The influence of periportal (pipestem) fibrosis on long term results of surgical treatment for schistosomotic portal hypertension

AIM: To evaluate the degree of influence that periportal fibrosis has on clinical development and the long term results of surgical treatment on patients with hepatic-splenic schistosomiasis with previous gastrointestinal hemorrhages. METHODS: During the period of 1992-1998, 111 patients underwent surgical treatment for the treatment of hepatic-splenic schistosomiasis with previous gastrointestinal hemorrhages. The degree of fibrosis was classified as: degree I - the portal spaces show a rich increase of young connective cells, a slight collagen production and a varying presence of inflammatory infiltrate. The periportal blade unchangeable (29/111); degree II - there is an expansion of the connective tissue with the emission of radial collagen septa, producing a star shaped aspect (38/111); degree III - the connective septa form bridges with other portal spaces or with the vein, with evident angiomatoid neo-formation (44/111). CONCLUSION: The patients with periportal fibrosis degree I present recurrent hemorrhages statistically less than patients with periportal fibrosis degrees II and III, and that the intensity of the periportal fibrosis is not the only pathophysiological factor of the esophageal varices, gastric varices, prevalence of post-operative portal vein thrombosis and hematological and biochemical alterations of the patients with pure mansoni schistosomiasis.     

Intraabdominal arterio-venous fistulae and their relation to portal hypertension

BACKGROUND/AIMS: The aim of the study was to present, on the base of own experience, clinical importance of arterio-venous fistulae involving the vascular system of the abdomen. METHODOLOGY: Clinical material consists of 18 patients in whom abnormal arterio-venous leakage in the abdomen was disclosed by means of imaging diagnostic techniques and Doppler sonographic hemodynamic investigations. Three groups of patients were determined: 1. Patients in whom arterio-venous fistula was a primary cause of portal hypertension (N = 6), 2. Patients in whom the presence of arterio-venous fistulae aggravated portal hypertension due to other pathology (N = 7). 3. Patients in whom the arterio-venous fistulae did not directly affect portal flow (N = 5). As each case presented a different clinical problem, the therapeutic approach had to be individualized. In 12 patients perarterial embolization was performed, 13 patients were operated on, one patient was listed for liver transplantation. RESULTS: Perarterial embolization was fully effective only in 4 cases. In the remaining 8 cases its effect was transient, but in 4 cases of liver tumors it allowed us to proceed with chemoembolization and the others were subsequently treated surgically. In 12 surgically treated patients the operation proved to be curative. In 1 case of multiple arterio-venous fistulae related to diffuse angiomatosis, surgical procedure was unfeasible. One patient, awaiting liver transplantation, died of liver failure. CONCLUSIONS: 1. Arterio-venous fistulae (of various etiology) are rarely found in the abdominal cavity, but their presence means usually serious consequences depending on their morphology and localization. 2. Arterio-venous fistulae involving the portal system may result in severe portal hypertension. 3. Individually chosen method of treatment, aimed at the occlusion of arterio-venous fistula often proves to be curative. 4. Overlooking or ignoring the presence of intraabdominal arterio-venous fistulae leads to unsuccessful, if not harmful treatment.     

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.     

Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics

The prevalence of pulmonary hypertension in 507 patients hospitalized with portal hypertension but without known pulmonary hypertension who underwent cardiac catheterization was prospectively studied. Ten (2%) of these patients, 6 of whom were clinically asymptomatic, had primary pulmonary hypertension. Second, 26 patients with symptomatic pulmonary hypertension complicating portal hypertension were reviewed. Pulmonary hypertension occurred later after diagnosis of portal hypertension in patients with a surgical shunt (10 patients) than in those without a shunt (147 +/- 49 vs. 44 +/- 27 months; P less than 0.0001). Cardiac index correlated inversely with pulmonary arterial pressure (r = -0.45; P less than 0.01) and was lower in the 5 patients who died of pulmonary hypertension than in the 5 who died of liver failure (1.52 +/- 0.14 vs. 3.69 +/- 1.88 L/min.m2; P less than 0.05). Third, systemic and splanchnic hemodynamics were compared in 285 patients with alcoholic cirrhosis and 29 controls. No significant relation was found between elevated pulmonary vascular resistance and increased portal pressure, zzygos blood flow, or cardiac index. Pulmonary hypertension is considerably more frequent than was previously estimated in patients with portal hypertension. The risk of developing pulmonary hypertension could increase with the duration of portal hypertension without any clear relation to the degree of portal hypertension, hepatic failure, or amount of blood shunted.     

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.     

