Abstract Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Resumo Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação agu-da de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96%(74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.

SUMMARY OBJECTIVES: The present study compared cardiorespiratory capacity between cirrhotic patients and healthy subjects. METHODS: Nineteen cirrhotic patients and 19 healthy subjects, paired by age and gender, participated in the study. Volunteers performed an incremental cardiopulmonary test with a ramp protocol, a ventilatory and metabolic variables were obtained and analyzed. The recovery was analyzed by calculating the time needed for 50% of oxygen consumption (VO2) recovery to occur as the median between the peak of the exercise and the end of recovery on the VO2 curve (T1/2). The VE/VCO2 slope were performed by the linear regression of ventilation (VE) and carbon dioxide production (VCO2) data. RESULTS: During resting condition, cirrhotic patients presented significantly higher levels of VO2 compared to healthy subjects. The VE/ VO2 and VE/ VCO2 values were significantly higher in the control group at the anaerobic threshold and at the peak of the test compared to cirrhotic patients. Time under effort was significantly higher for healthy subjects. CONCLUSIONS: Based on these findings, it is possible to conclude that liver cirrhosis can compromise the patients’ quality of life, mainly by inducing metabolic alterations which can impair functional capacity and lead to a sedentary lifestyle.

Abstract Chronic hepatitis B is an important health problem that can progress to cirrhosis and complications such as hepatocellular carcinoma. There is approximately 290 million of people with chronic hepatitis B virus (HBV) infection worldwide, however only 10% of patients are currently identified.Most part of Brazil is considered of low prevalence of HBV infection but there are some regions with higher frequency of carriers. Unfortunately, many infected patients are not yet identified nor evaluated for treatment.The Brazilian Society of Infectious Diseases (SBI) and the Brazilian Society of Hepatology worked together to elaborate a guideline for diagnosis and treatment of hepatitis B. The document includes information regarding the population to be tested, diagnostic tools, indications of treatment, therapeutic schemes and also how to handle HBV infection in specific situations (pregnancy, children, immunosuppression, etc).Delta infection is also part of the guideline, since it is an important infection in some parts of the country.

Resumo O objetivo deste ensaio é rever o espectro de lesões hepáticas que contêm gordura e caracterizar seus aspectos de imagem na ressonância magnética, com foco nas características radiológicas que auxiliam no diagnóstico diferencial. As lesões hepáticas que contêm gordura compreendem um grupo heterogêneo de tumores com aspectos de imagem variáveis. A ressonância magnética exibe claramente os componentes de gordura microscópica e macroscópica das lesões e outras características que são úteis para fazer diagnósticos diferenciais.

Abstract The aim of this pictorial essay is to review the spectrum of fat-containing liver lesions and their characterisation on magnetic resonance imaging with focus on the radiological features that aid in the differential diagnoses. Fat-containing liver lesions comprise a heterogeneous group of tumours with variable imaging findings. Magnetic resonance imaging clearly displays the micro- and macroscopic fat components of the lesions and other characteristic features that are helpful tools to make the differential diagnosis.

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.

Abstract Brazil is one of the 22 countries that concentrates 80% of global tuberculosis cases concomitantly to a large number of hepatitis C carriers and some epidemiological risk scenarios are coincident for both diseases. We analyzed tuberculosis cases that occurred during α-interferon-based therapy for hepatitis C in reference centers in Brazil between 2001 and 2012 and reviewed their medical records. Eighteen tuberculosis cases were observed in patients submitted to hepatitis C α-interferon-based therapy. All patients were human immunodeficiency virus-negative. Nine patients (50%) had extra-pulmonary tuberculosis; 15 (83%) showed significant liver fibrosis. Hepatitis C treatment was discontinued in 12 patients (67%) due to tuberculosis reactivation and six (33%) had sustained virological response. The majority of patients had a favorable outcome but one died. Considering the evidences of α-IFN interference over the containment of Mycobacterium tuberculosis, the immune impairment of cirrhotic patients, the increase of tuberculosis case reports during hepatitis C treatment with atypical and severe presentations and the negative impact on sustained virological response, we think these are strong arguments for latent tuberculosis infection screening before starting α-interferon-based therapy for any indication and even to consider IFN-free regimens against hepatitis C when a patient tests positive for latent tuberculosis infection.

