Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Hepatology Reports
Published in: Current Hepatology Reports 3/2023

28-07-2023 | Hypertension

Nodular Regenerative Hyperplasia

Authors: Pooja Abbey, Shalimar

Published in: Current Hepatology Reports | Issue 3/2023

Login to get access

Abstract

Nodular regenerative hyperplasia (NRH) is a diffuse liver disease characterized by multiple hepatic nodules in the absence of significant fibrosis.

Purpose of Review

To discuss the etiopathogenesis, imaging features, pathological diagnosis, clinical features, and management of NRH.

Recent Findings

NRH may occur in patients with various predisposing systemic conditions, and also post liver transplant. Not all patients are symptomatic, and portal hypertension occurs only in a subset of cases. Imaging features often show overlap with cirrhosis. Transient elastography and magnetic resonance elastography may have a role in differentiation. The term “porto-sinusoidal vascular disease” (PSVD) has been defined as a clinical entity, which includes all patients with the absence of cirrhosis and characteristic histological findings, with or without portal hypertension. NRH is one of the specific histological lesions in the defining criteria for PSVD.

Summary

Management of portal hypertension in NRH is similar to patients with cirrhosis, but overall prognosis is better.
Literature
1.
2.
Wanless IR. Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules. Hepatology. 1990;11:787–97.PubMedCrossRef
3.
Galdeano S, Drut R. Nodular regenerative hyperplasia of fetal liver: a report of two cases. Pediatr Pathol. 1991;11:479–85.PubMedCrossRef
4.
Barge S, Grando V, Nault J-C, Broudin C, Beaugrand M, Ganne-Carrié N, et al. Prevalence and clinical significance of nodular regenerative hyperplasia in liver biopsies. Liver Int. 2016;36:1059–66.PubMedCrossRef
5.
Sood A, Castrejón M, Saab S. Human immunodeficiency virus and nodular regenerative hyperplasia of liver: a systematic review. World J Hepatol. 2014;6:55–63.PubMedPubMedCentralCrossRef
6.
Rha SE, Lee MG, Lee YS, Kang GH, Ha HK, Kim PN, et al. Nodular regenerative hyperplasia of the liver in Budd-Chiari syndrome: CT and MR features. Abdom Imaging. 2000;25:255–8.PubMedCrossRef
7.
Peker A, Ucar T, Kuloglu Z, Ceyhan K, Tutar E, Fitoz S. Congenital absence of portal vein associated with nodular regenerative hyperplasia of the liver and pulmonary hypertension. Clin Imaging. 2009;33:322–5.PubMedCrossRef
8.
Bell PD, Thung S, Weiss S, Levstik M, Zhang D, Liu X, et al. Hepatocellular adenoma(s) arising in nodular regenerative hyperplasia in a patient with systemic lupus erythematosus. Pathol Res Pract. 2020;216:152770.PubMedCrossRef
9.
Graf L, Dobrota R, Jordan S, Wildi LM, Distler O, Maurer B. Nodular regenerative hyperplasia of the liver: a rare vascular complication in systemic sclerosis. J Rheumatol. 2018;45:103–6.PubMedCrossRef
10.
Morlà RM, Ramos-Casals M, García-Carrasco M, Cervera R, Font J, Bruguera M, et al. Nodular regenerative hyperplasia of the liver and antiphospholipid antibodies: report of two cases and review of the literature. Lupus. 1999;8:160–3.PubMedCrossRef
11.
Reshamwala PA, Kleiner DE, Heller T. Nodular regenerative hyperplasia: not all nodules are created equal. Hepatology. 2006;44:7–14.PubMedCrossRef
12.
De Boer NKH, Tuynman H, Bloemena E, Westerga J, Van Der Peet DL, Mulder CJJ, et al. Histopathology of liver biopsies from a thiopurine-naïve inflammatory bowel disease cohort: prevalence of nodular regenerative hyperplasia. Scand J Gastroenterol. 2008;43:604–8.PubMedCrossRef
13.
Ozturk NB, Fiel MI, Schiano TD. Identification and clinical significance of nodular regenerative hyperplasia in primary sclerosing cholangitis. JGH Open. 2022;6:607–11.PubMedPubMedCentralCrossRef
14.
Agrawal M, Rahmani R, Nakkala K, Fiel MI, Schiano T. Hepatoportal sclerosis (obliterative portal venopathy) and nodular regenerative hyperplasia in a patient with myasthenia gravis: a case report and review of the published work. Hepatol Res. 2013;43:999–1003.PubMedCrossRef
15.
Cancado ELR, Medeiros DM, Deguti MM, Dos Santos MSC, de Mello ES, Vendramini MBG, et al. Celiac disease associated with nodular regenerative hyperplasia, pulmonary abnormalities, and IgA anticardiolipin antibodies. J Clin Gastroenterol. 2006;40:135–9.PubMedCrossRef
