Assessment of portal hypertension in humans

Patients suspected of having portal hypertension (either by clinical history, physical examination, or previous diagnosis) should undergo ultrasonography and upper gastrointestinal endoscopy. Ultrasonography, preferably using the duplex technique, can disclose the patency of the portal venous system, the presence of signs of portal hypertension (splenomegaly, portocollateral vessels, repermeabilization of the umbilical vein, and so forth) and provide additional information about liver, biliary, or pancreatic diseases that may be the cause of portal hypertension. Endoscopy can assess the presence and size of gastroesophageal varices, the appearance of the variceal wall, and the presence and severity of portal hypertensive gastropathy. Patients showing a patent portal vein should have hepatic vein catheterization to evaluate the presence of presinusoidal, sinusoidal, or postsinusoidal portal hypertension. Patients in whom presinusoidal portal hypertension is suspected (those having esophageal varices with an HVPG below 10 mm Hg) should have liver biopsy and percutaneous transhepatic measurement of portal pressure. In sinusoidal portal hypertension, the results of endoscopy and HVPG measurement are decisive for the therapeutic management of the patients. The authors' results indicate that, before starting prophylactic therapy with beta-blockers, all patients should undergo at least an hepatic vein catheterization to assess HVPG; it would be preferable to have a variceal pressure measurement also. These measurements must be repeated 3 to 4 weeks after the final dose of therapy has been reached to assess the risk of variceal bleeding or rebleeding.     

Idiopathic portal hypertension.

Idiopathic portal hypertension is reported in five cases including one case of chronic arsenical intake and one case of chronic industrial vinyl chloride exposure. In all five cases the patients presented with gastrointestinal bleeding as the chief complaint. Physical examination was within normal limits except for splenomegaly in all. Results of liver function tests were normal, except for the relative clearance of sulfobromophtalein. A surgical liver biopsy specimen was obtained in all cases and showed moderate degrees of portal fibrosis, but no cirrhosis. Combined umbilicoportal, hepatic vein and superior mesenteric artery catheterization was performed in all cases. Hepatoportographies showed distortion of the intrahepatic portal venous system and cut-off of small portal venules. Porto-hepatic gradients ranged from 14.0 to 20.5 mm Hg. The portal hypertension was both sinusoidal and presinusoidal in nature but mainly presinusoidal. Hepatic extraction of indocyanine green and of albumin microaggregates was normal, thereby suggesting normal functional portal blood supply to the liver. The patients with arsenical or vinyl chloride exposure could not be differentiated from the other three patients with idiopathic portal hypertension. These results suggest that idiopathic portal hypertension may be related to domestic or industrial exposure to other hepatotoxins.     

Case Report: Secondary biliary cirrhosis possibly related to congenital hepatic fibrosis. Evidence for decreased number of portal branch veins and hypertrophic peribiliary vascular plexus

A 30-year-old man with presinusoidal portal hypertension was transplanted for cryptogenic cirrhosis. On the explanted liver, few intrahepatic stones, biliary cirrhosis, chronic cholangitis of the large bile ducts and a peculiar proliferation of small dilated bile ducts at the periphery of the portal tracts led to the diagnosis of secondary biliary cirrhosis and cholangitis, possibly linked to ductal plate malformation, including congenital hepatic fibrosis associated with a minor form of Caroli's disease. Ex vivo portogram and histology showed the paucity of portal vein branches and the hypertrophy of the peribiliary vascular plexus. This hypertrophy, which has been reported in livers with presinusoidal hypertension, is another indirect argument to suggest the diagnosis of congenital hepatic fibrosis.     

Portal hypertension and primary biliary cirrhosis.

Portal hypertension has been regarded as an uncommon and late complication of primary biliary cirrhosis (PBC). 24 patients with PBC were investigated for portal hypertension. Esophageal varices were present in 20, 50, and 90% of the patients 1, 3, and 9 years, respectively, after the onset of pruritus and/or jaundice. Portal hypertension was responsible for gastrointestinal bleedings in 11 patients; bleeding was the first clinical manifestation of PBC in two of them. Wedged hepatic venous pressure was increased in all the patients with portal hypertension whether regenerative nodules were present or absent. Portacaval shunt was performed in five patients and was well tolerated in three of them. It is concluded that (a) portal hypertension is common in PBC; (b) the intrahepatic block is of the so-called postsinusoidal type, even in patients without regenerative nodules; (c) gastro-intestinal bleeding due to portal hypertension occurs in about half of the patients and may be the first manifestation of PBC; (d) portacaval shunt seems to be indicated when gastro-intestinal bleeding occurs in earlier stage of the disease.     

