Cardiac dysfunction in portal hypertension among patients with cirrhosis and non-cirrhotic portal fibrosis

BACKGROUND/AIMS: In cirrhosis, diastolic dysfunction of heart is well documented. Contribution of portal hypertension towards cardiac changes in cirrhosis is difficult to assess. We examined the patients of non-cirrhotic portal fibrosis who have portal hypertension without liver insufficiency to understand the contribution of portal hypertension in causing cardiac changes. METHODS: Cardiac function was studied in four groups of patients: normal controls, patients with non-cirrhotic portal fibrosis (having portal hypertension without liver dysfunction) and cirrhotics with and without ascites. Cardiac function was evaluated by echocardiography. Additional measurements of plasma renin activity and aldosterone levels were performed. RESULTS: Diastolic function as assessed by the ratio between E wave and A wave (E/A ratio), was significantly lower in patients with non-cirrhotic portal fibrosis (median 1.3) compared to normal controls (median 1.52). However, even lower values were observed in cirrhotics without ascites (median 1.05) and with ascites (median 0.94). There was a significant correlation (r=-0.75) between plasma aldosterone levels and the E/A ratio in cirrhotics. CONCLUSIONS: Diastolic dysfunction is not only present in cirrhosis but also in non-cirrhotic portal fibrosis. It indicates that portal hypertension is an important factor in the genesis of cardiac dysfunction.     

Ultrastructure of the liver in non-cirrhotic portal fibrosis with portal hypertension

The aetiology of the ultrastructural abnormalities of non-cirrhotic portal fibrosis is not known. In an attempt to elucidate the pathophysiology of this condition, the hepatic ultrastructure in nine cases of non-cirrhotic portal fibrosis with portal hypertension has been studied.     

Immunological profile of patients with non-cirrhotic portal fibrosis

The aetiopathogenesis of non-cirrhotic portal fibrosis (NCPF), a common cause of portal hypertension in India, is not known. To study the immune status of NCPF patients and to see whether immunological mechanisms have a role to play, humoral and cell-mediated immunological studies were carried out in 43 patients with NCPF and compared with equal number of matched healthy controls and 31 patients with compensated liver cirrhosis. Serum immunoglobulin A (IgA) and complement (C3, C4) levels were significantly (P less than 0.001) lower in NCPF patients compared with controls and cirrhotics. There was no significant difference between the total or the relative concentration of the immunoglobulins and complements between NCPF patients and healthy controls, but, in patients with cirrhosis, concentration of all the immunoglobulins was higher. The cutaneous response to dinitrochlorobenzene was poorer in patients with NCPF, but the difference between cirrhotics and controls was not significant. A decrease in the suppressor/cytotoxic (T8) phenotype of lymphocytes in the peripheral blood and an increase in the ratio of helper/inducer (T4) and T8 lymphocytes was seen in patients with NCPF and cirrhosis. Although these results indicate definite immunological abnormalities in NCPF patients, their role in the pathogenesis of NCPF remains to be investigated.     

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。     

Prolonged survival after portal decompression of patients with non-cirrhotic intrahepatic portal hypertension

In a series of 251 good-risk patients undergoing portal decompression for intrahepatic portal hypertension, one fifth have been found not to have hepatic cirrhosis. Of these, 44 had only minor changes in hepatic architecture, and the clinical features and subsequent course have been compared and contrasted with a group of 201 cirrhotic patients who underwent portal decompression for similar indications.The degree of portal hypertension was comparable in both groups and it was not possible confidently to differentiate the condition from hepatic cirrhosis on either clinical or biochemical grounds in the individual case.The histological lesion was not progressive in the non-cirrhotic group and this was reflected in the far better survival of these patients. After five years 83% (30 of 36) of this group were alive compared with 43% (65 of 152) of the cirrhotic patients. After 10 years the cumulative survival was 77% (20 of 26) for those without cirrhosis, contrasted with 22% (19 of 87) for the cirrhotic patients.     

Subclinical encephalopathy after portosystemic shunts in patients with non-cirrhotic portal fibrosis

Cerebral function was studied in patients with non-cirrhotic portal fibrosis who had no clinically detectable neurological abnormality, 14 before and 29 after a proximal lienorenal shunt operation. In each patient electroencephalography (EEG) and psychometric tests (the number connection test, construction of a five-pointed star and the reverse counting test) were performed. Psychometric tests were also done in an equal number of matched, healthy controls. Subclinical encephalopathy was diagnosed when any of these tests was abnormal. In the unoperated group the EEG was normal in all patients and there was no difference in the psychometric test results between patients and healthy controls. After portosystemic shunt operations, the EEG was abnormal in 10%, the number connection test in 38%, construction of a five-pointed star in 19% and the reverse counting test in 30% of the patients. Detection of subclinical hepatic encephalopathy in such a high proportion of operated patients with non-cirrhotic portal fibrosis suggests that the surgical procedure and its haemodynamic consequences per se could have been responsible.     

