Introductory Chapter: Liver Cirrhosis – Innovations in Diagnosis and Management

1. Introduction

Liver cirrhosis is the end-stage of various chronic liver diseases, frequently caused by viral hepatitis, chronic alcohol abuse, non-alcoholic fatty liver disease, autoimmune liver disease, genetic diseases, and cholestatic liver diseases. Liver cirrhosis is a significant health burden globally; it is currently the 9th cause of death in Europe and South East Asia, representing the 15th leading cause of disability-adjusted life-years globally [1]. Early diagnosis and management of cirrhosis and its complications are imperative to improving outcomes for individuals with cirrhosis. Our research group has consistently focused on the diagnosis and treatment of liver cirrhosis and its complications, achieving significant progress in various aspects. These efforts and work provide a solid foundation for inviting experts worldwide to collaboratively write this book and share the newly developed innovations in the diagnosis and management of liver cirrhosis with the readers.

2. Non-invasive diagnostic methods in esophageal varices

Gastroesophageal varices (GEVs) appear in approximately 50% of cirrhotic patients and represent one of the most prevalent and severe complications of liver cirrhosis [2]. Acute variceal bleeding is a major cause of death in cirrhotic patients. Despite the advancement of treatment strategies, variceal bleeding is still associated with a 6-week mortality rate of 15–20% [3, 4]. Upper gastrointestinal endoscopy is the gold standard for diagnosing GEVs. However, it is an invasive procedure, complicated with poor patient’s tolerance. Recent studies have demonstrated significant progress in the non-invasive diagnosis of GEVs.

Our research indicates that traditional non-invasive markers for assessing liver fibrosis have limitations in predicting esophageal varices (EVs) [5]. In contrast, scoring systems based on clinical laboratory results may be more helpful for the non-invasive diagnosis of EVs. Therefore, we innovatively developed the Liaoning scoring system. Qi et al. created the Liaoning score from a group of prospective cirrhotic patients who had their first endoscopy at 11 hospitals in Liaoning Province, China [6]. A total of 363 patients with cirrhosis participated in this study, of whom 71.63% (260 out of 363) had EVs. EVs were independently associated with acute upper gastrointestinal bleeding (AUGIB), platelet count, and ascites. In cirrhotic patients, the Liaoning score had an area under curves (AUC) of 0.807 (p < 0.0001). With a cutoff value of 0.474, sensitivity was 70%, and specificity was 77.67%. This study found that Liaoning score, a new scoring system, can predict EVs in cirrhotic patients. Li et al. externally validated the Liaoning score in a nationwide multicenter cross-sectional study for EVs and high-risk EVs prediction [7]. A total of 612 cirrhotic patients with AUGIB participated in this study. The incidence of EVs and high-risk EVs was 96.2% and 95.6%, respectively. The results revealed that the Liaoning score’s AUC for predicting EVs was 0.708 (p = 0.0016), and that of high-risk EVs was 0.702 (p = 0.0147).

Computed tomography (CT) plays an important tool in assessing complications of cirrhosis and screening for hepatocellular carcinoma. Our study findings support CT’s potential in non-invasive diagnosis of EVs. Contrast-enhanced CT was utilized in a study by Li et al. to predict GEVs non-invasively [8]. A total of 279 patients were enrolled in this retrospective study. High-risk varices, which include EVs and gastric varices, are defined as varices requiring treatment. Based on endoscopic surveillance, drug prophylaxis (primary or secondary prophylaxis), and history of bleeding events, all patients were categorized into four groups. Only contrast-enhanced CT was significantly correlated with EVs, high-risk EVs, and gastric varices in the general population. The cutoff value of high-risk EVs was determined to be a diameter of less than 0.5 cm, less than 0.38 cm, less than 0.46 cm, and less than 0.33 cm for the primary prophylaxis, acute bleeding, previous bleeding, and secondary prophylaxis populations, respectively, which avoids 47.8%, 10.5%, 12.1%, and 7.8% of endoscopic surveillance without high-risk EVs. This study demonstrated the high diagnostic accuracy of contrast-enhanced CT in patients with GEVs.