Immunohistochemical characterization of inflammatory infiltrates in primary biliary cirrhosis

Ten liver biopsy specimens from nine patients with PBC stages II to IV were studied immunohistochemically with a broad panel of monoclonal antibodies. In areas of bile-duct proliferation, many BA1+ B-lymphocytes and OKT4+/Leu3a+ helper/inducer T-cells were observed, admixed with some C3b-receptor positive, mono- and polymorphonuclear OKM1+ cells. Numerous IgM-containing plasma cells were seen in portal tracts showing bile-duct proliferation. In contrast, areas of piecemeal necrosis and intralobular spotty necrosis consisted mainly of OKT4+/Leu3a+ helper/inducer, and OKT8+ suppressor/cytotoxic T-cells, admixed with some OKM1+ polymorphonuclear granulocytes. Almost no BA1+ B-lymphocytes or Ig-containing plasma cells were observed in areas of piecemeal necrosis and spotty necrosis. Major histocompatibility complex (MHC)-class I antigens (i.e. HLA-A,B,C) were demonstrated either on the liver cell membrane, or on sinusoidal lining cells. The latter also expressed MHC-class II antigens (i.e. HLA-DR). In two liver biopsies, an increased expression of HLA antigens was observed near areas of piecemeal and spotty necrosis. Our results indicate that several immune mechanisms each with a particular topographical distribution, are operative in PBC. Inflammatory cells, involved in humoral immunity, are present mainly in areas of bile duct proliferation. In contrast, the effector cells of antigen-specific cellular cytotoxicity are present in areas of piecemeal necrosis and spotty necrosis. In the latter areas, a pronounced expression of MHC products representing the afferent limb of the cell-mediated immune response, may permit an optimal T-cell-mediated immune effect or, eventually, result in adverse effects.     

Real-time tissue elastography for evaluation of hepatic fibrosis and portal hypertension in nonalcoholic fatty liver diseases

The aim of this study was to prospectively measure liver stiffness with real-time tissue elastography in patients with nonalcoholic fatty liver diseases (NAFLD) and to compare the result with the clinical assessment of fibrosis using histological stage. One hundred and eighty-one prospectively enrolled patients underwent real-time tissue elastography, with the first 106 being analyzed as the training set and the remaining 75 being evaluated as the validation set. Hepatic and splenic elastic ratios were calculated and compared with stage of histological fibrosis. Portal hypertension (PH) was assessed. Real-time tissue elastography cut-off values by stage in the training set were 2.47 for F1, 2.67 for F2, 3.02 for F3, and 3.36 for F4. Using these cut-off values, the diagnostic accuracy of hepatic fibrosis in the validation set was 82.6%-96.0% in all stages. Only portal fibrosis correlated with the hepatic elastic ratio by multivariate analysis. The area under the receiver operating characteristic curve of elastic ratio better correlated than serum fibrosis markers in both early and advanced fibrosis stages. Patients with PH, defined by splenic elasticity, had early fibrosis. Patients with severe PH were found only in the group with cirrhosis. Conclusion: Real-time tissue elastography is useful in evaluating hepatic fibrosis and PH in patients with NAFLD. (HEPATOLOGY 2012).     

