A case of idiopathic portal hypertension after renal transplantation

A case of idiopathic portal hypertension (IPH) developing after renal transplantation is reported. A 33-year-old Japanese male who had undergone renal transplantation 8 years previously was transferred to our hospital because of hematemesis from ruptured esophageal varices. He had no history of any liver disease before the renal transplantation, but had a history of receiving blood transfusion. Abdominal computed tomography (CT) and ultrasonography revealed marked splenomegaly and collateral channels, but no obliteration which might cause portal hypertension in the hepatic or portal vein. No findings suggestive of hepatitis or liver cirrhosis were found either macroscopically on laparoscopy or by liver biopsy. Light microscopic study of the liver biopsy specimen showed mild periportal fibrosis, inconspicuous portal branches in the most peripheral tracts, but no pseudolobule formation or piecemeal necrosis. However collagen deposition was found in the perisinusoidal space and partly in intercellular space on electron microscopy. We consider that the development of portal hypertension in this case is responsible for the collagen deposition, which may be related to the administration of azathioprine after renal transplantation. There are few reports on IPH after renal transplantation, and it is stressed that a lower amount of azathioprine than previously reported may induce IPH under such conditions.     

Portal-systemic shunting in a patient with normal portal vein pressures and histological evidence of idiopathic portal hypertension

Although idiopathic portal hypertension (IPH) is clinically characterized by portal hypertension and marked splenomegaly, we have experienced a case of spontaneous portal-systemic shunt without splenomegaly in whom the liver histology resembled IPH but with normal portal pressure. We admitted a 64 year old man who had suffered from hepatic encephalopathy for 2 years. Laparoscopy revealed a dark grey liver with a sharp edge and a concave surface. Examination of a liver biopsy specimen revealed peri-portal fibrosis consistent with IPH. A single, large, portal-systemic shunt was identified by percutaneous transhepatic portography. The shunt arose from the left gastric vein and flowed through the left renal vein into the inferior vena cava. No varices were identified. There were no morphological changes in the hepatic or portal veins. Portal vein pressure was normal. There was a slight difference between the portal pressure and the wedged hepatic vein pressure, suggesting a presinusoidal block. This case raises important questions concerning the aetiology of IPH and the relationship between portal hypertension and the development of collateral venous circulation.     

特发性门脉高压肝移植术后随访第3年再发1例报告及文献复习

目的 复习1例特发性门脉高压(IPH)患者接受肝移植(LT)后第3年出现病情“再发”,并进行了相关文献复习,以提高对该病的认识。方法 报道1例我们诊治的IPH患者的病例资料,并检索MEDLINE、EMBASE、万方等数据库经LT治疗的IPH患者的研究报道,分析其治疗和转归。结果 本文报道的病例为57岁女性,因消化道出血、腹水行LT术,组织病理学检查诊断为IPH;术后随访第3年病情复发,行经皮肝穿刺活检术,病理学检查提示结节性再生性增生(NRH)、轻度汇管区炎症及纤维化,提示IPH再发;文献检索到81例LT治疗的IPH患者,其中42例在LT前诊断为肝硬化;LT后最长随访时间为248个月,8例死亡,其中5例分别在首次LT后3.5月～14年进行肝活检,组织病理学检查提示NRH,3例分别于LT后第7月、第3年和第14年出现具有门脉高压表现的NRH。结论 具有严重的门脉高压或肝功能衰竭的IPH患者需要LT治疗。少数患者在LT后可能出现IPH“再发”。     

Acute Deterioration of Idiopathic Portal Hypertension Requiring Living Donor Liver Transplantation: A Case Report

Case reports of severe idiopathic portal hypertension (IPH) requiring liver transplantation are very rare. We report the case of a 65-year-old woman who was diagnosed as having IPH. At the age of 60 years, her initial symptom was hematemesis, due to ruptured esophageal varices. Computed tomography of the abdomen showed splenomegaly and a small amount of ascites, without liver cirrhosis. She was diagnosed as having IPH and followed-up as an outpatient. Five years later, she developed symptoms of a common cold and rapidly progressive abdominal distension. She was found to have severe liver atrophy, liver dysfunction, and massive ascites. Living donor liver transplantation was then performed, and her postoperative course was uneventful. Histopathological findings of the explanted liver showed collapse and stenosis of the peripheral portal vein. The areas of liver parenchyma were narrow, while the portal tracts and central veins were approximate one another, leading to a diagnosis of IPH. There was no liver cirrhosis. The natural history of refractory IPH could be observed in this case. Patients with end-stage liver failure due to severe IPH can be treated by liver transplantation.     

