Resumo Esta revisão integrativa propôs-se a analisar na literatura da área estudos sobre fatores associados à adesão ao tratamento da hepatite C. Foram pesquisados artigos, publicados em inglês, ...espanhol e português, nas bases de dados Lilacs, Medline, PsycINFO, Web of Science, Scopus e CINAHL, entre os anos 2000 a 2019. Foram obtidas, inicialmente, 540 publicações e, posteriormente, aplicando-se os critérios de inclusão estabelecidos, foram selecionados 22 artigos. Constatou-se nos artigos analisados que a porcentagem de não adesão ao tratamento variou de 12% a 32%. Foram identificados como facilitadores da adesão: receber tratamento para transtornos psiquiátricos identificados durante o tratamento, ter conhecimento sobre os medicamentos e doença, receber tratamento menos complexo e com maior possibilidade de cura, apresentar menor número de eventos adversos, ter apoio social e bom vínculo com o médico. Foram identificadas como barreiras à adesão: presença de sintomas depressivos e de outros transtornos mentais, uso abusivo de álcool e substâncias psicoativas, baixa escolaridade, idade (ser mais jovem); etnia (afro-americanos), desemprego, não ter parceiro fixo, relatar estigma, distância do serviço de saúde, complexidade e eventos adversos do tratamento. Foram também identificadas lacunas nas pesquisas sobre adesão.
Abstract This integrative review examined factors associated with hepatitis C treatment adherence. The articles included were published in English, Spanish and Portuguese in the Lilacs, Medline, PsycINFO, Web of Science, Scopus and CINAHL databases, between 2000 and 2019. Initially, 540 publications were found and, after applying the study inclusion criteria, 22 articles were selected. Percentage non-adherence to treatment ranged from 12% to 32%. The variables identified as facilitating adherence were: receiving treatment for psychiatric disorders identified during treatment; knowing about medications and disease; receiving less complex treatment with greater likelihood of cure; fewer adverse events; social support; doctor-patient communication; and/or being in relationships. Barriers to adherence identified were: presence of depressive symptoms and other mental disorders; abuse of alcohol and psychoactive substances; education; age; ethnicity; unemployment; not having a steady partner; stigma; distance from health services; and the complexity and adverse effects of treatment. This review identified gaps in research on adherence.
Despite the high prevalence of osteoporosis in liver cirrhosis, the indication of bisphosphonates for patients with esophageal varices has been avoided due to risk of digestive mucosal damage. ...Therefore, this study aimed to evaluate the safety profile of risedronate treatment for patients with osteoporosis, liver cirrhosis and esophageal varices with low risk of bleeding. A total of 120 patients were allocated into two groups according to their bone mineral density measured by dual-energy X-ray absorptiometry. In the intervention group, 57 subjects with osteoporosis received oral risedronate at 35 mg weekly plus daily calcium and vitamin D supplementation. In the control group, 63 subjects with osteopenia received only calcium and vitamin D. The groups received the treatment for one year and underwent surveillance endoscopies at six and 12 months, as well as a control dual-energy X-ray absorptiometry after a 12-month follow-up. The study received Institutional Review Board approval. The groups had not only comparable Model for End-stage Liver Disease score and esophageal varices degree, but also similar incidence of digestive adverse effects. A significant improvement was achieved in the intervention group in the lumbar spine T score (p < 0.001). The results suggest that risedronate may be safely used in liver cirrhosis and esophageal varices with low bleeding risk under endoscopic surveillance, thus allowing bone mass recovery.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with ...overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD.
A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria.
Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment.
A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.
Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for ...glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis.
EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1–6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored.
100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0–99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed.
Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis.
ClinicalTrials.gov NCT03219216.
Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, ...they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C.
Patients (159) with chronic hepatitis C of both genders were analyzed.
Women showed association between HPA-3 polymorphisms and RM.
An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.
Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done ...according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs.
Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included.
As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions.
The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.
The infection for the hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality through its evolution to liver cirrhosis, end-stage liver complications and hepatocellular ...carcinoma. Currently, the new drugs for the HCV infection, based on direct antiviral agents, have changed the outcomes in this setting.
To assess death incidence, during the wait for the treatment with the new drugs, and to analyze which independent variable (age, sex, ascite, HDA, albumin, α-fetoprotein, platelets and Meld score) had relation with death.
Prospective study with cirrhotic patients by HCV. Inclusion: cirrhotic patients by hepatic biopsy (METAVIR), clinic or image, detectable RNA (HCV). Exclusion: Other stages of hepatic fibrosis and hepatocellular carcinoma. Descriptive statistic in continue variables. Fisher Exact and Kaplan Meier and Cox Regression Analysis to assess the association of variables studied with death. P<0.05.
A total of 129 patients were included. Of this, 73% were men. Mean age was 57.8±12.1, albumin of 3.5±0.6 mg/dL, platelets of 123.4±59.6 and Meld score of 10.59±3.56. The time of observation was 11.2±3.26 months, and the number of death 9/129 (6,9%). The Kaplan-Meier showed association between death with albumin lower than 2.9 (0.0006), MELD score higher than 15 (0.007) and α-fetoprotein higher than 40 ng/mL (<0.0001). Adjusted Cox Regression Analysis showed that α-fetoprotein higher than 40 ng/ml could be considered an independent risk for death.
We conclude that, patients with advanced cirrhosis should be prioritized for treatment with direct antiviral agents.
•New mutations of NS3 were associated with HCV resistance: D168N and L153I.•Substitution D168N causes destabilization of hydrogen bonds of NS3/boceprevir.•Substitution L153I impairs the covalent ...binding between S139/boceprevir.
NS3 is an important therapeutic target for direct-acting antiviral (DAA) drugs. However, many patients treated with DAAs have unsustained virologic response (UVR) due to the high mutation rate of HCV. The aim of this work was to shed some light on the puzzling molecular mechanisms of the virus’s of patients who showed high viral loads even under treatment with DAA. Bioinformatics tools, molecular modelling analyses were employed to identify mutations associated with HCV resistance to boceprevir and possible structural features related to this phenomenon. We identified two mutations of NS3 that may be associated with HCV resistance: D168N and L153I. The substitution D168N was previously reported in the literature as related with drug failure. Additionally, we identified that its molecular resistance mechanism can be explained by the destabilization of receptor-ligand hydrogen bonds. For the L153I mutation, the resistance mechanism is different from previous models reported in the literature. The L153I substitution decreases the S139 deprotonation susceptibility, and consequently, this mutation impairs the covalent binding between the residue S139 from NS3 and the electrophilic trap on boceprevir, which can induce drug failure. These results were supported by the time course analysis of the mutations of the NS3 protease, which showed that boceprevir was designed for enzymes with an L residue at position 153; however, the sequences with I153 are predominant nowadays. The results presented here could be used to infer about resistance in others DAA, mainly protease inhibitors.
Paracoccidioidomycosis (PCM) is a systemic granulomatous fungal infection rarely associated with solid organ transplantation. We report the second case of PCM in an adult after liver transplantation. ...A 47-year-old woman who had undergone liver transplantation was hospitalized for flu-like symptoms and multiple erythematous ulcerated skin papules. There was lymphadenopathy, pulmonary compromise, and quickly progression to septic shock. PCM was confirmed by skin biopsy and serologic tests, and a satisfactory response to amphotericin B was achieved.
Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained ...virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear.
To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin.
A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004).
Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis OR=2.01 (95%CI: 0.986-4.119) P=0.05 and age OR=1.06 (95%CI: 1.022-1.110) P=0.002 as negative predictors of sustained virological response.
In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.
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