Effect of hepatic nerves, norepinephrine, angiotensin, and elevated central venous pressure on postsinusoidal resistance sites and intrahepatic pressures in cats

Portal venous pressure was controlled by resistance localized to specific sites in hepatic lobar veins in cats. All of the pressure drop from the portal vein to the vena cava occurred across postsinusoidal vessels; portal pressure, lobar venous pressure, and, therefore, sinusoidal pressure were not significantly different. Norepinephrine and angiotensin infusions (intraportal) caused elevation in portal pressure due to constriction of hepatic venous resistance sites as well as some constriction of presinusoidal (portal or sinusoidal) resistance sites. At low doses of norepinephrine presinusoidal constriction dominated whereas at higher doses the postsinusoidal constriction increased proportionately more. Hepatic nerve stimulation produced a similar response measured at an early time (1 min), but by 3 min the presinusoidal constriction showed complete escape so that elevated portal pressure was entirely due to hepatic venous constriction. The same site that provided basal vascular resistance also provided the increased hepatic venous resistance with nerve stimulation and infusion of angiotensin and norepinephrine. Rapid elevation of central venous pressure (CVP) caused elevated sinusoidal pressure. At high CVP (16 mm Hg), 75% of a rise in CVP was transmitted whereas at normal CVP (less than 4.5 mm Hg) less than 20% transmission occurred. The presence of a high resistance in the hepatic veins protected intrahepatic pressure from the effects of normal fluctuation of CVP.     

Plasma catecholamines in patients with presinusoidal portal hypertension: comparison with cirrhotic patients and nonportal hypertensive subjects

During a hemodynamic study, plasma catecholamine concentrations were measured in the pulmonary artery and in the hepatic vein in 18 presinusoidal portal hypertensive patients. Results were compared with those in 15 nonportal hypertensive subjects and in 24 cirrhotic patients in good condition (grade A, according to Pugh's classification). Plasma norepinephrine concentrations in the pulmonary artery or in the hepatic vein were not significantly different between nonportal hypertensive subjects (mean +/- S.E.M.: 271 +/- 36 and 83 +/- 11 pg/ml, respectively) and presinusoidal portal hypertensive patients (273 +/- 33 and 84 +/- 11 pg/ml, respectively). These concentrations were, however, elevated in cirrhotic patients (408 +/- 47 and 256 +/- 45 pg/ml, p less than 0.05 in comparison with the two other groups). These differences suggest that increased sympathetic nervous activity in cirrhosis is associated with the presence of liver disease or increase in sinusoidal pressure. Differences in plasma epinephrine concentrations were not significant among the three groups of patients. However, the existence of a significant correlation between pulmonary artery plasma epinephrine concentration and cardiac index (r2 = 0.46, p less than 0.01) in patients with presinusoidal portal hypertension suggests that the adrenal medulla could play a role in the pathophysiology of the hyperkinetic syndrome of these patients.     

原发性胆汁性肝硬化的临床与肝脏病理相关性研究

目的 研究原发性胆汁性肝硬化(PBC)患者临床与肝脏病理变化的相关性.方法 24例初诊未经治疗的PBC患者的肝脏穿刺标奉常规进行苏木素-伊红染色,记录病理分期、纤维化、汇管区炎症、汇管区周围碎屑坏死、肝细胞坏死性损害、胆管增生及胆管减少程度;分析前述指标的临床相关性.正态资料组间比较用x2或t检验,非正态资料及等级资料进行Mann-Whitmey U非参数检验,相关分析用Pearson和Spearman相关分析.结果 病理分期、纤维化程度与总胆红素、直接胆红素(DBIL)、总胆汁酸、总胆固醇、IgG均呈正相关,与白蛋白、血嗜酸细胞(EOS)比例呈负相关(r=-0.527,P=0.030;r=-0.503,P=0.039和r=-0.554,P=0.021;r=-0.502,P=0.040).汇管区周围碎屑坏死与碱性磷酸酶(ALP)、总胆红素、DBIL、总胆汁酸呈正相关,还与血肿瘤坏死因子(TNF)-α水平呈正相关[r=0.617,P=0.006].结论 总胆红素、DBIL、总胆汁酸、总胆固醇、IgG与白蛋白、EOS比例反映了疾病严重程度和不可逆性,而ALP、TNF-α、总胆红素、DBIL、总胆汁酸反映疾病活动程度.