特发性非肝硬化门静脉高压症患者肝脏影像学和病理学特征分析

目的 分析特发性非肝硬化门静脉高压症(INCPH)患者肝脏影像学和病理学特征,并与肝硬化的鉴别要点。方法 2016年1月～2021年7月我院收治的INCPH患者16例和乙型肝炎肝硬化患者28例,常规进行超声、CT和MRI及肝穿刺活检检查。结果 INCPH与肝硬化患者在影像学检查发现的弥漫性结节样改变(0.0%对35.7%)、门静脉直径【9.7(7.2,11.6)mm对13.6(9.2,15.7)mm】、门静脉壁厚【2.6(1.4,4.0)mm对1.4(1.1,1.6)mm】方面比较,差异具有统计学意义(P<0.05);肝组织学检查发现,INCPH与肝硬化患者在门静脉区域纤维化、肝膈膜纤维化、肝小叶间静脉闭塞、肝细胞坏死和肝细胞水肿或脂肪变性方面【分别为100.0%对0.0%、18.7%对92.8%、56.2%对10.7%、0.0%对75.0%和12.5%对89.3%】,差异具有统计学意义(P<0.05)。结论 INCPH仍是一种病因不明的疾病,注意分析影像学和组织病理学特征可以作出与肝硬化的鉴别诊断。     

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.     

IgA nephropathy in non-cirrhotic portal hypertension

Renal glomerular changes are a well recognised complication of cirrhosis and are frequently characterised by mesangial IgA deposition. We report a patient with non-cirrhotic portal hypertension who developed IgA nephropathy and a nephrotic syndrome with renal histological changes classically associated with cirrhosis. Splenectomy with resection of a splenic artery aneurysm resulted in remission of the nephrotic syndrome. This case illustrates the factors which contribute to the pathogenesis of IgA nephropathy in liver disease.     

Association of celiac disease with non-cirrhotic portal fibrosis

Both celiac disease and non‐cirrhotic portal fibrosis are known to be associated with various autoimmune diseases and have numerous immunological abnormalities. Herein two patients with celiac disease having associated non‐cirrhotic portal fibrosis are reported. An autoimmune link between the two conditions is likely to explain coexistence in the same patient.     

非肝硬化性门静脉高压症的研究现状

肝硬化是门静脉高压的最常见原因,但仍有约20%的门静脉高压继发于非肝硬化因素,称为非肝硬化性门静脉高压症(NCPH),在发展中国家发病率较高。NCPH是一组异源性的肝脏血管疾病,临床上多见的是特发性门静脉高压(IPH)、肝外门静脉血管阻塞(EHPVO),以及布加综合征、先天性肝纤维化和结节再生性增生等少见病。此类患者常常具有门静脉高压的证据,如反复发生的静脉曲张出血和脾脏肿大,但肝功能保存尚好。目前尚无诊断NCPH的统一标准,对其诊断仍是一个挑战。临床上往往采用排除性诊断,必要时可行肝穿刺活组织检查来确诊。介绍了IPH和EHPVO的发病机制、病理表现、诊断方法及治疗策略的选择,若能有效控制上消化道出血,NCPH被认为是预后相对良好的一类疾病。     

Coagulation profile and platelet function in patients with extrahepatic portal vein obstruction and non-cirrhotic portal fibrosis

BACKGROUND AND AIMS: Coagulation disorders commonly develop in patients with cirrhosis of the liver. They have also been reported in patients with non-cirrhotic portal fibrosis (NCPF) and extra-hepatic portal venous obstruction (EHPVO); the two conditions with portal hypertension and near-normal liver functions. The spectrum and prevalence of coagulation abnormalities and their association with the pathogenesis of these diseases and with hypersplenism was prospectively studied. METHODS: Eighteen EHPVO patients that included an equal number of NCPF patients and 20 healthy controls were prospectively studied. The coagulation parameters assessed included: international normalized ratio, partial thromboplastin time, and fibrinogen and fibrinogen degradation products. Platelet aggregation and malondialdehyde levels were measured. RESULTS: Both EHPVO (83%) and NCPF (78%) patients had a significantly prolonged international normalized ratio and a decrease in fibrinogen and platelet aggregation. The EHPVO patients had a significant prolongation in partial thromboplastin time (67% patients), with increased levels of fibrinogen degradation product levels occurring in all patients; these were normal in NCPF patients. Platelet malondialdehyde levels were normal in both groups. Hypersplenism was present in four EHPVO and seven NCPF patients. It did not significantly influence the coagulation profile in either NCPF or EHPVO patients. CONCLUSIONS: Coagulation anomalies are common and significant in both NCPF and EHPVO patients, suggestive of a mild disseminated intravascular coagulation disorder. These imbalances could be caused by chronic subclinical endotoxemia and cytokine activation after the initial portal thromboembolic event. The persistence of these abnormalities in adolescent patients indicates an ongoing coagulation derangement.     

Ultrasonography in non-cirrhotic portal hypertension: correlation with splenoportography

Real time sonography followed by splenoportography was performed in 38 cases with non-cirrhotic portal hypertension. Eleven of these cases, in whom porto-systemic shunt surgery was done, were also evaluated by real time sonography post-operatively. The ultrasound findings correlated well in 37 cases (98%) with splenoportography. All the post-operative cases also revealed a patent portosystemic shunt on sonography. Ultrasonography, a valuable, non-invasive, initial investigation of portal hypertension, may thus be used as the only investigation to distinguish intra- from extra-hepatic obstruction and to evaluate patency of surgically created porto-systemic shunts. Invasive portography may be performed only if surgical treatment is anticipated.     

