Noncirrhotic portal hypertension in association with juvenile nephropathic cystinosis: Case presentation and review of the literature

Abstract

We report a case of portal hypertension and oesophageal varices arising in an 18-year-old female renal transplant recipient with juvenile nephropathic cystinosis diagnosed at 6 years of age. The patient had a history of poor compliance with her prescribed cysteamine therapy. Routine examination revealed normal liver function without hepatomegaly but asymptomatic splenomegaly. An abdominal ultrasound suggested mild oesophageal varices, confirmed later on endoscopy. A liver biopsy revealed an abundance of cystine crystals within the hepatic Kupffer cells, with preserved hepatic architecture. Although the pathophysiology of this rare complication is unclear, in the absence of other aetiologies the likely cause is the patient's poorly controlled cystinosis. As cystinotic patients live longer with improved renal transplant management and cysteamine therapy, it is of interest to characterize the long-term course of the illness after renal transplantation. An understanding of the pathophysiology of hepatic dysfunction will be required to manage this potential late complication of the disease.

Nephropathic cystinosis: late complications of a multisystemic disease

“…Cystine deposition in Kupffer cells is common, and hepatocyte atrophy, regenerative nodules and gastropathy with varices have also been described [122]. Portal hypertension has been reported in the absence of bridging fibrosis [122][123][124]. Some patients have required portocaval shunting, for esophageal varices and gastrointestinal bleeding, or splenectomy for hypersplenism, thrombocytopenia, leucopenia, and anemia [56].…”

Cholestatic liver disease in long‐term infantile nephropathic cystinosis

“…They suggested that the deposition of collagen by Ito cells activated by the cystine‐laden Kupffer cells led to hepatic fibrosis and eventual portal hypertension. But, in DiDomenico's case report, however, there was portal hypertension without fibrosis or Ito cell hyperplasia 5 …”

“…Cases in the literature most frequently describe non‐cirrhotic portal hypertension due to liver accumulation of cystine with nodular regenerative hyperplasia 4 . DiDomenico reported a patient with cystinosis who developed splenomegaly and mild esophageal varices 5 . Liver biopsy revealed an abundance of cystine crystals within the Kupffer cells but with preserved hepatic architecture.…”

Developmental and Inherited Liver Disease

“…991 Additional cases of noncirrhotic portal hypertension have been ascribed to cystine accumulation in Kupffer cells. 1418,1419 In two patients, long-term infantile nephropathic cystinosis was associated with a form of sclerosing cholangitis, which responded to therapy with UDCA. 1420 Liver biopsy specimens showed severe accumulation of cystine, predominantly localized in Kupffer cells, together with morphological features of sclerosing cholangitis.…”