ABSTRACTIn coinfected HBV/HCV patients, HBV replication is usually suppressed by HCV over the time. No study to date has evaluated the HBV viremia in long-term follow-up after HCV treatment in hemodialysis patients with HBV/HCV coinfection. This study aimed to assess the evolution of HBV viremia after HCV treatment in this special population. Ten hemodialysis patients with HBV/HCV coinfection with dominant HCV infection (HBV lower than 2000 IU/mL) and significant fibrosis were treated with interferon-alpha 3 MU 3×/week for 12 months and could be followed for at least 36 months after HCV treatment. Six cases of HBV reactivation (60%) during follow-up were observed and 5/6 had been successfully treated for HCV. Patients with HBV reactivation received anti-HBV therapy. Our preliminary findings indicate that treatment of hepatitis C in HBV/HCV coinfected hemodialysis patients may favor HBV reactivation. Thus, continued monitoring of HBV viremia must be recommended and prompt anti-HBV therapy should be implemented.

Introduction Six genotypes of the hepatitis C virus (HCV) have been identified thus far, and their distribution is well defined. Genotype 1, which is the most prevalent worldwide, is always compared to genotypes 2 and 3, particularly in terms of treatment response. However, little is known about the differences between genotypes 2 and 3 because these genotypes are analyzed together in most studies. Therefore, the aim of this study was to evaluate differences in the clinical, epidemiological, laboratory, and histological parameters between HCV-2 and HCV-3. Methods Patients with chronic hepatitis C infected with genotypes 2 and 3 were studied retrospectively and compared according to clinical, laboratory, and histological aspects. Hepatitis C virus-ribonucleic acid (HCV-RNA) was analyzed quantitatively by TaqMan® real-time PCR, and the HCV genotype was determined by sequencing the 5′-untranslated region. Results A total of 306 patients with chronic HCV-2 (n=50) and HCV-3 (n = 256) were studied. Subtype 2b (n=17/50) and subtype 3a (n=244/256) were the most prevalent among patients infected with HCV-2 and HCV-3, respectively. The mean age was 47 ± 10 years, and there was a predominance of men in the group studied (61%). Comparative analysis between HCV-2 and HCV-3 showed a younger age (p=0.002), less prevalence of arterial hypertension (p=0.03), higher serum albumin levels (p=0.01), more advanced stage of liver fibrosis (p=0.03), and higher frequency of steatosis in patients with HCV-3 (p=0.001). After multivariate regression analysis, all the variables, except serum albumin, remained as variables associated with HCV-3 in the final model. Conclusions Clinical and histological differences exist between HCV-2 and HVC-3, which suggests the need for separate analyses of these genotypes.

In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area.

Single nucleotide polymorphisms (SNPs) in the interleukin (IL)28B locus have been associated with a sustained virological response (SVR) in interferon-ribavirin (IFN-RBV)-treated chronic hepatitis C virus (HCV)-infected patients in European and African populations. In this study, the genotype frequency of two IL28B SNPs (rs129679860 and rs8099917) in a cohort of chronic HCV-monoinfected patients in Brazil was evaluated and the SNP sufficient to predict the treatment response outcome was determined. A total of 66 naïve genotype-1 chronic HCV-infected patients were genotyped and the associated viral kinetics and SVR were assessed. The overall SVR was 38%. Both the viral kinetics and SVR were associated with rs129679860 genotypes (CC = 62% vs. CT = 33% vs. TT = 18%, p = 0.016). However, rs8099917 genotypes were only associated with SVR (TT = 53% vs. TG = 33% vs. GG = 18%; p = 0.032). In this population, the analysis of a single SNP, rs12979860, successfully predicts SVR in the IFN-RBV treatment of HCV.

Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.