Adrenomedullin in cirrhotic and non-cirrhotic portal hypertension

AIM:Adrenomedullin (ADM) is a potent vasodilator peptide.ADM and nitric oxide (NO) are produced in vascular endothelial cells. Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatation in cirrhotic portal hypertension (CPH). The role of ADM in non-cirrhotic portal hypertension (NCPH) is unknown, plasma ADM levels were studied in patients with NCPH, compensated and decompensated cirrhosis in order to determine its contribution to portal hypertension (PH) in these groups.METHODS: There were 4 groups of subjects. Group 1consisted of 27 patients (F/M: 12/15) with NCPH due to portal and/or splenic vein thrombosis (mean age: 41±12years), group 2 consisted of 14 patients (F/M: 6/8) with compensated (Child-Pugh A) cirrhosis (mean age: 46±4),group 3 consisted of 16 patients (F/M: 6/10) with decompensated (Child-Pugh C) cirrhosis (mean age: 47±12).Fourteen healthy subjects (F/M: 6/8) (mean age: 44±8) were used as controls in Group 4. ADM level was measured by ELISA. NO was determined as nitrite/nitrate level by chemoluminescence.RESULTS: Adl level in Group 11 (236±61.4 pg/mL) was significantly higher than that in group 2 (108.4±28.3 pg/mL)and group 4 (84.1±31.5 pg/mL) (both P＜0.0001) but was lower than that in Group3 (324±93.7 pg/mL) (P=0.002). NO level in group 1 (27±1.4 μmol/L) was significantly higher than that in group 2 (19.8±2.8 μmol/L) and group 4 (16.9±1.6μmol/L) but was lower than that in Group 3 (39±3.6 μmol/L)(for all three P＜0.0001). A strong correlation was observed between ADM and NO levels (r=0.827, P＜0.0001).CONCLUSION: Adrenomedullin and NO levels were high in both non-cirrhotic and cirrhotic portal hypertension and were closely correlated, Adrenomedullin and NO levels increased proportionally with the severity of cirrhosis, and were significantly higher than those in patients with NCPH.Portal hypertension plays an important role in the increase of ADM and NO. Parenchymal damage in cirrhosis may contribute to the increase in these parameters.     

Natural/spontaneous shunts in non-cirrhotic portal fibrosis

Large natural/spontaneous shunts on splenoportovenography were demonstrated in 10 of 93 patients with non-cirrhotic portal fibrosis. There was significantly less bleeding in patients with spontaneous shunt than in those having no shunt. Large oesophageal varices (grade III-IV) were seen more frequently in patients without spontaneous shunt.     

Surgical treatment of non-cirrhotic presinusoidal portal hypertension

BACKGROUND/AIMS: Non-cirrhotic portal hypertension has a better prognosis than other forms of portal hypertension because of a well-preserved liver function in most cases. These patients are good candidates to receive surgical treatment, which is the therapeutic choice available with the lowest rebleeding rate. Because of abnormalities in the splanchnic vessels due to the nature of the diseases, many of them cannot be shunted. An extensive esophagogastric devascularization, the complete portoazygos disconnection, was evaluated. METHODOLOGY: A retrospective review of files of 31 patients, among 491 operations between 1991 an 2001 was carried out in a tertiary care Academic University Hospital. Patients comprised those with non-cirrhotic bleeding portal hypertension treated by means of complete portoazygos disconnection. Extensive two-stage (thoracic and abdominal) esophagogastric devascularization with modified transection of the esophagus was performed. Main outcome measures: recurrence of hemorrhage, encephalopathy and survival. RESULTS: Thirty-one patients were treated. In 17 cases (54%) a hypercoagulable state was demonstrated. No operative mortality was observed (0-30 days) with a total of 62 operations (two stages per patient). No case of encephalopathy was observed and in 3 cases (9%) rebleeding was recorded. The survival curve showed a 5-year survival of 97% and a 10-year survival of 93%. CONCLUSIONS: Complete portoazygos disconnection is an excellent surgical alternative for patients with non-cirrhotic portal hypertension, with a low morbidity and mortality as well as a low rebleeding rate and good long-term survival.     

Obliteration of portal systemic shunts as therapy for hepatic encephalopathy in patients with non-cirrhotic portal hypertension.

The effects of obliteration of portal systemic shunts (PSS) in 5 patients with non-cirrhotic hepatic encephalopathy is reported. All patients had a history of disturbance of consciousness for several years, and examinations revealed large PSS, most of which connecting the left gastric vein to the left renal vein. After the obliteration of PSS, portal vein pressure elevated, the shunt ratio of the portal blood flow decreased, the indocyanine green disappearance rate increased, and serum albumin increased. Blood ammonia (NH3) decreased significantly accompanied by disappearance of hepatic encephalopathy. This treatment may open a way to improve the quality of life in patients with large PSS without severe hepatic injury.