Nodular regenerative hyperplasia:Evolving concepts on underdiagnosed cause of portal hypertension

Nodular regenerative hyperplasia(NRH)is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules.NRH may lead to the development of non-cirrhotic portal hypertension.There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series.NRH may develop via autoimmune,hematological,infectious,neoplastic,or drug-related causes.The disease is usually asymptomatic,slowly or nonprogressive unless complications of portal hypertension develop.Accurate diagnosis is made by histopathology,which demonstrates diffuse micronodular transformation without fibrous septa.Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver.While the initial treatment is to address the underlying disease,ultimately the therapy is directed to the management of portal hypertension.The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension.In this review we detail the epidemiology,pathogenesis,diagnosis,management,and prognosis of NRH.

Nodular Regenerative Hyperplasia of Liver Mimicking Cirrhosis: a Case Report

A 34-year-old man with no history of any abdominal pain or fatigue was admitted to our hospital in June 2008 due to the cirrhosis found incidentally during a physical examination. Laboratory examination, electrocardiograph, abdominal ultrasonography and magnetic resonance imaging were carried out during his hospitalization. However, according to the results of the above measures, the diagnosis of nodular regenerative hyperplasia of the liver (NRHL) could not be made. The result of electrocardiograph showed there was no sinus bradycardia. The abdominal ultrasonography showed evidence of hepatosplenomegaly, and magnetic resonance imaging showed multiple non-enhancing hepatic nodules. Histologic conifrmation was available by means of liver biopsy and the deifnitive diagnosis of NRHL was conifrmed histologically by liver biopsy. NRHL always presents with signs of portal hypertension with little evidence of obvious liver disease, NRHL may mimick the cirrhosis of liver and be easily confused with cirrhosis of the liver nodules, so liver biopsy should be recommended for correct diagnosis. The clinical, radiological and pathologic features of this case with NRHL was reported in order to familiarize the physicians with its clinical manifestations.

Non-cirrhotic portal hypertension with large regenerative nodules: A diagnostic challenge

Non-cirrhotic portal hypertension is a poorly understood condition characterized by portal hypertension in the absence of conventional hepatic cirrhosis and described in association with blood coagulation disorders, myeloproliferative and immunological diseases and with exposure to toxic drugs. Very recently, precise classification criteria have been proposed in order to define four distinct subcategories. The present case highlights how the clinical presentation, the confounding results from imaging studies, and the difficulties in the histological evaluation often render cases of non-cirrhotic portal hypertension a real diagnostic challenge. It also underscores the classification problems which can be faced once this diagnosis is performed. Indeed, the different subcategories proposed result from the prevalent subtypes in a spectrum of hepatic regenerative responses to a variety of injuries determining microcirculatory dis-turbances. More flexibility in classification should derive from this etiopathogenic background.

Pseudocirrhosis in a pancreatic cancer patient with liver metastases: A case report of complete resolution of pseudocirrhosis with an early recognition and management

We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.

Prevalence of significant liver disease in human immunodeficiency virus-infected patients exposed to Didanosine: A cross sectional study

AIM To identify significant liver disease [including nodular regenerative hyperplasia(NRH)] in asymptomatic Didanosine(DDI) exposed human immunodeficiency virus(HIV) positive patients.METHODS Patients without known liver disease and with > 6 mo previous DDI use had liver stiffness assessed by transient elastography(TE). Those with alanine transaminase(ALT) above upper limit normal and/or TE > 7.65 k Pa underwent ultrasound scan(U/S). Patients with:(1) abnormal U/S; or(2) elevated ALT plus TE > 7.65 k Pa;or(3) TE > 9.4 k Pa were offered trans-jugular liver biopsy(TJLB) with hepatic venous pressure gradient(HVPG) assessment.RESULTS Ninety-nine patients were recruited, median age 50 years(range 31-70), 81% male and 70% men who have sex with men. Ninety-five percent with VL < 50 copies on antiretroviral therapy with median CD4 count 639 IU/L. Median DDI exposure was 3.4 years(range 0.5-14.6). Eighty-one had a valid TE readings(interquartile range/score ratio < 0.3): 71(88%) < 7.65 k Pa, 6(7%) 7.65-9.4 k Pa and 4(6%) > 9.4 k Pa. Seventeen(17%) met criteria for TJLB, of whom 12 accepted. All had HVPG < 6 mm Hg. Commonest histological findings were steatosis(n = 6), normal architecture(n = 4) and NRH(n = 2), giving a prevalence of previously undiagnosed NRH of 2%(95%CI: 0.55%, 7.0%).CONCLUSION A screening strategy based on TE, liver enzymes and U/S scan found a low prevalence of previously undiagnosed NRH in DDI exposed, asymptomatic HIV positive patients. Patients were more likely to have steatosis highlighting the increased risk of multifactorial liver disease in this population.

Challenge of liver disease in systemic lupus erythematosus:Clues for diagnosis and hints for pathogenesis

Systemic lupus erythematosus(SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows:(1) immunological comorbilities(overlap syndromes);(2) non-immunological comorbilities associated to SLE; and(3) a putative liver damage induced by SLE itself, referred to as "lupus hepatitis". In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus(e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis.