Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.

Coffee has hepatoprotective benefits in Brazilian patients with chronic hepatitis C even in lower daily consumption than in American and European populations

The potential role of coffee as a hepatoprotective substance for chronic liver diseases has been widely discussed. Our main aim was to evaluate the effect of coffee intake regarding clinical, biochemical tests and liver biopsy data in treatment naïve patients with chronic hepatitis C. One hundred and thirty-six patients with chronic hepatitis C, diagnosed through liver biopsy, or by means of clinical, ultrasound or endoscopic signs of cirrhosis, were assessed by determination of biochemical tests, metabolic and morphological alterations. Food frequency was scrutinized by using a structured questionnaire. Coffee intake represented more than 90% of the total daily caffeine, and the 75th percentile was 4-Brazilian coffee-cup/day (>255mL/day or >123mg caffeine/day). According to caffeine intake, patients were divided into two groups (< or >123mg caffeine/day). Patients with higher ingestion of caffeine had lower serum levels of aspartate aminotransferase (× upper limit of normal) (1.8±1.5 vs 2.3±1.5, p=0.04), lower frequencies of advanced (F3, F4) fibrosis (23.5% vs 54.5%, p<0.001) and of histological activity grade (A3, A4) observed in liver biopsies (13.8% vs 36.9%, p<0.001). By multivariate logistic regression, fibrosis was independently associated with caffeine intake (OR- 0.16; 95%CI - 0.03-0.80; p=0.026), γ-glutamil transferase serum levels and morphological activity. But only fibrosis was associated with histological activity. In conclusion caffeine consumption greater than 123mg/day was associated with reduced hepatic fibrosis. In addition, this study supports the assumption that coffee intake has hepatoprotective benefits for Brazilian patients with chronic hepatitis C, even in lower doses than that of American and European population intake.

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

Introduction: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. Methods: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. Results: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. Conclusions: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction. .

Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels / Progressão da fibrose hepática em portadores de coinfecção HIV/vírus da hepatite C com níveis de aminotransferases normais

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

INTRODUÇÃO: Aproximadamente, 30% dos portadores de hepatite crônica C apresentam níveis de aminotransferases persistentemente normais (APNL). A maioria destes pacientes tem lenta progressão da fibrose hepática. Em portadores de coinfecção VHC-HIV, estudos têm demonstrado que a progressão da fibrose hepática é mais rápida que a observada em indivíduos infectados somente pelo VHC. Há poucos estudos que verificaram as características histológicas da hepatite crônica C em pacientes coinfectados pelo HIV APNL. MÉTODOS: Portadores de coinfecção VHC-HIV (HCV-RNA e anti-HIV positivos) com tempo de infecção pelo VHC conhecido (uso de drogas intravenosas) foram selecionados. Aqueles com hepatitis B surface antigen (HbsAg) positivo ou que tenham sido submetidos à terapia antiviral para hepatite C antes da biópsia hepática foram excluídos. Pacientes com pelo menos 3 determinações normais da ALT nos últimos 6 meses antes da biópsia hepática foram considerados como tendo APNL. Todos foram submetidos a biópsia hepática que foi classificada de acordo com a escala METAVIR. RESULTADOS: Foram incluídos 50 pacientes, 40 (80%) homens. Todos receberam terapia antirretroviral. Os níveis de ALT foram persistentemente normais em 13 (26%) pacientes. Pacientes coinfectados com APNL apresentaram menor média dos estágiosde fibrose hepática (0,77±0,44 versus 1,86±1,38; p<0,001), dos índices de atividade inflamatória periportal (0,62±0,77 versus 2,24±1,35; p<0,001) e progressão mais lenta da fibrose hepática (0,058±0,043 unidades de fibrose /ano versus 0,118±0,102 unidades de fibrose/ano) quando comparados àqueles com aminotransferases elevadas. CONCLUSÕES: Portadores de coinfecção VHC-HIV com APNL apresentam progressão mais lenta da fibrose hepática. Nesses pacientes o desenvolvimento de cirrose hepática é improvável.

