Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study

Abstract Introduction The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. Patients and methods This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. Results One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p< 0.001). Conclusions Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.

Limited cardiopulmonary capacity in patients with liver cirrhosis when compared to healthy subjects

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.

Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.

Brazilian Society of Hepatology and Brazilian Society of Infectious Diseases Guidelines for the Diagnosis and Treatment of Hepatitis B

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.

O uso do Endoguide no tratamento de canais calcificados: relatos de casos clínicos / The use of Endoguide for treatment of calcified root canals: clinical case reports

Introdução: o tratamento endodôntico em dentes com canais calcificados é extremamente desafiador. Durante o procedimento de localização do canal residual, uma quantidade excessiva de dentina pode ser removida, o que pode implicar em maior risco de fratura do elemento dentário. Somado a isso, a calcificação pulpar é o motivo mais comum de perfuração radicular durante o tratamento endodôntico. Métodos: tendo em vista a importância do desenvolvimento de técnicas seguras e precisas para o tratamento endodôntico de canais parcial ou totalmente calcificados, serão apresentados dois relatos de casos clínicos conduzidos segundo uma estratégia terapêutica recentemente descrita na literatura endodôntica. Resultados: o Endoguide tornou mais segura e eficaz a realização do tratamento endodôntico nos dois casos relatados. Conclusão: o guia endodôntico auxiliou na localização do canal radicular calcificado e ajudou a evitar iatrogenias durante sua localização (AU).

Introduction: Endodontic treatment in teeth with calcified root canals is extremely challenging. During the procedure of locating the root canal, an excessive amount of residual dentin can be removed, which may lead to a greater risk of tooth fracture. In addition, pulp calcification is the most common reason for root perforation during endodontic treatment. Methods: Considering the importance of developing safe and efficient techniques for endodontic treatment of partially or completely calcified root canals, these two clinical cases were conducted in accordance with the therapeutic strategy recently described in the endodontic literature. Results: Endoguide made endodontic treatment safer and more effective in the two reported cases Conclusion: The endodontic guide used in the present cases have helped to locate the calcified root canal and to prevent iatrogenies during location (AU).

Fat-containing liver lesions: a pictorial review / Lesões hepáticas que contêm gordura: ensaio iconográfico

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.

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.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

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.

Micro-CT Evaluation of Non-instrumented Canal Areas with Different Enlargements Performed by NiTi Systems

The aim of this study was to compare the percentage of non-instrumented area of root canals prepared with different enlargements using single-file reciprocating systems (Reciproc and WaveOne) and a conventional multi-file rotary (BioRaCe) system by micro-computed tomographic analysis. Thirty mesial roots of mandibular molars with moderate curvature (10° to 20°) presenting a type II Vertucci canal configuration and similar internal volume were chosen and scanned at an isotropic resolution of 14.16 µm. The sample was assigned to 3 groups (n=10) according to the system used for root canal preparation: Reciproc, WaveOne, and BioRaCe groups. Second and third scans were taken after the canals were prepared with instruments sizes 25 and 40, respectively. The recorded images of the surface area voxels of the canals, before and after preparation were examined from the furcation level to the apex to quantify the non-instrumented surface. Statistical data were compared using GLM for repeated-measures with a significance level set at 5%. Instrumentation systems did not influence the percentage of untouched root canal surfaces (p=0.690) whilst a significant reduction in the percentage of static voxels was observed after the enlargement of the root canal (p=0.010) in all groups (p=0.507). None of the systems was able to prepare the entire surface area of the mesial root canal of mandibular molars. The increased final apical size resulted in a significant positive effect on the shaping ability of the tested systems.

