Novel inflammatory biomarkers of portal pressure in compensated cirrhosis patients.

UNLABELLED: The rationale for screening inflammatory serum biomarkers of the hepatic vein pressure gradient (HVPG) is based on the fact that portal hypertension is pathogenically related to liver injury and fibrosis, and that in turn these are associated with the activation of inflammatory pathways. This was a nested cohort study in the setting of a randomized, clinical trial to assess the development of gastroesophageal varices (GEV) (N Engl J Med 2005;353:2254). Patients had cirrhosis and portal hypertension but did not have GEV. A total of 90 patients who had baseline day-1 sera available were enrolled in the present study. The objective of this study was to determine whether inflammatory biomarkers in conjunction with clinical parameters could be used to develop a predictive paradigm for HVPG. The correlations between HVPG and interleukin (IL)-1ß (P=0.0052); IL-1R-α (P=0.0085); Fas-R (P=0.0354), and serum VCAM-1 (P=0.0007) were highly significant. By using multivariate logistic regression analysis and selected parameters (transforming growth factor beta [TGFß]; heat shock protein [HSP]-70; at-risk alcohol use; and Child class B) we could exclude HVPG ≥ 12 mmHg with 86% accuracy (95% confidence interval [CI]: 67.78 to 96.16%) and the sensitivity was 87.01% (95% CI: 69.68 to 96.34%). Therefore, the composite test could identify 86% of compensated cirrhosis patients with HVPG below 12 mmHg and prevent unnecessary esophagogastroduodenoscopy with its associated morbidity and costs in these patients. Our diagnostic test was not efficient in predicting HVPG ≥ 12 mmHg. CONCLUSION: A blood test for HVPG could be performed in cirrhosis patients to prevent unnecessary esophagogastroduodenoscopy.

Macrophage activation is a prognostic parameter for variceal bleeding and overall survival in patients with liver cirrhosis.

BACKGROUND & AIMS: Soluble CD163 (sCD163) is shed in the blood circulation by activated macrophages, correlates strongly with the hepatic venous pressure gradient (HVPG) and is thereby a good indicator of portal hypertension. It is unknown whether sCD163 correlates with the risk of variceal bleeding and overall survival (OS) in patients with liver cirrhosis. We performed a prospective study to investigate if sCD163 serum levels correlate with the risk of variceal bleeding and OS in cirrhotic patients. METHODS: Patients with liver cirrhosis were prospectively enrolled and followed until death or last contact. At the day of inclusion in the study, blood samples were taken and sCD163 serum levels were assessed by ELISA (enzyme-linked immunosorbent assay). The time until the end points death and variceal bleeding was assessed and the risks of death or variceal bleeding were calculated with uni- and multivariate Cox regression analyses. RESULTS: High sCD163 levels (>4100 ng/L) were associated with death independently of the MELD (model of end stage liver disease) score, CRP (C-reactive protein), age and gender. Furthermore, high sCD163 levels were associated with gastrointestinal bleeding independently of the variceal stage and red spots. CONCLUSIONS: The sCD163 serum level is a new independent non-invasive risk factor for death and variceal bleeding in cirrhotic patients.

Effect of esophagogastric devascularization with splenectomy on schistossomal portal hypertension patients' immunity.

BACKGROUND: Surgical treatment of hemorrhagic complication in schistosomal portal hypertension in our hospital is an esophagogastric devascularization procedure with splenectomy. Infectious risks and immunological alterations imputed to splenectomy may have significant importance. To minimize the consequences of spleen absence, the use of subtotal splenectomy and spleen auto-transplantation were stimulated. AIM: To verify the immunologic alterations imposed by this procedure in our patients. METHOD: Twenty-eight patients with schistosomal portal hypertension and previous history of upper digestive bleeding due to esophagogastric varices rupture underwent elective esophagogastric devascularization and splenectomy. They were prospectively studied before esophagogastric devascularization procedure with splenectomy, 15 and 30 days, 3 and 6 months after the procedure. T and B-lymphocytes, CD4 and CD8 subpopulations were determinated by monoclonal antibodies. Immunoglobulins A, M, G and C3, C4 components of the complement were determinated by radial immunodiffusion. RESULTS: We observed important reduction of all immune cells, increase of IgG and normal levels of IgM, IgA, C3 and C4 at preoperative. CD4/CD8 relation was normal. Six months after esophagogastric devascularization procedure with splenectomy, significant increase in T-lymphocytes, CD4, CD8 and B-lymphocytes were observed. CD4/CD8 relation remained normal. We noted significant increase in C3. IgA, IgM, IgG and C4 had increased, but without significant difference. CONCLUSION: Esophagogastric devascularization procedure with splenectomy determines an increase in T and B-lymphocytes, CD4 and CD8 subpopulations without compromising immunoglobulins and components of complement levels.

Chronology of histological changes after band ligation of esophageal varices in humans.

