少见、罕见疾病所致门静脉高压症的诊断与治疗

少见、罕见疾病所致门静脉高压症多属于窦前性(肝前)或肝后性门静脉高压症。因多数为非肝硬化门静脉高压症,故肝静脉压力梯度不能准确反映其门静脉压力,临床诊治存在较大困难。此类疾病种类较多,重点介绍了6种少见、罕见疾病所致门静脉高压症的机理和治疗进展,并就目前的治疗现状进行了总结,希望对提高临床医生对此类疾病的认识有所帮助。     

非肝硬化性门脉高压的临床诊断

门静脉高压症是指各种原因导致的门静脉压力升高,临床表现为脾肿大、脾功能亢进症、食管胃底静脉曲张和腹水等临床症候群。根据病变部位的不同,门脉高压可分为肝前性、窦前性、窦性、窦后性和肝后性门脉高压[1]。引起门脉高压的最常见病因是肝硬化,属于窦性门脉高压,约占我国患者的80%~85%,而非肝硬化性门脉高压(non-cirrhotic portal hypertension,NCPH)是指患者有明显的门脉高压表现,但临床生化、影像学或组织学上无肝硬化证据的一组疾病,包括肝外门静脉闭塞症、先天性肝纤维化、特发性非硬化性门脉高压、肝窦阻塞综合征和布加综合征等[2]。NCPH患者与肝硬化门脉高压症患者在病因、治疗和预后方面有明显的不同,因此应重视对该组疾病的认识。本文对常见的NCPH疾病进行了简述,期待提高临床医生对该组疾病的认识。     

特发性门静脉高压症1例

特发性门静脉高压症(IPH)是一类比较罕见的肝脏血管病变, 主要临床表现为肝内门静脉小分支的闭塞或狭窄诱发的门静脉高压。国内外研究显示, 该病与感染、药物、毒素、血栓倾向、免疫及遗传等因素相关。特发性门静脉高压又称特发性非肝硬化性门静脉高压症(INCPH), 为肝窦前性非肝硬化性门静脉高压, 较难与隐源性肝硬化相鉴别, 该病国内外鲜少报道。现报道1例人类白细胞DR3等位基因(HLA-DR3)阳性的IPH, 讨论该患者的诊治经过以及对该病的认识, 为临床提供借鉴。     

特发性非肝硬化性门静脉高压症的研究进展

特发性非肝硬化性门静脉高压症(INCPH)是一种罕见的血管性肝病，近年来引起了人们新的关注。INCPH在组织学改变、血流动力学特征和临床结果方面与肝硬化不同。重要的是，其病因和发病机制尚不清楚，但已确定与肝内血管疾病的发展有关，并在排除引起门静脉高压的其他原因(如肝硬化以及其他导致门静脉高压的窦前性、窦性、窦后性原因和内脏静脉血栓形成)后做出的。此外，特发性非肝硬化性门静脉高压症的总体预后优于肝硬化患者，但对症治疗(控制胃食管静脉曲张出血和预防血栓形成)仍是主要治疗方法。目前临床上对INCPH的认识相对不足，对该病易发生误诊，本文通过目前对INCPH研究进展的阐述，以提高临床医生对此病的认识。     

特发性非肝硬化性门静脉高压症的研究进展

特发性非肝硬化性门静脉高压是一种原因不明的门静脉高压症,无明显肝硬化特征;本病的发病机制尚不清楚,目前认为慢性感染、免疫、毒物接触、凝血机制障碍等均可能参与发病。临床主要表现为门静脉高压征象,如食管胃底静脉曲张或破裂出血、显著脾肿大,而肝功能基本正常,腹水及肝性脑病少见;病理改变主要表现为门静脉闭塞性病变,但无肝硬化改变。临床诊断主要是排他性诊断,有门静脉高压的临床证据,组织病理学检查除外肝硬化,排除引起肝硬化的慢性肝病以及引起非肝硬化性门静脉高压的其他临床疾病即可考虑本病。有关特发性非肝硬化性门静脉高压症研究较少,推荐按照肝硬化所致门静脉高压指南进行治疗。预后主要取决于门静脉高压的严重程度及其并发症的处理,一般优于肝硬化并食管胃底静脉曲张破裂出血。     

