Association of serum levels of C-reactive protein with CRP-717 T/C polymorphism and viremia in HCV and HBV carriers

Abstract INTRODUCTION: The present study investigated the association of the rs2794521 polymorphism in the CRP gene in individuals with chronic hepatitis B and C, correlating it with markers of hepatic inflammation, fibrosis scores, viral load, and plasma protein levels. METHODS: The study analyzed 185 blood samples obtained from patients with hepatitis B (n=74) and hepatitis C (n=111) and 300 samples from healthy donors. Genotyping was performed by real-time polymerase chain reaction, and protein levels were quantified using the automated immunoturbidimetric method. RESULTS: The TT genotype was the most frequent in all studied groups and was associated with higher plasma levels of the protein but not with the progression of liver disease. Low levels of C-reactive protein were associated with increased viremia and scores indicative of severe fibrosis and cirrhosis. CONCLUSIONS: The present results demonstrated a close relationship between the ability of the virus to replicate and cause liver damage and low serum concentrations of C-reactive protein. Future research may determine if these results can be interpreted as a possible form of escape for the virus by decreasing its action as an opsonin and decreasing phagocytosis, which are functions of C-reactive protein in the immune response.

Accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C

OBJECTIVES: Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. METHODS: We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. RESULTS: A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION: Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.

Is there an association between vitamin D and liver fibrosis in patients with chronic hepatitis C? / Existe associação entre vitamina D e fibrose hepática em pacientes com hepatite C crônica?

ABSTRACT BACKGROUND Vitamin D is known for its immunomodulatory, anti-inflammatory and antifibrotic properties, which are quite relevant in the pathogenesis and treatment of many causes of chronic liver disease. OBJECTIVE This study aimed to evaluate the association between serum vitamin D levels and the histopathological findings in patients with chronic hepatitis C virus infection. METHODS Cross-sectional study composed of patients with chronic hepatitis C. All patients underwent vitamin D 25 dosage and anthropometric data analysis. Liver biopsy was performed in a maximum 36-month period before inclusion in the study. RESULTS Of the 74 patients included in the study, 45 (60.8%) were women, mean age was 57.03±9.24 years, and 63 (85.1%) were white. No association was observed between the serum levels of vitamin D and inflammatory activity (P=0.699) nor with the degree of liver fibrosis (P=0.269). CONCLUSION In this study, no association was observed between vitamin D and inflammatory activity, as well as the degree of liver fibrosis, in patients with chronic hepatitis C.

RESUMO CONTEXTO A vitamina D é conhecida por possuir propriedades imunomoduladoras, anti-inflamatórias e antifibróticas, relevantes na patogênese e tratamento de muitas causas de doença hepática crônica. OBJETIVO Este estudo tem como objetivo avaliar a associação entre os níveis séricos de vitamina D e os achados histopatológicos em pacientes com infecção crônica do vírus da hepatite C. MÉTODOS Estudo transversal, composto por pacientes com hepatite C crônica. Todos os pacientes foram submetidos à dosagem de vitamina D 25 e análise de dados antropométricos. A biópsia hepática foi realizada em um período máximo de 36 meses antes da inclusão no estudo. RESULTADOS Dos 74 pacientes incluídos no estudo, 45 (60,8%) eram mulheres, média de idade de 57,03±9,24 anos e 63 (85,1%) eram brancos. Não foi observada associação entre os níveis séricos de vitamina D e atividade inflamatória (P=0,699), nem com o grau de fibrose hepática (P=0,269). CONCLUSÃO No presente estudo, não foi observada associação entre a vitamina D e a atividade inflamatória, bem como com o grau de fibrose hepática, em pacientes com hepatite C crônica.

Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C

Abstract: INTRODUCTION: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. METHODS: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. RESULTS: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with early-stage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB. CONCLUSIONS: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.

