Nodular regenerative hyperplasia of the liver: an under-recognized cause of portal hypertension in hematological disorders

Portal hypertension has been described in a wide variety of hematological disorders, especially myeloproliferative and lymphoproliferative disorders. Its clinical manifestations may include bleeding esophageal varices, ascites, or hepatic encephalopathy. In patients with hematological disorders, there are a number of potential causes of portal hypertension, including nodular regenerative hyperplasia of the liver (NRH). This lesion is characterized by diffuse replacement of normal hepatic parenchyma by multiple small nodules composed of regenerating hepatocytes with minimal or no fibrosis. This lack of fibrosis distinguishes NRH from cirrhosis. Unlike cirrhosis, NRH only rarely results in compromised hepatic synthetic function. The major manifestation is portal hypertension related to increased resistance to blood flow within hepatic sinusoids. NRH has been linked to a variety of systemic diseases including collagen vascular diseases, myeloproliferative and lymphoproliferative disorders, as well as various medications. Although NRH is commonly associated with blood dyscrasias, the diagnosis is overlooked because of the complexity and wide differential diagnosis of liver diseases in the setting of hematological malignancy. We review herein nodular regenerative hyperplasia of the liver, including aspects of epidemiology, pathogenesis, differential diagnosis, clinical course, and treatment. We highlight its association with different forms of hematological disease, aiming to increase the awareness of this entity to the internist and the treating hematologist/oncologist.     

Nodular regenerative hyperplasia: evolving concepts on underdiagnosed cause of portal hypertension

Nodular regenerative hyperplasia(NRH)is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules.NRH may lead to the development of non-cirrhotic portal hypertension.There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series.NRH may develop via autoimmune,hematological,infectious,neoplastic,or drug-related causes.The disease is usually asymptomatic,slowly or nonpr...     

Nodular regenerative hyperplasia and severe portal hypertension in cystinosis.

BACKGROUND & AIMS: Cystinosis is a rare autosomal-recessive disorder characterized by the intralysosomal accumulation of cystine, which is responsible for widespread tissue destruction. Liver biopsy specimens of patients with cystinosis show cystine crystal formation in Kupffer cells. However, significant liver disease and portal hypertension is not a common complication of cystinosis. We report the case histories of 2 young men with poorly treated nephropathic cystinosis who developed noncirrhotic portal hypertension with evidence of nodular regenerative hyperplasia (NRH). METHODS: Liver biopsy examinations, upper and lower endoscopy with biopsy examination, imaging studies, venous pressure measurements, and laboratory investigations were used to evaluate the causes of the liver disease and portal hypertension. RESULTS: Histologic examination of liver biopsy specimens from both patients showed changes characteristic of NRH with portal hypertension documented by measurement of pressure gradients. In addition, endoscopy in the first patient showed varices and portal hypertensive gastropathy. CONCLUSIONS: NRH was confirmed by histologic examination of the liver in both patients and is the likely cause of their portal hypertension. NRH may represent a rare, late complication of cystinosis, although the mechanism remains undefined.     

Nodular regenerative hyperplasia related portal hypertension in a patient with hypogammaglobulinaemia

Nodular regenerative hyperplasia (NRH) of liver is a relatively rare liver disorder, but a frequent cause of noncirrhotic portal hypertension. We present a lady with common variable immune deficiency who presented with upper gastrointestinal bleeding and deranged liver function tests but preserved synthetic function. Upper gastrointestinal endoscope showed bleeding gastric varices and non-bleeding oesophageal varices. Although her oesophageal varices were eradicated by repeated endoscopic band ligation, the gastric varices failed to resolve after repeated endoscopic histocryl injection and she eventually needed transjugular intrahepatic portosystemic shunt placement. Liver biopsy showed NRH. We review the association of hypogammaglobinaemia and NRH and discuss the appropriate management of portal hypertension in NRH.     

Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients

OBJECTIVE: To describe and explain the syndrome of HIV-associated cryptogenic liver disease in eight consecutive patients suffering from portal hypertension. METHODS: The study was undertaken at a liver disease centre in Paris and involved eight of 97 consecutive HIV-infected patients presenting abnormal liver function tests and/or symptomatic portal hypertension of unknown origin. Serology, pathology, and liver function tests were performed. RESULTS: A clear nodular architecture corresponding to nodular regenerative hyperplasia was observed in seven patients and suggested in one, based on the presence of sinusoidal dilatation in a clinical context of portal hypertension, without overt liver disease. CONCLUSIONS: Nodular regenerative hyperplasia appears to be a new cause of portal hypertension in HIV-infected patients. This syndrome can be of critical importance as patients can be exposed to the significant complications of portal hypertension and to refractory ascites which may require liver transplantation.     

Nodular regenerative hyperplasia of the liver.

Nodular regenerative hyperplasia of the liver, an uncommonly reported and poorly defined clinicopathological entity, obscured clinical diagnosis and was misdiagnosed on hepatic biopsy in a recent case. Approximately 19 cases are recorded in the English literature. Six patients had Felty's syndrome, about 12 patients had congestive heart failure, and the patient under discussion had subacute bacterial endocarditis. Light- and electron-microscopic examination was utilized to define nodular regenerative hyperplasia pathologically. Features common to all reported cases are discussed but elucidation of the pathogenesis of nodular regenerative hyperplasia must await further investigation.     

Nodular regenerative hyperplasia following liver tuberculosis

We reported a case of nodular regenerative hyperplasia revealed by hemorrhage from portal hypertention and ascites in a 81 years old patient. This patient presented two years ago hepatic tuberculosis well documented by liver biopsy. If this patient do not have exhaustive etiologic research of nodular regenerative hyperplasia, the relationship between the tuberculosis infection and the developpement of this nodular regenerative hyperplasia appears highly probable and must be researched.     

Nodular regenerative hyperplasia of the liver with portal vein thrombosis and hyperplasia of the adrenal gland.

Nodular regenerative hyperplasia (NRH) of the liver is an uncommon entity of unknown origin and pathogenesis. We report here a case of NRH of the liver which was associated with portal vein thrombosis and adrenal hyperplasia. A 48-year-old man who was admitted for further examination of portal hypertension and splenomegaly, died of acute myocardial infarction. Autopsy revealed an enlarged heart with occluded coronary arteries and fresh multiple necrosis in the myocardium. The spleen and the liver were enlarged. In the liver diffusely distributed nodules of regenerative hyperplasia were noted. Organized thrombi of the portal vein and adenomatous hyperplasia of the left adrenal gland were also noted. Antinuclear antibody was positive in the serum.     

肝结节性再生性增生1例

肝结节性再生性增生(Noducar regenerative hyperplasia of liver,NRHL)是一种临床少见的肝脏疾病,临床主要表现为非肝硬化性肝源性门静脉高压症,因对其临床病理特征缺乏认识,易引起漏诊或误诊,我院收治1例,现报道如下。     

Systemic mastocytosis: A rare cause of non-cirrhotic portal hypertension

Mastocytosis is a clonal neoplastic disorder of the mast cells(MC) that can be limited to the skin(cutaneous mastocytosis) or involve one or more extracutaneous organs(systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis(ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology.     

Ultrastructure of the liver in non-cirrhotic portal fibrosis with portal hypertension

The aetiology of the ultrastructural abnormalities of non-cirrhotic portal fibrosis is not known. In an attempt to elucidate the pathophysiology of this condition, the hepatic ultrastructure in nine cases of non-cirrhotic portal fibrosis with portal hypertension has been studied.     

Nodular regenerative hyperplasia mimicking cirrhosis of the liver.

Nodular regenerative hyperplasia of the liver usually presents with signs of portal hypertension with little evidence of obvious liver disease. We report a 47 year old man who presented with clinical signs of decompensated cirrhosis, recurrent encephalopathy, and tense ascites but at liver transplant was found to have nodular regenerative hyperplasia associated with a portal vein thrombosis.     

Nodular regenerative hyperplasia of the liver in idiopathic hypereosinophilic syndrome

We report a 52-year-old man with idiopathic hypereosinophilic syndrome and nodular regenerative hyperplasia of the liver. We postulate that nodular regenerative hyperplasia may be the result of an eosinophil-induced vascular lesion.