Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2023; 15(10): 1140-1152
Published online Oct 27, 2023. doi: 10.4254/wjh.v15.i10.1140
Prevalence and risk factors of lymphatic dysfunction in cirrhosis patients with refractory ascites: An often unconsidered mechanism
Rahul Arya, Ramesh Kumar, Tarun Kumar, Sudhir Kumar, Utpal Anand, Rajeev Nayan Priyadarshi, Tanmoy Maji
Rahul Arya, Ramesh Kumar, Sudhir Kumar, Tanmoy Maji, Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
Tarun Kumar, Department of Pathology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
Utpal Anand, Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
Rajeev Nayan Priyadarshi, Department of Radiodiagnosis, All India Institute of Medical Sciences, Patna 801507, Bihar, India
Author contributions: Arya R and Kumar R designed the manuscript, collected data, and wrote the manuscript; Kumar T contributed to the histopathological examination and data collection; Kumar S, Anand U, Priyadarshi RN, and Maji T collected data and provided critical input for the manuscript.
Institutional review board statement: The study was reviewed and approved by the Institute research board (Reference No: AIIMS/Pat/IRC/2020/PGTh/Jan 21-22).
Informed consent statement: Informed written consent was obtained from all study participants.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ramesh Kumar, MD, Additional Professor, Department of Gastroenterology, All India Institute of Medical Sciences, Phulwari Sharif, Patna 801507, Bihar, India. docrameshkr@gmail.com
Received: August 17, 2023
Peer-review started: August 17, 2023
First decision: September 5, 2023
Revised: September 14, 2023
Accepted: October 8, 2023
Article in press: October 8, 2023
Published online: October 27, 2023
Processing time: 67 Days and 14.4 Hours
Abstract
BACKGROUND

The lymphatic system is crucial in maintaining the body fluid homeostasis. A dysfunctional lymphatic system may contribute to the refractoriness of ascites and edema in cirrhosis patients. Therefore, assessment of lymphatic dysfunction in cirrhosis patients with refractory ascites (RA) can be crucial as it would call for using different strategies for fluid mobilization.

AIM

To assessing the magnitude, spectrum, and clinical associations of lymphatic dysfunction in liver cirrhosis patients with RA.

METHODS

This observational study included 155 consecutive cirrhosis patients with RA. The presence of clinical signs of lymphedema, such as peau d’orange appearance and positive Stemmer sign, intestinal lymphangiectasia (IL) on duodenal biopsy seen as dilated vessels in the lamina propria with strong D2-40 immunohistochemistry, and chylous ascites were used to diagnose the overt lymphatic dysfunctions.

RESULTS

A total of 69 (44.5%) patients out of 155 had evidence of lymphatic dysfunction. Peripheral lymphedema, found in 52 (33.5%) patients, was the most common manifestation, followed by IL in 42 (27.0%) patients, and chylous ascites in 2 (1.9%) patients. Compared to patients without lymphedema, those with lymphedema had higher mean age, median model for end-stage liver disease scores, mean body mass index, mean ascitic fluid triglyceride levels, and proportion of patients with hypoproteinemia (serum total protein < 5 g/dL) and lymphocytopenia (< 15% of total leukocyte count). Patients with IL also had a higher prevalence of lymphocytopenia and hypoproteinemia (28.6% vs. 9.1%, P = 0.004). Seven (13%) patients with lymphedema had lower limb cellulitis compared to none in those without it. On multivariate regression analysis, factors independently associated with lymphatic dysfunction included obesity [odds ratio (OR): 4.2, 95% confidence intervals (95%CI): 1.1–15.2, P = 0.027], lymphocytopenia [OR: 6.2, 95%CI: 2.9–13.2, P < 0.001], and hypoproteinemia [OR: 3.7, 95%CI: 1.5–8.82, P = 0.003].

CONCLUSION

Lymphatic dysfunction is common in cirrhosis patients with RA. Significant indicators of its presence include hypoproteinemia and lymphocytopenia, which are likely due to the loss of lymphatic fluid from the circulation. Future efforts to mobilize fluid in these patients should focus on methods to improve lymphatic drainage.

Keywords: Cirrhosis; Lymphedema; Lymphangicetasia; Refractory ascites; Chylous ascites; Lymphocytopenia

Core Tip: Lymphatic dysfunction is often underappreciated in advanced cirrhosis patients. Our study evaluated the magnitude, spectrum, and associations of lymphatic dysfunction in cirrhosis patients with refractory ascites (RA). Nearly half (44.5%) of the studied population (n = 155) revealed evidence of overt lymphatic dysfunction in the forms of peripheral lymphedema (33.5%), intestinal lymphangiectasia (27.0%), and chylous ascites (1.9%). Obesity, hypoproteinemia, and lymphocytopenia were independently associated with lymphatic dysfunction in said patients. From a therapeutic standpoint, it can be extremely important to evaluate lymphatic dysfunction in cirrhosis patients with RA since it would call for using different strategies for fluid mobilization.