Trace elements in plasma and nutritional assessment in patients with compensated cirrhosis on a liver transplant list

ABSTRACT Background - In chronic liver disease, trace element levels in plasma are usually low. However, the specific cause and functional implications of this abnormality are yet not well understood. These element levels may decrease as a result of abnormal liver function in patients with cirrhosis and/or malnutrition. Objective - To evaluate the nutritional status and the profile of trace elements in plasma of patients with cirrhosis on a liver transplant list and to correlate them with disease severity. Methods - This cross-sectional study evaluated 31 male patients diagnosed with compensated liver cirrhosis on a waiting list for liver transplant. Nutritional status was objectively evaluated through anthropometry using Mendenhall score and Blackburn classification, subjectively through the Detsky questionnaire and severity of the disease by MELD and CTP score. Trace elements (Zn, Se, Cu, Ca, Fe, Mg and Mn) in plasma were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis was performed using Mann-Whitney test. Results - According to the nutritional assessment 19 (61.3%) were malnourished and 12 (38.7%) were overweight. Regarding disease severity 12 (39%) were classified as Child A, 17 (55%), Child B and 2 (6%) Child C, with 46.9% of patients with MELD score >17. The trace element analysis indicated that 31 (100%) had Mn levels above the reference range, 23 (74.2%) low levels of Cu, 29 (93.5%) with deficiency of Se, and 31 (100%) low levels of Ca and Mg. Disease severity did not show statistical difference between the studied trace elements, in contrast to the nutritional status, in which the malnourished group showed higher levels of Mn (P=0.01) and Fe (P=0.01) and low levels of Zn (P=0.03) when compared to the overweight group. Conclusion - The results showed that the trace elements in plasma are altered in chronic liver disease; without significant correlation to disease severity, but correlated to nutritional status. Malnutrition is present in the patients studied, nonetheless a new scenario with an increase in the prevalence of overweight was verified regardless of the degree of hepatic decompensation.

RESUMO Contexto - Na doença hepática crônica os níveis plasmáticos de oligoelementos normalmente apresentam-se baixos, mas a causa específica e implicações funcionais desta anormalidade ainda não estão bem esclarecidas. Estes elementos podem estar diminuídos em consequência da função hepática alterada em pacientes com cirrose e/ou desnutrição. Objetivo - Avaliar o estado nutricional e o perfil de oligoelementos plasmáticos dos pacientes com cirrose hepática em lista para transplante e correlacionar com a gravidade da doença. Métodos - Trata-se de um estudo transversal, no qual foram avaliados 31 pacientes do sexo masculino com diagnóstico de cirrose hepática compensada em lista de espera para transplante de fígado. O estado nutricional foi avaliado objetivamente por medidas antropométricas através do escore de Mendenhall e classificado segundo Blackburn, subjetivamente por um questionário sistematizado por Detsky e a gravidade da doença pelo escore MELD e CTP. Os oligoelementos plasmáticos (Zn, Se, Cu, Ca, Fe, Mg e Mn) foram analisados pelo método de espectrometria de massas com fonte de plasma indutivamente acoplado (ICP-MS). Para análise estatística foi utilizado o Teste de Mann-Whitney. Resultados - De acordo com a avaliação nutricional 19 (61,3%) estavam com desnutrição e 12 (38,7%) com sobrepeso. Em relação à gravidade da doença 12 (39%) foram classificados como Child A, 17 (55%), Child B e 2 (6%) Child C, sendo 46,9% dos pacientes com o escore MELD >17. Na análise dos oligoelementos 31 (100%) apresentaram níveis de Mn acima dos valores de referência, 23 (74,2%) níveis baixos de Cu, 29 (93,5%) com deficiência de Se, e 31 (100%) níveis baixos de Ca e Mg. Em relação à gravidade da doença não houve diferença estatística entre os oligoelementos estudados, já em relação ao estado nutricional o grupo desnutrido apresentou níveis maiores de Mn (P=0,01) e Fe (P=0,01) e níveis diminuídos de Zn (P=0,03) quando comparado ao grupo sobrepeso. Conclusão - Os resultados mostraram que os oligoelementos estão alterados na doença hepática crônica, sem associação significativa com a gravidade da doença, mas sim com o estado nutricional. A desnutrição está presente nos pacientes estudados, porém um novo cenário com aumento na prevalência de sobrepeso foi verificado independente do grau de descompensação hepática.

