The Histopathological Study For The New CSPH Classification Of Hepatocellular Carcinoma

Background and aim:Hepatocellular carcinoma (HCC) is one of the most common maligmancies worldwide and a common cause of death in patients with chronic liver diease. Liver cirrhosis is a special stage of progressive liver disease, and it is the important risk facter of HCC. The research have showed that HCC develops in approximately 80% of cirrhotic patients with an increasing incidance worldwide. Due to the existence of double factors of hepatocellular carcinoma and liver cirrhosis, this type of patients will have higher risk of surgical treatment, worse prognosis, and more complex assessment. The hemorrhage of the patients during the operation and the incidence of postoperative complications are significantly increased, especially the incidence of posthepatectomy liver failure (PHLF). Cinically significant portal hypertension(CSPH) is another important risk factor of liver disease complication. CSPH significantly increases the risk of 3-and 5-year mortality and of clinical decompensation after surgery for HCC. Therefore, in the course of the development of liver disease, its risk can not be ignored.Child-Pugh A patients with clinically significant portal hypertension (CSPH) are likely to develop posthepatectomy liver failure (PHLF), but the occurrence rate will be different. Whether we can predict the occurrence of PHLF and develop treatment programs according to the CSPH level is controversial. Therefore, we have to evaluate the liver function of patients with cirrhosis before operation to choise suitable patients and grasp the safe liver resection range. It has important clinical significance for reducing the incidence of PHLF and perioperative mortality. According to the early study, Child-Pugh A patients were classified into three subtypes according to the patients’clinical manifestations:no CSPH (no oesophageal varices, splenomegaly or low platelet count), mild CSPH (oesophageal varices alone, or splenomegaly plus low platelet count alone) and severe CSPH (oesophageal varices plus splenomegaly plus low platelet count) groups. And the result has showed that patients with severe CSPH was more likely to develop persistent PHLF after partial hepatectomy and was the important reason of death. In this research, we want to study the relationship between specific histological parameters in hepatocellular carcinoma associated with cirrhosis and the new CSPH classification. In order to confirm each type of CSPH patients will have the histopathological change of liver tissue and further distinguish the severity of liver cirrhosis. At last realizing the assessment of liver functional status before operation with the clinical symptoms of CSPH in hepatocellular carcinoma associated with cirrhosis and proving the possibility of clinical application of the new CSPH classification.Methods:We retrospectively collected the clinical datas and pathological specimens of 238 consecutive Child-Pugh A patients who underwent radical hepatectomy. All liver pathological specimens performed for medical disorders were formalin-fixed and paraffin-embedded, and stained with the hemotoxylin-eosin (H&E), Masson trichrome, immunohistochemistry and sirius red. Slides of each specimen were reviewed by two observers who blinded to the clinical datas and gave a final score to each of histological parameters using the semiquantitative scoring. Then the patients were divided into three groups according to the new CSPH classification. The histopathological risk factors of the new CSPH classfication were analyzed by univariate and multivariate analyses, the difference between numerical variables in different groups using analysis of variance, and the correlation analysis between variables using the Spearman or Pearson test.Results:Univariate analyses showed that septal thickness (P<0.001), nodule size (P=0.001), inflammation (P=0.001), bile duct proliferation (P=0.002), portal tracts lost (P<0.001) and central veins lost (P=0.011) significantly correlated with the new CSPH classification. These factors were entered into a stepwise multivariable Logistic regression model, which revealed septal thickness (OR=3.626,95%CI 2.177-6.044, P<0.001) and portal tracts lost (OR=1.795,95%CI 1.141-2.824, P=0.011) as the independent predictive factors for the new CSPH classification. With the increase of septal thickness and the degree of portal tracts lost, the level of CSPH increases gradually. The septal thickness of three groups is no-CSPH:0.07±0.05mm (0.01-0.39), mild-CSPH:0.15 ± 0.11mm (0.02-0.49), severe-CSPH 0.21±0.13mm (0.02-0.52) and the nodule size is no-CSPH:1.14±0.56mm (0.15-3.40), mild-CSPH:0.93±0.55mm (0.15-2.10), severe-CSPH:0.67±0.46mm (0.21-1.88), variance analysis showed that there was significant difference between three groups of variables(P<0.001). The Laennec fibrosis scoring system was tightly correlated with the new CSPH classification (r=0.569, P<0.001)Conclusion:Septal thickness, nodule size, inflammation, bile duct proliferation, portal tracts lost and central veins lost significantly correlat with the new CSPH classification. Septal thickness and portal tracts lost are the independent predictors of the new CSPH classification. The Laennec fibrosis scoring system is tightly correlated with the new CSPH classification. The Laennec fibrosis scoring system and new CSPH classification are significantly correlated with PHLF. We can predict the occurrence of posthepatectomy liver failure according to the CSPH classification in patients with cirrhosis, and indirectly evaluate the long-term survival of the patients.