BACKGROUND AND STUDY AIMS: While the histological effects of endoscopic sclerotherapy in humans have been extensively described, the effects of endoscopic ligation have been reported in only two cases. The purpose of this study was to reconstruct the chronological sequence of histological changes after ligation of esophageal varices. PATIENTS AND METHODS: Autopsy specimens from six patients who received ligation of varices from nine hours to 22 months ante-mortem were evaluated for gross and microscopic changes. RESULTS: Early after ligation, the appearance was that of a polyp with its base compressed by the band. Variceal thrombosis was seen on day 2. Varying degrees of ischemic necrosis of the polyp were present on days 0-5. If the bands did not remain in situ for two days (premature loss), necrosis of the polyp and dilated variceal vessels were seen. On day 22, superficial ulcers were observed. After complete healing, fibrosis was seen in the submucosa. CONCLUSIONS: The changes seen in the present study are similar to those described in animals. The delay in ulcer healing, compared with the gross changes reported during follow-up endoscopic examinations, may be related to the severity of the underlying illness and the compromised immune status of patients in the present series.

Histologic factors of the esophageal transection ring as clues to the pathogenesis of bleeding varices.

In the absence of other precipitating factors, such as Sengstaken intubation, there is little evidence for acute esophagitis being a major factor in precipitating hemorrhage from varices. Superficial blood filled channels are described lying within the epithelium. They appear to arise from papillae, extend close to the esophageal lumen and are lined by epithelial-like cells. It is proposed that rupture of these channels may initiate variceal bleeding and, being connected to the underlying larger vessels, give rise to substantial hemorrhage. It is also suggested that these superficial vascular channels may correspond to the cherry red spots seen on endoscopic examination.

Effect of esophagogastric devascularization with splenectomy on schistossomal portal hypertension patients' immunity

BACKGROUND: Surgical treatment of hemorrhagic complication in schistosomal portal hypertension in our hospital is an esophagogastric devascularization procedure with splenectomy. Infectious risks and immunological alterations imputed to splenectomy may have significant importance. To minimize the consequences of spleen absence, the use of subtotal splenectomy and spleen auto-transplantation were stimulated. AIM: To verify the immunologic alterations imposed by this procedure in our patients. METHOD: Twenty-eight patients with schistosomal portal hypertension and previous history of upper digestive bleeding due to esophagogastric varices rupture underwent elective esophagogastric devascularization and splenectomy. They were prospectively studied before esophagogastric devascularization procedure with splenectomy, 15 and 30 days, 3 and 6 months after the procedure. T and B-lymphocytes, CD4 and CD8 subpopulations were determinated by monoclonal antibodies. Immunoglobulins A, M, G and C3, C4 components of the complement were determinated by radial immunodiffusion. RESULTS: We observed important reduction of all immune cells, increase of IgG and normal levels of IgM, IgA, C3 and C4 at preoperative. CD4/CD8 relation was normal. Six months after esophagogastric devascularization procedure with splenectomy, significant increase in T-lymphocytes, CD4, CD8 and B-lymphocytes were observed. CD4/CD8 relation remained normal. We noted significant increase in C3. IgA, IgM, IgG and C4 had increased, but without significant difference. CONCLUSION: Esophagogastric devascularization procedure with splenectomy determines an increase in T and B-lymphocytes, CD4 and CD8 subpopulations without compromising immunoglobulins and components of complement levels.

RACIONAL: A cirurgia de desconexão ázigo-portal com esplenectomia é utilizada no tratamento da complicação hemorrágica varicosa dos esquistossomóticos hepatoesplênicos com hipertensão do sistema portal, no Serviço de Fígado e Hipertensão Portal da Santa Casa de São Paulo. Envolvendo a esplenectomia, os riscos infecciosos e alterações imunológicas imputados a ela têm importância significativa. A esplenectomia subtotal e o auto-implante esplênico foram alternativas descritas para minimizar as conseqüências da esplenectomia nesses doentes. OBJETIVO: Avaliar o estado imunológico dos esquistossomóticos hepatoesplênicos e qual a alteração imunológica imposta pelo procedimento nesses doentes. MÉTODO: Vinte e oito esquistossomóticos com hipertensão portal e episódio hemorrágico varicoso foram estudados prospectivamente antes, 15 e 30 dias e 3 e 6 meses após a desconexão ázigo-portal com esplenectomia. Realizou-se contagem de linfócitos T, B, células CD4+ e CD8+ através de anticorpos monoclonais e dosagem das imunoglobulinas A, M, G e frações C3 e C4 do sistema complemento por imunodifusão radial. RESULTADOS: Obteve-se diminuição importante de todas as células, aumento de IgG e níveis normais de IgM, IgA, C3 e C4 no pré-operatório. A relação CD4+/CD8+ foi normal. Seis meses após a cirurgia, houve aumento significativo do número de linfócitos T, CD4+, CD8+ e linfócitos B. A relação CD4+/CD8+ manteve-se normal, sem variação. Houve aumento significativo nos níveis de C3. IgA, IgM, IgG e C4 também aumentaram, mas sem diferença significativa. CONCLUSÃO: Os linfócitos T, suas subpopulações CD4+ e CD8+, e os linfócitos B estão diminuídos no pré-operatório. Decorridos 6 meses da desconexão ázigo-portal com esplenectomia houve aumento do número de linfócitos T, das subpopulações CD4+ e CD8+, e dos linfócitos B. Após a desconexão ázigo-portal com esplenectomia não houve alteração das dosagens de imunoglobulinas nem diminuição do sistema complemento.