Correlation beteeen platelet count and both livr fibrosis and spleen diameter in patients with schistosomiasis mansnni / Correlação entre o número de plaquetas e o grau de fibrose hepática e o tamanho do baço em pacientes com Esquistossomose mansoni

Context Studies have described the correlation between platelet count and the stages of fibrosis in chronic viral hepatitis, but few publications have studied this correlation in Schistosomiasis mansoni. Objectives Therefore, this study aimed to correlate platelet count with both the periportal fibrosis pattern and spleen diameter evaluated by ultrasound exam in patients with Schistosomiasis mansoni. Methods Patients with Schistosomiasis mansoni were evaluated by abdominal ultrasound by a single examiner for the determination of periportal fibrosis pattern (Niamey classification) and spleen diameter. Platelet counts were performed in an automated cell counter. Results One hundred eighty-seven patients with Schistosomiasis mansoni (mean age: 50.2 years) were included in the study, 114 of whom (61%) were women. Based on the Niamey classification, the ultrasound analysis revealed that 37, 64, 64 and 22 patients exhibited patterns C, D, E and F, respectively. In these four groups, the mean number of platelets was 264, 196, 127 and 103 x 109/L and mean spleen diameter was 9.2, 11.9, 14.9 and 16.2 centimeters, respectively. A reduction in platelet count was significantly associated with both the progression of the periportal fibrosis and the increase in spleen size. Conclusions Platelet count in patients with Schistosomiasis mansoni was inversely correlated with the severity of periportal fibrosis and spleen diameter. .

Contexto Estudos vem descrevendo correlação entre o número de plaquetas e o grau de fibrose hepática na hepatite viral crônica, mas poucas publicações estudaram esta correlação em pacientes com Esquistossomose mansoni. Objetivos Correlacionar a contagem de plaquetas com o padrão de fibrose periportal e com o diâmetro do baço, avaliados pela ultrassonografia em pacientes com Esquistossomose mansoni. Métodos Os pacientes com Esquistossomose mansoni foram avaliados pela ultrassonografia abdominal, por um único examinador, para determinação do padrão de fibrose periportal (classificação de Niamey) e do diâmetro do baço. A contagem de plaquetas foi realizada em contador automatizado. Resultados Cento e oitenta e sete pacientes com Esquistossomose mansoni com média de idade de 50,2 anos foram incluídos no estudo, 114 (61%) dos quais eram mulheres. De acordo com a classificação de Niamey, a ultrassonografia revelou que 37, 64, 64 e 22 pacientes exibiam padrões C, D, E e F, respectivamente. Nestes quatro grupos, o número médio de plaquetas foi 264, 196, 127 e 103 x 109/L, respectivamente, e o diâmetro médio do baço foi 9,2, 11,9, 14,9 e 16,2 centímetros, respectivamente. Observou-se, portanto, redução significativa na contagem de plaquetas associada à progressão da fibrose periportal e ao aumento do tamanho do baço. Conclusões Neste estudo verificou-se que a contagem de plaquetas foi inversamente correlacionada com o padrão de fibrose periportal, como também com o diâmetro do baço nos pacientes com Esquistossomose mansoni. .

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV) paediatric patients (8-14 years) were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA), procollagen type III amino-terminal peptide (PIIINP) and osteopontin (OPN), were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05). The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

Etiología de la hipertensión prta: primera parte / Etiology of prta hypertension: part one

Un obstáculo al flujo venoso porta con aumento de la resistencia periférica puede presentarse en una gran diversidad de entidades patológicas y a través de diferentes mecanismos fisiopatógenos. Cuando el hígado recibe un caudal mayor del habitual se desencadena una serie de mecanismos adaptativos entre los cuales está el de vasoconstricción por estimulación simpática. La causa más frecuente de obstrucción intraluminal es la trombosis. Una serie de alteraciones estructurales que deforman la anatomía de la red venosa puede ser causa de hipertensión porta (HTP). Independientemente de la causa de la cirrosis el resultado final en la arquitectura hepática es la disorsión del lobulillo por el depósito de tejido fibroso y la regeneración de los hepatocitos. Algunos procesos mieloproliferativos como son las leucemias y los linfomas, las histiocitosis X, la sarcaidosis, la hepatitis crónica, etcétera, pueden causar HTP. En los niños los tumores hepáticos suelen expresarse clínicamente por masas palpables.

