Characteristics of a hepatitis C patient cohort at a specialized tertiary care facility: Identifying criteria to improve the allocation of public health resources

OBJECTIVES: Our objective was to analyze, in a population treated for hepatitis C infection at a tertiary care treatment unit, the prevalence of comorbidities and extrahepatic manifestations, the range and degree of the clinical complexity and the associations between advanced liver disease and clinical variables. METHODS: Medical records from chronically infected hepatitis C patients seen at a dedicated treatment facility for complex cases in the Infectious Diseases Division of Hospital das Clı´nicas in Brazil were analyzed. Clinical complexity was defined as the presence of one or more of the following conditions: advanced liver disease (Metavir score F3 or F4 and/or clinical manifestations or ultrasound/endoscopy findings consistent with cirrhosis) or hepatocellular carcinoma and/or 3 or more extrahepatic manifestations and/or comorbidities concomitantly. RESULTS: Among the 1574 patients analyzed, only 41% met the definition of being clinically complex. Cirrhosis or hepatocarcinoma was identified in 22.2% and 1.8% of patients, respectively. According to multiple logistic regression analysis, male sex (p=0.007), age440 years (po0.001) and the presence of metabolic syndrome (p=0.008) were independently associated with advanced liver disease. CONCLUSION: The majority of patients did not meet the criteria for admittance to this specialized tertiary service, reinforcing the need to reevaluate public health policies. Enhanced utilization of existing basic and intermediate complexity units for the management of less complex hepatitis C cases could improve care and lower costs

Frequency and factors associated with hospital readmission after COVID-19 hospitalization: the importance of post-COVID diarrhea

Purpose: The aim of this study was to describe the incidence and risk factors for hospital readmission and infection during the months after COVID-19 hospital admission. Methods: This prospective study included adult patients who were hospitalized due to COVID-19 and had been discharged from April 2020 to August 2020. All patients had a medical evaluation with a structured questionnaire 6 to 11 months after hospital admission. The authors included only patients with confirmed COVID-19 by RT-PCR. Patients with pregnant/postpartum women, with a proven COVID-19 reinfection or incapable of answering the questionnaire were excluded. Results: A total of 822 patients completed the follow-up assessment, and 68% reported at least one recurrent symptom related to COVID-19. The most frequent symptom was myalgia (42%). Thirty-two percent of patients visited an emergency room after COVID-19 hospitalization, and 80 (10%) patients required re-hospitalization. Risk factors for hospital readmission were orotracheal intubation during COVID-19 hospitalization (p = 0.003, OR = 2.14), Charlson score (p = 0.002, OR = 1.21), congestive heart failure (p = 0.005, OR = 2.34), peripheral artery disease (p = 0.06, OR = 2.06) and persistent diarrhea after COVID-19 hospitalization discharge (p = 0.02, OR = 1.91). The main cause of hospital readmission was an infection, 43 (54%). Pneumonia was the most frequent infection (29%). Conclusions: The presence of symptoms after six months of COVID-19 diagnosis was frequent, and hospital readmission was relatively high

Hepatitis C among blood donors: cascade of care and predictors of loss to follow-up

OBJECTIVE To investigate the HCV cascade of care and to identify the factors associated with loss or absence to follow-up of patients identified as infected with hepatitis C through blood donation. METHODS Blood donors from 1994 to 2012, identified with positive anti- HCV by enzyme immunoassay and immunoblot tests were invited to participate in the study, through letters or phone calls. Patients who agreed to participate were interviewed and their blood samples were collected for further testing. The following variables were investigated: demographic data, data on comorbidities and history concerning monitoring of hepatitis C. Multiple regression analysis by Poisson regression model was used to investigate the factors associated with non-referral for consultation or loss of follow-up. RESULTS Of the 2,952 HCV-infected blood donors, 22.8% agreed to participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian. Of the 676 participants, 39.7% did not receive proper follow-up or treatment after diagnosis: 45 patients referred not to be aware they were infected, 61 did not seek medical attention and 163 started a follow-up program, but were non-adherent. The main reasons for inadequate follow-up were not understanding the need for medical care (71%) and health care access difficulties (14%). The variables showing a significant association with inadequate follow-up after multiple regression analysis were male gender (PR = 1.40; 95%CI 1.15–1.71), age under or equal to 50 years (PR = 1.36; 95%CI 1.12–1.65) and non-Caucasians (PR = 1.53; 95%CI 1.27–1.84). CONCLUSIONS About 40.0% of patients did not receive appropriate follow-up. These data reinforce the need to establish strong links between primary care and reference centers and the need to improve access to specialists and treatments

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10;

