TY - JOUR
T1 - Outcomes of idiopathic versus secondary nodular regenerative hyperplasia of the liver
T2 - A longitudinal study of 167 cases
AU - Penrice, Daniel D.
AU - Thakral, Nimish
AU - Kezer, Camille A.
AU - Lennon, Ryan
AU - Moreira, Roger K.
AU - Graham, Rondell P.
AU - Kamath, Patrick S.
AU - Simonetto, Douglas A.
N1 - Funding Information:
A cohort of 167 patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was made by expert liver pathologists and it was based on previously established criteria proposed by Wanless and colleagues, however, individual biopsy nodularity grades were not available.6,16 Ninety-three slides were still stored at our institution in 2021 and were independently re-reviewed by two expert pathologists. Of the 93 slides that were re-reviewed, 77 (83%) were definitively confirmed to have NRH, with the remaining 16 slides showing indeterminate features. For slides to be considered NRH on re-review, they were required to have biopsy with minimum length of 1 cm and include at least 10 portal spaces. These 16 subjects whose slides showed indeterminate features were excluded from our cohort. Liver tissue in all cases was obtained by percutaneous needle biopsy. Additionally, reticulin staining to confirm the presence of nodules was performed in the majority of cases (81%). Patients with metastatic liver disease, history of liver transplantation, or younger than 18 years of age were excluded. Demographical data, family history, associated conditions, drug exposure prior to diagnosis, initial presenting symptoms, laboratory values and outcomes were abstracted from electronic medical records (EMR). Time zero was considered the date of liver biopsy from which the diagnosis of NRH was made. Follow-up data were collected through 2018. Patients were classified as idiopathic or primary NRH if no known associated, possibly causal, conditions were identified. Associated conditions were classified as haematological, rheumatological, drug-associated or other/multiple based on documentation of the various disorders in the medical history. The EMR was manually reviewed for each patient to assess for documentation of the following haematological diseases: amyloidosis, idiopathic thrombocytopenic purpura, polycythaemia vera, monoclonal gammopathy, multiple myeloma, POEMS syndrome, chronic lymphocytic leukaemia, myelofibrosis, myelodypslasic syndrome/myeloprofliferative neoplasm, Hodgkin’s lymphoma, diffuse large B-cell lymphoma, T-cell lymphoma and non-Hodgkin’s lymphoma. The following rheumatological diagnoses were included in the chart review: rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, progressive systemic sclerosis, CREST syndrome, Felty’s syndrome and mixed connective tissue disease. The EMR was also reviewed for documentation of primary biliary cholangitis, coeliac disease, tuberculosis and other malignancies. For each of the aforementioned associated, possibly causal, conditions, the individual charts were evaluated using a search function. If there was no documentation of the associated diagnosis, the patient was not considered to have the medical condition. The following drugs were considered as relevant drug exposures in the development of NRH: azathioprine, 6-thioguanine, doxorubicin, cyclophosphamide, chlorambucil and bleomcyine. The patient was considered as having a drug exposure if this drug was prescribed at any point in their history for a minimum duration of 6 months prior to the diagnosis of NRH. The time between drug exposure and NRH diagnosis was variable. If upon searching the EMR, the drug was not listed as a prior medication for a minimum of 6 months duration, they were not considered to have exposure to the drug. Continuous variables are summarized as mean (standard deviation) while discrete data are presented as frequency (percentage). Group differences were compared using Wilcoxon sign rank test for continuous variables and Pearson’s chi-squared test for discrete variables. Long-term mortality and transplant-free mortality were estimated using Kaplan-Meier methods. Unadjusted associations with mortality are presented as hazard ratios (95% confidence intervals) and estimated via Cox proportional hazards regression models. The incidence of hepatic complications over time was estimated using competing risks analysis, with mortality as a competing event. Summaries of these complications are given as overall number of events observed, and the estimated incidence rate at 10 years as a percentage. A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models.
Publisher Copyright:
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2022/6
Y1 - 2022/6
N2 - Background: Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non-cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. Methods: A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models. Results: One hundred and sixty-seven consecutive patients with pathology-confirmed NRH were analysed over a 15-year period and followed for a median time of 50 months (1–306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension-related complications at diagnosis were common, with ascites present in one-third of patients. Overall transplant-free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. Conclusions: The rates of liver-related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver-related outcomes do not appear to differ based on associated, possibly causal, conditions.
AB - Background: Nodular regenerative hyperplasia (NRH) is a rare condition characterized clinically by the development of non-cirrhotic portal hypertension. NRH is the histopathological result in the liver of various systemic disease processes including autoimmune disorders, haematological malignancies and medications. However, natural history of this condition has been limited to small case series while patient outcomes pertaining to different aetiologies of NRH are largely unknown. Methods: A retrospective cohort of consecutive patients diagnosed with pathology-confirmed NRH at Mayo Clinic between 2002 and 2017 was identified. The histological diagnosis of NRH was determined by expert liver pathologists. Patients with metastatic liver disease, history of liver transplantation or younger than 18 were excluded. Potential aetiologies of NRH were classified as haematological, rheumatological, drug-associated, miscellaneous or idiopathic. Long-term mortality was analysed using Kaplan-Meier estimation and Cox regression models. Results: One hundred and sixty-seven consecutive patients with pathology-confirmed NRH were analysed over a 15-year period and followed for a median time of 50 months (1–306 months). The mean age at diagnosis was 53 years. No aetiology or risk factor for NRH was identified in the majority of patients (94, 56.3%), whereas an associated, possibly causal, condition was found in 73 patients (secondary NRH). The most common presenting feature was elevated liver tests (80%), but no significant differences in laboratory tests were seen based on aetiology of NRH. Compared to idiopathic NRH, those with an identified cause had a higher rate of splenomegaly at presentation (54% vs. 27%, p = 0.002). Portal hypertension-related complications at diagnosis were common, with ascites present in one-third of patients. Overall transplant-free survival was 63% at 5 years. Median survival in idiopathic NRH was 9.4 years compared to 7.3 years in secondary NRH. Age, renal function and volume status at presentation were significantly associated with survival; however, MELD score was not. Conclusions: The rates of liver-related complications and mortality in NRH are low, and only a small number of patients ultimately require liver transplantation. Most patients do not have an identified risk factor or aetiology for NRH, and liver-related outcomes do not appear to differ based on associated, possibly causal, conditions.
KW - cirrhosis
KW - nodular regenerative hyperplasia
KW - non-cirrhotic portal hypertension
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U2 - 10.1111/liv.15202
DO - 10.1111/liv.15202
M3 - Article
C2 - 35187783
AN - SCOPUS:85125409145
SN - 1478-3223
VL - 42
SP - 1379
EP - 1385
JO - Liver International
JF - Liver International
IS - 6
ER -