21例特发性门脉高压临床及病理特点分析

目的分析特发性门脉高压(idiopathic portal hypertension,IPH)的临床及病理特点。方法回顾性分析2012年1月—2016年12月在解放军第三〇二医院住院治疗(资料完整)的21例IPH患者的临床及病理特点。结果 21例IPH患者中,男女比例6∶15,平均发病年龄(38.1±12.7)岁,临床以门脉高压症表现为主,肝功能无明显减退,主要并发症为上消化道出血及腹水。21例肝组织病理主要表现为肝细胞板排列基本正常,无假小叶形成,汇管区扩大,门静脉周围纤维化,门脉周围有不同程度的细胞浸润,血管紊乱,中央静脉及小叶间静脉扩张,肝窦扩张,窦周纤维化。结论 IPH患者门脉高压和肝功能损害不平行,门脉高压表现较重,确诊仍须病理学检查,治疗以防治并发症为主。     

A case of idiopathic portal hypertension associated with systemic lupus erythematosus

A 29-year-old male who was diagnosed as having systemic lupus erythematosus (SLE) with hemolytic anemia and renal dysfunction at the age of 18 was diagnosed as having idiopathic portal hypertension (IPH) by angiography and liver biopsy. Improvement of thrombocytopenia and proteinuria, and transient increase of complement was observed after transabdominal devascularization with splenectomy (Hassab’s operation). The present case suggests that one of the aspects of the pathogenesis of IPH may be related with autoimmune mechanisms seen in patients with SLE.     

Peliosis hepatis in dermatomyositis treated with azathioprine and corticoids

We report a case of peliosis hepatis in a 47-year old male patient with dermatomyositis treated with azathioprine and corticosteroids. Three months after the combined treatment was initiated, the patient developed right thoracic herpes zoster, agranulocytosis and liver enlargement with signs of portal hypertension. Needle biopsy of the liver revealed peliosis. Azathioprine was withdrawn. The clinical and laboratory abnormalities disappeared progressively. The main causes of peliosis hepatis are considered. Up to now, azathioprine had been held responsible for peliosis hepatis only in renal transplant recipients.     

Hepatoportal sclerosis (obliterative portal venopathy) and nodular regenerative hyperplasia in a patient with myasthenia gravis: A case report and review of the published work

Nodular regenerative hyperplasia (NRH) and hepatoportal sclerosis, also known as obliterative portal venopathy (OPV), are two causes of non‐cirrhotic portal hypertension (NCPH). NCPH is an increasingly recognized entity that can be seen in association with collagen vascular diseases and with the use of medications such as azathioprine and didanosine, but oftentimes the etiology remains unidentified. We herein report a case of NCPH occurring due to OPV and NRH in a 64‐year‐old woman with myasthenia gravis (MG), status post‐thymectomy. Portal hypertension was diagnosed incidentally on computed tomography in the absence of predisposing factors. Extensive work‐up to determine the etiology of any underlying liver disease was unrevealing. NRH and OPV were identified on liver biopsy. Subsequently, the patient had variceal bleeding that necessitated transjugular intrahepatic portosystemic shunt placement. A few similar cases of NCPH occurring in the setting of MG have been previously reported, suggesting that the immunological mechanisms involved in the pathogenesis of myasthenia may also have contributed to the development of NCPH.     