16.
Riestra S, Domínguez F, Rodrigo L. Nodular regenerative hyperplasia of the liver in a patient with celiac disease. J Clin Gastroenterol. 2001;33:323–6.PubMedCrossRef
17.
Seiderer J, Zech CJ, Diebold J, Schoenberg SO, Brand S, Tillack C, et al. Nodular regenerative hyperplasia: a reversible entity associated with azathioprine therapy. Eur J Gastroenterol Hepatol. 2006;18:553–5.PubMedCrossRef
18.
Ganta N, Prasad A, Aknouk M, Ghodasara K, Nair A, Taqvi Z, et al. A case report of nodular regenerative hyperplasia and non-cirrhotic portal hypertension post oxaliplatin chemotherapy. Cureus. 2022;14:e28740.PubMedPubMedCentral
19.
• Takaya H, Kawaratani H, Nakanishi K, Takeyama S, Morioka C, Sawai M, et al. Development of nodular regenerative hyperplasia (NRH) with portal hypertension following the administration of oxaliplatin for the recurrence of colon cancer. Intern Med Tokyo Jpn. 2015;54:383–7. (Study of a large number of patients post liver transplant, which showed a 5% incidence of NRH post LT, while 25% cases of NRH exhibited symptomatic portal hypertension. The authors evaluated data from protocol liver biopsies and follow-up biopsies, and even demonstrated reversibility of post-LT NRH in a few cases.)CrossRef
20.
Ghabril M, Vuppalanchi R. Drug-induced nodular regenerative hyperplasia. Semin Liver Dis. 2014;34:240–5.PubMedCrossRef
21.
Boursier J, Foulet A, Pilette C. Nodular regenerative hyperplasia following liver tuberculosis. Gastroenterol Clin Biol. 2005;29:1051–3.PubMedCrossRef
22.
Kounis I, Sebagh M, Evain M, Cailliez V, Roche B, De Martin E, et al. Nodular regenerative hyperplasia is not a rare condition after liver transplantation: incidence, predictive factors, and impact on survival. Transplantation. 2023;107:410–9.PubMedCrossRef
23.
• Bakshi N, Gulati N, Rastogi A, Chougule A, Bihari C, Jindal A. Nodular regenerative hyperplasia - an under-recognized vascular disorder of liver. Pathol Res Pract. 2020;216:152833. (A recent study which evaluated histopathological, and especially, immunohistochemistry findings in cases of NRH, and looked for patterns of expression of CK7 and CD34 in hepatocytes and sinusoidal endothelial cells in patients with NRH.)PubMedCrossRef
24.
Duseja A, Chawla Y. Portal hypertension in nodular regenerative hyperplasia: a mixed bag! J Gastroenterol Hepatol. 2012;27:1260–2.PubMedCrossRef
25.
Kumar A, Sharma P, Sarin SK. Hepatic venous pressure gradient measurement: time to learn! Indian J Gastroenterol. 2008;27:74–80.PubMed
26.
Bissonnette J, Généreux A, Côté J, Nguyen B, Perreault P, Bouchard L, et al. Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. J Gastroenterol Hepatol. 2012;27:1336–40.PubMedCrossRef
27.
Penrice D, Simonetto DA. Nodular regenerative hyperplasia associated with primary liver malignancies. Hepatology. 2020;71:760–1.PubMedCrossRef
28.
29.
• Chen AK, Lunow-Luke T, Yamaguchi S, Praglin C, Agudelo E, Mehta N, et al. Nodular regenerative hyperplasia after liver transplant; it’s all in the presentation. Front Surg. 2022;9:876818. (A study evaluating data from a large number of post-LT cases to determine risk factors and outcomes in post-LT NRH cases. The authors found that cases with liver function test abnormalities alone had excellent long-term survival, in contrast to more than 50% mortality seen in patients who presented more than 48 months after LT with symptomatic portal hypertension at diagnosis.)PubMedPubMedCentralCrossRef
30.
Caturelli E, Ghittoni G, Ranalli TV, Gomes VV. Nodular regenerative hyperplasia of the liver: coral atoll-like lesions on ultrasound are characteristic in predisposed patients. Br J Radiol. 2011;84:e129–34.PubMedPubMedCentralCrossRef
31.
Siegelman ES, Outwater EK, Furth EE, Rubin R. MR imaging of hepatic nodular regenerative hyperplasia. J Magn Reson Imaging. 1995;5:730–2.PubMedCrossRef
32.
Ames JT, Federle MP, Chopra K. Distinguishing clinical and imaging features of nodular regenerative hyperplasia and large regenerative nodules of the liver. Clin Radiol. 2009;64:1190–5.PubMedCrossRef
33.