Resumo O objetivo deste estudo foi comparar a porcentagem de área não-instrumentada de canais radiculares preparados com diferentes ampliações utilizando sistemas reciprocantes de lima única (Reciproc e WaveOne) e um sistema rotatório convencional de múltiplas limas (BioRaCe) usando a análise da micro tomografia computadorizada. Trinta raízes mesiais de molares inferiores com curvatura moderada (10º a 20º) apresentando a configuração classe II de Vertucci e semelhança de volume do canal foram selecionadas e escaneadas em uma resolução isotrópica de 14,16 µm. A amostra foi dividida em 3 grupos (n=10) de acordo com o sistema utilizado para a preparação do canal radicular: grupo Reciproc, grupo WaveOne e grupo BioRaCe. Segundo e terceiro escaneamentos foram realizados após os canais serem preparados com instrumentos tamanhos 25 e 40, respectivamente. As imagens registradas de voxels da área de superfície dos canais, antes e após o preparo, foram examinadas desde o nível da furca até o ápice para quantificar a superfície não instrumentada. Os dados foram comparados estatisticamente através de GLM para medidas repetidas com um nível de significância de 5%. Os sistemas de instrumentação não influenciaram o percentual de superfícies não tocadas dos canais radiculares (p=0,690), enquanto que uma redução significativa no percentual de voxels estáticos foi observada após o alargamento do canal radicular (p=0,010) em todos os grupos (p=0,507). Nenhum dos sistemas foi capaz de preparar toda a área de superfície do canal mesial dos molares inferiores. O aumento do tamanho final apical resultou num efeito positivo significativo sobre a capacidade de modelar dos sistemas testados.

Acute exacerbation of chronic hepatitis B virus infection in renal transplant patients

Introduction: There is scarce information regarding clinical evolution of HBV infection in renal transplant patients. Aims: To evaluate the prevalence of acute exacerbation in HBV-infected renal transplant patients and its association with the time after transplantation, presence of viral replication, clinical evolution, and use of antiviral prophylaxis. Materials and methods: HBV infected renal transplant patients who underwent regular follow-up visits at 6-month intervals were included in the study. The criteria adopted to characterize exacerbation were: ALT >5 × ULN and/or >3 × baseline level. Predictive factors of exacerbation evaluated were age, gender, time on dialysis, type of donor, post-transplant time, ALT, HBeAg, HBV-DNA, HCV-RNA, immunosuppressive therapy, and use of antiviral prophylaxis. Results: 140 HBV-infected renal transplant patients were included (71% males; age 46 ±10 years; post-renal transplant time 8 ±5 years). During follow-up, 25% (35/140) of the patients presented exacerbation within 3.4 ±3 years after renal transplant. Viral replication was observed in all patients with exacerbation. Clinical and/or laboratory signs of hepatic insufficiency were present in 17% (6/35) of the patients. Three patients died as a consequence of liver failure. In univariate analysis variables associated with exacerbation were less frequent use of prophylactic/preemptive lamivudine and of mycophenolate mofetil. Lamivudine use was the only variable independently associated with exacerbation, with a protective effect. Conclusions: Acute exacerbation was a frequent and severe event in HBV-infected renal transplant patients. Prophylactic/preemptive therapy with antiviral drugs should be indicated for all HBsAg-positive renal transplant patients. .

Do differences exist between chronic hepatitis C genotypes 2 and 3?

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. .

Prevalence of occult hepatitis B virus infection in kidney transplant recipients

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.

A single nucleotide polymorphism, rs129679860, in the IL28B locus is associated with the viral kinetics and a sustained virological response in a chronic, monoinfected hepatitis C virus genotype-1 Brazilian population treated with pegylated interferon-ribavirin

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.

Hepatitis B virus genotypes in Southeast Brazil and its relationship with histological features

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.

Association of hepatitis C virus NS5B variants with resistance to new antiviral drugs among untreated patients

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 percent. 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 percent) 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.

Alfapeguinterferon-2a e ribavirina versus alfapeguinterferon-2b e ribavirina: avaliação custo-efetividade e do impacto orçamentário do tratamento do genótipo 1 da hepatite C crônica / Alfa-pegylated interferons (2a and 2b) and ribavirin for treatment chronic hepatitis C, genotype 1: a cost-effectiveness analysis

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 por cento 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 por cento, 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 percent 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 percent if all patients were treated using the selected treatment regimens.

