"The Natural Course of Portal Vein Thrombosis in Cirrhosis."

The "Hepatology Digest -Liver Vascular Diseases Column" , initiated by Dr. Xingshun Qi of the Northern Theater Command General Hospital's Department of Gastroenterology at the invitation of the "Hepatology Digest" editorial office, is a scholarly column that regularly gathers and reviews advances in the field of liver vascular diseases. It selects one significant paper every two weeks (Wednesday) for in-depth discussion, aiming to enhance readers' understanding and inspire clinical research and application.

Article Summary

Portal vein thrombosis (PVT) refers to the formation of a blood clot in the main trunk of the portal vein and/or its left and right branches, sometimes accompanied by thrombosis in other visceral veins (European Association for the Study of the Liver. J. Hepatol. 2016; 64: 179–202). PVT is a common complication of cirrhosis, closely linked to the rebalancing of the patient’s coagulation system and portal vein blood flow speed (Shukla A, et al. J. Clin. Exp. Hepatol. 2022; 12: 965–79). Recent meta-analysis reveals that the prevalence and incidence of PVT in patients with cirrhosis are 13.9% and 10.4%, respectively (Pan J, et al. Eur. J. Intern. Med. 2022; 104: 21–32). Patients with Child-Pugh class B or C have a higher prevalence of PVT (23.7%) compared to class A (13.5%). Additionally, patients with ascites have a higher rate of PVT than those without (23.7% vs. 12.1%) (Pan J, et al. Eur. J. Intern. Med. 2022; 104: 21–32). Therefore, baseline liver function status is a significant determinant of PVT in cirrhosis. A meta-analysis on the impact of PVT on the prognosis of cirrhotic patients not undergoing liver transplantation shows that PVT patients have a lower one-year survival rate than non-PVT patients, but their 3-year, 5-year, and 10-year cumulative survival rates are similar (Xian J, et al. Medicine (Baltimore) 2021; 100: e25439). For patients requiring liver transplantation, pre-transplant PVT increases the risk of transplantation failure, death, and post-transplant PVT recurrence (Yeo JW, et al. Clin. Transplant. 2022; 36: e14520). Early anticoagulation therapy is needed in cirrhosis patients to prevent PVT-related complications. However, the challenge in treatment choice arises from cirrhosis-related coagulation abnormalities and increased bleeding risk (Shukla A, et al. J. Clin. Exp. Hepatol. 2022; 12: 965–79). Therefore, understanding the natural course of the disease is crucial in determining the optimal treatment strategy for cirrhosis PVT.

The Journal of Gastroenterology and Hepatology published an article online in June 2023 titled ” Natural history of portal vein thrombosis in cirrhosis: A systematic review with meta-analysis”. This article aims to analyze the natural course of cirrhosis PVT in patients not undergoing anticoagulant therapy, identifying factors predicting spontaneous recanalization or progression of cirrhosis PVT.

Giri and colleagues searched MEDLINE, Embase, and Scopus databases for studies on the outcomes of cirrhosis PVT patients not treated with anticoagulants from 2000 to August 2022. A random-effects model was used to calculate pooled rates and their 95% confidence intervals (CI). The final analysis included 26 studies with 1441 patients. The results showed that about 25% of cirrhosis PVT cases are progressive, 30% improved, and 45% remained stable. The pooled rates for PVT recanalization and complete recanalization were 29.3% (95%CI: 20.9–37.7) and 10.4% (95%CI: 5.0-15.8), respectively. During follow-up, the pooled recurrence rate among initially improved PVT patients was 24.0% (95%CI: 14.7-33.4).

In summary, further research is needed to explore predictive factors for spontaneous recanalization of cirrhosis PVT.

Analysis of Important Research Findings and Their Clinical Significance

1. Study Selection Process

– 3809 relevant publications identified; 2662 screened after excluding 1147 duplicates; 26 studies (1441 patients) ultimately included.

2. Quality Assessment of Included Studies

– Of the 26 studies included, 12 were high-quality, 9 medium-quality, and 5 low-quality.

3. Baseline Characteristics of Included Studies

– 10 were prospective; most patients had Child-Pugh class B; viral hepatitis and alcoholic liver disease were the most common causes of cirrhosis; most studies excluded hepatocellular carcinoma patients; PVT prevalence ranged from 48%-100%.

4. No Progression of PVT

– 21 studies reported on 1160 patients with stable PVT, the pooled rate of no progression was 77.7% (95%CI: 71.6-83.9; I²=90.6%).

5. Spontaneous Recanalization of PVT

– 24 studies reported on 1073 patients experiencing partial or complete spontaneous recanalization of PVT. The pooled rate of spontaneous recanalization was 29.3% (95%CI: 20.9-37.7; I²=91.9%). 13 studies reported complete recanalization in 635 patients, with a pooled rate of 10.4% (95%CI: 5.0-15.8; I²=84.1%).

6. Progression and Recurrence of PVT

– 20 studies reported on 1160 patients with PVT progression. The pooled rate of progression during follow-up was 22.2% (95%CI: 16.1-28.4; I²=90.6%).

– 7 studies reported on 286 patients with PVT recurrence, with a pooled recurrence rate of 24.0% (95%CI: 14.7-33.4; I²=73.6%).

7. Publication Bias

– Funnel plots indicated publication bias across all outcomes.

8. Heterogeneity Analysis

– Meta-regression analysis found heterogeneity in PVT improvement due to sample size (P=0.0475), average MELD score (P=0.0498), proportion of patients with ascites (P=0.0472), and median follow-up time (P=0.0489). Heterogeneity in PVT stability was due to the proportion of patients with ascites (P=0.0341) and median follow-up time (P=0.0493). No heterogeneity sources were found for PVT progression.

Summary and Outlook

Approximately one-fourth of cirrhosis PVT cases are progressive, while the rest are non-progressive; about 30% improve (10% achieve complete recanalization), and 45% remain stable. Baseline liver function and collateral circulation might help predict the natural course of cirrhosis PVT. Future research should further explore predictive factors for the progression or recanalization of cirrhosis PVT, which will aid in determining the treatment and management of cirrhosis PVT.

Column Initiator and Reviewer