The role of pericentral fibrosis in experimental portal hypertension in rats

To clarify the relation of pericentral fibrosis to portal hypertension, measurements of portal vascular resistance in vitro and blood pressures of several key points in hepatic vascular pathways in vivo were undertaken in rats given dimethylnitrosamine. Administration of dimethylnitrosamine induced tortuosity and narrowing of the peripheral branches of the hepatic vein due to pericentral fibrosis. No significant change was produced in the sinusoids and the portal vein branches. The portal vascular resistance was increased and the portal vein pressure was elevated markedly. The blood pressure gradient was steep in the intrahepatic vein, but not in the intrahepatic portal vein or the sinusoids, as compared to control. These data suggest that deformation of the peripheral branches of the hepatic vein due to pericentral fibrosis causes a marked increase in vascular resistance in the intrahepatic hepatic vein, i.e. postsinusoidal portal hypertension.     

Delayed periportal enhancement: a characteristic finding on contrast ultrasound in idiopathic portal hypertension

Purpose  

Differentiation of idiopathic portal hypertension (IPH) from cirrhosis is not always easy because of their similar clinical features. This prospective study aimed to use contrast-enhanced ultrasound (US) in studying dynamic behavior of microbubble for characteristic enhancement features in IPH.     

Liver cirrhosis and portal hypertension in cystic fibrosis

OBJECTIVES: Liver disease is the second cause of death in cystic fibrosis. The most deleterious complication of liver disease is portal hypertension, which has an estimated prevalence of up to 8%. Portal hypertension may manifest itself by splenomegaly, hypersplenism, gastro-oesophageal bleeding and ascites. The aim of our study was to determine the prevalence, risk factors and invasive management of portal hypertension at our centre. METHODS: One hundred and fifty patients with cystic fibrosis were followed up between 1975 and 2000 in the national cystic fibrosis centre in Israel. Forty patients (27%) had liver disease. All underwent clinical evaluation and laboratory and imaging studies. RESULTS: Portal hypertension was diagnosed in 10 patients (7%), of whom eight were male. The mean age at diagnosis was 11 years (range, 4-17 years). All had severe mutations of the cystic fibrosis transmembrane conductance regulator gene (the CFTR gene), pancreatic insufficiency, meconium ileus or distal intestinal obstruction syndrome and variceal bleeding. Seven patients underwent sclerotherapy to control acute bleeding. Four underwent portosystemic shunting (functioning up to 37 years). Two patients with severe lung and liver disease underwent transjugular intrahepatic portosystemic shunting, which provided bleeding control, but both died while waiting for lung/liver transplantation. One patient underwent liver transplantation due to liver failure and still had good liver and lung function 10 years later. CONCLUSIONS: Portal hypertension is more common among Israeli patients with cystic fibrosis. The unique genetic composition of our population may explain this phenomenon. Risk factors include male gender, pancreatic insufficiency, severe CFTR mutations, meconium ileus and meconium ileus equivalent. Sclerotherapy is the main option to control oesophageal variceal bleeding, while portosystemic shunts offer a prolonged alternative treatment for refractory bleeding. A transjugular intrahepatic portosystemic shunt and liver transplantation may also be effective, but further research is required in order to establish their role.     

Expression of angiotensin II type 1 receptor in human cirrhotic livers: Its relation to fibrosis and portal hypertension.

Angiotensin II (ANG-II) and its receptor (AT1) have been potential targets of therapy for liver cirrhosis. However, AT1 expression in human cirrhotic livers has not been clarified. We studied AT1 and ANG-II generating enzymes in human autopsy (20 cirrhotics and 20 normal controls) and biopsy (10 cirrhotics) livers. AT1 immunoreactivity in tissue sections was quantified by computer-aided morphometry. AT1 protein and mRNA levels were assessed by Western blotting and real-time polymerase chain reaction. Concerning ANG-II generating system, angiotensin-converting enzyme (ACE) and mast cell chymase were examined. AT1 expression was seen not only in vascular smooth muscle cells, but also in activated stellate cells/myofibroblasts and liver parenchymal cells. AT1-positive vessels and myofibroblasts were significantly increased in fibrous septa of cirrhosis, although overall hepatic AT1 expression was reduced in the cirrhotic livers compared with the controls. Augmentation of AT1-positive vessels was related to severity of portal hypertension. Expressions of ACE and chymase were enhanced in the cirrhotic livers. These results suggest that hepatic AT1 expression is shifted to and concentrated in vessels and myofibroblasts in cirrhotic settings, and increased ANG-II generation by ACE and chymase contributes to portal hypertension and liver fibrosis via binding to AT1 expressed on vessels and myofibroblasts.     

Changes in the portal and splenic veins in portal hypertension and their relation to splenomegaly

This paper is a pathological study on the portal veins demonstrating that the changes in the portal circulation and in the spleen reflect the degree or duration of portal hypertension.     