非肝硬化性门静脉高压症研究进展

正门静脉高压的定义为门静脉和下腔静脉压力梯度大于5 mm Hg。根据门静脉系统阻塞部位,可分为肝前性、肝性和肝后性。根据肝血窦累及情况,肝性门静脉高压又可以细分为窦前性、窦性和窦后性。继发于肝硬化的窦性门静脉高压是最常见的类型,表现为肝静脉压力梯度(HVPG)升高,即肝静脉楔入压与肝静脉游离压的差值升高~([1,2])。有约20%门静脉高压继发于非肝硬化因素,统称为非肝硬化性门静脉高压症(NCPH),其中包括窦后性或窦性NCPH,临床上多为肝窦阻塞综合症(HSOS),     

门静脉肝窦血管性疾病的疾病特点与诊疗进展

门静脉肝窦血管性疾病(PSVD)的概念最早于2017年由欧洲肝病学会血管性肝病研究小组提出，是对特发性非肝硬化性门静脉高压症(INCPH)概念做出的重要补充，但PSVD涵盖范围更广，更便于临床应用。PSVD患者的临床表现具有高度异质性，当伴有门静脉高压时易与肝硬化患者相混淆，因此提高对该病临床特征的认识、完善疾病的诊疗流程对临床医生十分重要。     

重视非肝硬化性门静脉高压的诊断和治疗

非肝硬化性门静脉高压(NCPH)是指除肝硬化外多种疾病导致的门静脉高压症。NCPH常见的原因有门静脉血栓形成、先天性肝纤维化和特发性门静脉高压等。这组疾病的主要特点是门静脉高压相关的表现突出,而肝功能储备相对较好,鉴别该类疾病需要临床,影像学和病理学的深入检查。通过适当的内外科治疗,多数患者预后较好。     

肝(窦)前型非肝硬化门静脉高压症的诊断与治疗及其面临的困境

肝(窦)前型非肝硬化性门静脉高压症(NCPH)是一组以门静脉高压症为突出表现的血管异质性疾病,病因复杂。与肝硬化门静脉高压症相比,NCPH患者肝功能基本正常,肝静脉压力梯度正常或轻度增加,预后较好,极易误诊为不明原因肝硬化门静脉高压症,肝脏病理是诊断"金标准"。目前,非选择性β受体阻滞剂及内镜是NCPH的主要治疗方法,但是缺乏前瞻性多中心、大样本、高质量的临床证据。     

儿童门静脉高压症研究进展

儿童门静脉高压症是指在多种病因作用下,门静脉系统的血流受阻和（或）血流量增加、血管舒缩功能障碍,引起门静脉及其属支的压力持续增高,门静脉压力＞5 mmHg（1 mmHg=0.133 kPa）,或门静脉、肝静脉压力梯度＞10 mmHg,最终导致脾大、门腔侧支循环形成和开放、腹水等临床表现,是一种血流动力学异常综合征。儿童门静脉高压症根据病因不同分为肝硬化性门静脉高压症和非肝硬化性门静脉高压症;根据压力来源的解剖部位,可将门静脉高压症分为肝前性、肝内性（窦前性、窦性、窦后性）及肝后性。治疗方法有药物治疗、曲张静脉套扎或硬化、手术治疗等。虽然儿童门静脉高压症发病率较低,但可以引起胃食管静脉曲张破裂出血、肝性脑病等严重并发症。为加强对本病的认识,减少并发症,提高治愈率,现将其病因分类、发病机制、诊断和治疗方面的研究进展作一综述。     

Surgical treatment of a descending aortic aneurysm in a patient with noncirrhotic portal hypertension and a portal systemic shunt.

A 63-year-old male with atrial fibrillation and mild mitral valve regurgitation was referred to hospital because of a descending aortic aneurysm. During the evaluation, he developed an encephalopathy because of hyperammoniaemia. Further examination revealed a portal systemic shunt, perhaps caused by the noncirrhotic portal hypertension. The patient underwent successful replacement of the aneurysm after controlling the blood ammonia level by eliminating protein from the diet and removal of nitrogen from the gastrointestinal tract. Cardiovascular surgery in a patient with noncirrhotic portal hypertension and a portal systemic shunt has not been previously reported. Meticulous management of the perioperative blood ammonia concentration is essential.     

Hepatoportal sclerosis as a cause of noncirrhotic portal hypertension in patients with HIV

BACKGROUND: Hepatoportal sclerosis (HPS) is a cause of noncirrhotic portal hypertension, with patients typically presenting with variceal bleeding. It is idiopathic in nature but is felt to be due to an abnormality of the intrahepatic vasculature. HPS is characterized by varying degrees of portal fibrosis, sclerosis of portal vein branches and dilatation of sinusoidal spaces. Nodular regenerative hyperplasia (NRH), another cause of noncirrhotic portal hypertension, has also been recently described in HIV patients initially diagnosed as having cryptogenic liver disease. METHODS/RESULTS: We describe four cases of HIV+ patients presenting with noncirrhotic portal hypertension; liver biopsies were reviewed by an experienced liver pathologist and found to be consistent with HPS. No other etiologies for their liver disease were found. CONCLUSIONS: HPS has been recently identified as a cause of noncirrhotic portal hypertension in patients with HIV. It should be considered in the differential diagnosis of HIV patients presenting with variceal bleeding. We postulate that it may be due to intrahepatic microthrombosis or an altered hepatic fibrogenesis related to highly active antiretroviral therapy or due to HIV itself.     

A case of progressive systemic sclerosis complicated by idiopathic portal hypertension with severe anemia]

A 44-year-old woman had been diagnosed with progressive systemic sclerosis (PSS) at the age of 39 years old and mild pancytopenia was noted at that time. At the age of 41 years symptoms of dry mouth appeared. In April 1997, anemia was in progress (Hb 5.8 g/dl) and severe esophageal varices were found by gastrointestinal fiber scope, and massive splenomegaly by abdominal CT. Serological examination was negative for hepatitis virus and for anti-mitochondrial antibody. In addition, Indocyanine Green test was normal and typical findings of liver cirrhosis were not demonstrated by CT scan. Also, the bone marrow result was normal. Therefore hypersplenism with idiopathic portal hypertension (IPH) was suggested and the patient was referred for splenectomy with the aim of improving the pancytopenia. The weight of the spleen was 2100 g and the pressure of the portal vein was measured at 390 mm H2O. The diagnosis of IPH was determined because pathologically there were no findings for liver cirrhosis. After splenectomy, pancytopenia was remarkably improved (Hb 9.6 g/dl). Consequently, this case was diagnosed as IPH complicated with PSS and Sj?gren syndrome.     

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.     

Hepatopulmonary syndrome in noncirrhotic portal hypertensive patients

Hepatopulmonary syndrome has yet not been sufficiently assessed in noncirrhotic portal hypertension. The prevalence of hepatopulmonary syndrome was determined in 31 consecutive patients with noncirrhotic portal hypertension (19 idiopathic portal hypertension, 7 portal vein thrombosis, 5 congenital hepatic fibrosis) and 46 patients with liver cirrhosis. Contrast echocardiography was carried out in all patients. Macroaggregated albumin lung perfusion scans were performed in patients with positive contrast echocardiogram. Hepatopulmonary syndrome was detected in 5 (10.8%) cirrhotic and 3 (9.7%) noncirrhotic portal hypertensive patients (2 idiopathic portal hypertension, 1 portal vein thrombosis). All patients with hepatopulmonary syndrome had an increased shunt fraction (13–62%) and a decreased diffusion capacity of carbon monoxide (40–79%), and 7 of them were hypoxemic (P_aO₂, 31.6–69.8 mm Hg). These findings show that hepatopulmonary syndrome may occur in both liver cirrhosis and noncirrhotic portal hypertension and that portal hypertension is the predominant etiopathogenic factor related to hepatopulmonary syndrome.     

A case of systemic sclerosis complicated by idiopathic portal hypertension: case report and literature review

We encountered a 62-year-old woman who had systemic sclerosis (SSc) complicated by idiopathic portal hypertension (IPH). She had a 10-year history of scleroderma and Raynaud's phenomenon. She also had pancytopenia, splenomegaly, and esophageal varices. Treatment with prednisolone and endoscopic variceal ligation resulted in improvement of her symptoms. According to our literature review, the prognosis of patients with SSc complicated by IPH is relatively poor. However, the factors that predict outcome of these patients have not been elucidated.     