One obstacle to portal venous flow with increased peripheral resistance may occur in a variety of pathological conditions and through different pathophysiologic mechanisms. When the liver is a higher flow rate than usual triggers a series of adaptive mechanisms among which is the vasoconstriction by sympathetic stimulation. The most common cause of intraluminal obstruction is thrombosis. A series of structural changes that distort the anatomy of the venous network may cause pulmonary hypertension. Regardless of the cause of cirrhosis, the final result in the hepatic architecture of the lobule is distortion by deposition of fibrous tissue and regeneration of h e p a t o c y t e s . S ome p r o c e s s e s s u c h a s myeloproliferative leukemia and lymphomas, histiocytosis X, sarcaidosis, chronic hepatitis, etc. can cause portal hypertension. In children liver tumors are often expressed clinically as palpable masses.

Hyaluronic acid in the evaluation of liver fibrosis in patients with hepatitis C on haemodialysis

BACKGROUND: This study evaluated the role of HA as a marker of liver fibrosis in patients with hepatitis C on haemodialysis. METHODS: This is a cross-sectional study in which 52 patients were divided into two groups: Group 1: patients with hepatitis C and end-stage renal disease (ESRD) undergoing haemodialysis (n = 23); and Group 2: patients with hepatitis C without ESRD (n = 29). Plasma levels of HA were associated with histological data of the samples obtained by liver biopsy and classified by METAVIR group scoring system. RESULTS: Higher plasma levels were significantly correlated to significant liver fibrosis (METAVIR > F2). In Group 1, the HA cutoff to discriminate significant fibrosis was 984.8 ng/mL, with accuracy, sensitivity and specificity of 80.8 percent, 83.0 percent, and 70.0 percent, respectively. In Group 2, the HA cutoff was 222.3 ng/mL, with accuracy, sensitivity and specificity of 74.5 percent, 70.0 percent, and 94.0 percent, respectively. CONCLUSION: HA was an accurate noninvasive marker in predicting significant fibrosis in patients with hepatitis C on haemodialysis.

Soluble inflammatory markers as predictors of hepatocellular damage and therapeutic response in chronic hepatitis C

Hepatitis C is an important burden worldwide being an important cause of cirrhosis and liver cancer in different parts of the world. Host immune response, especially T helper type 1 (Th1) cell-mediated, seems to play an important role in disease progression but is also crucial for viral elimination following specific therapy. Immune activation can be evaluated using peripheral levels of different cytokines, such as different chemokines (e.g. CCL5, CXCL10) and tumor necrosis factor alpha (TNF-á), and their soluble receptors (e.g. soluble TNF-á receptors 1 (sTNF-R1) and 2 (sTNF-R2). This review article focuses on the potential use of peripheral inflammatory markers as predictors of liver histological changes and therapeutic response among patients with chronic hepatitis C.

Relationship between serum concetrations of type III procollagen, hyluronic acid and histopathological findings in the liver of HCV-positive blood donors

BACKGROUND: Serologic markers have been proposed for monitoring hepatic fibrosis in chronic liver disease. Among fibrosis markers, type III procollagen (PIIIP) and hyaluronic acid have been studied in these patients. AIM: To evaluate the association between these serum markers with histological findings. METHODS: A prospective cross-sectional study was carried out with HCV-positive blood donors. The studied population included men and women whose age ranged from 18 to 60 years, with elevated liver function tests [ALT levels > 1.5 times the normal value and alterations of two or more of the following: any changes in the levels of ALT, aspartate aminotransferase, conjugated bilirrubin, gammaglobulin, gammaglutamyltranspeptidase, albumin, platelet count; alkaline phosphatase levels >1.5 times the normal value, or prothrombin time below 70 percent and above 60 percent]. Fourty-nine patients were submitted to liver biopsy, blood analysis of PIIIP, hyaluronic acid, besides liver function tests. RESULTS: Liver function tests were not associated with tissular fibrosis, as assessed by ALT (>1.5 times above normal, fibrosis risk=18.8 percent; <1.5 times, 11.8 percent). Elevated PIIIP was correlated with 66.7 percent chance of fibrosis, whereas normal levels, 9.3 percent. Hyaluronic acid, when elevated, gave a chance of 33.3 percent of fibrosis; when normal, 12.5 percent. CONCLUSION: There was no association between liver function tests, hyaluronic acid and fibrosis. However, PIIIP was related with liver fibrosis. Maybe, this marker should be useful to assess fibrosis in patients with chronic hepatitis C.