Hepatic fibrosis, stellate cells, and portal hypertension

Hepatic fibrogenesis is the common result of injury to the liver. It is believed to be a critical factor that leads to hepatic dysfunction and may be important in portal hypertension. The fibrogenic response is a complex process in which accumulation of extracellular matrix proteins, tissue contraction, and alteration in blood flow are prominent. A critical event in fibrogenesis is activation of resident perisinusoidal cells that are termed "hepatic stellate cells". Stellate cell activation is characterized by many important phenotypes, including enhanced extracellular matrix synthesis and prominent contractility. Given the central role of stellate cell activation in hepatic fibrogenesis (and portal hypertension), effective therapy for hepatic fibrogenesis is most likely will be directed at this event.     

The relationship of hemorrhoids to portal hypertension

Records of 188 patients with documented portal hypertension were reviewed to determine the incidence of hemorrhoids as well as bleeding complications associated with this condition. The incidence of hemorrhoids among these patients was not increased compared to the normal population. Six of the patients with portal hypertension did, however, bleed massively from hemorrhoids. Elevated portal venous pressure is an important factor in those patients having severe hemorrhoidal bleeding. The presence of coagulation defects may also be of considerable importance.     

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.     

门静脉系统血流动力学与肝硬化门静脉高压的相关性

肝硬化门静脉高压导致的食管胃底静脉曲张出血是晚期肝硬化患者死亡的主要原因之一.目前仍缺乏简便易行的检测门静脉压力的方法和手段.本研究拟通过对89例肝病患者进行腹部彩色多普勒超声检查,了解门静脉系统血管直径和血流速度与肝硬化门静脉高压的相关性,为临床门静脉高压食管胃底静脉曲张出血的防治提供参考依据.     

Short term effect of diltiazem on portal hypertension in patients with non-cirrhotic portal fibrosis

Fourteen patients of non-cirrhotic portal fibrosis (NCPF) with portal hypertension were put on oral diltiazem hydrochloride (90 mg/day) or placebo on a prospective, randomised, single blind basis for 15 days. Predrug hemodynamic and biochemical status were similar in both groups. Diltiazem produced significant reduction (p less than 0.001) in mean intrasplenic pressure: from 41.88 (SD +/- 6.18) to 21.5 (+/- 7.91) cm of normal saline as against 45.56 (+/- 9.45) to 43.33 (+/- 8.27) in the placebo group. Mean arterial pressure (MAP), heart rate and cardiac output (CO) did not change in either group. Thus, the calcium channel blocker diltiazem reduces portal pressure in patients with NCPF, independent of reduction in MAP and CO; this is advantageous in situations where compromised cardiac hemodynamics may prove deleterious.     

Diastolic dysfunction and its relation to myocardial fibrosis in essential hypertension

This study elucidated diastolic left ventricular dysfunction and whether myocardial interstitial fibrosis correlates with diastolic dysfunction in mild to moderate systemic hypertension (HT). Six normotensive subjects, 18 hypertensive patients without left ventricular hypertrophy (LVH) and 10 hypertensive patients with significant LVH were evaluated. M-mode echocardiography was used to determine fractional shortening (FS), isovolumic relaxation time (IRT), and left ventricular filling volume during rapid and slow filling periods and the atrial contraction period (RFV, SFV, ACV). The quotients of the left ventricular filling volume and the end-diastolic volume and stroke volume were also calculated. Simultaneous biventriculography was used to determine the end-diastolic thickness of the interventricular septum and posterior wall. Right ventricular endomyocardial biopsies were performed to calculate the percentages of fibrosis. The FS was normal in all groups. The percentages of fibrosis in the two HT groups were significantly greater than those in the normals. The IRT of the HT groups was significantly greater, and the RFV, RFV/EDV and RFV/SV were significantly less than those of the normals. Multiple regression analysis showed that the wall thickness and the percentages of fibrosis correlated significantly with IRT, RFV, RFV/EDV and RFV/SV. The standard coefficients of correlation of wall thickness and the percentages of fibrosis were 0.333 and 0.239 in respect to IRT, and -0.304 and -0.473 in respect to RFV. There were significant correlations between the percentages of fibrosis and RFV (r = -0.675), RFV/EDV (r = -0.664) and RFV/SV (r = -0.602) in the normals and in cases of HT without LVH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noncirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and treatment

The Asian Pacific Association for the Study of the Liver (APASL) Working Party on Portal Hypertension has developed consensus guidelines on the disease profile, diagnosis, and management of noncirrhotic portal fibrosis and idiopathic portal hypertension. The consensus statements, prepared and deliberated at length by the experts in this field, were presented at the annual meeting of the APASL at Kyoto in March 2007. This article includes the statements approved by the APASL along with brief backgrounds of various aspects of the disease.