Results of modified Sugiura operation in variceal bleeding in cirrhotic and noncirrhotic patients

BACKGROUND/AIMS: Esophageal variceal bleeding is a major complication of portal hypertension and the optimal therapeutic modality for each individual patient differs. We reviewed the results of modified Sugiura procedure in patients with variceal bleeding of esophagus. METHODOLOGY: We retrospectively reviewed the charts of 13 patients who were subjected to modified Sugiura procedure (transabdominal esophagogastric devascularization + esophageal stapled transection + splenectomy) for bleeding esophageal varices between 1996 and 2001. Three patients disappeared from routine follow-up and were excluded from the study. Survival, rebleeding and encephalopathy were evaluated. RESULTS: The mean age was 46 (18-56). The etiology of portal hypertension was cirrhosis of liver in six (60%) and portal vein thrombosis in four (40%). One patient had Child-Pugh's Class A, two had Class B and three had Class C cirrhosis. Previous variceal bleeding were confirmed by endoscopy in all patients who had recurrent variceal bleeding despite treatment with beta-blockers (three patients) or endoscopic sclerotherapy +/- band ligation (seven patients). Two were subjected to emergency surgery while the remaining eight were operated on electively. No postoperative mortality was seen. The bleeders were stopped immediately in the emergent cases. During a mean follow-up of 27 (4-53) months, one (10%) patient suffered from encephalopathy and one (10%) from rebleeding at 20th and 28th months after the operation respectively. Three (30%) patients with Child C cirrhosis died due to bleeding (one) and hepatic failure (two) at 4, 25, and 28 months after the surgery. The prognoses of other patients are well at the present time. CONCLUSIONS: In our small number of patients, modified Sugiura procedure was found to be a safe and effective procedure for urgent and long-term control of bleeding varices in patients with portal hypertension due to cirrhosis and noncirrhotic etiology. The outcomes are encouraging in noncirrhotic patients and cirrhotic patients with good liver functions.     

Chronic portal-systemic encephalopathy with normal portal vein pressure possibly due to noncirrhotic portal fibrosis

Summary This is the report of a 50-year-old man with a more than 20-year history of chronic progressive portal-systemic encephalopathy. Liver tests were normal except for increased serum ammonia and indocyanine green plasma retention. The liver pathology was compatible with idiopathic portal hypertension or noncirrhotic portal fibrosis, demonstrating localized surface nodularity and portal fibrosis. Percutaneous transhepatic catheterization of the portal vein revealed near top normal portal vein pressure and a large shunt connecting the left gastric or superior mesenteric vein and the left renal vein. Presumably, the patient had portal hypertension in the past and formation of a short, largecaliber shunt between the portal system and the renal vein effectively decompressed the portal circulation.     

Systemic Mastocytosis: A Rare Cause Of Noncirrhotic Portal Hypertension Simulating Autoimmune Cholangitis—Report of Four Cases

Four patients with systemic mastocytosis, two men and two women, are presented. Three of them (patients 1, 2, and 4) developed portal hypertension and ascites without histological evidence of cirrhosis in liver biopsy. The remaining patient (patient 3) had severe bone lesions with multiple vertebral fractures. None of the patients had skin or lymph node involvement. Two patients (patients 1 and 2) died 12 and 9 months after diagnosis with acute nonlymphocytic leukemia and overt mastocytic leukemia, respectively, while the other two (patients 3 and 4) are alive 58 and 14 months after diagnosis. Treatment with hydroxyurea or cytosine arabinoside had not any beneficial effect in two patients, while a substantial amelioration of back pain had been obtained by local irradiation and recombinant human interferon-a-2b administration in one patient (patient 3). All patients had laboratory findings compatible with autoimmune cholangitis. We concluded that systemic mastocytosis is a rare cause of noncirrhotic portal hypertention often simulating autoimmune cholangitis and leading to the erroneous diagnosis of liver cirrhosis. Diagnosis is based on the presence of mast cells in Giemsa-stained liver histological sections, and it may be confirmed by immunohistochemical detection of tryptase in the cytoplasm of these abnormally proliferating cells.     

Idiopathic portal hypertension complicating systemic sclerosis: a case report

Background  

Patients with systemic sclerosis may develop mild abnormalities of liver function tests. More serious hepatic involvement has been well documented but is rare. Idiopathic portal hypertension had been reported only in a few female patients with systemic sclerosis.