Histological characterization of liver involvement in systemic mastocytosis.

BACKGROUND AND AIMS: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools. METHODS: Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist. RESULTS: A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002). CONCLUSIONS: MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation.

Evidence for Alloimmune Sinusoidal Injury in De Novo Nodular Regenerative Hyperplasia After Liver Transplantation.

Posttransplant nodular regenerative hyperplasia (NRH) mostly remains unexplained. Microvascular injury due to antibody-mediated rejection (AMR) is suspected, but lack of donor specific antibody (DSA) testing makes it difficult to prove. Centered around a 1-year period of routine DSA testing, concomitant protocol, and indicated posttransplant liver biopsies (LB), recipients with NRH (n = 18) were compared with a matched control group (n = 36). All index, previous, and subsequent LB were reviewed. Both groups were similar in terms of demographics, timing of index LB, and DSA. In the index LB, the NRH group had higher sinusoidal C4d positivity (p = 0.029) and perisinusoidal fibrosis (p = 0.034), both independently associated with NRH (p = 0.038 and 0.050, respectively). Features of "possible" chronic AMR were detected in 28.5% of the NRH group without a known cause and 0% of the control group (p = 0.009). The NRH group had more preceding indicated LB with increased incidence of rejection and biliary obstruction pattern. In the follow-up histology, overall, sinusoidal and portal C4d positivity, sinusoidal microvasculitis, and perisinusoidal fibrosis were also higher (all p < 0.050). In conclusion, we provide evidence towards the hypothesis that some cases of posttransplant NRH are related to preceding active and persistent AMR. Large multicenter studies with protocol DSA testing are required to confirm.

Porto-sinusoidal vascular disorder.

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.

Evaluation of Laboratory and Sonographic Parameters for Detection of Portal Hypertension in Patients with Common Variable Immunodeficiency.

Timely detection of portal hypertension as a manifestation in a subgroup of patients with common variable immunodeficiency (CVID) represents a challenge since it is usually not associated with liver cirrhosis. To identify relevant markers for portal hypertension, we evaluated clinical history, laboratory parameters, and abdominal ultrasound including liver elastography and biomarkers of extracellular matrix formation. Twenty seven (6%) of 479 CVID patients presented with clinically significant portal hypertension as defined by either the presence of esophageal varices or ascites. This manifestation occurred late during the course of the disease (11.8 years after first diagnosis of CVID) and was typically part of a multiorgan disease and associated with a high mortality (11/27 patients died during follow up). The strongest association with portal hypertension was found for splenomegaly with a longitudinal diameter of > 16 cm. Similarly, most patients presented with a liver stiffness measurement (LSM) of above 6.5 kPa, and a LSM above 20 kPa was always indicative of manifest portal hypertension. Additionally, many laboratory parameters including Pro-C4 were significantly altered in patients with portal hypertension without clearly increasing the discriminatory power to detect non-cirrhotic portal hypertension in CVID. Our data suggest that a spleen size above 16 cm and an elevated liver stiffness above 6.5 kPa should prompt further evaluation of portal hypertension and its sequelae, but earlier and better liquid biomarkers of this serious secondary complication in CVID are needed.

Outcomes of idiopathic versus secondary nodular regenerative hyperplasia of the liver: A longitudinal study of 167 cases.

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.

Trastuzumab Emtansine-Induced Nodular Regenerative Hyperplasia: Is Dose Reduction Enough as a Preventable Measure?

INTRODUCTION: Trastuzumab emtansine (T-DM1) is a novel antibody-drug conjugate targeting the human epidermal growth factor receptor 2, used in some recurrent metastatic cancers. It was linked to modest increases in serum aminotransferase elevations and bilirubin. More recently, some cases of noncirrhotic portal hypertension have been described in patients on long-term T-DM1. The underlying liver condition is usually nodular regenerative hyperplasia (NRH) with elements of sinusoidal obstruction. CASE REPORT: We report the case of a 52-year-old woman who started T-DM1 therapy for recurrent metastatic lung adenocarcinoma. Although a progressive reduction in lung nodules was noticed, there was a new-onset cytocholestasis and elevation in bilirubin. A reduction in platelet count was also apparent over several months during the T-DM1 therapy. Liver biopsy revealed NRH and so the dose of T-DM1 was reduced. Thereafter, the patient had normalization of liver tests and platelet count. T-DM1 was continued for more than 9 months with no signs of portal hypertension or cancer progression. CONCLUSIONS: We presented a rare case of NRH induced by T-DM1 in a patient with lung adenocarcinoma. A high index of suspicion for liver injury and NRH must be maintained for patients who develop liver test abnormalities and/or signs of portal hypertension during treatment with T-DM1. This is the first report of a successful dose reduction in a patient with NRH induced by T-DM1, suggesting that it is possible to maintain the drug while it is being effective for lung cancer treatment.

