Remission of long-term hepatic and renal disease induced by HCV after direct-acting antivirals therapy / Remissão de doença hepática e renal a longo prazo induzida pelo HCV após terapia antiviral de ação direta

Abstract In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.

Resumo Além da doença hepática, o vírus da hepatite C (HCV) tem sido associado a fenômenos autoimunes, como crioglobulinemia mista (CM) e glomerulonefrite (GN). Até recentemente, a hepatite crônica e as manifestações extra-hepáticas do HCV eram tratadas com peg-interferon com ribavirina; no entanto, essas drogas apresentavam baixa eficácia e induziam efeitos colaterais graves. Atualmente, a hepatite crônica por HCV tem sido tratada com antivirais de ação direta (AAD), mas estudos sobre a terapia com AAD para glomerulonefrite associada ao HCV são escassos. Aqui, descrevemos dois casos de glomerulonefrite associada ao HCV que foram tratados com AAD. Nestes dois casos, previamente tratados com peg-interferon e ribavirina, a terapia com sofosbuvir com simeprevir foi eficaz, sem efeitos colaterais significativos, e interrompeu a evolução de pelo menos 20 anos de doenças hepáticas e renais. Esses casos se juntam aos sete casos descritos anteriormente que foram tratados com essa associação de AAD.

Remission of long-term hepatic and renal disease induced by HCV after direct-acting antivirals therapy.

In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.

Association between the IFNA1 (-2Cx2192;T) Polymorphism and Increased IFNAR1 Gene Expression Levels in Chronic Hepatitis B Infection.

BACKGROUND: Single nucleotide polymorphisms and variant expression of some interferon (IFN) genes in individuals with chronic hepatitis B virus (HBV) infection might be related to higher viral load and disease complications. Thereby, whole blood samples of 208 patients (94 chronic HBV-infected patients and 114 HBV immune subjects) were analyzed to investigate the association between IFNG (-5Ax2192;G), IFNA1 (-2Cx2192;T) and IFNAR1 (-97Tx2192;C) genes with their expression levels and HBV viral load. METHODS: Genotyping was performed by high-resolution melting analysis with quantitative PCR (qPCR). Viral load quantification and gene expression were also carried out using qPCR. RESULTS: Chronic HBV-infected subjects with IFNA1 CT genotype and T allele were more likely to develop protection against HBV when compared to immune subjects with wild-type genotype (IFNA1 CT/CC: OR = 0.45, p = 0.01, and T/C allele: OR = 0.55; p < 0.01). In patients with IFNAR1 wild-type TT genotype, the expression levels of this receptor may explain the lower viral load (r(2) = 0.40; p = 0.04) and protection against chronic infection. CONCLUSIONS: These findings suggest that the polymorphic variant of IFNA1 (-2) gene is associated with chronic HBV infection, and high expression levels of the IFNAR1 gene and low levels of IFNA1 might contribute to the pathogenesis of chronic infection in these subjects.

Phylogenetic analysis and subgenotypic distribution of the hepatitis B virus in Recife, Brazil.

The analysis of the genomes of the hepatitis B virus in human hosts identifies phylogenetic variants called viral genotypes. Indeed, clinical and epidemiological observations suggest that differences in viral genotypes lead to distinct biological and clinical behaviors. The aim of this study was to evaluate the subgenotypic distribution and to conduct a phylogenetic analysis by Bayesian method of the hepatitis B virus (HBV) in patients from Recife, Brazil. From July 2009 to December 2010, 60 HBV infected patients were examined, 39 (65%) were males, whose mean age was 50years old. 33 (55%) were genotyped by obtaining and amplifying a 1306bp fragment comprising part of the DNA polymerase and the surface antigen of the HBV. The sequencing was performed on an ABI 3500 Automatic Sequencer and the consensus sequences were obtained by aligning both the sequenced strands (clockwise and anti-clockwise) using SEQUENCHER software. Phylogenetic analysis was conducted using the Markov Chain Monte Carlo simulation implemented by Bayesian evolutionary method by sampling trees. The following subgenotypic distribution was observed: A1 (79%), F2a (12%), A2 (6%) and F4 (3%) as was that those identified as subgenotype A1 were in the same cluster in the phylogenetic tree. In this study, the majority of patients presented the A1 subgenotype from the same viral strain. As per the distribution in the phylogenetic tree by Bayesian method, possibly this subgenotype was in the genetic make-up of Africans brought in centuries past to Brazil as slaves.