Abstract：

Objective The aim of this study was to describe the clinical and pathological features of primary biliary cirrhosis(PBC) and their correlation.Methods Liver biopsy specimens were obtained through percutaneous needle puncture from twenty four patients with PBC who had not been diagnosed or treated before.These samples were fixed in formaldehyde and embedded in paraffin for routine histological examination.Pathologic stages based on Ludwig criteria,fibrosis,portal and periportal inflammation,lymphocytic periportal piecemeal necrosis,ductular proliferation,intralobular hepatocyte necrosis,the degree of ductopenia and relevant laboratory results were recorded.Statistics method used was x2 or t-test,Mann-whitmey U nonperametric test and Pearson's or Spearman's correlation analysis.Results The pathological stages,degree of fibrosis were positively correlated with total bilirubin (TBIL) level,total bile acid (TBA),cholesterol (CHO),IgG levels,and were negatively correlated with serum albumin(ALB) level(r=-0.527,P=0.030; r=-0.503,P=0.039) ,percentage of eosinophilic cells (EOS) ( r=-0.554,P=0.021; r=-0.502,P=0.040).Lymphocytic periportal piecemeal necrosis was positively correlated with alkaline phosp-hatase (ALP),TBIL,DBIL,TBA,and also tumor necrosis factor-αt (TNF-αα) levels(r=0.617,P=0.006).Conclusion TBIL,DBIL,TBA,CHO,IgG and ALB,EOS are good surrogate markers for disease sever ity and reversibility of PBC,while ALP,TNF-Cα,TBIL,DBlL,TBA can be used as markers for disease activity.     

Portal hypertension secondary to myelofibrosis: a study of three cases

BACKGROUND: In patients with idiopathic myelofibrosis (IM), portal hypertension (PHT) without thrombosis of the hepatic or splenoportal veins is infrequent. OBJECTIVE: To ascertain the mechanisms responsible for the development of PHT in IM and their therapeutic implications. PATIENTS AND METHODS: Color Doppler ultrasound with portal flow quantification, hepatic hemodynamic studies, and histological examinations of the liver biopsies were performed in three IM patients with PHT in whom hepatic and splenoportal thrombosis were ruled out. RESULTS: Two patients showed sinusoidal PHT (increased hepatic venous pressure gradient), normal portal flow, and massive myeloid metaplasia of the liver. Transjugular intrahepatic portosystemic shunt (TIPS) was indicated for variceal bleeding and ascites unresponsive to medical therapy, and resulted in an adequate control of these PHT complications. At the time of TIPS placement, direct portal pressure measurement showed a marked presinusoidal component in the PHT. A third patient died as a consequence of the IM before treatment of PHT could be instituted. This patient showed an extremely increased portal flow and lesser hepatic infiltration. CONCLUSIONS: IM patients with PHT might have a marked presinusoidal component contributing to PHT that is underestimated by hepatic vein catheterization. Treatment of the complications of PHT might not differ from that of patients with cirrhosis.     

Nature and Incidence of Liver Involvement in Agnogenic Myeloid Metaplasia

Clinical, biochemical and histopathological data of 33 patients with agnogenic myeloid metaplasia (AMM) were examined with reference to liver disease and dysfunction. Clinical manifestations of hepatic or portal system involvement included hepatomegaly, jaundice, hepatitis, gall stones, ascites and bleeding esophageal varices. The liver was smooth and firm; it became larger with progression of the disease, but to a lesser degree than the spleen. Mild indirect bilirubinaemia occurred in the course of the disease in about half of the patients. Hepatitis was diagnosed in 5 (15 %) patients and in 3 (10 %) cases it was the cause of death. Cholelithiasis was found in 4 (12 %) patients. Biochemical liver dysfunction occurred in 22 (66 %) patients. A progressive increase in serum alkaline phosphatase and a gradual decrease in serum albumin were observed in 4 patients, who were followed for 5 to 15 years. Hepatic myeloid metaplasia was found in all 20 patients examined histologically. The liver architecture was grossly distorted in 4 cases: in 2 this was due to impaction of the sinusoid with haemopoietic cells, and in the remaining 2 to necrosis and haemorrhage following viral hepatitis. Periportal fibrosis was observed in 6 (30 %) of the liver specimens. Ascites, portal hypertension, or both, were found in 7 (64 %) of the 11 autopsies and in 5 (22 %) of the remaining patients. Liver histology, examined in 11 patients, revealed periportal fibrosis in 5 cases and myeloid metaplasia only, in the remaining 5. Patients with ascites or portal hypertension exhibited more frequently increased levels of serum alkaline phosphatase and vitamin B₁₂, and lower levels of plasma prothrombin and serum albumin. The pathogenesis of the hepatic and portal system involvement in agnogenic myeloid metaplasia (AMM) remains uncertain. Mechanical pressure by foci of myeloid metaplasia, chronic passive congestion, hepatitis or combinations of the above may lead to atrophy or necrosis of the parenchyma, followed by reparative fibrosis. Portal hypertension and ascites, a common complication of advanced AMM, could be due to the combined effect of an increased blood flow in the portal system, hypoalbuminaemia and sinusoidal obstruction.     