[Nodular regenerative hyperplasia of liver caused by chemotherapy: magnetic resonance imaging features].

Objective: To investigate the MRI features of hepatic nodular regenerative hyperplasia (NRH) induced by chemotherapy. Methods: The clinical data and MRI of 20 cases with hepatic NRH induced by chemotherapy and confirmed by pathology in Zhongshan Hospital Fudan University from August 2014 to May 2019 were retrospectively analyzed. There were 13 males and 7 females, with an average age of 49.8 ± 9.7 years. Contrast-enhanced MR scan with Gd-DTPA was performed eighteen patients, and two patients underwent contrast-enhanced MR scan with hepatobiliary specific contrast (Gd-EOB-DTPA). The image analysis includes the number, location, size, shape, signal intensity in plain scan and enhancement pattern of lesions. The apparent diffusion coefficient (ADC) values of the lesions and adjacent hepatic parenchyma were measured on the ADC map, and the difference was compared with paired sample t test. Results: A total of 36 lesions in 20 patients were rounded or oval, including 23 (63.9%) lesions in the right lobe, 12 (33.3%) in the left lobe and 1 (2.8%) in the caudate lobe. The average diameter of all lesions was 15.4 ± 6.4 (7.0-37.0) mm. The boundary was clear in 9 (25.0%) lesions and blurred in 27 (75%) lesions. In T1WI, 35 (97.2%) lesions showed slightly hypointensity, and in 1 (2.8%) lesion was iosintensity. All 36 lesions showed slightly hyperintensity in T2WI. 33 (91.7%) lesions showed slightly hyperintensity in DWI, and 3 (8.3%) lesions showed iosintensity. 31 lesions with Gd-DTPA enhanced MR scan were significantly enhanced in the arterial phase and showed slightly high signal intensity in early portal vein phase, late portal vein phase and equilibrium phase. 5 lesions with Gd-EOB-DTPA enhanced MR scan were also significantly enhanced in the arterial phase and showed slightly high signal intensity in early portal vein phase, late portal vein phase and equilibrium phase, then all lesions showed circular high signal intensity in hepatobiliary specific phase. The average ADC value of 29 lesions was (1.471 ± 0.253) × 10(-3) mm(2)/s, and that of adjacent liver parenchyma was (1.460 ± 0.235) ×10(-3) mm(2)/s. There was no significant difference between the two groups (P > 0.05). Conclusion: MR findings of NRH induced by chemotherapy have certain characteristics, and the morphological manifestations, diffusion-weighted imaging, enhanced imaging and hepatobiliary specific phase features of the lesions can help to diagnose the disease.

Aberrant von Willebrand factor expression of sinusoidal endothelial cells and quiescence of hepatic stellate cells in nodular regenerative hyperplasia and obliterative portal venopathy.

AIMS: Nodular regenerative hyperplasia (NRH) and obliterative portal venopathy (OPV), entities that comprise idiopathic non-cirrhotic portal hypertension (INCPH), are under-recognised diseases of uncertain aetiology and the diagnosis can be easily missed on liver biopsy. The expression of CD34 and von Willebrand factor (vWF) in liver sinusoidal endothelial cells (LSEC) and alpha-smooth muscle actin (ASMA) in hepatic stellate cells (HSCs) is unknown in NRH and OPV. We sought to investigate the pathogenesis and potential immunomarkers that might aid in making the diagnosis of NRH and OPV. METHODS AND RESULTS: Immunohistochemical (IHC) staining for CD34, vWF and ASMA was performed in clinically and histologically well-characterised NRH (n = 15) and OPV (n = 47) liver specimens. Among the 47 OPV cases, 37 (78.7%) had concurrent features of NRH. CD34 positive staining was mainly confined to small vessels in the portal tracts and LSECs in periportal areas, a finding similar to that in non-NRH/OPV livers. However, expression of vWF in LSECs was positive in the compressed sinusoids of NRH and in a patchy or geographic pattern, particularly prominent in the perivenular areas and dilated sinusoids of OPV cases. HSCs were negative for ASMA in all NRH and OPV cases. CONCLUSION: Our findings indicate that NRH may be a subtle but common concurrent morphological feature in OPV. The aberrant expression of vWF in LSECs suggests that endothelial injury may play a role in the pathogenesis, which may thus aid in the recognition and diagnosis of NRH and OPV, particularly when confronted with otherwise apparent normal liver histology on needle biopsy.

Safety of trastuzumab after trastuzumab emtansine-induced nodular regenerative hyperplasia: A case report.

INTRODUCTION: Trastuzumab emtansine is an antibody-drug conjugate targeting the human epidermal growth factor receptor 2 use in recurrent metastatic breast cancer. Cases of trastuzumab emtansine-induced nodular regenerative hyperplasia are often reported as overt noncirrhotic portal hypertension with ascites and variceal bleeding. CASE REPORT: We report the case of a 61-year-old woman who present multiple stellate angiomas with gradual increased liver transaminases and reduced platelet count during a 27-months course on trastuzumab emtansine therapy for recurrent metastatic breast cancer. After the nodular regenerative hyperplasia was histologically confirmed, the trastuzumab emtansine was stopped. After two months, trastuzumab was restarted together with exemestane. During trastuzumab therapy, the patient had a normalization of liver transaminases, platelet count and a gradual improvement of her stellate angiomas. Trastuzumab was continued for 15 months without any reoccurrence of nodular regenerative hyperplasia. MANAGEMENT AND OUTCOME: Nodular regenerative hyperplasia should be suspected after one year of trastuzumab emtansine treatment in patients with signs of portal hypertension without cirrhosis. Definitive cessation of trastuzumab emtansine is required after a diagnosis of nodular regenerative hyperplasia and complete resolution of symptoms generally takes several months. DISCUSSION: Based on fundamental studies, nodular regenerative hyperplasia is probably caused by the emtansine (DM1) part of the trastuzumab emtansine. It is still unclear if trastuzumab therapy can be reintroduced after nodular regenerative hyperplasia induced by trastuzumab emtansine, depriving the patient of a HER2-targeted therapy. Only one case reported having given trastuzumab in this situation over one month. In our case, trastuzumab was reintroduced without any complications for a long extent following TDM1-associated nodular regenerative hyperplasia.

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

Background: Thioguanine is associated with liver toxicity, especially nodular regenerative hyperplasia (NRH). We assessed if liver histology alters during long-term maintenance treatment with thioguanine in patients with inflammatory bowel disease (IBD). Methods: Liver specimens of thioguanine treated IBD patients with at least two liver biopsies were revised by two independent liver pathologists, blinded to clinical characteristics. Alterations in histopathological findings between first and sequential liver specimen were evaluated and associated clinical data, including laboratory parameters and abdominal imaging reports, were collected. Results: Twenty-five IBD patients underwent sequential liver biopsies prior to, at time of, or after cessation of thioguanine treatment. The median time between the first and second biopsy was 25 months (range: 14-54). Except for one normal liver specimen, any degree of irregularities including inflammation, steatosis, fibrosis and some vascular disturbances were observed in the biopsies. The rates of perisinusoidal fibrosis (91%), sinusoidal dilatation (68%) and nodularity (18%) were the same in the first and second liver biopsies. A trend towards statistical significance was observed for phlebosclerosis (36% of the first vs. 68% of the second biopsies, p = .092). Presence of histopathological liver abnormalities was not associated with clinical outcomes. Furthermore, two patients in this cohort had portal hypertension in presence of phlebosclerosis. In another two patients, nodularity of the liver resolved upon thioguanine withdrawal. Conclusion: Vascular abnormalities of the liver were commonly observed in thioguanine treated IBD patients, although these were not progressive and remained of limited clinical relevance over time.

Clinicopathologic characteristics of de novo nodular regenerative hyperplasia in pediatric liver transplant.

Liver NRH is seen in all patients age; however, more frequently in those over the age of 60 years and associated with multiple systemic diseases. In liver allograft recipients, the development of DnNRH has been linked with the use of azathioprine or vascular abnormalities. We present the clinicopathologic characteristics of 17 pediatric patients who underwent liver transplantation and subsequently developed DnNRH. The patients were divided into early and late onset depending if DnNRH was diagnosed within or beyond 4 years after transplant. Eight patients (47%) presented as early onset, of which two had normal ultrasound at time of diagnosis. One patient (12.5%) with early onset lost the graft secondary to DnNRH. Nine patients (53%) presented as late onset, of which two (22%) had normal ultrasound at time of diagnosis. Two patients (25%) of the late onset lost their graft secondary to chronic rejection and DnNRH. Two patients (12%) died secondary to cytomegalovirus pneumonitis and pancolitis. Furthermore, both groups presented with symptoms differing from the adult population in prior studies and were not associated with the use of azathioprine or vascular abnormalities. Interestingly, episodes of acute cellular rejection were more common in the early-onset group compared to the late-onset group. In conclusion, DnNRH in the pediatric age group has a different clinical presentation, possibly reflecting a different pathogenesis compared to the adult population.