Distribution and molecular characterization of hepatitis C virus (HCV) genotypes in patients with chronic infection from Pernambuco State, Brazil.

Hepatitis C virus (HCV) is a public health problem throughout the world and 3% of the world population is infected with this virus. It is estimated that 3-4 millions individuals are being infected every year. It has been estimated that around 1.5% of Brazilian population is anti-HCV positive and the Northeast region showed the highest prevalence in Brazil. The aim of this study was to characterize HCV genotypes circulating in Pernambuco State (PE), Brazil, located in the Northeast region of the country. This study included 85 anti-HCV positive patients followed up between 2004 and 2011. For genotyping, a 380bp fragment of HCV RNA in the NS5B region was amplified by nested PCR. Phylogenetic analysis was conducted using Bayesian Markov chain Monte Carlo simulation (MCMC) using BEAST v.1.5.3. From 85 samples, 63 (74.1%) positive to NS5B fragment were successfully sequenced. Subtype 1b was the most prevalent in this population (42-66.7%), followed by 3a (16-25.4%), 1a (4-6.3%) and 2b (1-1.6%). Twelve (63.1%) and seven (36.9%) patients with HCV and schistosomiasis were infected with subtypes 1b and 3a, respectively. Brazil is a large country with many different population backgrounds; a large variation in the frequencies of HCV genotypes is predictable throughout its territory. This study reports HCV genotypes from Pernambuco State where subtype 1b was found to be the most prevalent. Phylogenetic analysis suggests the presence of the different HCV strains circulating within this population.

Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis.

OBJECTIVE: The present study was designed to analyze the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the hematocrit in patients with chronic kidney disease who were undergoing peritoneal dialysis or hemodialysis. PATIENTS AND METHODS: Twenty patients on peritoneal dialysis and 40 on hemodialysis were assessed, and the patients were matched according to the length of time that they had been on dialysis. Blood samples were collected (both before and after the session for those on hemodialysis) to measure the enzymes and the hematocrit. RESULTS: In the samples from the patients who were undergoing peritoneal dialysis, the aspartate and alanine aminotransferase levels were slightly higher compared with the samples collected from the patients before the hemodialysis session and slightly lower compared with the samples collected after the hemodialysis session. The levels of gamma-glutamyl transferase in the hemodialysis patients were slightly higher than the levels in the patients who were undergoing peritoneal dialysis. In addition, the levels of aminotransferases and gamma-glutamyl transferase that were collected before the hemodialysis session were significantly lower than the values collected after the session. The hematocrit levels were significantly lower in the patients who were on peritoneal dialysis compared with the patients on hemodialysis (both before and after the hemodialysis session), and the levels were also significantly lower before hemodialysis compared with after hemodialysis. CONCLUSION: The aminotransferase levels in the patients who were undergoing peritoneal dialysis were slightly higher compared with the samples collected before the hemodialysis session, whereas the aminotransferase levels were slightly lower compared with the samples collected after the session. The hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the samples collected after the hemodialysis session were significantly higher than the samples collected before the session. Taken together, the present data suggest that hemodilution could alter the serum levels of liver enzymes.

Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis

OBJECTIVE: The present study was designed to analyze the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the hematocrit in patients with chronic kidney disease who were undergoing peritoneal dialysis or hemodialysis. PATIENTS AND METHODS: Twenty patients on peritoneal dialysis and 40 on hemodialysis were assessed, and the patients were matched according to the length of time that they had been on dialysis. Blood samples were collected (both before and after the session for those on hemodialysis) to measure the enzymes and the hematocrit. RESULTS: In the samples from the patients who were undergoing peritoneal dialysis, the aspartate and alanine aminotransferase levels were slightly higher compared with the samples collected from the patients before the hemodialysis session and slightly lower compared with the samples collected after the hemodialysis session. The levels of gamma-glutamyl transferase in the hemodialysis patients were slightly higher than the levels in the patients who were undergoing peritoneal dialysis. In addition, the levels of aminotransferases and gamma-glutamyl transferase that were collected before the hemodialysis session were significantly lower than the values collected after the session. The hematocrit levels were significantly lower in the patients who were on peritoneal dialysis compared with the patients on hemodialysis (both before and after the hemodialysis session), and the levels were also significantly lower before hemodialysis compared with after hemodialysis. CONCLUSION: The aminotransferase levels in the patients who were undergoing peritoneal dialysis were slightly higher compared with the samples collected before the hemodialysis session, whereas the aminotransferase levels were slightly lower compared with the samples collected after the session. The hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the samples collected after the hemodialysis session were significantly higher than the samples collected before the session. Taken together, the present data suggest that hemodilution could alter the serum levels of liver enzymes.

[Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis]. / Níveis séricos de globulinas e a intensidade da fibrose hepática em pacientes com esquistossomose mansônica.

BACKGROUND: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS: Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols. RESULTS: The average age was 41 years old and 25 female patients (61%). Ten patients (24%) from 41 showed serum globulins levels raised and 21 (51%) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0.047), as well as those who showed standards D and E as compared to C (P = 0.011). There was no association between the globulins levels and the intensity of fibrosis. CONCLUSION: In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.

Níveis séricos de globulinas e a intensidade da fibrose hepática em pacientes com esquistossomose mansônica / Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis

CONTEXTO: Tem sido descrita correlação entre os níveis séricos de globulinas e o grau de fibrose hepática nas hepatites crônicas, mas não se encontram relatos na esquistossomose mansônica. OBJETIVO: Avaliar os níveis séricos de globulinas e de IgG, e a intensidade da fibrose periportal mensurada pela ultrassonografia em pacientes com esquistossomose mansônica. MÉTODOS: Entre novembro de 2006 e fevereiro de 2007, foram estudados 41 pacientes que preencheram ficha clínica e realizaram dosagens de IgG por imunoturbidimetria e de globulinas indiretamente pelo método do biureto. A ultrassonografia foi realizada por um único pesquisador, seguindo os protocolos do Cairo e de Niamey. RESULTADOS: A média de idade foi 41 anos, sendo 25 pacientes (61 por cento) do sexo feminino. Dez dos 41 pacientes (24 por cento) apresentaram elevação dos níveis séricos de globulinas e 21 (51 por cento) dos de IgG. Conforme a classificação do Cairo, 21 pacientes apresentaram grau I de fibrose, 18 grau II e 2 grau III, e pela classificação de Niamey 8 apresentavam padrão C, 20 D e 13 E. Aqueles com graus II ou III de fibrose tiveram maiores níveis de IgG do que os de grau I (P = 0,047), assim como aqueles que apresentaram padrões D e E em relação ao C (P = 0,011). Não houve associação entre os níveis de globulinas e o grau ou padrão de fibrose. CONCLUSÃO: Em pacientes com esquistossomose mansônica, observou-se elevação dos níveis séricos de IgG de acordo com a progressão do grau e do padrão de fibrose periportal, mas o mesmo não se observou com os níveis de globulinas.

BACKGROUND: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS: Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols. RESULTS: The average age was 41 years old and 25 female patients (61 percent). Ten patients (24 percent) from 41 showed serum globulins levels raised and 21 (51 percent) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0,047), as well as those who showed standards D and E as compared to C (P = 0,011). There was no association between the globulins levels and the intensity of fibrosis. CONCLUSION: In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.

Hepatitis G virus infection in patients with hepatocellular carcinoma in Recife, Brazil.

The evidence of a higher incidence of hepatitis G virus (HGV) infection among patients with hepatocellular carcinoma (HCC) and the relatively high prevalence of patients with primary liver carcinoma without apparent risk factors in our country motivated the present study, the objective of which was to determine the frequency of HGV-ribonucleic acid (RNA) in a series of patients with HCC. The diagnosis of HCC was established based on alpha-fetoprotein levels (>400 ng/ml), a compatible image and/or biopsy of the hepatic nodules. Markers of hepatitis B virus (HBV) (HBsAg and anti-HBc), hepatitis C virus (HCV) (anti-HCV) and HGV (HGV-RNA) were investigated using MEIA and RT-PCR (reverse transcriptase polymerase chain reaction). There were 32 patients evaluated, including 20 males (63%), with a mean age of 58 years. Twenty-eight (88%) patients were cirrhotic (Child-Pugh: A = 8 patients, B = 14, and C = 6) and 50% reported alcohol consumption. Serological hepatitis markers were detected in 26 (81%) patients, including HBV in 19 (59%), HCV in 12 (38%) and HGV in 9 (28%). Only one (3%) patient was positive for HGV alone. The prevalence of HGV in blood donors from the same region is 10%. The findings suggest that, despite the frequent detection of HGV markers in patients with HCC, isolated infection with this agent does not seem to be a relevant factor in the etiology of this carcinoma.