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.7595% CI 0.58-0.99p=0.045) and to early treatment interruption due to SAE (PR 0.3695% CI 0.20-0.68p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.0695% CI 1.02-1.10p<0.001) and occurrence of liver cirrhosis (PR 2.0695% CI 1.11-3.83p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.Univ Sul Santa Catarina, Fac Med, Dept Ciencias Biol & Saude & Ciencias Sociais Apl, Disciplina Doencas Infecciosas, Av Pedra Branca 25, BR-88137270 Palhoca, SC, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Div Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Estado Rio de Janeiro, Dept Clin Med, Disciplina Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Espirito Santo, Serv Infectol, Vitoria, ES, SpainUniv Sao Paulo, Fac Med Ribeirao Preto, Div Gastroenterol, Ribeirao Preto, SP, BrazilInst Infectol Emilio Ribas, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Doencas Infecciosas & Parasitarias, Sao Paulo, SP, BrazilSecretaria Estadual Saude, Unidade Mista Saude, Unimista 508 509, Brasilia, DF, BrazilUniv Sao Paulo, Inst Med Trop Sao Paulo, Lab Virol, LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc

Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography–mass spectrometry

Abstract\ud \ud Background\ud Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers.\ud \ud \ud Methods\ud An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases.\ud \ud \ud Results\ud The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols.\ud \ud \ud Conclusions\ud UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population.The Fleury SA Group supported this work and AMPC received a doctorate\ud scholarship from Fundação de Amparo à Pesquisa do Estado de São Paulo –\ud FAPESP (no. 2013/03701-0). The funding agencies did not interfere in the\ud scientific aspects of the study

Genetic factors associated with spontaneous clearance and response to treatment of hepatitis C infection

O vírus da hepatite C (HCV) é uma importante causa de doença hepática crônica e de complicações associadas, tais como cirrose e hepatocarcinoma (HCC). Fatores virais e do hospedeiro são conhecidos preditores da terapia antiviral. Fatores do hospedeiro preditores da resposta viral sustentada (RVS) foram descobertos por estudos de associação genômica ampla (GWAS), correspondendo a polimorfismos de nucleotídeo único (SNPs) nos genes IFNL3 e IFNL4 (rs8099917, rs12979860 e rs368234815). O objetivo do presente trabalho foi verificar as frequências genotípicas dos SNPs rs8099917, rs12979860 e rs368234815 e avaliar a associação entre estes SNPs e a evolução clínica e a resposta ao tratamento da infecção pelo HCV tendo em conta a ancestralidade genética da população estudada. Neste estudo, foi observada a associação dos três polimorfismos tanto com o desfecho clínico quanto com a resposta ao tratamento com interferon peguilado (PEG-IFN) e ribavirina (RBV). Os polimorfismos rs12979860 e rs368234815 foram associados com aumento da sensibilidade (respectivamente 97,7%, IC 95% 87,2-100, e 93,3%, IC 95% 81,3-98,3) e com um maior valor preditivo de uma resposta positiva ao tratamento. Na análise multivariada ajustada por sexo, idade e ancestralidade genética, o haplótipo G/T/?G foi relacionado com a não-resposta ao tratamento (OR = 21,09, IC 95% 5,33-83,51; p < 0,001) e com uma chance maior de desenvolver infecção crônica (OR = 5,46, IC 95% 2,06-14,46; p=0,001), quando comparado com haplótipo T/C/TT. Estes resultados podem ajudar a ajustar políticas de tratamento para a infecção por HCV em populações com tais características genéticas, assim como nos permitem conhecer o perfil genético da nossa população em relação a esses polimorfismosHepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated complications such as liver cirrhosis and hepatocellular carcinoma (HCC). Viral and host factors are known to be predictors for anti-viral therapy. Host factors predictors of sustained viral response (SVR) were discovered by Genome-Wide Association Studies (GWAS), including single nucleotide polymorphisms (SNPs) near or on genes IFNL3 and IFNL4 (rs8099917, rs12979860 and rs368234815). The aim of the present work was verify the genotype frequencies of SNPs rs8099917, rs12979860 and rs368234815, and evaluate the association between these SNPs and HCV infection outcome taking into account the genetic ancestry of the population. In this study, there was an association of the three polymorphisms with both clinical outcome and response to treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). The polymorphisms rs12979860 and rs368234815 showed increased sensitivity (97.7%, 95% CI 87.2-100, and 93.3%, 95% CI 81.3-98.3 respectively) and greater predictive value of a positive response to treatment. In multivariable analysis adjusted by gender, age and genetic ancestry, the haplotype G/T/?G was related to non-response to treatment (OR = 21.09, 95% CI 5.33-83.51; p < 0.001) and to a higher chance to develop chronic infection (OR = 5.46, 95% CI 2.06-14.46; p=0.001) when compared to haplotype T/C/TT. These findings may help to adjust our treatment policies for HCV infection in populations with such genetic characteristics, as well as allowing us to get to know the genetic profile of our population for these polymorphism

