To the Editor:
A 32-year-old man was referred for the consideration of liver transplantation because of hepatitis B–related cirrhosis with the complication of hepatic encephalopathy, spontaneous bacterial peritonitis, and refractory ascites. Physical examination showed the presence of right pleural effusion, ascites, and splenomegaly. Full blood count showed an anemia of 9.6 g/dL and a lymphopenia of 0.8 (normal, 1.5–4 × 109/L). Serum biochemistry results were as follows: albumin, 12 g/L; globulin, 31 g/L; total bilirubin, 14 μmol/L (normal, 7–19 μmol/L); aspartate transaminase, 44 U/L (normal, 6–53 U/L); alanine transaminase, 115 U/L (normal, 13–33 U/L); and prothrombin time, 15.4 seconds. Investigations for protein loss were performed in view of the severe hypoalbuminemia, which was disproportional to the normal bilirubin and the only mildly prolonged prothrombin time. Twenty-four-hour urine for protein, autoimmune markers, and stool culture were all negatives. Stool for α1-antitrypsin clearance was increased to 139.4 mL/d (normal, <13 mL/d), suggestive of protein-losing enteropathy. Upper endoscopy revealed the presence of grade II esophageal varices and portal hypertensive gastropathy. Biopsies obtained from the duodenum showed diffuse, bloated villi with prominent dilated lymphatic channels, which were intact without rupture and with no evidence of parasitic infestation. Duodenal aspirate for culture showed commensals only. Barium meal and follow-through showed diffusely edematous bowel folds compatible with hypoalbuminemia. Echocardiogram results were essentially normal. Secondary intestinal lymphangiectasia caused by portal hypertension was suspected. Doppler ultrasound showed features of portal hypertension. The patient was put on a diet low in saturated and unsaturated fatty acids with a supplementation of medium-chain triglycerides; however, the hypoalbuminemia persisted and his α1-antitrypsin clearance remained high at 291.1 mL/d. A 10-day trial of continuous octreotide infusion was given to lower the portal pressure, but the α1-antitrypsin clearance remained abnormally elevated at 109 mL/d. 1 Subsequently, the patient underwent a living-related extended right-lobe liver transplantation. His ascites and pleural effusion resolved, the albumin level improved (42 g/L), his diarrhea symptoms subsided, and his α1-antitrypsin clearance returned to normal. Duodenal biopsy repeated 4 months after the transplantation showed resolution of duodenal pathology. Posttransplantation Doppler study showed further improvement of portal blood flow.
In patients with cirrhosis, a disproportionately low albumin level should alert physicians to the possibility of protein loss through intestinal lymphangiectasia. There is only one previous case report in the literature of portal hypertension causing protein-losing enteropathy and its reversal after transjugular intrahepatic portosystemic stent shunt. 2 The cause of intestinal lymphangiectasia can be primary or secondary. The most common causes of secondary lymphangiectasia include right heart failure, constrictive pericarditis, inflammatory or infective conditions of the small intestine, lymphoma, and postirradiation fibrosis. 3 The mechanism of protein loss in right heart failure 4 and constrictive pericarditis 5 is caused by secondary elevation of portal pressure. Thus, similar mechanism may operate in patients with portal hypertension secondary to cirrhosis of the liver. The complete reversal of protein-losing enteropathy after orthotropic liver transplantation strongly suggests that portal hypertension is the underlying cause of protein-losing enteropathy. To our knowledge, our patient is the first reported to have total correction of this abnormality by liver transplantation.
The authors thank the liver transplant team of Queen Mary Hospital in performing the liver transplantation.
Wai-Man Wong, M.D.
Chee-Kin Hui, M.D.
Man-Fung Yuen, M.D.
Ching-Lung Lai, M.D.
Irene Oi-Lin Ng, M.D.
Nigel Trendell-Smith, M.D.
Gaik C. Ooi, M.D.
Sheung-Tat Fan, M.D.
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2. Stanley AJ, Gilmour HM, Ghosh S, et al. Transjugular intrahepatic portosystemic shunt as a treatment for protein-losing enteropathy caused by portal hypertension. Gastroenterology 1996; 111:1679–82.
3. Levin MS. Miscellaneous diseases of the small intestine: Protein-losing gastroenteropathy. In: Yamada T, Alpers DH, Owyang C, et al. Textbook of Gastroenterology
, 2nd ed. Philadelphia: J.B. Lippincott Company, 1995:1727–9.
4. Davidson JD, Waldmann RA, Goodwin DS, et al. Protein-losing enteropathy in congestive heart failure. Lancet 1961; 1:899.
5. Wilkinson P, Pinto B, Senior JR. Reversible protein-losing enteropathy with intestinal lymphangiectasia secondary to chronic constrictive pericarditis. N Engl J Med 1965; 273:1178–81.