Novel Preoperative Type IV Collagen to Predict the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Related Cirrhotic Portal Hypertension After Laparoscopic Splenectomy and Azygoportal Disconnection

Abstract

Purpose

Although laparoscopic splenectomy and azygoportal disconnection (LSD) can significantly decrease portal vein pressure and even the incidence of hepatocellular carcinoma (HCC) in patients with cirrhotic portal hypertension (CPH), postoperative HCC inevitably occurs in certain patients. The purpose of this study was to seek a novel preoperative non-invasive predictive indicator to predict the occurrence of postoperative HCC.

Patients and Methods

From April 2012 to April 2022, we collected clinical data of 178 hepatitis B virus (HBV)-related CPH patients. Based on inverse treatment probability weighting, candidate variables for predicting postoperative HCC were determined by means analysis. Then, a novel preoperative non-invasive prediction indicator (ie, type IV collagen-alpha fetoprotein-fibrosis-4 score [IVAF-FIB-4]) was established based on candidate variables, and its predictive ability was explored.

Results

Postoperative HCC occurred in 9 (5.1%) patients. Correlation analyses showed that the IVAF-FIB-4 had a significant positive correlation with HCC (r = 0.835, P < 0.001). IVAF-FIB-4 showed a high accuracy (the area under the receiver operating characteristic curve: 0.939, 95% confidence interval [CI]: 0.818–1.000; sensitivity: 88.9%; specificity: 93.5%). At the end of follow-up, the incidence density of HCC in patients with IVAF-FIB-4 (1) was significant higher than that in patients with IVAF-FIB-4 (0) (138.1/1000 vs 1.1/1000 person-years; rate ratio: 130.475, 95% CI: 16.318–1043.227). In logistic regression, IVAF-FIB-4 was an independent risk factor for HCC (odds ratio: 668.000, 95% CI: 53.895–8279.541; P < 0.001).

Conclusion

IVAF-FIB-4 is a novel preoperative noninvasive predictive indicator for predicting postoperative HCC in HBV-related CPH patients after LSD, with satisfactory predictive ability.

Keywords:

• liver fibrotic markers
• splenectomy
• azygoportal disconnection
• hepatocellular carcinoma
• risk

Abbreviations

LSD, laparoscopic splenectomy and azygoportal disconnection; HCC, hepatocellular carcinoma; CPH, cirrhotic portal hypertension; HBV, hepatitis B virus; LT, Liver transplantation; TIPS, transjugular intrahepatic portosystemic shunt; C-IV, type IV collagen; IPTW, inverse treatment probability weighting; LN, laminin; HA, hyaluronidase; PC-III, procollagen type III; AFP, alpha fetoprotein; FIB-4, fibrosis-4 score; IVAF-FIB-4, type IV collagen-alpha fetoprotein-fibrosis-4 score; POM, postoperative months; BMI, body mass index; WBC, white blood cells; HGB, hemoglobin; PLT, platelets; ALT, alanine aminotransferase; INR, international normalized ratio; BUN, blood urea nitrogen; Cr, creatinine; ROC, Receiver operating characteristic; AUC, area under the receiver operating characteristic curve; ECM, extracellular matrix; MMPs, matrix metalloproteinase; OR, odds ratio.

Acknowledgments

This study is a joint effort of many investigators and staff members, and their contribution is gratefully acknowledged. We especially thank all patients who participated in this study.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 82173353).