Nodular regenerative hyperplasia rarely leads to liver transplantation: A 20‐year cohort study in all Dutch liver transplant units

Abstract

Background: Nodular regenerative hyperplasia is an uncommon liver condition associated with several autoimmune disorders and drugs. The clinical symptoms of nodular regenerative hyperplasia vary from asymptomatic to severe complications of portal hypertension (nodular regenerative hyperplasia-syndrome). Objective: The purpose of this study was to identify the prognosis and optimal management, as well as the role of liver transplantation, in nodular regenerative hyperplasia. Methods: The pathology databases of all three Dutch liver transplant units were retrospectively scrutinised for explanted livers diagnosed with nodular regenerative hyperplasia or without clear diagnosis. Pre-and post-transplantation clinical, biochemical, radiological and histological information was obtained from electronic and paper records. Results: In total, 1886 patients received a liver transplant. In 255 patients, nodular regenerative hyperplasia could not be excluded. After detailed chart review, the native livers of 11 patients (0.6%) (82% male, median age: 44 years) displayed nodular regenerative hyperplasia. Seven patients (64%) had underlying disorders or drug exposure which possibly caused nodular regenerative hyperplasia. Laboratory and imaging abnormalities were present in all patients but did not contribute to the diagnosis of nodular regenerative hyperplasia. Five-year survival was 73% (median follow-up: four years, range: 2-248 months). Conclusion: Nodular regenerative hyperplasia is a rare finding in patients, predominantly young males, transplanted for end-stage liver disease with unknown aetiology. Nonetheless, liver transplantation may have an important role in end-stage nodular regenerative hyperplasia-syndrome.

Heterogeneity of Liver Disease in Common Variable Immunodeficiency Disorders

“…The diagnosis of NRH is challenging due to different interpretations of the histopathologic features and the absence of either symptoms or laboratory abnormalities in most patients. Although nodularity and heterogeneous hepatic parenchyma suggestive of NRH may be detected by magnetic resonance imaging or ultrasound scan, diagnosis has to be histologically confirmed (45,46). Recently, the revision of the histopathological definition proposed by Wanless in 1990 led to the description of NRH as focal or diffuse appearance of hepatocellular nodules less than 3 mm in diameter detected on both H&E and reticulin staining compressing peripheral sinuses, where perisinusoidal but not septal fibrosis may occur (47,48).…”

“…Irrespectively of the ethiopathogenesis and despite the adequate treatment of complications (i.e., portal hypertension, jaundice, and oesophageal varices), chronic liver inflammation may cause a progressive disruption of liver function that is not improved by immunoglobulin replacement therapy. Moreover, there are no available medical treatments to arrest the histopathologic progression of NRH, which is the most common form of liver involvement in CVID and is complicated, in a subset of patients, by portal hypertension or overt hepatic cirrhosis with end-stage liver disease (44)(45)(46)(47). In these cases, LT is the only therapeutic approach that has the potential to provide a long-term survival advantage (135).…”

Vascular tumours of the liver: a particular story

“…NRH of the liver is a rare condition, which can cause intrahepatic portal hypertension in the absence of cirrhosis (82). Its prevalence is estimated between 0.7% and 2.6% in autopsy series (83).…”

“…In the ELITA-ELTR study, six cases of NRH are reported, of whom four did well and two died due to heart failure. Five larger series and some case reports about successful LT for this condition have been reported in literature (82,(86)(87)(88)90). In the Dutch LT series, 7 out of 11 patients (64%) had underlying disorders or drug exposure.…”

Limited relevance and progression of histological alterations in the liver during thioguanine therapy in inflammatory bowel disease patients

“…In recent studies, drug-induced liver injury appeared to be dose-dependent and substantially lower during the currently advocated TG dosages (0.2-0.3 mg/ kg, not exceeding 25 mg/day) [9,10]. Furthermore, it had been observed that histopathological vascular abnormalities such as NRH rarely led to symptoms of portal hypertension or liver transplantation, and were clinically insignificant in most patients [10][11][12].…”