RACIONAL: Marcadores sorológicos têm sido propostos para monitorar fibrose hepática em doença crônica do fígado. Dentre os marcadores de fibrose, ácido hialurônico e procolágeno tipo III têm sido estudados nestes pacientes. OBJETIVO: Avaliar a associação de marcadores séricos de fibrose com achados histológicos. MÉTODOS: Foi realizado estudo transversal prospectivo em doadores de sangue anti-HCV positivos. A população estudada incluiu homens e mulheres com idade entre 18-60 anos com provas de função hepática alteradas (níveis de alanina aminotransferase >1.5 vezes do normal e alterações de dois ou mais dos seguintes: qualquer alteração nos níveis de alanina aminotransferase, aspartato aminotransferase, bilirrubina conjugada, gamaglobulina, gamaglutamiltranspeptidase, albumina, plaquetas, níveis de fosfatase alcalina >1,5 vezes o valor normal, tempo de protrombina abaixo de 70 por cento e acima de 60 por cento). Quarenta e nove pacientes foram submetidos a biopsia hepática e coleta de sangue para análise de procolágeno tipo III, ácido hialurônico e provas funcionais hepáticas. RESULTADOS: Não houve relação entre elevação de provas de função hepática e a presença de fibrose - ALT (>1,5 vezes acima do normal, risco de fibrose = 18,8 por cento; <1,5 vezes, 11,8 por cento). Procolágeno tipo III elevado foi correlacionado com 66,7 por cento chances de fibrose, enquanto nível normal, 9,3 por cento. Ácido hialurônico, quando elevado, demonstrou chance de 33,3 por cento de fibrose; quando normal, 12.5 por cento. CONCLUSÕES: Não houve associação entre provas de função hepática, ácido hialurônico e fibrose, mas houve entre esta última e procolágeno tipo III. Talvez este marcador possa ser útil para avaliar fibrose em pacientes com hepatite crônica pelo vírus C.

Correlação entre a contagem de plaquetas no sangue e o gradiente de pressão venosa hepática em pacientes cirróticos / Correlation between platelet blood levels and the hepatic venous pressure gradient among patients with cirrhosis

RACIONAL: A medida do gradiente de pressão venosa hepática é o método mais utilizado para a avaliação da pressão portal. Mais recentemente, a contagem de plaquetas no sangue tem sido apontada como um marcador não-invasivo da presença de hipertensão portal. OBJETIVO: Correlacionar a contagem de plaquetas com os valores do gradiente de pressão venosa hepática em uma população de pacientes cirróticos. PACIENTES E MÉTODOS: Foram estudados 83 pacientes com hepatopatia crônica que realizaram estudo hemodinâmico hepático, em período de 6 anos. Os pacientes foram divididos em grupos conforme a classificação de Child-Pugh e todos realizaram endoscopia digestiva alta para constatar a presença de varizes de esôfago, assim como tiveram a contagem sérica de plaquetas determinada. RESULTADOS: O número de plaquetas variou entre 45.000/mm³ e 389.000/mm³, com média 104.099 e desvio-padrão 58.776. O gradiente de pressão venosa apresentou média igual a 15,2 mm Hg e desvio-padrão igual a 6,4 mm Hg, variando de 1 a 29 mm Hg. Realizou-se regressão linear simples para verificar a correlação entre o gradiente de pressão venosa e o número de plaquetas, o que permitiu constatar fraca correlação entre ambos. Embora se tenha observado menor número de plaquetas, à medida que o calibre das varizes aumentava e nos pacientes com maior grau de disfunção hepatocelular - medida pela classificação de Child-Pugh - não se encontrou significância estatística. CONCLUSÃO: A despeito de não haver demonstrado correlação estatística entre o número de plaquetas com o gradiente de pressão venosa hepática e o grau de disfunção hepatocelular, pelas tendências observadas, acredita-se que ambos os fatores podem estar implicados na patogenia da plaquetopenia em pacientes cirróticos.