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.     

A Comparative Study Between Laparoscopic Findings and Histological Stages in Primary Biliary Cirrhosis

Abstract: Histopathologically, early lesions of primary biliary cirrhosis (PBC) are focal within the liver and there is segmental involvement of the bile ducts. In addition, the development of PBC is variable within the liver. PBC is characterized by the following laparoscopic findings: reddish patch, mesh-like white marking and gentle undulation, etc. In the present study, we analyzed the correlation between the laparoscopic findings and the histological stage as per Scheuer's classification in 22 patients with PBC. The results of this study are summarized as follows: 1) Reddish patch was frequently observed in the early stage of PBC. 2) Mesh-like white marking was observed in cases of stage I, II and III. 3) Gentle undulation was seen in stage II and III. The absence of this finding is useful in the diagnosis of stage I. 4) In stage IV, these three findings were not observed. 5) From these three findings, it was difficult to differentiate stage II or III. But the presence of portal hypertension and increased vascularity of the liver capsule were observed in accordance with the progression of the disease. Indications of portal hypertension were seen even in the early stage and in some asymptomatic cases of PBC. In conclusion, the laparoscopic findings such as reddish patch, mesh-like white marking, gentle undulaion and portal hypertension are very valuable for stage diagnosis and the evaluation of prognosis in patients with PBC.     

Pulmonary hypertension in primary biliary cirrhosis: A prospective study in 178 patients

Objective. To analyze the incidence, clinical features, and prognosis of patients with primary biliary cirrhosis (PBC) complicated by pulmonary hypertension (PH). Material and methods. A total of 178 consecutive PBC patients, who were admitted to Peking Union Medical College Hospital from January 2001 to March 2007, were included in this prospective study. A structured interview, systemic rheumatological examination, laboratory tests (including autoantibodies), and Doppler echocardiography were conducted for each patient and compared between patients with and without PH. Results. Twenty-one PBC patients (11.8%) had PH. Among them, four patients (19.0%) had moderate to severe PH, and one patient died of right heart failure instead of liver failure. The incidences of Raynaud's phenomenon, interstitial lung disease, Sjögren's syndrome, and portal hypertension, the proportion of patients with a positive anti-SSA, the level of serum IgA, as well as the Mayo risk score in the PH–PBC patients were significantly higher than in the non-PH-PBC group (p = 0.02, 0.001, 0.02, 0.03, 0.006, 0.04 and 0.02, respectively). Conclusions. PH, including moderate to severe PH, is not a rare complication of PBC. This complication is closely associated with portal hypertension and immunological dysregulation and indicates a poor prognosis.     

The use of ursodeoxycholic acid in patients with primary biliary cirrhosis: sense or nonsense

Ursodeoxycholic acid is the most widely evaluated drug for the treatment of primary biliary cirrhosis. The results of the first randomized controlled trials are very discordant in terms of survival benefit. This, however, can be explained by differences in methodology and insufficiently long period of treatment and follow-up. It has clearly been demonstrated that serum bilirubin levels and histological parameters such as piecemeal necrosis and fibrosis are validated predictors of prognosis in PBC. We re-analyzed the already published data using these parameters as surrogate endpoints. This analysis reveals that there is a significant positive effect of treatment of PBC with UDCA on serum bilirubin levels as well as on the progression of piecemeal necrosis and fibrosis. We therefore conclude that UDCA has a positive effect on the prognosis of PBC and can slow down the progression to end stage liver disease.     

