PARK2 polymorphisms predict disease progression in patients infected with hepatitis C virus.

 Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer. The present study investigated the association of single nucleotide polymorphisms (SNPs) in the PARK2 gene with the development of hepatitis C virus (HCV) infection and its progression to severe liver diseases. MATERIAL AND METHODS: A total of 800 subjects, including 400 normal healthy subjects and 400 HCV-infected patients, were analyzed in this study. The patients were classified as chronic HCV patients (group I), patients with cirrhosis (group II) and patients with hepatocellular carcinoma (HCC) in the context of cirrhosis (group III). DNA was extracted and was genotyped for the SNPs rs10945859, rs2803085, rs2276201 and rs1931223. RESULTS: Among these SNPs, CT genotype of rs10945859 was found to have a significant association towards the clinical progression of chronic HCV infection to cirrhosis alone (OR = 1.850; 95% C. I. 1.115-3.069; p = 0.016) or cirrhosis and HCC (OR = 1.768; 95% C. I. 1.090-2.867; p value = 0.020). CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients.

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.

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.

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. .

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 (≥ 255 mL/day or ≥ 123 mg caffeine/day). According to caffeine intake, patients were divided into two groups (< or ≥ 123 mg 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 123 mg/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.

Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels.

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.

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.

Pegylated interferon-alpha2b plus ribavirin for the treatment of chronic hepatitis C virus genotype 4 infection in patients with normal serum ALT.

BACKGROUND: Approximately one-third of patients with chronic hepatitis C virus infection have persistently normal liver enzymes reflected by a normal serum alanine transaminase (ALT). Data with regards the efficacy and safety of treatment in patients chronically infected with Hepatitis C virus genotype 4 and normal serum ALT are limited. AIM: To evaluate the efficacy and safety of peginterferon alfa-2b plus ribavirin combination therapy in this population. MATERIAL AND METHODS: Twenty-two patients with chronic hepatitis C virus genotype 4 infection were enrolled in an open-labeled, uncontrolled pilot study. All patients had biopsy proven chronic hepatitis and persistently normal serum ALT levels. Patients were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 µg/kg body weight once per week plus oral ribavirin (15 mg/kg/day) for 48 weeks. Patients were followed for 24 weeks post-treatment. RESULTS: Sixteen patients out of twenty two completed the study (9 [40.9%] females, mean age 43.8 years). The ALT level were normal in all patients, with a mean of 38.6 U/L. Sustained viral response was achieved in 13 patients (59%), 4 patients (18.1%) were non-responders and 2 patients (9%) relapsed while 1 patient had a viral breakthrough during treatment. Two patients (9%) discontinued the treatment because of adverse events. CONCLUSIONS: Combination therapy of pegylated interferon-alpha2b and ribavirin is safe and resulted in a sustained virological response in a significant number of patients with chronic Hepatitis C, genotype 4, and persistently normal serum ALT.

No association of promoter variations of HMOX1 and UGT1A1 genes with liver injury in chronic hepatitis C.

BACKGROUND: Heme oxygenase-1 (HMOX1) and bilirubin UDP-glucuronosyltransferase (UGT1A1), both enzymes involved in bilirubin homeostasis, play an important role in oxidative stress defense. OBJECTIVE: To assess the effect of promoter variations of HMOX1 and UGT1A1 genes on the progression of fibrosis in patients chronically infected with the hepatitis C virus (HCV). MATERIAL AND METHODS: The study was performed on146 chronic HCV infection patients, plus 146 age- and sex-matched healthy subjects. The (GT)n and (TA)n dinucleotide variations in HMOX1 and UGT1A1 gene promoters, respectively, were determined by fragment analysis in all subjects. RESULTS: No differences were found in the frequencies of each particular allele of both genes, between HCV patients and a control group (p > 0.05). Furthermore, no association was detected (p > 0.05) between either the HMOX1 or the UGT1A1 promoter variants and the individual histological stages of liver disease in the HCV positive patients. Finally, no differences in the HMOX1 and UGT1A1 genotype prevalence rates were found between pre-cirrhotic and cirrhotic patients (p > 0.05). CONCLUSION: Based on our data, microsatellite variations in the HMOX1 and UGT1A1 genes are not likely to protect from progression of liver disease in patients with chronic hepatitis C.

Hormone therapy in Brazilian postmenopausal women with chronic hepatitis C: a pilot study.

OBJECTIVE: To evaluate liver function and hemostatic parameters in postmenopausal women who have chronic infection with the hepatitis C virus and climacteric symptoms and are undergoing hormone therapy (HT) (standard dose of transdermal continuous combined hormone therapy). DESIGN: Fifty out of 336 postmenopausal patients with chronic infection with the hepatitis C virus were selected. The non-inclusion criteria were other chronic or systemic liver diseases, severe vascular diseases, autoimmune diseases or malignant tumors. The patients were randomized into two groups: the HT group with 25 patients to be given transdermal hormone therapy (50 microg estradiol plus 170 microg norethisterone/day) and the control group with the other 25 patients (no medication). Hepatic tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total alkaline phosphatase, albumin, serum bilirubin) and hemostatic parameters (prothrombin time, factor V, fibrinogen) were evaluated at baseline and at 1, 4, 7 and 9 months of treatment. RESULTS: No significant changes in parameters were found in the comparison between the treated group and the controls, except for a decrease in total alkaline phosphatase (p = 0.002), presumably due to changes in bone remodelling. CONCLUSIONS: There were no changes in liver function after a 9-month treatment with transdermal estradiol plus norethisterone in symptomatic postmenopausal patients with hepatitis C.