Weight-based combination therapy with peginterferon alpha-2b and ribavirin for Naïve, relapser and non-responder patients with chronic hepatitis C

Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naïve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week) plus ribavirin (800-1,200 mg/day) for 48 weeks in naïve, relapser and non-responder (to previous treatment with interferon plus ribavirin) patients with chronic hepatitis C. Sixty-seven naïve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR) for the intention-to-treat population was 54 percent for naïve, 62 percent for relapser and 38 percent for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67 percent) compared to those with genotype 1 (45 percent). In relapsers and non-responders, SVR was, respectively, 69 percent and 24 percent in patients with genotype 1 and 43 percent and 73 percent in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges (< 65 kg, 65-85 kg and > 85 kg) in any of the subgroups. Early virological response (EVR) was reached by 78 percent, 81 percent and 58 percent of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63 percent, 67 percent and 61 percent, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13 percent of the patients, due to loss to follow-up, hematological abnormalities or depression.

Low bone mineral density in noncholestatic liver cirrhosis: prevalence, severity and prediction

RACIONAL: Existe associação entre doença óssea metabólica e doença hepática colestática. Contudo, a associação com cirrose não-colestática ainda é pouco conhecida. OBJETIVOS: Determinar a prevalência e a gravidade da perda de densidade mineral óssea na cirrose não-colestática e investigar fatores preditivos do seu diagnóstico. MÉTODOS: Oitenta e nove pacientes e 20 controles foram estudados de março a setembro de 1998. Todos foram submetidos a exames laboratoriais e densitometria óssea da coluna lombar e do colo do fêmur. RESULTADOS: A massa óssea estava significativamente reduzida em ambos os sítios nos pacientes quando comparado aos controles. A prevalência da perda de massa óssea na cirrose não-colestática, de acordo com os critérios da Organização Mundial da Saúde, foi de 78 por cento na coluna lombar e 71 por cento no colo do fêmur. A massa óssea diminuiu significativamente com a idade em ambos os sítios, especialmente em pacientes acima de 50 anos. Pacientes mulheres pós-menopausa tinham massa óssea significativamente menor do que pacientes mulheres pré-menopausa e homens em ambos os sítios. Não houve diferença significativa na massa óssea entre as etiologias não-colestáticas. A massa óssea da coluna lombar diminuiu significativamente com a progressão da disfunção hepática. Nenhuma variável bioquímica foi associada com a perda da massa óssea. CONCLUSÕES: A perda de massa óssea foi freqüente em pacientes com cirrose não-colestática. Pacientes idosos, do sexo feminino na pós-menopausa e com disfunção hepática grave apresentaram doença óssea mais avançada. Os exames laboratoriais rotineiramente dosados nos pacientes com doença hepática não puderam predizer com segurança a presença de redução na massa óssea.

Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV). We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use), and who gave information about alcohol consumption.Patients were divided into two groups for analysis: group 1 - grades 0 to 2; group 2 - grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism. The rate of fibrosis progression (index of fibrosis) was determined based on the relationship between disease stage and duration of infection (years). Logistic regression analysis revealed that age at the time of infection (P<0.01; 95 percent CI 1.06-1.22) and the duration of infection (P<0.01; 95 percent CI 1.06-1.32) were independently associated with a more advanced stage of hepatitis C. The median index of fibrosis was 0.14 for the group as a whole. A significant difference in the index of fibrosis was observed between patients aged < 40 years at infection (median = 0.11) and patients aged > or = 40 years (median = 0.47). The main factors associated with a more rapid fibrosis progression were age at the time of infection and the estimated duration of infection. Patients who acquired HCV after 40 years of age showed a higher rate of fibrosis progression

Infecçäo pelo vírus da hepatite C em transplantados renais: estudo comparativo com pacientes imunocompetentes e portadores de insuficiência renal crônica em hemodiálise / Hepatitis C virus infection in kidney transplant recipients: a comparative study with immunocompetent and end-stage renal disease patients on hemodyalisis