原发性胆汁性肝硬化的临床及病理分析

目的　研究原发性胆汁性肝硬化 (PBC)的临床病理特点、伴发疾病及治疗反应 ,以提高对PBC的认识。方法　分析 37例PBC的临床资料及其中 13例肝穿刺病理资料 :抗线粒体抗体(AMA)采用间接免疫荧光法检测 ,M2 亚型采用ELISA法检测。结果　① 37例患者 ,发病年龄 (5 0±10 )岁。②症状 :乏力 2 0例 (5 4 1% ) ,瘙痒 10例 (2 7 0 % ) ,腹痛 8例 (2 1 6 % ) ,肝性脑病 1例(2 7% ) ;体征 :肝大 2 6例 (70 3% ) ,脾大 2 0例 (5 4 1% ) ,黄疸 16例 (43 2 % ) ,腹水 4例 (10 8% ) ,门脉高压症 7例 (18 9% )。③实验室检查 :血清碱性磷酸酶水平升高 37例 (10 0 0 % ) ,(45 0± 32 2 )U/L ;总胆红素升高 31例 (83 8% ) ,(12 6± 14) μmol/L ;丙氨酸转氨酶升高 32例 (86 5 % ) ,(71± 17)U/L ;IgM升高 32例 (86 5 % ) ;ANA阳性 10例 (2 7 0 % ) ;抗SSA和 /或抗SSB抗体阳性 5例(13 5 % )。④合并干燥综合征 (SS) :符合哥本哈根标准 17例 (45 9% ) ,符合董怡标准 10例(2 7 0 % )。⑤肝穿刺病理 :取材满意 9例中 ,胆管炎 9例 ,肝细胞点状及碎片状坏死 1例 ,纤维化 8例。⑥治疗反应 :单纯皮质激素和 /或免疫抑制剂治疗者 2 6例 ,有效 10例 ,无效 16例 ,有效组IgG升高及合并SS例数均显著高于无效组 (P分别 <0 0 1     

Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis

The predictive role of antinuclear antibodies (ANAs) remains elusive in the long-term outcome of primary biliary cirrhosis (PBC). The progression of PBC was evaluated in association with ANAs using stepwise Cox proportional hazard regression and an unconditional stepwise logistic regression model based on the data of 276 biopsy-proven, definite PBC patients who have been registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). When death of hepatic failure/liver transplantation (LT) was defined as an end-point, positive anti-gp210 antibodies (Hazard ratio (HR) = 6.742, 95% confidence interval (CI): 2.408, 18.877), the late stage (Scheuer's stage 3, 4) (HR = 4.285, 95% CI:1.682,10.913) and male sex (HR = 3.266, 95% CI: 1.321,8.075) were significant risk factors at the time of initial liver biopsy. When clinical progression to death of hepatic failure/LT (i.e., hepatic failure type progression) or to the development of esophageal varices or hepatocellular carcinoma without developing jaundice (Total bilirubin < 1.5 mg/dL) (i.e., portal hypertension type progression) was defined as an end-point in the early stage (Scheuer's stage 1, 2) PBC patients, positive anti-gp210 antibodies was a significant risk factor for hepatic failure type progression [odds ratio (OR) = 33.777, 95% CI: 5.930, 636.745], whereas positive anti-centromere antibodies was a significant risk factor for portal hypertension type progression (OR = 4.202, 95% CI: 1.307, 14.763). Histologically, positive anti-gp210 antibodies was most significantly associated with more severe interface hepatitis and lobular inflammation, whereas positive anticentromere antibodies was most significantly associated with more severe ductular reaction. CONCLUSION: These results indicate 2 different progression types in PBC, hepatic failure type and portal hypertension type progression, which may be represented by positive-anti-gp210 and positive-anticentromere antibodies, respectively.     

