ABSTRACT Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1. Objective , (NAFLD) (NASH methods Epidemiological 57 examined Results 43 included 398 39 8 39.8 95 2 (HOMA 25 5 2. 0001 0 001 0.00 0016 016 0.016 respectively. respectively . respectively) group 26 ASTALT AST ALT (AST/ALT 1 highdensity density HDLc HDL c (HDL-c 4 mgdL mg dL mg/dL TC (TC 20 gammaglutamyl gamma glutamyl GGT (GGT 3 UL U L (TG 15 HDLc, c, HDL-c Conclusion (NAFLD 39. 9 000 00 0.0 01 0.01 0.

SUMMARY OBJECTIVE: The aim of the study was to compare the epidemiology and clinical profiles of hospital admissions in a single Brazilian Hepatology Unit from the period 2014–2017 to 2019–2022. METHODS: A retrospective analysis of hospital database from the abovementioned periods was done. The study included patients over the age of 18 years who were hospitalized due to complications of diseases such as viral hepatitis, alcoholic disease, nonalcoholic fatty liver disease, and autoimmune liver and drug-induced hepatitis. RESULTS: In both study periods, middle-aged males were predominant and were younger than females. In the first period (2014–2017), hepatitis C (33.5%) was the most prevalent cause of admission, followed by alcoholic liver disease (31.7%). In the second period (2019–2022), nonalcoholic fatty liver disease (38%) and alcoholic liver disease (27.6%) were the most frequent causes of admission. No changes were observed in the proportion of alcoholic liver disease or drug-induced hepatitis in both study periods. The prevalence of viral hepatitis decreased in both genders, with hepatitis C decreasing from 32.4 to 9.7% for males and 35.4 to 10.8% for females, and OR=0.2; 95%CI 0.1–0.3 for both males and females. Similarly, the prevalence of hepatitis B decreased from 19.1 to 8.1% and OR=0.3; 95%CI 0.2–0.5 for males and 8.2 to 3.7% and OR=0.4; 95%CI 0.1–0.9 for females. The prevalence of autoimmune liver diseases increased only in males, from 2.1 to 5.9% and OR=2.9; 95%CI 1.2–6.6. CONCLUSION: Over the past 4 years, there has been a shift in hospital admission profile at a Brazilian Hepatology Unit, with a decrease in viral hepatitis and an increase in autoimmune diseases and nonalcoholic fatty liver disease. Males were more affected at younger ages than females. Furthermore, ascites was the most prevalent cause of complications in both periods analyzed. OBJECTIVE 20142017 2014 2017 2014–201 20192022 2019 2022 2019–2022 METHODS done 1 druginduced drug induced RESULTS middleaged middle aged females 2014–2017, , (2014–2017) 33.5% 335 33 5 (33.5% 31.7%. 317 31.7% . 31 7 (31.7%) 2019–2022, (2019–2022) 38% 38 (38% 27.6% 276 27 6 (27.6% genders 324 32 32. 97 9 9.7 354 35 35. 108 10 8 10.8 OR=0.2 OR02 OR 0 2 95CI CI 95 0103 3 0.1–0. Similarly 191 19 19. 81 8.1 OR=0.3 OR03 0205 0.2–0. 82 8. 37 3.7 OR=0.4 OR04 0109 21 2. 59 5.9 OR=2.9 OR29 1266 1.2–6.6 CONCLUSION Furthermore analyzed 2014201 201 2014–20 2019202 202 2019–202 (2014–2017 33.5 (33.5 31.7 (31.7% (2019–2022 (38 27.6 (27.6 9. 10. OR=0. OR0 010 0.1–0 020 0.2–0 3. 5. OR=2. OR2 126 1.2–6. 201420 20 2014–2 201920 2019–20 (2014–201 33. (33. 31. (31.7 (2019–202 (3 27. (27. OR=0 01 0.1– 02 0.2– OR=2 12 1.2–6 20142 2014– 20192 2019–2 (2014–20 (33 (31. (2019–20 ( (27 OR= 0.1 0.2 1.2– 2019– (2014–2 (31 (2019–2 (2 0. 1.2 (2014– (2019– 1. (2014 (2019 (201 (20

SUMMARY BACKGROUND: Routine screening for viral infections at blood donation is important to avoid transfusion-transmitted infections. It also offers an opportunity to detect an asymptomatic infection. OBJECTIVE: To study changes in serology positivity for viral infections (B and C hepatitis, HTLV-1/2, and HIV) at blood donation in a blood bank from Southern Brazil, comparing two periods of 5 years: the period from 2013 to 2017 with the period from 2018 to 2022. In addition, data on the donor fidelity rate during the studied period were sought. METHODS: Retrospective study using data from 2013 to 2022 from a single blood center electronic database from Curitiba, Southern Brazil. RESULTS: A significant drop in positive serology for all studied viruses was observed: highest in HIV (OR=0.39; 95% CI=0.27–0.57) and lowest in total anti HBc (0.56; 95 CI=0.50–0.63). Anti HBc serology became more commonly seen in women in the period of 2018–2022 when compared to men. No changes in the distribution of positive serology according to donors’ ages were observed. Loyalty rates had a median of 70%, with the lowest being 60% in 2013, while the highest was 73% in 2018 and 2022. CONCLUSION: A significant reduction in discarded blood bags due to viral serology was observed when the period of 2013–2017 was compared to 2018–2022 on this blood bank; the highest reduction was observed in HIV serology and the lowest in HBc serology, which became more common in women in the second period. High rates of donor fidelity were observed during the period studied. BACKGROUND transfusiontransmitted transfusion transmitted infection OBJECTIVE B hepatitis HTLV1/2, HTLV12 HTLV 1/2, 1 2 HTLV-1/2 Brazil years 201 addition sought METHODS 202 Curitiba RESULTS OR=0.39 OR039 OR 0 39 (OR=0.39 CI=0.27–0.57 CI027057 CI 27 57 0.56 056 56 (0.56 9 CI=0.50–0.63. CI050063 CI=0.50–0.63 . 50 63 CI=0.50–0.63) 20182022 2018–202 men donors 70 70% 60 73 CONCLUSION 20132017 2013–201 HTLV1 HTLV1/2 12 1/2 HTLV-1/ 20 OR=0.3 OR03 3 (OR=0.3 CI=0.27–0.5 CI02705 0.5 05 (0.5 CI05006 CI=0.50–0.6 6 2018202 2018–20 7 2013201 2013–20 HTLV1/ 1/ HTLV-1 OR=0. OR0 (OR=0. CI=0.27–0. CI0270 0. (0. CI0500 CI=0.50–0. 201820 2018–2 201320 2013–2 HTLV- OR=0 (OR=0 CI=0.27–0 CI027 (0 CI050 CI=0.50–0 20182 2018– 20132 2013– OR= (OR= CI=0.27– CI02 ( CI05 CI=0.50– (OR CI=0.27 CI0 CI=0.50 CI=0.2 CI=0.5 CI=0. CI=0 CI=

ABSTRACT Background and aims: 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. Patients and methods: 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. Results: 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. Conclusion: 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.

RESUMO CONTEXTO: No Brasil, desde 2015, o tratamento da hepatite C é prestado pelo Sistema Público de Saúde (SUS) com antivirais de ação direta. OBJETIVO: Avaliar a taxa de não adesão de pacientes ao tratamento da hepatite C pelo antiviral de ação direta investigando os dados epidemiológicos em um banco de dados de Curitiba, Brasil. MÉTODOS: Estudo retrospectivo com pacientes atendidos entre janeiro de 2015 e junho de 2019. Os pacientes foram considerados aderentes quando receberam todas as doses da medicação durante o tratamento. Foram avaliados os seguintes dados: sexo, idade, tipo de tratamento, tempo de tratamento, presença de diabetes ou HIV, terapia anterior, proveniente do SUS ou medicina privada, grau de fibrose e genótipo da hepatite C. RESULTADOS: Um total de 1.248 pacientes (56,8% homens) foram estudados e desses, 102/1248 (8,2%) não aderiram ao tratamento. Idade ou sexo não influenciou significativamente; 10,2% pacientes do SUS e 3,7% da medicina privada eram não aderentes (P<0,0001; OR=2,9; IC95%=1,6-9,1); 13,1% dos pacientes foram coinfectados pelo HIV e, entre eles, 15,9% abandonaram o tratamento. Indivíduos sem coinfecção apresentaram 7,0% de não adesão (P<0,0001; OR=2,5; IC=1,5-4,1). Todas as outras variáveis não mostraram diferenças na taxa de adesão. CONCLUSÃO: Nosso estudo mostrou que 8,2% dos pacientes não aderiram ao tratamento para hepatite C e que os pacientes do SUS e coinfectados pelo HIV eram significativamente menos aderentes.

ABSTRACT BACKGROUND: In Brazil, since 2015, the treatment of hepatitis C is provided by SUS (Public Health System) with direct-acting antiviral (DAA). OBJECTIVE: To describe the rate of non-adherence patients to hepatitis C treatment by DAA, investigating the epidemiological data in a large database from Curitiba, Brazil. METHODS: Retrospective study with patients treated between January 2015 and June 2019. Patients were considered adherent when received all medication doses during their treatment. The following data were evaluated: gender, age, type of treatment, period of treatment, presence of diabetes or HIV, previous therapy, originated from SUS or private medicine, fibrosis grade and HCV genotype. RESULTS: 1248 patients (56.8% males) were studied and 102/1248 (8.2%) were non-adherent to treatment. Age or gender not influenced significantly; 10.2% patients from SUS and 3.7% individuals from private medicine were non-adherent (P<0.0001; OR=2.9; CI95%=1.6-9.1); 13.1% patients were co-infected with HIV and among them, 15.9% abandoned treatment. Individuals without co-infection presented 7.0% of non-adherence (P<0.0001; OR=2.5; CI=1.5-4.1). All the other variables showed no differences in the adhesion rate. CONCLUSION: Our study showed that 8.2% of patients were non-adherent to HCV treatment, and that patients from the Public Health System and co-infected with HIV were significantly less adherent.

RESUMO CONTEXTO: A hepatite C crônica ainda figura como importante causa de morbimortalidade na população brasileira, e está associada a alterações metabólicas, incluindo a resistência insulínica (RI), que pode ser avaliada pelo índice HOMA-IR. A RI pode inclusive implicar em menores taxas de reposta virológica sustentada (RVS) em certos regimes terapêuticos e à uma mais rápida progressão para fibrose hepática avançada. Com o advento dos novos antivirais de ação direta (DAA) oferecidos para hepatite C, há crescente necessidade de observar o impacto dos mesmos no perfil de RI em pacientes submetidos à tais terapêuticas. OBJETIVO: - 1) Comparar os valores do HOMA-IR dos pacientes com hepatite C crônica antes do tratamento com os DAAS com os valores deste índice após 12 meses do término do tratamento com RVS. 2) Avaliar evolução do peso após obtenção da cura da hepatite C crônica. MÉTODOS: Foram incluídos pacientes maiores de 18 anos de dois serviços terciários de Curitiba - PR, de ambos os sexos, portadores de hepatite C crônica, com tratamento com os antivirais de ação direta, no período de julho de 2015 a setembro de 2017. Tais pacientes também foram submetidos a dosagem dos níveis de insulina de jejum, glicemia de jejum e hemoglobina glicada antes de iniciar o tratamento da hepatite C e até 12 meses após o término. Também foram utilizados dados como idade, sexo, grau de fibrose hepática, índice de massa corporal, circunferência abdominal, genótipo viral e presença de diabetes mellitus antes e depois do tratamento. A RI foi estimada antes e após 12 meses do término do tratamento e calculada pelo HOMA-IR. Os resultados de variáveis quantitativas foram descritos por médias, medianas, valores mínimos, valores máximos e desvios padrões. Valores de P<0,05 indicaram significância estatística. RESULTADOS: Foram incluídos 75 pacientes no estudo com média de idade de 55,2 anos, sendo 60% do sexo masculino. Destes pacientes, 43 tinham fibrose avançada. Vinte e um (28%) pacientes tinham o diagnóstico de diabetes mellitus. A RI foi observada em 31 (41,3%) pacientes antes do tratamento antiviral, sendo que este número aumentou para 39 (52%) de acordo com a dosagem do HOMA-IR 12 meses após o término do tratamento. Não houve diferença estatística entre os valores de insulina, glicemia e HOMA-IR antes e após a cura da hepatite. Houve um ganho de peso inicial após a obtenção da cura da hepatite C, mas que não se manteve ao final do estudo. CONCLUSÃO: Não foi vista diferença estatística significante entre os valores do HOMA-IR apresentados pelos pacientes portadores de hepatite C crônica antes do tratamento e 12 meses após a cura da doença. Embora tenha ocorrido ganho de peso após obtenção da cura da doença, este não se deu de forma estatisticamente significativa (P=0,131) ao final de um ano.

ABSTRACT BACKGROUND: Chronic hepatitis C still figures as an important cause of morbidity among the Brazilian population, and is closely associated with metabolic disturbances, including insulin resistance (IR), which can be evaluated by the Homeostatic Model Assessment (HOMA-IR). IR may entail lower sustained virologic response (SVR) on certain therapeutic regimens and faster progression to advanced hepatic fibrosis. With the arrival of the direct acting agents (DAA) in hepatitis C treatment, there is an increased need in observing the impact in patients’ IR profile while using such therapies. OBJECTIVE: - 1) To compare the results of HOMA-IR in patients affected by chronic hepatitis C before treatment with DAA and 12 months after finishing it with SVR. 2) To evaluate the evolution of weight after curing chronic hepatitis C. METHODS: We included patients older than 18 from two tertiary care in Curitiba - PR, of both sexes, with chronic hepatitis C, treated with DAA, from July 2015 to September 2017. We also evaluated the patients’ levels of fasting insulin, fasting glucose and glycated hemoglobin before starting treatment and 12 months after finishing it. We also used epidemiologic data, such as age, sex, hepatic fibrosis degree, body mass index, abdominal circumference, viral genotype and the presence of diabetes mellitus before and after treatment. IR was assessed before and after treatment and calculated by the HOMA-IR score. Insulin resistance was defined by a HOMA-IR greater than 2.5. We excluded patients who lost follow-up, those who did not achieve SRV and those who did not have a laboratory profile. The results of quantitative variables were described by means, medians, and standard deviations. P values <0.05 indicated statistical significance. RESULTS: We included 75 patients in this study, with a mean age of 55.2 years and 60% of males. Forty-three patients had advanced fibrosis. Twenty one (28%) had a previous diabetes mellitus diagnosis. We identified 31 (41.3%) patients with IR before antiviral treatment, and this number increased to 39 (52%) after 12 months of finishing treatment, according to HOMA-IR. There was no statistic difference between insulin, glucose and HOMA-IR measurements before and after curing hepatitis C. We observed a weight gain in patients shortly after curing hepatitis C, but this did not persist at the end of the study. We also had no significant difference in IR prevalence when viral genotype was concerned. CONCLUSION: In this study, there was no statistically significant difference between HOMA-IR results in patients before and 12 months after treatment for hepatitis C. Even though patients gained weight after the cure, this was not statistically significant after a year (P=0.131).

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.