特发性门脉高压症的临床病理学特点

目的 探讨特发性门脉高压症(idiopathic portal hypertension,IPH)的临床病理学特点.方法 回顾性分析了9例IPH的临床及病理学资料,并对其肝脏标本进行常规病理学及免疫组化研究.结果 9例IPH中,5例首发症状为上消化道出血和黑便,3例体检发现脾大脾亢而无临床症状,1例以血管瘤入院.人院检查脾肿大7例,胃底食道静脉曲张6例,腹水征4例,贫血者6例,肝功能正常或接近正常9例.病理组织学显示9例肝小叶结构基本正常.均未见假小叶形成及肝细胞坏死;9例均有不同程度汇管区纤维化,3例汇管区纤细的不全纤维间隔形成并向肝实质延伸,6例有门脉末支管壁纤维化;9例中有6例小叶内肝细胞有不同程度的水肿变性,5例肝窦有不同程度的扩张,2例肝窦扩张较明显,肝细胞萎缩,呈血管瘤样结构,2例有轻-中度肝腺胞3区大泡脂变.脾脏组织学符合淤血性脾肿大病理表现.结论 IPH的临床表现与其他原因所致的肝硬化门脉高压相似,肝穿组织病理学可除外肝硬化,并有一定的特征.诊断时应与各种原因所致肝硬化门脉高压,肝窦阻塞综合征等相鉴别.     

Azathioprine and hepatic venocclusive disease in renal transplant patients

We report 3 cases of hepatic venocclusive disease occurring in renal transplant patients receiving azathioprine and combine our experience with 4 other previously reported cases. The data suggest a clinical syndrome characterized by (a) delayed clinical onset, (b) striking male predominance, (c) presentation with jaundice followed by evidence of portal hypertension, and (d) poor prognosis. One of our patients, who is still alive 40 mo after the first onset of symptoms of liver disease, showed striking clinical improvement with discontinuation of azathioprine and subsequent deterioration on reinstitution. We suggest that azathioprine may be closely linked with the development of venocclusive disease in renal transplant patients and that the frequency of this disorder may be more common than previously reported. To attempt to prevent a fatal outcome, this group of patients should be closely monitored for the earliest signs of hepatic venocclusive disease through periodic serum bilirubin and alkaline phosphatase determinations. Patients with abnormal tests should undergo liver biopsy. If hepatic venocclusive disease is found, prompt withdrawal of azathioprine is indicated.     

Nodular regenerative hyperplasia of the liver associated with azathioprine therapy]

Three cases of nodular regenerative hyperplasia of the liver associated with azathioprine therapy are reported. The indication of azathioprine differed in each of the 3 cases including kidney transplantation, graft-versus-host disease following bone marrow transplantation, and suspicion of bowel inflammatory disease, respectively. In all three patients, nodular regenerative hyperplasia was discovered after a prolonged administration of azathioprine (24 to 40 months), with a cumulative dose of 52 to 120 g. Under light microscopy, vascular lesions were associated with nodular regenerative hyperplasia in the 3 cases and consisted of sinusoidal dilatation (2 cases), perisinusoidal fibrosis (2 cases), and peliosis (1 case). In two patients, nodular regenerative hyperplasia was responsible for severe portal hypertension which was treated by portacaval shunt. These findings are strongly suggestive of a role of azathioprine in the occurrence of nodular regenerative hyperplasia. The mechanism of azathioprine-induced nodular regenerative hyperplasia could be related to sinusoidal lesions caused by azathioprine and responsible for liver hypoperfusion, with regenerative hyperplasia in the areas remaining normally perfused. Patients receiving long-term therapy with azathioprine should be followed-up regularly and liver biopsy should be performed when clinical or biochemical liver abnormalities are observed.     

Pathology and pathogenesis of portal venopathy in idiopathic portal hypertension: Hints from systemic sclerosis

Idiopathic portal hypertension (IPH) is a non-cirrhotic presinuosidal portal hypertension of unknown etiology. Stenosis of smaller portal veins with portal fibrosis is a pathologic hallmark of IPH. Association of systemic sclerosis (SSc) with IPH is recognized, and similar pathologic features are reported in small portal tracts and skin of IPH and SSc, respectively. In addition, levels of transforming growth factor-β (TGF-β) and connective tissue growth factor are elevated in serum and in affected skin and portal tracts of these two diseases, suggesting that IPH share fibrogenetic mechanisms with SSc. Endothelial to mesenchymal transition (EndMT) of microvasculatures of skin could be responsible for dermal fibrosis in SSc. In IPH, EndMT of portal vein endothelium via TGF-β/Smad activation may also be involved in small portal venpathy. In IPH, enhanced expression of pSmad2 in venous endothelium of smaller portal veins was associated with reduced CD34 expression. CD34 and S100A4, and CD34 and type I collagen were colocalized to portal vein endothelium in IPH. Such myofibroblastic phenotypes may be responsible for periportal-venous deposition of collagen and compressive portal venous obliteration. These small portal venous lesions may in turn lead to portal venous insufficiency followed by subcapsular atrophy in IPH.     