Hyperkinetic circulatory syndrome in patients with presinusoidal portal hypertension : Effect of propranolol

This study evaluates systemic and splanchnic haemodynamics and the effect of propranolol in 15 patients with presinusoidal portal hypertension (portal vein obstruction, n = 11; schistosomiasis, n = 4). These patients exhibited a hyperkinetic circulatory syndrome characterized by high cardiac index (4.4 +/- 1.61.min-1.m-2, mean +/- S.D.) and by low systemic vascular resistance despite normal liver function and sinusoidal pressure. Hepatic blood flow was decreased in half of the patients with portal vein obstruction. Azygos blood flow, an estimate of superior portal-systemic collateral circulation, was markedly increased in all patients (0.46 +/- 0.19 l/min, upper limit of normal: 0.19 l/min). Therefore, in these patients with normal hepatic venous pressure gradient, azygos blood flow measurement provides an index of splanchnic haemodynamic changes. Propranolol administration (15 mg, i.v.) reduced the hyperkinetic circulatory syndrome, with a significant decrease in heart rate (-17 +/- 6%), cardiac index (-25 +/- 12%) and azygos blood flow (-40 +/- 26%) and a significant increase in systemic vascular resistance (+40 +/- 40%). These results suggest that the hyperkinetic circulatory syndrome observed in these patients, could be related to an increase in beta-adrenergic activity. The decrease in azygos blood flow, after propranolol administration, was significantly correlated (r = 0.94) with the increase in right atrial pressure. This finding suggests that propranolol may act through an increase in portal-systemic collateral venous tone. These haemodynamic results justify, in patients with presinusoidal portal hypertension, clinical trials investigating the beneficial effect of beta-blockers on gastrointestinal bleeding caused by portal hypertension.     

The relation of periportal fibrosis to portal hypertension

To clarify the relation of periportal fibrosis to portal hypertension, the present study was undertaken in rats given lithocholate. Portal vascular resistance measured by an isolated liver perfusion method increased with the length of lithocholate administration. In vivo portal vein pressure elevation was closely correlated to the increase in portal vascular resistance. The blood pressure difference between the portal vein and the terminal portal venule increased compared to control rats. The blood pressure differences between the terminal portal venule and the terminal hepatic venule, and between the terminal hepatic venule and the inferior vena cava, were almost the same as those in control rats. Lithocholate administration induced narrowing and meandering of the portal vein branches due to periportal fibrosis with proliferation of bile ductules. There was no perceptible change in the sinusoids and the hepatic vein branches. These data suggest that periportal fibrosis causes deformation of the peripheral branches of the portal vein and leads to presinusoidal portal hypertension.     

定量磁共振成像诊断原发性胆汁性肝硬化患者门静脉高压症价值分析*

目的 探讨应用定量MRI和血清学指标诊断原发性胆汁性肝硬化(PBC)患者门静脉高压症的价值。方法 2010年1月～2018年12月我院收治的PBC患者45例,获得并计算天门冬氨酸氨基转移酶/血小板比值指数(APRI)和纤维化指数-4(FIB-4)评分,行腹部磁共振成像检查,提取肝脾硬度、T1、T2和表观弥散系数(ADC)值,绘制受试者工作特征曲线下面积(AUC),分析各指标诊断门静脉高压症的效能。结果 在45例PBC患者中,发现14例(31.1%)存在门静脉高压症;14例门静脉高压症患者APRI评分为2.21(1.82,2.74)分,FIB-4评分为1.65(1.02,1.94)分,肝脏硬度为4.87(4.15,5.46)kPa,脾脏硬度为9.75(7.54,11.77)kPa,肝脏T1为1024.8(975.4,1078.5)ms,肝脏T2为62.7(57.4,68.4)ms,ADC值为1.29(1.11,1.62)×10^-3mm²/s,显著高于31例无门静脉高压症患者[分别为0.68(0.21,0.94)分、0.24(0.18,0.42)分、2.51(2.11,2.98)kPa、5.23(4.62,6.08)kPa、930.8(870.9,980.4)ms、56.8(55.3,58.7)ms和1.08(1.02,1.25)×10^-3mm²/s,P<0.05];APRI、FIB-4、MR检测肝硬度和脾硬度诊断门脉高压的灵敏度分别为90.4%、82.3%、92.4%和90.3%,特异度分别为79.6%、91.2%、92.0%和93.2%。结论 采用MRI检测肝脾硬度联合APRI和FIB-4评分可以帮助诊断PBC患者门静脉高压症,值得临床进一步验证。