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Copyright ©The Author(s) 2021.
World J Hepatol. Mar 27, 2021; 13(3): 300-314
Published online Mar 27, 2021. doi: 10.4254/wjh.v13.i3.300
Table 1 Assessment of risk factors, clinical markers and investigations for lymphatic dysfunction in cirrhosis
Parameters
Findings that support or indicate lymphatic dysfunction
Risk factors(1) Old age; (2) metabolic syndrome (obesity, diabetes, dyslipidemia); and (3) concomitant inflammatory disorders
Clinical examination(1) Diuretic-resistant ascites; (2) severe generalised edema, scrotal/penile swelling; (3) lymphedema: Peau-d’orange appearance and a positive stemmer sign; (4) frequent cellulitis/lymphangitis of affected limbs; and (5) hyperkeratotic skin lesions, yellow nail
Blood investigations(1) Hypoproteinaemia and hypoalbuminemia; (2) lymphocytopenia; and (3) hypogammaglobulinemia
Ascitic fluid analysisChylous ascites: Milky appearance, fluid triglyceride level ≥ 110mg/dL
Upper endoscopyIntestinal lymphangiectasia: Whitish congested villi in duodenum
Radiological imaging: (lymphography, lymphoscintigraphy)Abnormal lymphatic structure and/or lymph flow dynamics: Dilated lymphatic vessels, lymph stasis, lymph leakage
Histopathological examination (liver/intestine)(1) Increase in number and size of lymphatic structures; and (2) specific lymphatic endothelial markers for accurate identification: Prox-1, podoplanin, LYVE-1
Table 2 Possible therapeutic strategies for treatment of lymphatic dysfunction in cirrhosis
To decrease formation of lymph
Decrease water retentionLow salt diet, diuretic therapy
Control of portal hypertensionBeta-blocker, octreotide, transjugular intrahepatic portosystemic shunt
Increase interstitial pressureCompression therapy
To promote lymphatic drainage
Facilitate fluid movement into the lymphatic vesselsCompression therapy, limb elevation, diuretic therapy (limited role)
Increase contractility of the lymphatic vesselsNor-adrenaline, phenylephrine, nitric oxide-inhibitors (experimental)
Facilitate lysis of interstitial proteinBenzopyrones (coumarin and flavoids)
Promote lymphangiogenesisProstaglandins E2 (experimental), vascular endothelial growth factor-C (experimental)
To control aggravating factors for lymphatic dysfunction
Care of lymphedemaControl of infection (aggressive use of antibiotics), avoidance of trauma, hot bath and other heat-producing treatment
Control risk factorsControl of diabetes, dyslipidemia and obesity
To decrease leakage of lymph
Decrease stimulants of intestinal lymph flowLow fat diet, octreotide
Decrease leakage of lymph by interventionCompression therapy, antiplasmin (tranexamic acid); radiological intervention to obliterate the site of leak
To correct underlying condition
Definitive therapy of cirrhosisLiver transplantation