Analysis of GB virus C infection among HIV-HCV coinfected patients.

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.

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.

Clinical and histological characteristics of HIV and hepatitis C virus-co-infected patients in Brazil: a case series study.

UNLABELLED: 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% and 25.5% of cases respectively; 2 - Structural liver alterations were found to be mild or absent in 48.2% (113/234) of the analyzed patients; 3 - Fifty-three patients (23%) had normal ALT levels and 4 - Significant liver architectural changes (F2-F3) were evident in 22.5% of the patients with normal ALT levels.

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.

The results of a randomized trial looking at 24 weeks vs 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and ribavirin combination therapy in patients with chronic hepatitis C genotype 1.

Peginterferon-alpha plus ribavirin is the most effective therapy for chronic hepatitis C. This study was designed to evaluate the effect of peginterferon alpha-2a (40 kDa) plus ribavirin on sustained virological response (SVR) when administered for 24 vs 48 weeks in genotype 1 naïve patients. One hundred and seventeen patients were enrolled in this controlled trial. Genotype 1 patients were randomized to 24 weeks treatment vs 48 weeks treatment. Genotype non-1 patients received 24 weeks treatment as an observational group. Outcomes were SVR (defined by hepatitis C virus-RNA-negative at week 24 of follow-up) and tolerability across the study period. The end-of-treatment response was 59% for genotype 1 (24 weeks treatment), 80% for genotype 1 (48 weeks treatment) and 92% for genotype non-1 (24 weeks treatment). The end-of-follow-up response was 19% (95% confidence interval (CI): 7.2-36.4) (genotype 1, 24 weeks) and 48% (95% CI: 30.2-66.9; P = 0.0175) (genotype 1, 48 weeks). Among genotype non-1, SVR was 76% (95% CI: 62.3-86.5). There were no unexpected adverse events. Almost half of the genotype 1 patients achieved an SVR after 48 weeks treatment with peginterferon alpha-2a (40 kDa) and low-dose ribavirin and confirmed that they should be treated for 48 weeks. Safety profile was acceptable.

Efficacy and tolerance of interferon-alpha in the treatment of chronic hepatitis C in end-stage renal disease patients on hemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) show a high prevalence of hepatitis C, with a negative impact on the survival on hemodialysis and after renal transplantation. We evaluated the efficacy and tolerance of interferon-alpha (IFN-alpha) in HCV-infected ESRD patients on dialysis. METHODS: Forty-six HCV-RNA-positive ESRD patients were studied. IFN-alpha regimen consisted of 3 million units three times a week for 12 months, and the patients were followed up for 6 months. End-of-treatment, and sustained biochemical and virological responses were evaluated and tolerance was assessed monthly. RESULTS: A sustained virological response (SVR) was observed in 10/46 patients (22%) and in 10/29 who completed the treatment (34%). Alanine aminotransferase was elevated in 63% of the patients at the beginning of the study and returned to normal levels within the first month in all patients with SVR. Treatment was discontinued because of side effects in 11/46 patients (24%) and six patients (13%) were lost to follow-up. CONCLUSIONS: IFN-alpha monotherapy for hepatitis C in dialysis patients shows a high frequency of adverse effects. However, the SVR is high (34%) in patients who complete treatment, emphasizing the importance of careful selection and close follow-up in order to minimize and control possible side effects.

Patients with chronic hepatitis C and normal transaminases.

Hepatitis C virus infection evolves progressively persisting in the majority of patients (85%). Most patients have high ALT (alanine aminotransferase) levels and approximately 25% normal ALT. The latter are usually female and there is no association between genotype and severity of hepatic lesion. Histologic analysis usually shows small lesion and absence or low amount of fibrosis, despite cirrhosis having been reported. Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we have carried out a study of 68 chronic hepatitis C patients between January 1997 and April 2000. There was a prevalence of 13.8% chronic hepatitis C patients with normal ALT levels, 45.6% of which were male and 54.4% female, the mean age being 38 +/- 13 years. We found a predominance of genotype 1 in 84.7% of the patients, genotype 2 in 6.8% and genotype 3 in 10.7%. In 52.9% of the cases liver biopsies revealed liver reaction, periportal activity score 0-1 was observed in 85.3% of the patients and score 2-4 was seen in 14.7%. Structural activity score 0-1 was seen in 73.5% of the patients and score 2-4 in 26.5% of them. Periportal activity > or = 2 and structural activity > 1 was seen in 29%, but steatosis was not seen in 73.5%. Our results suggest the need to revisit for liver biopsy practice in patients with chronic hepatitis C and normal transaminases.

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.