Nodular regenerative hyperplasia of the liver and antiphospholipid antibodies: report of two cases and review of the literature

Nodular regenerative hyperplasia of the liver (NRHL) is a rare disorder characterized by diffuse micronodular transformation of the hepatic parenchyma without fibrous septa between the nodules. This condition appears to be associated in many occasions with systemic autoimmune diseases. We describe two new patients with NRHL in whom antiphospholipid antibodies (aPL) were detected in their sera and review the few similar cases reported previously. We also discuss the possible relationship between aPL and NRHL and suggest that these antibodies may play a role in the pathogenesis of some cases of NRHL, specially those with an associated antiphospholipid syndrome.     

Nodular regenerative hyperplasia of the liver. Study of 15 cases and review of the literature

The authors report 15 cases of nodular regenerative hyperplasia (NRH) of the liver observed in 10 women and 5 men during a 9 year period. Gastrointestinal bleeding due to ruptured esophageal varices revealed the liver disease in 11 cases. Hepatomegaly and splenomegaly were noted in 9 cases and ascites in 7. Anicteric cholestasis was demonstrated in 10 cases. Another disease, e. g. myelofibrosis and monoclonal gammapathy, was present in 11 patients. In 10 patients, portal diversion was performed; outcome being favorable with a follow-up of one to six years. The analysis of these cases and of the 113 previously published reports calls for the following comments: 1) In most cases, NRH is characterized by small-sized hepatocytic nodules scattered throughout the entire liver with no surrounding fibrosis; however this histological pattern may vary somewhat, with adjacent normal zones being found adjacent to typical cirrhotic fibrosis; although a precise morphometric study was not performed in our patients, obstruction of the tiny branches of intrahepatic portal veins was not observed. 2) Histological diagnosis of NRH is difficult and in most cases requires surgical biopsy specimens and specific coloration of the reticulin network. 3) NRH must be considered as a new cause of intrahepatic (sinusoidal or presinusoidal) portal hypertension and/or of chronic anicteric cholestasis. 4) A number of various conditions may be associated with NRH, the most frequent being Felty's syndrome and myeloproliferative disorders. 5) The pathogenesis of NRH remains unknown. 6) Portal diversion generally has a favorable outcome in this disease.     

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。     

Nodular regenerative hyperplasia of the liver. A review of 14 cases.

BACKGROUND/AIMS: Nodular regenerative hyperplasia of the liver, is a noncirrhotic liver disease, characterized by nodules in the hepatic parenchyma, which clinically presents primarily with manifestations of portal hypertension. The aims of this study are i) to review the clinical, histological and diagnostic aspects of 14 documented cases of NRHL, and ii) to assess the evolution and management of this condition in the cases reviewed. METHODOLOGY: The diagnosis of nodular regenerative hyperplasia of the liver was based on liver biopsy in all cases. Imaging studies (ultrasonography, computed tomography scan and magnetic resonance imaging scan) were performed as part of the diagnostic evaluation. Clinical manifestations and biochemical tests were recorded at the time of diagnosis. Management and prognosis were also reviewed. RESULTS: The most common clinical manifestations were those of portal hypertension, namely splenomegaly, esophageal varices and variceal bleeding. The histological findings were nodules in the hepatic parenchyma, the typical histologic feature of nodular regenerative hyperplasia of the liver, with mild periportal fibrosis and intraportal lymphocytic infiltration. Biochemical tests showed normal synthetic liver function, as evidenced by normal serum albumin, bilirubin and prothrombin time. Elevation of gamma-glutamyl transpeptidase and alkaline phosphatase due to cholestasis was noted. Management was directed to portal hypertension and variceal bleeding, with beta-blockers, sclerotherapy, mesenteric-caval shunt and transjugular intrahepatic portosystemic shunt with satisfactory results. CONCLUSIONS: Nodular regenerative hyperplasia of the liver is an uncommon condition but it should be considered in patients with unexplained portal hypertension and distinguished from liver cirrhosis, in view of the differences in the natural history and prognosis. Liver biopsy confirms the diagnosis. Management is directed primarily to portal hypertension and variceal bleeding, which is the main source of mortality. Liver failure is uncommon due to satisfactory preservation of liver function.     

Nodular regenerative hyperplasia of the liver and Hodgkin's disease: a case report

Nodular regenerative hyperplasia (NRH) of the liver is a rare entity characterized by the presence of nodules in the hepatic parenchyma, not surrounded by fibrous septa. The pathogenesis and etiology are unknown but an association with different diseases including some hematological disorders has been described. Its association with Hodgkin's disease is infrequent. We report the case of a 63 years old man who presented symptoms and signs of portal hypertension, hepatocellular failure with progressive deterioration and death. Postmortem examination disclosed Hodgkin's disease with hepatosplenic involvement and NRH of the liver. The association of these entities could be explained by the presence of portal infiltration contributing to portal venous obliteration and leading to portal hypertension and formation of the parenchymal nodules characteristic of this entity. Other mechanisms that could cause or influence this association can not be ruled out.     