Vilgrain V, Lewin M, Vons C, Denys A, Valla D, Flejou JF, et al. Hepatic nodules in Budd-Chiari syndrome: imaging features. Radiology. 1999;210:443–50.PubMedCrossRef
34.
Laharie D, Vergniol J, Bioulac-Sage P, Diris B, Poli J, Foucher J, et al. Usefulness of noninvasive tests in nodular regenerative hyperplasia of the liver. Eur J Gastroenterol Hepatol. 2010;22:487–93.PubMedCrossRef
35.
Navin PJ, Hilscher MB, Welle CL, Mounajjed T, Torbenson MS, Kamath PS, et al. The utility of MR elastography to differentiate nodular regenerative hyperplasia from cirrhosis. Hepatology. 2019;69:452–4.PubMedCrossRef
36.
• Cannella R, Minervini MI, Rachakonda V, Bollino G, Furlan A. Liver stiffness measurement in patients with nodular regenerative hyperplasia undergoing magnetic resonance elastography. Abdom Radiol. 2020;45:373–83. (The authors used MR elastography to evaluate LSM values in cases of NRH, along with two control groups. They found that LSM values in NRH cases were significantly higher than cases with non-advanced fibrosis, but significantly lower than patients with advanced fibrosis.)CrossRef
37.
Nakhleh RE, Snover DC. Use of alpha-1-antitrypsin staining in the diagnosis of nodular regenerative hyperplasia of the liver. Hum Pathol. 1988;19:1048–52.PubMedCrossRef
38.
Jharap B, van Asseldonk DP, de Boer NKH, Bedossa P, Diebold J, Jonker AM, et al. Diagnosing nodular regenerative hyperplasia of the liver is thwarted by low interobserver agreement. PLoS ONE. 2015;10:e0120299.PubMedPubMedCentralCrossRef
39.
De Gottardi A, Rautou P-E, Schouten J, Rubbia-Brandt L, Leebeek F, Trebicka J, et al. Porto-sinusoidal vascular disease: proposal and description of a novel entity. Lancet Gastroenterol Hepatol. 2019;4:399–411.PubMedCrossRef
40.
de Franchis R. on behalf of the Baveno VI. Faculty Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63:743–52.PubMed
41.
Elfeki MA, Singal AK, Kamath PS. Pharmacotherapies for portal hypertension: current status and expanding indications. Curr Hepatol Rep. 2023;22:44–50.CrossRef
42.
Meijer B, Simsek M, Blokzijl H, de Man RA, Coenraad MJ, Dijkstra G, et al. Nodular regenerative hyperplasia rarely leads to liver transplantation: a 20-year cohort study in all Dutch liver transplant units. United Eur Gastroenterol J. 2017;5:658–67.CrossRef
43.
Krasinskas AM, Eghtesad B, Kamath PS, Demetris AJ, Abraham SC. Liver transplantation for severe intrahepatic noncirrhotic portal hypertension. Liver Transpl. 2005;11:627–34.PubMedCrossRef
44.
Druet A, Mosnier J-F, Corbineau E, Matysiak-Budnik T, Touchefeu Y, Viala C. Defibrotide for sinusoidal obstruction syndrome and nodular regenerative hyperplasia after oxaliplatin-based hepatic intra-arterial chemotherapy: a case report. Clin Colorectal Cancer. 2022;21:e98–101.PubMedCrossRef
45.
Chawla Y, Dhiman RK. Intrahepatic portal venopathy and related disorders of the liver. Semin Liver Dis. 2008;28:270–81.PubMedCrossRef
46.
Plessier A, Rautou P-E, Valla D-C. Management of hepatic vascular diseases. J Hepatol. 2012;56(1):S25–38.PubMedCrossRef
47.
• De Gottardi A, Sempoux C, Berzigotti A. Porto-sinusoidal vascular disorder. J Hepatol. 2022;77:1124–35. (An important review describing porto-sinusoidal vascular disorder as a novel clinical entity.)PubMedCrossRef
48.
Pugliese N, di Tommaso L, Lleo A, Alfarone L, Mastrorocco E, Terrin M, et al. High prevalence of porto-sinusoidal vascular disease in patients with constantly elevated gamma-glutamyl transferase levels. Liver Int. 2022;42:1692–5.PubMedCrossRef
Metadata
Title
Nodular Regenerative Hyperplasia
Authors
Pooja Abbey
Shalimar
Publication date
28-07-2023

Other articles of this Issue 3/2023

Current Hepatology Reports 3/2023 Go to the issue

ReviewPaper

Chemoprevention in hepatocellular carcinoma

ReviewPaper

Evidence-Based Strategies for Micro-elimination of Chronic Hepatitis B Virus Infection

ReviewPaper

An Overview of the Therapeutic Development of Cholangiocarcinoma with Special Emphasis on Targeted and Biologic Therapies

ReviewPaper

Non-invasive Assessment of Clinically Significant Portal Hypertension

ReviewPaper

Management of Portal Biliopathy

ReviewPaper

Extrahepatic Manifestations of Hepatitis B
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits