermorreação exacerbada. Nestes casos a hipersensibilidade granulomatosa, associando-se ã hipersensibilidade mediada por células — agora ampliada pelo seqüestro do antígeno —, reforçaria o processo granulomatoso, através da reverberação do estímulo antígênico; isso tornaria o tratamento mais difícil e pior o prognóstico para o caso

Encefalopatia hepática: relatório da 1º reunião monotemática da Sociedade Brasileira de Hepatologia

Hepatic encephalopathy (HE) is a functional disorder of the central nervous system (CNS) associated with liver failure, either end-stage chronic liver disease or fulminant hepatic failure. Its pathogenesis remains complex and poorly understood. In view of recent advances in the management of HE, the Brazilian Society of Hepatology endorsed a monothematic meeting regarding HE in order to gather experts in the field to discuss related data and to draw evidence-based recommendations concerning: management of HE and intracranial hypertension in FHF, treatment of episodic HE in cirrhosis, controversies in the management of EH including difficult to treat cases and diagnostic and treatment challenges for minimal HE. The purpose of this review is to summarize the lectures and recommendations made by the panel of experts of the Brazilian Society of Hepatology.A encefalopatia hepática (EH) é um distúrbio funcional do sistema nervoso central (SNC) associado à insuficiência hepática, de fisiopatologia multifatorial e complexa. Devido aos avanços no conhecimento sobre o manejo da EH na cirrose e na insuficiência hepática aguda (IHA), a diretoria da Sociedade Brasileira de Hepatologia (SBH) promoveu uma reunião monotemática acerca da fisiopatologia, diagnóstico e tratamento da EH, abordando aspectos controversos relacionados ao tema. Com a utilização de sistemática da medicina baseada em evidências, foram abordados o manejo da EH e da hipertensão intracraniana na IHA, o manejo da EH episódica na cirrose, as controvérsias no manejo da EH e a abordagem da EH mínima. O objetivo desta revisão é resumir os principais tópicos discutidos na reunião monotemática e apresentar recomendações sobre o manejo da síndrome votadas pelo painel de expertos da SBH