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 of the liver associated with the toxic oil syndrome: report of five cases

Nodular regenerative hyperplasia of the liver developed in five patients who had the toxic oil syndrome caused by ingestion of adulterated cooking oil. This hepatic complication was detected from 19 to 37 months (mean-2.5 years) after the onset of the toxic oil syndrome. Nodular regenerative hyperplasia was asymptomatic, although all patients had persistently abnormal liver function. Hepatomegaly was present in four cases, mild jaundice in three and signs of portal hypertension in two. Pathogenesis of nodular regenerative hyperplasia in toxic oil syndrome is unknown, but probably microcirculatory disturbances within the liver might have played a role. Fibrosis in Zone 3, sinusoidal dilatation and occasionally intralobular hemorrhage were seen in three cases; in one of them, characteristic lesions of veno-occlusive disease were also present. In another case, endarteritis changes of hepatic arterioles were evident.     

12例肝结节状再生性增生临床分析

目的对肝结节状再生性增生（NRHL）的临床、病理及诊断分析总结，期望提高临床医师对本病的认识。方法从300例因脾功能亢进而行脾切除和肝脏活组织检查病例中选出病理诊断符合NRHL的病例12例，分析其病史、临床症状和体征、实验室检查、诊断及处理等资料，且随访治疗效果。结果12例NRHL中6例明确诊断为系统性红斑狼疮，1例克罗恩病，1例疑诊溃疡性结肠炎。应用肾上腺皮质激素治疗6例，免疫抑制剂3例。11例有门脉高压；所有患者均无病毒性肝炎史；肝功能轻度受损；病理特征为肝实质内结节状再生性增生，门脉周围轻度纤维化和汇管区散在淋巴细胞浸润，门静脉分支狭窄和闭塞，无肝坏死表现；术前均被诊断为肝硬化伴门脉高压；行手术治疗后临床症状明显缓解，随访患者多数病情稳定。结论NRHL可能与免疫和肝脏血液循环障碍有关；以门脉高压为主要表现，应与肝硬化鉴别；诊断依靠肝脏楔形活检；处理门脉高压可使临床状况得到改善。     

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 and the Budd-Chiari syndrome. Case report, review of the literature and reappraisal of pathogenesis

We report a case of nodular regenerative hyperplasia (NRH) of the liver associated with the Budd-Chiari syndrome in a patient whose clinical and radiological presentation suggested a diagnosis of multiple liver tumours. Based on both our study and a review of the literature, it appears that, in a number of cases of NRH associated with various clinical conditions, blood stasis at the sinusoidal level is the common denominator. We postulate that, in this situation, the prolonged exposure of hepatocytes to blood-borne hepatotrophic substances, such as hepatopoietins, glucagon and insulin, in combination with functional loss due to pressure injury within the congested areas, may be one of the mechanisms leading to the development of NRH.     

肝结节状再生性增生18例临床分析

我院自1983年至2008年共收治18例肝结节状再生性增生(NRH)患者,现将其临床资料总结分析如下. 一、临床资料 1.一般资料:本组患者男6例,女12例,发病年龄22～70岁(中位年龄39岁),病程1个月～6年.18例患者均无肝脏病史,其中3例因体检发现肝脏占位性病变就诊,15例因门静脉高压症就诊.后者中10例合并自身免疫性疾病,其中确诊系统性红斑狼疮5例,未分化型结缔组织疾病4例,炎症性肠病1例.     

Nodular regenerative hyperplasia of the liver diagnosed by needle biopsy of the liver: Report of a case and review of the literature

The authors report the case of a 45 year old woman in whom the diagnosis of nodular regenerative hyperplasia of the liver was made by needle biopsy of the liver, laparoscopy and hepatic venography. The patient did not have any underlying disorders and had not ingested any of the many drugs and chemicals which may produce the lesion. Clinical manifestations were hepatosplenomegaly, portal hypertension and iron deficiency anaemia, and her condition remains unchanged 5 years after diagnosis.     

Coexistence of nodular regenerative hyperplasia of the liver and pulmonary arterial hypertension in patients with connective tissue diseases: report of three cases and review of the literature

Abstract

Nodular regenerative hyperplasia of the liver (NRH) is known to be a rare condition in patients with connective tissue diseases (CTD). In this report, we document three patients with CTD who had both NRH and pulmonary hypertension (PH). All three patients developed PH during their course and thereafter developed NRH. The clinical course of these patients suggests that circulatory disturbance caused by PH might be a trigger for NRH.     

Coexistence of nodular regenerative hyperplasia of the liver and pulmonary arterial hypertension in patients with connective tissue diseases: report of three cases and review of the literature

Nodular regenerative hyperplasia of the liver (NRH) is known to be a rare condition in patients with connective tissue diseases (CTD). In this report, we document three patients with CTD who had both NRH and pulmonary hypertension (PH). All three patients developed PH during their course and thereafter developed NRH. The clinical course of these patients suggests that circulatory disturbance caused by PH might be a trigger for NRH.