Analysis of GB virus C infection among HIV-HCV coinfected patients / Análise da infecção pelo vírus GB-C em pacientes com coinfecção VIH-VHC

The aim of this study was to evaluate the effect of GB virus C on laboratory markers and histological parameters among HIV-seropositive patients coinfected with HCV. Lower degrees of hepatic lesions were observed in the triple-infected patients, in comparison with HIV-HCV coinfected patients who were negative for GBV-C RNA.

O objetivo do estudo foi avaliar o efeito da infecção pelo vírus GB-C em marcadores laboratoriais e parâmetros histológicos em pacientes HIV soropositivos coinfectados com VHC. Menor grau de lesão hepática foi observado nos pacientes com tripla infecção em comparação aos pacientes coinfectados com VIH-VHC negativos para GBV-C RNA.

Evaluation of AST/ALT ratio as a marker of liver fibrosis and cirrhosis in patients with chronic hepatitis C

To assess the relation between serum AST/ALT ratio [AAR] and hepatic fibrosis and cirrhosis associated with chronic hepatitis C. A cross sectional study. The study was conducted in the department of medicine Military Hospital Rawalpindi from Sep 2004 - Feb 2005. Fifty diagnosed patients of chronic hepatitis C were selected whose liver biopsy was performed as a workup plan fro treatment. Serum AST/ALT ratio [AAR] was determined and degree of liver fibrosis noted on histopathology, using Knodell scoring system. ANOVA was applied to study the difference in AAR in different stages of liver fibrosis. The mean AAR was found to be higher with each increasing stage of liver fibrosis. The mean AAR in cirrhotics [1.34] was significantly higher compared to noncirrhotics [0.77], p<0.001. AAR >/= 1 had 100% sensitivity and negative predictive value in distinguishing cirrhotic from non-cirrhotic patients with 87% specificity and 45% positive predictive value. There is only a modest relation between AAR and early hepatic fibrosis [stages 1-3] in patients with chronic hepatitis C, while AAR is significantly higher in patients with advanced fibrosis/ cirrhosis

Clinical and histological characteristics of HIV and hepatitis C virus-co-infected patients in Brazil: a case series study / Características clínicas e histológicas de pacientes co-infectados pelo HIV e vírus da hepatite C no Brasil: estudo de uma série de casos

Hepatitis C virus (HCV) is an important factor contributing to morbidity and mortality in patients co-infected with HIV and HCV. In addition, liver biopsy is an important tool in the clinical management of these patients. Although liver biopsy is controversial, it is recommended for all patients. Data regarding the clinical and histological characteristics of these patients are scarce not only in Brazil but in Latin America as a whole. With the goal of better understanding these characteristics and the benefit of liver biopsy indications in this disease setting, data collected from 234 patients followed from 1996 to 2004 at Casa da AIDS, São Paulo, were analyzed. The following variables were extracted from the patients' medical files at the time of liver biopsy: sex, age, hepatitis C infection risk factors, hepatitis C infection duration, ALT levels, CD4+ T cell counts, history of alcohol abuse, history of antiretroviral therapy, HCV genotype, and liver histological alterations. CONCLUSIONS: 1 - Hepatitis C virus 1 and 3 were the most frequently identified genotypes and were diagnosed in 72 percent and 25.5 percent of cases respectively; 2 - Structural liver alterations were found to be mild or absent in 48.2 percent (113/234) of the analyzed patients; 3 - Fifty-three patients (23 percent) had normal ALT levels and 4 - Significant liver architectural changes (F2-F3) were evident in 22.5 percent of the patients with normal ALT levels.

A infecção causada pelo vírus da hepatite C (VHC) constitui importante causa de morbidade e mortalidade entre pacientes co-infectados pelo HIV e VHC. A indicação da realização de biópsia hepática nesses pacientes é controversa, podendo constituir importante ferramenta no manejo clínico desses pacientes. São escassos os dados relativos às características clínicas e histopatológicas dos pacientes co-infectados no Brasil e em toda a América Latina. Com o objetivo de analisar as características clínicas e histopatológicas em co-infectados e avaliar os benefícios da realização de biópsia hepática nesse grupo de pacientes, analisamos dados relativos a 234 pacientes acompanhados na Casa da AIDS, São Paulo, de 1996 a 2004. A partir de informações obtidas em prontuários, foram analisadas as seguintes variáveis relativas aos pacientes, coletadas à época da realização da biópsia hepática: gênero, idade, fatores de risco para a transmissão da hepatite C, tempo estimado de infecção pelo VHC, níveis séricos de ALT, contagem de células CD4, antecedentes relativos ao uso de álcool, antecedente de uso de terapia antiretroviral, genótipo de VHC e alterações histológicas obtidas através da biópsia hepática. CONCLUSÕES: 1- Os genótipos 1 e 3 foram os mais freqüentes nessa população, representando cerca de 72 por cento e 25,5 por cento dos casos analisados respectivamente; 2- Alterações estruturais hepáticas leves ou ausentes foram observadas em 48,2 por cento dos pacientes (113/234); 3- Cinqüenta e três pacientes (23 por cento) apresentaram níveis de ALT persistentemente normais; 4- Alterações estruturais significativas (F2-F3) foram observadas em 22,5 por cento entre pacientes com níveis de ALT persistentemente dentro da normalidade.

Macro-aspartate Aminotransferase in a Patient with Chronic Hepatitis C / 대한소화기학회지

Macroenzymes are normal enzymes complexed with an immunoglobulin (usually IgG, rarely IgA or IgM). A number of macroenzymes have been reported in the literature. Among them, macro-AST has been detected in diseases such as acute and chronic hepatitis, various malignancies and autoimmune diseases, but usually not associated with any specific disease. We report a case of elevated AST activity in serum due to marco-AST formation in a female with chronic hepatitis C which was confirmed by AST isoenzyme electrophoresis. To our knowledge, this is the first report of macro-AST occurred in chronic hepatitis patient in Korea.

Patients with chronic hepatitis C and normal transaminases

Hepatite C é uma doença de evolução progressiva. A maioria dos pacientes tem nível de ALT elevada e 25% apresentam níveis normais. Os com ALT normal geralmente são do gênero feminino e sem associação entre genótipo e gravidade de lesão hepática. O exame histopatológico mostra geralmente ausência de ou leve fibrose (cerca de 20% tem fibrose), embora cirrose já tenha sido relatada. Visando estimar a prevalência, características demográficas, genotípicas e anatomopatológicas em pacientes com ALT normal, realizamos um estudo de série com 68 casos com diagnóstico de hepatite C crônica. Os pacientes foram selecionados de janeiro de 1977 a abril de 2002. Encontrou-se uma prevalência de 13,8% (45,6% masculinos). A média de idade foi 39 +/- 13 anos. Predomínio de genótipo 1 (84,8%), seguido pelo 3 (8,5%) e 2 (6,7%). Encontramos fígado reacional em 52,9% das biópsias, atividade periportal de 0-1 em 85,3% e atividade periportal de 2-4 em 14,7%. Apresentaram atividade estrutural de 0 a 1 73,5% e 26,5% com atividade estrutural de 2 a 4, sendo que 29% da amostra apresentou APP > 2 e AE > 1; 73,5% não apresentaram esteatose. Nossos dados reforçam a necessidade de biópsia em pacientes com hepatite C e níveis de ALT normais.