3. Management of portal vein thrombosis in liver cirrhosis

Portal vein thrombosis (PVT) is a common yet complicated complication that affects approximately 10–25% of cirrhotic patients [9]. Most cases are asymptomatic and diagnosed during routine screening. Some studies have even suggested the transient nature of PVT [10]. However, acute symptomatic PVT can precipitate a rapid deterioration in cirrhosis. Anticoagulation therapy stands as a primary treatment for PVT. Recent research confirms the efficacy and safety of anticoagulants in managing PVT in cirrhotic patients [11]. Analysis from 33 studies and 1696 patients highlights that anticoagulation therapy significantly boosts portal vein recanalization rates (RR = 2.61) and survival (RR = 1.11), without notably increasing bleeding risks (RR = 0.78). Early initiation of anticoagulation is particularly effective, enhancing recanalization (RR = 1.58). Direct oral anticoagulants (DOACs) are shown to be safer in reducing major bleeding events (OR = 0.55) compared to traditional anticoagulants, across 29 studies involving 2469 patients [12]. Gao et al. examined the role of thrombolytic therapy in PVT treatment through 29 cohort studies and 131 case reports or series [13]. The results indicate that early initiation of thrombolysis is effective, with a 58% rate of complete recanalization. However, the benefits may be reduced in cases of PVT secondary to acute pancreatitis, highlighting the importance of careful patient selection. These consolidated data support personalized, evidence-based management of PVT in cirrhotic patients, recommending anticoagulation and DOACs based on individual risk profiles. Early thrombolytic therapy may prove effective, but requires further validation through additional high-quality studies.

4. Prognosis assessment in cirrhosis

The assessment of prognosis in patients with liver cirrhosis is of critical importance for clinical management, as it facilitates the identification of high-risk individuals who may benefit from early liver transplantation and aids in the formulation of personalized treatment plans. Additionally, prognosis assessment facilitates the formulation of personalized treatment plans by clinicians and the ongoing monitoring of disease progression.

Peng et al. evaluated Child-Pugh, MELD, and ALBI scores for predicting in-hospital mortality in cirrhotic patients with acute-on-chronic liver failure [14]. The AUROCs were 0.63 for Child-Pugh, 0.75 for MELD, and 0.53 for ALBI, indicating marginal effectiveness in predicting outcomes. A similar study on acute upper gastrointestinal bleeding (UGIB) in cirrhosis [15], involving 145 patients, showed AUROCs of 0.796 for Child-Pugh and 0.810 for MELD scores, suggesting no significant difference in their predictive capacities for in-hospital mortality. A meta-analysis by Peng et al. compared the prognostic assessment capabilities of the Child-Pugh and MELD scores across various clinical settings in liver cirrhosis [16]. These findings advocate for developing more refined prognostic tools tailored to specific cirrhotic complications. Bai et al. developed and validated a novel model named CAGIB for predicting the prognosis of patients with liver cirrhosis [17]. The CAGIB score, which had an AUC of 0.829 in the training cohort and 0.714 in the validation cohort, outperformed other prognostic models, such as Child-Pugh, MELD, MELD-Na, and NLR. The results proved the CAGIB score to be a strong predictor of in-hospital death.

Our research in cirrhosis has advanced diagnostics, management, and prognostication, emphasizing early detection and innovative treatments. We introduced the Liaoning scoring system for non-invasive diagnosis of EVs, highlighting the potential of CT to reduce reliance on invasive procedures. Our studies on PVT validate the efficacy of anticoagulation therapy, notably DOACs, in improving outcomes without increasing bleeding risks. Additionally, we explored prognostic assessment models, including the development of the CAGIB score, to better predict patient outcomes. This book aims to enhance patient care in cirrhosis through scientific collaboration and sharing knowledge globally, fostering advancements in the field.