Clinical features of idiopathic portal hypertension in China: A retrospective study of 338 patients and literature review.

BACKGROUND AND AIM: Idiopathic portal hypertension (IPH) refers to a relatively rare condition characterized by intrahepatic portal hypertension in the absence of underlying disease such as liver cirrhosis. METHODS: We retrospectively reviewed 338 patients with IPH that were diagnosed at the pathological consultation center of our hospital. RESULTS: The ratio of male to female patients was 1:1. Mean age at onset was 35.1 ± 16.5 years; male patients on average were 12 years younger than female patients at onset. The median duration from onset to IPH diagnosis was 12 months. In 50 patients, medication use may have been an etiological factor. The most common clinical manifestations were splenomegaly (91.3%) and hypersplenism (68.9%); 57.0% patients presented varicosis, while 25.1% patients had a history of variceal bleeding. Nodular regenerative hyperplasia was found in 22.2% liver biopsies. Among patients for whom laboratory data were available, 65.0%, 50.3%, and 71.4% patients presented leukopenia, anemia, and thrombocytopenia due to hypersplenism. Liver function was mostly in the compensated stage. Female patients showed worse leukopenia and anemia, while male patients were more likely to have abnormal serum transaminase and bilirubin levels. Sixty-seven patients received surgical or interventional treatment. CONCLUSIONS: High-quality liver biopsy, detailed clinical information, and expert pathologist are necessary for diagnosis of IPH. IPH can occur concurrently with other liver disease such as hepatitis and drug-induced liver injury. Medication appears to be an important etiological factor for IPH in China. Management approach was largely focused on treatment of portal hypertension and its complications.

Idiopathic noncirrhotic portal hypertension.

Cirrhosis is the most common cause of portal hypertension but there are many causes of noncirrhotic portal hypertension. Many of these etiologies may be diagnosed by liver biopsy. Idiopathic noncirrhotic portal hypertension is being increasingly diagnosed and has varied histopathological findings as well as overlapping definitions. Many of these histological changes can be subtle, thus making it a challenging diagnosis for the pathologist to make. This review summarizes the clinical aspects of idiopathic noncirrhotic portal hypertension and outlines the different definitions and histological features of the entity. In addition, pearls and pitfalls for the pathologist in making this diagnosis are included.

Hepatic manifestations of telomere biology disorders.

A 51-year-old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia with no significant fibrosis or necroinflammatory activity. Hepatic venous pressure gradient was elevated at 31 mmHg, consistent with clinically significant portal hypertension. The clinical course was complicated by refractory gastric variceal bleeding requiring a surgical portosystemic shunt. Approximately seven years after the initial presentation, the patient developed progressive dyspnoea and a diagnosis of idiopathic pulmonary fibrosis was made. Contrast-enhanced echocardiogram was not suggestive of hepatopulmonary syndrome or portopulmonary hypertension. Given this new diagnosis a telomere biology disorder was suspected. A flow-fluorescence in situ hybridisation analysis for telomere length assessment revealed telomere lengths below the first percentile in both lymphocytes and granulocytes. Next generation sequencing analysis identified a heterozygous mutation involving the hTERT gene (Histidine983Threonine). The lung disease unfortunately progressed in the subsequent two years, leading to the patient's death nine years after his initial presentation with portal hypertension. During those nine years two brothers also developed idiopathic pulmonary fibrosis. The questions that arise from this case include.

Nodular Regenerative Hyperplasia Induced by Trastuzumab Emtansine: Role of Emtansine?

Trastuzumab is a monoclonal antibody targeted against the Human Epidermal Growth Factor Receptor 2 (HER2) overexpressed in some breast cancer. This targeted therapy significantly improves the prognosis of these cancers. Recently an anti-HER2 antibodydrug conjugate was shaped in order to facilitate the targeted delivery of potent cytotoxic drug to cancer cells and to reduce resistance. This formulation, called trastuzumab emtansine (T-DM1), consists of the monoclonal antibody trastuzumab linked to a cytotoxic drug (a derivative of maytansine) via a chemical linker. Little is known about adverse reactions due to this new formulation. Herein we described the case of a woman suffering from a HER2-positive breast cancer, treated with trastuzumab for 30 months followed by T-DM1 monotherapy. After 12 months of T-DM1 treatment, a nodular regenerative hyperplasia confirmed by liver biopsy occurred. T-DM1 was stopped and medical imagery showed a resolution of the nodular regenerative hyperplasia. Unfortunately, hepatic metastasis progressed. Few cases of nodular regenerative hyperplasia induced by T-DM1 have been described so far. Further studies are needed to explore pathogenesis of nodular regenerative hyperplasia with this new antibody-drug conjugate treatment.