Introduçao: Há poucos dados sobre o comportamento laboratorial e histológico da hepatite C em transplantados renais e ainda nao foram identificados, neste grupo, os fatores relacionados com graus mais avançados de estadiamento. Objetivos: Avaliar, em transplantados renais com infecçao pelo HCV, o valor da ALT como marcador de atividade inflamatória periportal (APP) e parenquimatosa (AP) e a influência de variáveis ligadas ao hospedeiro no estadiamento (E) da doença hepática. Comparar com aspectos bioquímicos e histológicos da infecçao crônica pelo HCV observados em pacientes imunocompetentes e em portadores de insuficiência renal crônica (IRC) em hemodiálise. Casuística e Métodos: Foram incluídos transplantados renais com HCV-RNA positivo, tempo de transplante >_ 1 ano e fragmento de biópsia adequado à análise histológica. Foram avaliadas variáveis epidemiológicas, laboratoriais e histológicas. Foram determinados valores de sensibilidade, especificidade, valor preditivo positivo (VPP) e negativo (VPN) da ALT elevada na detecçao de hepatite de interface elou necrose confluente. Para análise dos fatores associados a estadiamento mais avançado (E>_2), os pacientes foram categorizados em 2 grupos: G1 - ausência de septos fibrosos (E < 2 ); G2 - presença de fibrose septal (E>_2) e foi aplicada análise de regressao logística. As características bioquímicas e histológicas dos transplantados renais foram comparadas com aquelas dos pacientes imunocompetentes e portadores de IRC com infecçao pelo HCV, pareados na relaçao 1:1 por sexo, idade na infecçao e tempo de infecçao. Resultados: Foram incluídos no estudo 53 pacientes, 60 por cento do sexo masculino. A média da idade na época da infecçao foi de 31,7ñ8,9 anos e a média do tempo de infecçao foi de 9,9ñ4,1 anos. A mediana do tempo de transplante foi de 4 anos e 47 por cento dos transplantados eram receptores de enxerto de doador cadáver. Entre os pacientes avaliados, 26 (49 por cento) apresentavam ALT normal. A sensibilidade, especificidade, VPP e VPN da ALT elevada (>1x LSN) na detecçao de hepatite de interface elou necrose confluente foram, respectivamente, 87 por cento, 77 por cento, 74 por cento e 89 por cento. Na análise de regressao logística, a única variável que mostrou associaçao independente com estadiamento mais avançado foi o tempo de transplante (P=0,002; OR 1,36; IC:1,12-1,65). Os transplantados renais, quando comparados...(au)

Prevalência do anticorpo contra hepatite C (anti VHC) em doadores de sangue no Rio de Janeiro, Brasil: sua relaçäo com ALT e anti HBc / Prevalence of antibodies to hepatitis C (anti HCV) in blood donors in Rio de Janeiro, Brazil: its relation with ALT and anti HBC

Estudamos no período de maio a julho de 1990, 933 doadores de sangue atendidos no Serviço de Hemoterapia. Após entrevista e exames rotineiros, foram realizados testes de triagem: antiHBc total, antiVHC e transminase glutâmico pirúvica (ALT). Os marcadores virais foram determinados por técnica de enzimaimunoensaio. 94% dos doadores eram do sexo masculino com média de idade de 33 anos (19-65). A positividad para o antiVHC foi de 3,1%. Entre os doadores antiVHC+, 13,29(44,8%) apresentaram ALT>40UI/L, 9/29(31%) foram positivos para o antiHBc e 5(17,2%) tinham ambos os marcadores. De 109 doadores com ALT > UI/L 13(11.9%) foram anti VHC+. Enquanto de 153 doadores anti HBC+, a positividade para o anti VHC foi de 5,8%, pouco maior que a do grupo total. Conclusöes: 1) Nossos doadores apresentam elevada prevalência de anti VHC(método de ELISA) quando comparada à de outros países estudados; 2) a determinaçäo de ALT e a pesquisa de anti HBc no soro de doadores foi incapaz de detectar 41,4% de doadores anti VHC+; 3) houve maior prevalência de ALT elevada nos doadores antiVHC+ com relaçäo amostra/cutoff > 4