Mutations located in the 109-amino acid fragment of NS5B are typically associated with resistance to interferon (IFN) and ribavirin (RIB) and to new antiviral drugs. The prevalence of these mutations was examined in 69 drug-naïve individuals with hepatitis C virus (HCV) infections in Rio de Janeiro, Brazil. Mutations related to non-response to IFN/RIB were observed in all subtypes studied (1a, 1b, 2b, 3a and 4). The most common mutation was Q309R, present in all subtypes, except subtype 2b with frequency above 20%. D244N was detected only in subtype 3a and A333E was detected only in subtype 2b. We did not detect the S282T, S326G or T329I mutations in any of the samples analysed. Of note, the C316N mutation, previously related to a new non-nucleoside compound (HCV796 and AG-021541), was observed in only eight of 33 (24%) samples from subtype 1b. Site 316 was under positive selection in this HCV variant. Our data highlight the presence of previously described resistance mutations in HCV genotypes from drug-naïve patients.

Foi realizada análise de custo-efetividade e do impacto orçamentário de tratamentos indicados para adultos infectados com genótipo 1 do vírus da hepatite C, comparando o não-tratamento com terapias combinadas de alfapeguinterferon-2a e 2b associados a ribavirina. O modelo de Markov desenvolvido projetou a evolução da hepatite C em coorte de 1.000 pacientes, por um período de 30 anos, para os vários estados do desenvolvimento da doença. As terapias combinadas da ribavirina com o alfapeguinterferon 2a ou 2b apresentam efetividades estatisticamente idênticas quando avaliadas em 30 anos de evolução da doença. Quanto ao impacto do tratamento nos anos de vida e nos anos de vida ajustados por qualidade de vida; os anos de vida ganhos por qualidade de vida em relação à evolução da doença sem tratamento foram de 1,67 e 1,63, respectivamente, para a terapia combinada com alfapeguinterferon 2a e 2b, aplicando-se 5% de desconto. A estratégia de tratamento com alfapeguinterferon 2a mais ribavirina se revelou mais custo-efetiva, dominando a outra alternativa de tratamento. Embora não haja diferenças significativas de efetividade entre os dois tipos de alfapeguinterferon, a diferença de preço entre os dois medicamentos faz com que a alternativa do uso do alfapeguinterferon 2a mais ribavirina seja mais eficiente. Quanto à estimativa do impacto orçamentário para o período de 2008 a 2017, a utilização do alfapeguinterferon 2a mais ribavirina resulta em redução nos gastos de aproximadamente 19%, caso todos os doentes fossem tratados utilizando-se os esquemas terapêuticos selecionados.

A cost-effectiveness and budget impact of treatments given to adults infected with genotype 1 hepatitis C virus was performed by comparing the non-treatment with combined therapy alfapeguinterferon-2a and 2b and ribavirin. The Markov model developed engineered the development of hepatitis C in a cohort of 1,000 patients for a period of 30 years for the various states of disease development. The combined therapy of ribavirin with alfapeguinterferon 2a or 2b have statistically identical effectiveness when evaluated at 30 years of disease. As for the impact of treatment in life years and years of life adjusted for quality of life, the life years gained for quality of life in relation to the evolution of the disease without treatment were 1.67 and 1.63, respectively, for combined therapy with alfapeguinterferon 2a and 2b, applying a 5% discount. The strategy of treatment with alfapeguinterferon 2a plus ribavirin was more cost-effective, dominating the other treatment. Although there are significant differences in effectiveness between the two types of alfapeguinterferon, the price difference between the two products makes the alternative of using alfapeguinterferon 2a plus ribavirin more effective. Concerning the estimated budget impact for the period 2008 to 2017, using alfapeguinterferon 2a plus ribavirin results in a reduction in spending of about 19% if all patients were treated using the selected treatment regimens.

Foi realizada análise de custo-efetividade e do impacto orçamentário de tratamentos indicados para adultos infectados com genótipo 1 do vírus da hepatite C, comparando o não-tratamento com terapias combinadas de alfapeguinterferon-2a e 2b associados a ribavirina. O modelo de Markov desenvolvido projetou a evolução da hepatite C em coorte de 1.000 pacientes, por um período de 30 anos, para os vários estados do desenvolvimento da doença. As terapias combinadas da ribavirina com o alfapeguinterferon 2a ou 2b apresentam efetividades estatisticamente idênticas quando avaliadas em 30 anos de evolução da doença. Quanto ao impacto do tratamento nos anos de vida e nos anos de vida ajustados por qualidade de vida; os anos de vida ganhos por qualidade de vida em relação à evolução da doença sem tratamento foram de 1,67 e 1,63, respectivamente, para a terapia combinada com alfapeguinterferon 2a e 2b, aplicando-se 5% de desconto. A estratégia de tratamento com alfapeguinterferon 2a mais ribavirina se revelou mais custo-efetiva, dominando a outra alternativa de tratamento. Embora não haja diferenças significativas de efetividade entre os dois tipos de alfapeguinterferon, a diferença de preço entre os dois medicamentos faz com que a alternativa do uso do alfapeguinterferon 2a mais ribavirina seja mais eficiente. Quanto à estimativa do impacto orçamentário para o período de 2008 a 2017, a utilização do alfapeguinterferon 2a mais ribavirina resulta em redução nos gastos de aproximadamente 19%, caso todos os doentes fossem tratados utilizando-se os esquemas terapêuticos selecionados.

A cost-effectiveness and budget impact of treatments given to adults infected with genotype 1 hepatitis C virus was performed by comparing the non-treatment with combined therapy alfapeguinterferon-2a and 2b and ribavirin. The Markov model developed engineered the development of hepatitis C in a cohort of 1,000 patients for a period of 30 years for the various states of disease development. The combined therapy of ribavirin with alfapeguinterferon 2a or 2b have statistically identical effectiveness when evaluated at 30 years of disease. As for the impact of treatment in life years and years of life adjusted for quality of life, the life years gained for quality of life in relation to the evolution of the disease without treatment were 1.67 and 1.63, respectively, for combined therapy with alfapeguinterferon 2a and 2b, applying a 5% discount. The strategy of treatment with alfapeguinterferon 2a plus ribavirin was more cost-effective, dominating the other treatment. Although there are significant differences in effectiveness between the two types of alfapeguinterferon, the price difference between the two products makes the alternative of using alfapeguinterferon 2a plus ribavirin more effective. Concerning the estimated budget impact for the period 2008 to 2017, using alfapeguinterferon 2a plus ribavirin results in a reduction in spending of about 19% if all patients were treated using the selected treatment regimens.

O objetivo deste estudo foi avaliar os efeitos do diâmetro do caule e da poda de alporques sobre o desenvolvimento e o acúmulo de nutrientes em mudas de lichieira cultivadas em substrato. Para isso utilizou-se de alporques da variedade Bengal. O delineamento experimental foi o inteiramente casualizado, em esquema fatorial 3 x 2, com oito repetições, sendo três diâmetros do alporque: fino (1,0 ±0,5 cm); médio (2,0 ±0,5 cm) e grosso (3,0 ±0,5 cm), e alporques com e sem poda. As mudas de lichieira foram cultivadas durante 140 dias após o plantio dos alporques. Avaliaram-se a matéria seca das brotações da parte aérea e das raízes, e os teores de macro e micronutrientes. A melhor muda de lichieira foi obtida de alporque com diâmetro grosso, e podado. O alporque de diâmetro médio e fino não-podado, comparado ao podado, proporcionou maior desenvolvimento da muda de lichieira. O alporque com diâmetro grosso proporcionou maior acúmulo de nutrientes na parte aérea e na raiz da muda de lichieira.

This research was carried out to evaluate the effects of stem diameter and layer pruning on the development and nutrient accumulation in litchi grown on substrate. The variety used here was Bengal. The experiment was arranged in a completely randomized design in a factorial 3 x 2 with eight replications, with three layer diameters: thin (1.0 ± 0.5 cm); medium (2.0 ± 0.5 cm) and thick (3.0 ± 0.5 cm) and pruned and not pruned layers. Litchi plants were grown for 140 days after planting the layers. The dry matter of shoot branches and roots and the levels of macro and micronutrients were evaluated. The best litchi plants were obtained from thick, pruned layers. Not pruned layers with medium and thin diameter improved plant development in comparison to pruned ones. Thick layers showed higher nutrient accumulation in shoots and roots.