Reversibility of chemotherapy-related liver injury.

BACKGROUND & AIMS: Chemotherapy-associated liver injury (CALI) increases the risk of liver resection and may prejudice further surgery and chemotherapy. The reversibility of CALI is therefore important; however, no data concerning this are available. This study aimed to retrospectively analyze the reversibility of CALI in patients undergoing liver resection for colorectal metastases. METHODS: All resections of colorectal liver metastases after oxaliplatin and/or irinotecan-based chemotherapy were included. First, liver resections were stratified by time between end of chemotherapy and hepatectomy and several possible cut-off values tested. CALI prevalence in various groups was compared. Second, CALI in the two specimens from each patient who had undergone repeat liver resections without interval chemotherapy were compared. RESULTS: Overall, 524 liver resections in 429 patients were analyzed. The median interval chemotherapy-surgery was 56days (15-1264). CALI prevalence did not differ significantly between groups with a chemotherapy-surgery interval <270days. Grade 2-3 sinusoidal dilatation (SOS, 19.4% vs. 40.0%, p=0.022) and nodular regenerative hyperplasia (NRH, 6.5% vs. 20.1%, p=0.063) occurred less frequently in patients with an interval >270days (n=31); prevalence of steatosis and steatohepatitis was similar in all groups. A chemotherapy-surgery interval >270days was an independent protector against Grade 2-3 SOS (p=0.009). Forty-seven patients had repeat liver resection without interval chemotherapy. CALI differed between surgeries only for a chemotherapy-surgery interval >270days (n=15), Grade 2-3 SOS having regressed in 4/5 patients and NRH in 7/8; whereas steatosis and steatohepatitis had persisted. CONCLUSIONS: CALI persists for a long time after chemotherapy. SOS and NRH regress only after nine months without chemotherapy, whereas steatosis and steatohepatitis persist. LAY SUMMARY: The patients affected by colorectal liver metastases often receive chemotherapy before liver resection, but chemotherapy causes liver injuries that may increase operative risks and reduce tolerance to further chemotherapy. The authors analyzed the reversibility of the liver injuries after the chemotherapy interruption. Liver injuries persist for a long time after chemotherapy. Sinusoidal dilatation and nodular regenerative hyperplasia regress only nine months after the end of chemotherapy, whereas steatosis and steatohepatitis persist even after this long interval.

Prevalence and clinical significance of nodular regenerative hyperplasia in liver biopsies.

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare histological disorder associated with a wide variety of systemic diseases. AIMS: We aimed (i) to report the prevalence of NRH in a database of liver biopsies (LBs) and the frequency of portal hypertension (PHT) at diagnosis, and (ii) to investigate whether associated diseases and/or specific histological lesions, including abnormalities of the microvasculature, were related to PHT. METHODS: Patients with a histological diagnosis of NRH, referred by seven clinical departments, were retrospectively selected. Clinical, biological, radiological, haemodynamic and endoscopic data at diagnosis were recorded. LBs were reassessed for microvascular abnormalities. RESULTS: NRH was diagnosed in 4.4% of LBs (n = 159, male: 52%, mean age: 54). Among patients referred for unexplained liver enzyme abnormalities, 15% had NRH. PHT was present at diagnosis in 45 patients (38%), including 13 with portal thrombosis; 65% of patients had an associated disorder. Obliteration of portal vein branches, observed in the LBs of 17 patients (11%), was significantly associated with PHT (P = 0.02). Periportal angiomatosis, observed in 101 patients (63%), was associated with the absence of PHT (P < 10(-4) ). CONCLUSION: We suggest that NRH is a frequent histological lesion in the setting of unexplained liver enzyme abnormalities. PHT is present at the time of diagnosis in 1/3 of patients regardless of the presence of associated disease. The frequency of periportal angiomatosis in NRH without obliteration of portal vein branches, and its association with the absence of PHT suggest that obstructive portal venopathy would not represent the most frequent mechanism involved in NRH.