Liver histological alterations in patients with chronic hepatitis C and normal ALT levels in the city of Salvador, Northeast-Brazil

Patients with chronic hepatitis C can have variable clinical progression. Hepatic histological alterations appear to be milder in asymptomatic subjects who have persistently normal ALT levels. AIMS: To evaluate the severity of histological liver alterations in blood donors with normal and elevated ALT levels. METHODS: We evaluated volunteer blood donors from the main blood bank of the city of Salvador-Brazil. Those who were anti-HCV positive were invited to participate in the study. Serum ALT and AST levels were measured at two time points, two months apart. Donors were divided into two groups: group I, individuals with ALT > 1.5 times the upper limit of normal in at least one time point and group II, individuals with normal or near normal ALT, at both time points RESULTS: We evaluated 30,232 blood donors and 528 (1.7 percent) of them were anti-HCV positive. Eighty-two attended our service and HCV infection was confirmed in 66 individuals. Male gender predominated in both groups; the mean age was 36 for group I, and 33 for group II. Tattoos and intravenous illicit drug use were frequently-encountered risk factors. Liver biopsy was done in 43 subjects. Among donors with elevated ALT, two (10 percent) had minimum alterations, while in group II normal liver or minimum alterations were observed in six (26 percent) subjects. Chronic hepatitis or cirrhosis was encountered in 35 (81 percent) individuals: three (15 percent) and five (21 percent) subjects had chronic hepatitis without inflammatory activity, 10 (50 percent) and 11 (48 percent) had minimum to moderate activity and five (25 percent) and one (4.3 percent) had cirrhosis, in groups I and II, respectively (P was not significant). CONCLUSIONS: The prevalence of anti-HCV among this population of volunteer blood donors was 1.7 percent, and these subjects had few liver histological alterations or chronic hepatitis and cirrhosis. Liver injury severity was significant in patients with elevated ALT, however subjects with normal levels may also present chronic hepatitis and cirrhosis.

Relationship between serum alanine aminotransferase levels and liver histology in chronic hepatitis C-infected patients.

BACKGROUND: The efficacy of serum alanine aminotransferase (ALT) levels in predicting the severity of hepatitis C virus (HCV) infection is unclear. OBJECTIVE: To compare histologic scoring of liver pathology in patients with chronic HCV infection with normal or elevated serum ALT. METHODS: Liver biopsies were performed in patients with HCV infection and either normal (n=40) or elevated (n=76) serum ALT levels, and scored for activity and fibrosis using the modified histological activity index. RESULTS: Patients with normal ALT and elevated ALT had similar demographic features. Median (range) histological activity grade was higher in patients with elevated ALT than in those with normal ALT (6 [1-15] vs. 5 [0-11], respectively; p=0.001), as was the fibrosis stage (2 [0-6] vs. 1[0-6]; p=0.02). Two patients with normal ALT and 4 with elevated ALT had liver cirrhosis. CONCLUSIONS: Among patients with chronic HCV infection, liver lesions are milder in those with normal serum ALT levels than those with abnormal ALT levels. However, some patients with normal ALT too may have advanced liver disease.

The Relationship of Histologic Activity to Serum ALT, HCV genotype and HCV RNA titers in Chronic Hepatitis C

It is unclear whether serum ALT levels or virological characteristics of hepatitis C virus(HCV) including HCV genotypes and HCV RNA titers, can reflect the degree of histological injury in chronic hepatitis C. The aim of this study was to investigate the relationships between the levels of histological damage and serum ALT levels, HCV genotypes or circulating HCV RNA titers in chronic hepatitis C. A total of 56 patients underwent liver biopsy and the histological activity index (HAI) was evaluated by Knodell's scoring system. HCV genotype by RT-nested PCR and HCV RNA quantitation by competitive RT-PCR were performed. Thirty-four patients were infected with HCV genotype 1b, 20 patients with genotype 2a, and 2 patients with undetermined type. Serum ALT levels were not positively correlated with total HAI score or HCV RNA titers, but showed a linear correlation with scores of piecemeal necrosis (r=0.32, p<0.05) and portal inflammation (r=0.27, p<0.05). HCV genotype had no significant correlation with RNA titers, HAI score or with serum ALT levels. Also, no statistical relationship was seen between HCV RNA titer and HAI score. These results suggest that liver histology is essential to evaluate the severity of chronic hepatitis C precisely.