A case of idiopathic portal hypertension associated with systemic lupus erythematosus

Abstract

A 29-year-old male who was diagnosed as having systemic lupus erythematosus (SLE) with hemolytic anemia and renal dysfunction at the age of 18 was diagnosed as having idiopathic portal hypertension (IPH) by angiography and liver biopsy. Improvement of thrombocytopenia and proteinuria, and transient increase of complement was observed after transabdominal devascularization with splenectomy (Hassab’s operation). The present case suggests that one of the aspects of the pathogenesis of IPH may be related with autoimmune mechanisms seen in patients with SLE.     

Portal Hypertension in Felty's Syndrome

Idiopathic portal hypertension, usually with esophageal varices. minimal but definitely abnormal liver tests and subtle or no changes on percutaneous liver biopsy has been reported in only a few patients. A case associated with Felty's syndrome in a 65-year old woman with a 44-year history of rheumatoid arthritis is reported in which the liver tests and liver biopsy were normal. Portal hypertension, varices and a patent portal venous system were documented. No surgical procedure was undertaken and she has done well in the 18 months since these studies were performed. A conservative approach is probably warranted in such cases.     

Mixed connective tissue disease associated with idiopathic portal hypertension and chronic thyroiditis

We report a patient with mixed connective tissue disease (MCTD) associated with idiopathic portal hypertension (IPH) and chronic thyroiditis. The patient was a 68-year-old Japanese woman who was admitted to our hospital for treatment of bleeding esophageal varices. She had previously exhibited Raynaud's phenomenon and had had arthritis for about 30 years. She also had had high titers anti-U1 of ribonucleoprotein (RNP) anti-single strand-DNA autoantibodies for 2 years, and had been diagnosed with MCTD 1 year previously. The bleeding from esophageal varices was successfully stopped by endoscopic injection sclerotherapy. Results of laboratory examinations, imaging examinations, and laparoscopy, including liver biopsy, indicated that the esophageal varices were caused by portal hypertension due to IPH. The patient also had a diffusely firm and enlarged goiter and hypothyroidism, and she exhibited anti-thyroid microsomal antibodies and anti-thyroglobulin antibodies, she was diagnosed as having a complication of chronic thyroiditis. This association of MCTD, IPH, and chronic thyroiditis is quite rare and provides a unique opportunity to observe immunological involvement in the pathogenesis of IPH.     

Portal and pulmonary hypertension in a patient with MCTD]

A 42-year-old woman with mixed connective tissue disease (MCTD) died due to the rupture of esophageal varices. The autopsy revealed fresh thrombi in the main trunk of the portal vein. Microscopic examination disclosed wide-spread periportal fibrosis and stenosis of peripheral portal veins without remodeling of hepatic lobular architecture, which was compatible to idiopathic portal hypertension (IPH). Anti-phospholipid antibody was negative. Accordingly it is likely that portal vein thrombosis developed secondary to IPH. In the literature 6 (37.5%) of 16 collagen vascular disease patients with IPH died, and three of them were due to rupture of esophageal varices. Therefore IPH should be considered to be one of the most important complications affecting its grave prognosis in patients with collagen vascular disease. The patient also had had pulmonary hypertension (PH) when the diagnosis of portal hypertension was made. In the literature we found 5 collagen vascular disease patients with both PH and IPH like this case. The most outstanding common clinical feature among these 6 patients was Raynaud's phenomenon associated with positive anti-RNP antibody. Moreover 5 of 6 cases including this case simultaneously developed both PH and IPH. The clinical course of these patients suggests there may be a common pathogenetic factor for these two lesions. A possible candidate involved in the pathogenesis of PH and IPH may be endothelin, one of the vasoactive substances, since its receptor is said to be expressed abundantly in pulmonary and portal vasculatures. However, further investigation is necessary to elucidate the mechanism of PH and IPH in collagen vascular diseases.     

Idiopathic portal hypertension associated with high serum titer of antoantibodies and liver dysfunction

Idiopathic portal hypertension (IPH) is a condition marked by unexplained portal hypertension. Although a number of immunological abnormalities occur in patients with IPH, liver function is usually normal. We experienced an unusual case of IPH in a 49-year-old woman, who had pronounced splenomegaly. Laboratory data revealed pancytopenia, hypergammaglobulinemia, and liver dysfunction. Antinuclear antibodies were positive, with high titer at 1280 dilutions of sera. LE cell phenomena were also positive. Histological examination of biopsied liver showed only mild changes, but portal venous pressure was markedly elevated, at 38 cm H₂O. This case was thus characterized by both a high serum titer of autoantibodies and liver dysfunction.     

Case of idiopathic portal hypertension complicated with autoimmune hepatitis

We report a case of idiopathic portal hypertension (IPH) complicated with autoimmune hepatitis. A 60‐year‐old woman was admitted to our hospital with esophageal and gastric varices in February 2010. Abdominal ultrasonography and computed tomography showed splenomegaly and collateral veins without evidence of liver cirrhosis. Laboratory examinations and liver biopsy indicated that the esophageal and gastric varices were caused by IPH. She underwent endoscopic injection sclerotherapy and partial splenic embolization. Two years after these therapies, laboratory examinations showed liver dysfunction with elevated levels of aspartate aminotransferase (180 IU/L), alanine aminotransferase (190 IU/L), γ‐glutamyl transpeptidase (159 IU/L) and immunoglobulin G (2609 mg/dL). The titer of antinuclear antibodies was 1:320 and its pattern was homogeneous and speckled. Histological examination revealed plasma cell/lymphocyte infiltration and interface hepatitis in the portal tract. Based on these findings, a diagnosis of autoimmune hepatitis accompanied by IPH was made. After treatment with prednisolone (20 mg/day), liver functions were normalized immediately. Overlapping of IPH and AIH is extremely rare, but the present case is interesting considering the etiology of IPH because an autoimmune mechanism is thought to be involved in the pathogenesis of IPH.     

Liver pathology of idiopathic portal hypertension. Comparison with non-cirrhotic portal fibrosis of India The Japan idiopathic portal hypertension study*,+

ABSTRACT— Morphological changes of the liver were studied in 24 autopsy cases of noncirrhotic portal hypertension of unknown etiology (idiopathic portal hypertension, IPH), and in 123 surgical biopsies from such patients. For comparison, 15 whole-cut liver slices from autopsy cases of noncirrhotic portal fibrosis (NCPF) from India were also studied. Liver pathology was very similar in IPH and NCPF, characterized by phlebosclerotic changes and perivascular fibrosis of the portal vein system, and parenchymal atrophy perhaps secondary to portal circulatory insufficiency. The distribution of lesions was uneven, and despite marked fibrosis and occasional surface nodularity, there was no diffuse pseudonodule formation in the parenchyma. Surgical specimens showed similar changes except for more frequent portal cellular infiltrates, but the changes seen in one biopsy specimen were limited and not always diagnostic. It seems that IPH of Japan and NCPF of India are the same disease, and perhaps hepatoportal sclerosis elsewhere is also the same disease.     

Marked atrophy of the right lobe seen in idiopathic portal hypertension confirmed by laparoscopy

A 70‐year‐old‐male was hospitalized for the treatment of esophageal varices and close examination of the liver. Blood chemistry tests revealed mild liver dysfunction. Abdominal ultrasound and computed tomography scan revealed marked atrophy of the right and quadrate lobes of the liver without abnormalities of the biliary system. Abdominal angiography revealed marked atrophy of the right lobe of the liver, without obliteration in the portal venous system, but it could not be determined whether the atrophy was congenital or secondary. Subsequently performed laparoscopy revealed marked atrophy of the anterior segment of the right lobe and quadrate lobe with the whitish scarred edge demarcating the border between the edge and neighboring liver parenchyma. The liver surface appeared to be undulant, but non‐cirrhotic. These findings suggest secondary lobar atrophy of the liver, without cirrhosis. Liver biopsy of the left lobe showed the findings to be compatible with idiopathic portal hypertension (IPH), and we diagnosed IPH based on these findings and hepatic lobar atrophy was attributable to IPH. There have been few reports of cases with hepatic lobar atrophy associated with IPH, and the mechanism of atrophy is unclear. We report a case of IPH with marked liver atrophy in which laparoscopy is a decisive means whether liver atrophy is congenital or secondary.