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@#ObjectiveTo investigate the value of the four serum liver fibrosis markers, i.e., procollagen Ⅲ (PCⅢ), type Ⅳ collagen (C-Ⅳ), hyaluronic acid (HA), and laminin (LN), in the diagnosis of liver fibrosis. MethodsA retrospective analysis was performed for the clinical data of 155 patients with liver cirrhosis, 42 patients with liver cirrhosis and primary hepatic carcinoma (PHC), and 150 patients with chronic hepatitis who were admitted to The First Affiliated Hospital of Southwest Medical University from April 2018 to April 2019, and 73 healthy individuals who underwent physical examination were also enrolled. The serum levels of the above four markers were measured for all subjects and were compared between groups. The receiver operating characteristic (ROC) curve was plotted to compare the diagnostic efficiency of these four markers. The t-test was used for normally distributed continuous data between two groups; the Kruskal-Wallis H rank sum test was used for comparison of non-normally distributed continuous data between multiple groups, and the Wilcoxon rank-sum test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. ResultsThe patients with liver cirrhosis and the patients with liver cirrhosis and PHC had significantly higher serum levels and positive rates of the four markers than the patients with chronic hepatitis and the healthy subjects (all P＜0.05). while there were no significant differences in the levels and positive rates of PCⅢ, C-Ⅳ, and HA between the patients with liver cirrhosis and the patients with liver cirrhosis and PHC (all P＞0.05). Although the patients with liver cirrhosis and PHC had a significantly higher serum level of LN than those with liver cirrhosis (P＜0.05), there was no significant difference in the positive rate of LN between the two groups (P＞0.05). The patients with alcoholic cirrhosis had significantly higher serum levels of PCⅢ and C-Ⅳ than those with viral cirrhosis, viral-alcoholic cirrhosis, or autoimmune cirrhosis (all P＜0.05), the patients with autoimmune cirrhosis, alcoholic cirrhosis, or viral-alcoholic cirrhosis had a significantly higher serum level of HA than those with viral cirrhosis (all P＜0.05), and the patients with viral-alcoholic cirrhosis, viral cirrhosis, or alcoholic cirrhosis had a significantly higher serum level of LN than those autoimmune(all P＜0.05). The patients with chronic hepatitis of different etiologies had significantly lower serum levels and positive rates of these four markers than those with liver cirrhosis (all P＜0.05), and the patients with severe viral hepatitis had significantly higher positive rates of the four markers than the other patients (all P＜0.05). PCⅢ, C-IV, HA, LN, and the combination of these four markers had an area under the ROC curve of 0.836, 0.832, 0895, 0.808, and 0.901, respectively, in the diagnosis of liver cirrhosis. HA had a significantly larger area under the ROC curve than PCⅢ, C-Ⅳ, and LN (all P＜0.05), while there was no significant difference between HA and the combination of these four markers (P＞0.05). ConclusionHA has a high diagnostic efficiency in liver fibrosis.
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ABSTRACT BACKGROUND: Fibrosis are common structural hepatic change in patients with chronic hepatitis. Liver biopsy is the gold standard for determining the extent of liver fibrosis. Considering the technical difficulties and cost, improvements in non-invasive screening tools are greatly needed. Bioimpedance have been shown to be safe to evaluate tissue fibrosis. OBJECTIVE: To assess the utility of using monofrequential bipolar bioimpedance for the detection of severity of liver fibrosis consistent with chronic viral hepatitis C infections. METHODS: One hundred and ten patients were studied prospectively and formed two groups according to the lab tests results for the detection of HCV, ALT and AST: Group 1 Control (n=50 healthy patients with HCV negative and with ALT and AST values within the normal clinical range) and Group 2 Positive (n=60 patients positive for anti-HCV positive) which were biopsied. All patients underwent an examination with an Electro Sensor Complex, bioimpedance technology. To compare the groups 1 and 2, the ROC curves was used to determine the specificity and sensitivity of the bioimpedance to detect liver fibrosis. To identify liver fibrosis severity the Group 2 Positive was subdivided according to the liver biopsy results (Metavir fibrosis score) into: Sub Group 2A (F0-F1 n=25) - patients without or with minimal portal fibrosis and Sub Group 2B (F3-F4 n=20) patients with numerous septa/cirrhosis. A statistical analysis was conducted to analyze the bioimpedance data differences in delta of the conductance. RESULTS: From the comparison between Groups 1 and 2: 1) The delta value for conductance in the pathway representing the right foot-left hand minus left hand-right foot demonstrated a sensitivity of 85% and a specificity of 78% with a cutoff value ≤5 and P=0.0001. 2) For the comparison between Sub Group 2A (Metavir F0+F1) and Sub Group 2B (Metavir F3+F4), the neural network for the Electro Sensor Complex data demonstrated a sensitivity of 85% and a specificity of 72% with a cutoff probability >50% and P=0.001. AUCROC=0.81. CONCLUSION: Bioimpedance technology had good level sensitivity and acceptable specificity for detecting liver fibrosis using delta of the conductance. There is a potential for the use of bioimpedance technology as non-invasive approaches for screening of liver fibrosis.
RESUMO CONTEXTO: A fibrose é uma alteração hepática estrutural comum em pacientes com hepatite crônica. A biópsia hepática é o padrão ouro para determinar a extensão da fibrose hepática. Considerando as dificuldades técnicas e os custos, melhorias em ferramentas de rastreio não-invasivas são bastante necessárias. A tecnologia bioimpedância tem se mostrado ser segura para avaliar fibrose tecidual. OBJETIVO: Avaliar a utilidade do uso da bioimpedância bipolar para detectar a severidade da fibrose hepática compatível com a hepatite viral B e C. MÉTODOS: Cento e dez pacientes foram estudados, prospectivamente e dois grupos foram formados de acordo com os resultados dos testes laboratoriais para a detecção de HCV, ALT e AST: Grupo 1 Controle (n=50 pacientes saudáveis com HCV negativos e com valores de ALT e AST dentro do padrão de normalidade) e Grupo 2 Positivo (n=60 pacientes positivos para a infecção viral anti-VHC ou HBsAg positiva) que foram biopsiados. Todos os pacientes foram submetidos a um exame com o Electro Sensor Complex, que utiliza a bioimpedância bipolar. Para comparar os Grupos 1 e 2, a curva ROC foi utilizada para determinar a especificidade e sensibilidade da bioimpedância em detectar a fibrose hepática. Para identificar a severidade da fibrose hepática, o Grupo 2 Positivo foi subdividido de acordo com os resultados da biópsia (escore Metavir) em: Sub Grupo 2A (F0-F1 n=25 ) - pacientes sem ou com fibrose portal mínima e Sub Grupo 2B (F3-F4 n=20) pacientes com numerosos septos/cirrose. A análise estatística foi realizada para analisar as diferenças dos valores delta de condutância da bioimpedância. RESULTADOS: A comparação entre os Grupos 1 e 2 mostrou: 1) O valor delta de condutância na via do pé direito à mão esquerda menos o valor do delta da mão esquerda ao pé direito demonstrou uma sensibilidade de 85% e uma especificidade de 78%, com um valor de corte ≤5 e P=0,0001. 2). Na comparação entre o Sub Grupo 2A (Metavir F0+F1) e o Sub Grupo 2B (Metavir F3 + F4), a rede neural para os dados aferidos pelo Electro Sensor Complex demonstrou uma sensibilidade de 85% e uma especificidade de 72%, com um corte de probabilidade >50% P=0,001 e AUCROC=0,81. CONCLUSÃO: Bioimpedância apresentou boa sensibilidade e aceitável especificidade para a detecção da fibrose hepática utilizando o delta da condutância da bioimpedância. Existe um potencial para o uso da bioimpedância como abordagens não-invasivas para o rastreamento da fibrose hepática.