COINFECÇÃO HIV E HANSENÍASE: DOIS RELATOS DE CASO COM HANSENÍASE VIRCHOWIANA E ERITEMA NODOSO NECROTIZANTE

Introdução: Na coinfecção HIV e Mycobacterium leprae, a compreensão da interação entre os parasitas e o hospedeiro possui grandes lacunas de conhecimento. Aparentemente o vírus não altera profundamente a história natural da Hanseníase em indivíduos coinfectados. Por outro lado, sabe-se que nestes pacientes as reações hansênicas e neurite são mais frequentes, provavelmente por desregulação do sistema imune e por efeito neuropático do HIV, respectivamente. Dados de literatura apontam para aumento de reação tipo 1 quando em terapia antirretroviral (TARV). Aqui relata-se dois casos de coinfecção HIV-Hanseníase em pacientes com HIV fase AIDS e Hanseníase Virchowiana(HV) com reação hansênica do tipo 2. Métodos: Série de casos de pacientes com Hanseníase Virchowiana, reação hansênica do tipo 2 em pacientes com HIV fase AIDS. Resultados: Caso 1: Mulher trans, 31 anos, HIV desde 2018, em abandono de tratamento. Admitida com contagem de linfócitos CD4(LTCD4) 199 céls/mm3 e carga viral (CV) de 52 cópias/mL. Pápulas e placas acastanhadas infiltradas, difusamente distribuídas, com lesões exuberantes na região das mamas, supralabiais e hélice. Apresentava também, nos membros inferiores, vesículas e nódulos eritematosos, com áreas ulceradas e necróticas. Biópsia de pele evidenciou Hanseníase multibacilar com reação hansênica tipo 2 e eritema nodoso necrotizante. Iniciados rifampicina, clofazimina, dapsona, talidomida e prednisona. Reiniciada TARV com TDF/3TC/DTG, com melhora clínica. Caso 2: Mulher cis, 36 anos, HIV desde 2004 e com diagnóstico de HV em 2014. Após um mês de tratamento, relatava aparecimento de nódulos necróticos. Apresentava contagem de LTCD4 170 céls/mm3 e CV indetectável com 3TC/TDF/EFZ. Ademais, em uso de prednisona 1 mg/kg/dia. Apresentava placas infiltradas e nódulos necróticos em membros, tronco e glúteos, e espessamento bilateral do nervo ulnar, mão direita em garra e anestesia distal de extremidades. Talidomida foi associada ao tratamento. Após 12 meses de tratamento para HV, reduziu-se gradualmente talidomida e prednisona por 6 meses, com piora clínica. Feita nova biópsia de pele, sugestiva de reação tipo 2 e eritema nodoso, sendo reiniciado tratamento para HV. Conclusão: A coinfecção HIV/hanseníase é pouco estudada em suas manifestações e na interação entre os microrganismos. Como doença negligenciada a suspeição da hanseníase é baixa levando a atrasos de diagnóstico e de tratamento, levando a quadros clínicos de maior gravidade

Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure

Introduction and objectives: Direct antiviral agents (DAAs) are very efficient in inhibiting hepatitis C virus and might be used to treat infections caused by other flaviviruses whose worldwide detection has recently increased. The aim of this study was to verify the efficacy of DAAs in inhibiting yellow fever virus (YFV) by using drug repositioning (a methodology applied in the pharmaceutical industry to identify new uses for approved drugs). Materials and methods: Three DAAs were evaluated: daclatasvir, sofosbuvir and ledipasvir or their combinations. For in vitro assays, the drugs were diluted in 100% dimethyl sulfoxide. Vaccine strain 17D and a 17D strain expressing the reporter fluorescent protein were used in the assays. A fast and reliable cell-based screening assay using Vero cells or Huh-7 cells (a hepatocyte-derived carcinoma ell line) was carried out. Two patients who acquired yellow fever virus with acute liver failure were treated with sofosbuvir for one week as a compassionate use. Results: Using a high-content screening assay, we verified that sofosbuvir presented the best antiviral activity against YFV. Moreover, after an off-label treatment with sofosbuvir, the two female patients diagnosed with yellow fever infection displayed a reduction in blood viremia and an improvement in the course of the disease, which was observed in the laboratory medical parameters related to disease evolution. Conclusions: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use. These results offer insights into the role of nonstructural protein 5 (NS5) in YFV inhibition and suggest that nonstructural proteins may be explored as drug targets for YFV treatment