Lymphatic dysfunction in advanced cirrhosis: Contextual perspective and clinical implications

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 analysis	Chylous ascites: Milky appearance, fluid triglyceride level ≥ 110mg/dL
Upper endoscopy	Intestinal 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

LYVE-1: Lymphatic vessel endothelial hyaluronan receptor.