[Identification of the cutoff value for serum alanine aminotransferase in hepatitis C screening of patients with chronic renal failure on hemodialysis]. / Identificação de ponto de corte no nível sérico da alanina aminotransferase para rastreamento da hepatite C em pacientes com insuficiência renal crônica em hemodiálise.

The patients with chronic renal failure in hemodialysis present low levels of serum alanine aminotransferases. In order to establish a better cutoff value for ALT in hepatitis C screening of hemodialysis patients, the ALT levels were measured monthly in 235 patients, being excluded those that presented average above the upper limit of normality. The cutoff value was identified by construction of a ROC curve (receiver operating characteristic). Among 202 patients, 15 (7.4%) presented antibodies to hepatitis C virus (anti-HCV) and 187 (92.6%) were anti-HCV negative, with an ALT average of 0.7 and of 0.5 from ULN (p <0.0001), respectively. The better cutoff value for ALT was at 0.6 from ULN, with sensitivity of 67% and specificity of 75% in anti-HCV screening. These results suggest that ULN of ALT could be reduced for 60% from conventional limit, when we are evaluating patients with CRF in hemodialysis.

Identificaçäo de ponto de corte no nível sérico da alanina aminotransferase para rastreamento da hepatite C em pacientes com insuficiência renal crônica em hemodiálise / Identification of the cutoff value for serum alanine aminotransferase in hepatitis C screening of patients with chronic renal failure on hemodialysis

Pacientes com insuficiência renal crônica em hemodiálise apresentam níveis séricos mais baixos de alanina aminotransferase. Para estabelecer melhor ponto de corte nos níveis de ALT, no diagnóstico da hepatite C, avaliaram-se mensalmente, durante 6 meses os níveis desta enzima em 235 pacientes em hemodiálise, sendo excluídos aqueles que apresentassem média acima do limite superior da normalidade. O ponto de corte foi identificado através da construçäo de curva ROC. Entre 202 pacientes, 15 (7,4 por cento) apresentavam anti-VHC positivo e 187 (92,6 por cento) negativo, com média de ALT de 0,7 e de 0,5 do limite superior (p < 0,0001), respectivamente. O ponto de corte para ALT situou-se em 0,6 do limite superior, com sensibilidade de 67 por cento e especificidade de 75 por cento na identificaçäo do anti-VHC. Sugere-se que os limites superiores de normalidade da ALT sejam reduzidos para 60 por cento dos limites convencionais, quando se avaliam pacientes com IRC em hemodiálise.

Seroprevalence of Helicobacter pylori antibodies in medical students and residents in Recife, Brazil.

BACKGROUND: The epidemiology of Helicobacter pylori (Hp) still constitutes a relevant subject of investigation. GOAL: The goal of this study was to determine the seroprevalence rate of Hp antibodies in medical students and residents, and its relationship with medical practice, age, gender and parents' formal education level. STUDY: The study was carried out from March 1999 to March 2000, on a population of 1,119 medical students and residents, from which a randomized and stratified sample was drawn. Each stratum comprised students attending the basic training level, students attending the professional training level, and residents. Independent samples were calculated for each group, making a total of 405 subjects. Each participant was interviewed using a questionnaire. After the interview, serum samples were collected and stored at -20 degrees C for detecting IgG antibodies against Hp by an enzyme-linked immunosorbent assay. RESULTS: A 31.4% seroprevalence rate of Hp antibodies was observed, which significantly increased during the graduation course according to the medical practices, ranging from 23.4% in students up to 38.6% in residents. Seroprevalence rate increased according to the age (p = 0.002), where older individuals had spent more time in practical activities. Seroprevalence was higher in males and was smaller among those whose parents had a university degree. CONCLUSION: The seroprevalence rate of Hp antibodies amongst medical students and residents increases from the basic up to residence level, suggesting that contact with patients during clinical practice may constitute a risk factor for acquiring Hp infection.