Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis.

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices.     

Transjugular intrahepatic portosystemic shunt for the treatment of portal hypertension secondary to non-cirrhotic perisinusoidal hepatic fibrosis

Non-cirrhotic perisinusoidal hepatic fibrosis is a process of imprecise pathogenesis involving collagenization of the space of Disse. Exposure to chemicals, auto-immunity, thrombophilia and/or infections are suspected primary agents. Here, we present the case of a patient who developed severe portal hypertension with histological features suggesting a non-cirrhotic perisinusoidal hepatic fibrosis. A 52-year-old man was hospitalized for oesophageal variceal haemorrhage. Liver cirrhosis or portal vein thrombosis were absent as attested by laboratory tests, duplex sonography, computed tomography scan and histological examination of a liver biopsy specimen. Presinusoidal portal hypertension was suggested by a normal wedge-free hepatic vein gradient. Only electron microscopy examination of a liver biopsy specimen could disclose perisinusoidal fibrosis. This was most probably secondary to a combined chemotherapy received 4 years earlier for non-Hodgkin large-cell lymphoma. As variceal ligation failed to control oesophageal varices while liver function tests were normal, a transjugular intrahepatic portosystemic shunt (TIPS) was performed. This dramatically improved the signs of portal hypertension. This case illustrates the use of TIPS in the treatment of portal hypertension secondary to non-cirrhotic perisinusoidal fibrosis.     

Light chain deposition disease of the liver associated with AL-type amyloidosis and severe cholestasis

A 67-year-old man with a 3-month history of jaundice presented with hepatomegaly. Laboratory studies revealed abnormal liver tests with raised bilirubin. Renal function was normal. Endoscopic retrograde cholangiopancreatography revealed normal extrahepatic bile ducts. Liver biopsy showed severe bilirubinostasis and a typical bile infarct. Laminar and globular deposits of PAS-positive diastase-resistant non-congophilic material were observed in the sinusoidal walls. In addition, congophilic material was detected in the portal tracts. Immunohistochemistry revealed the presence of lambda-light chain deposits both in the sinusoids and in the portal tracts. Collagens type I and IV and fibronectin appeared markedly increased in the perisinusoidal space. On electron microscopy, the deposited material in the Disse spaces was mainly composed of fibrils indistinguishable from amyloid, admixed with small amounts of granular electron-dense material. The similarities of light chain deposition disease and AL amyloidosis are discussed.     

Portal hypertension due to intrahepatic obstruction in non-Hodgkin's lymphoma.

Portal hypertension is rare in the setting of non-Hodgkin's lymphoma. We report here the case of a 73-year-old man presenting with diffuse high-grade B-cell lymphoma affecting predominantly the liver with large space occupying lesions. Histological examination of liver specimens showed abnormal large lymphoid cells whereas adjacent non-tumoural liver was normal. Portal hypertension was documented by upper gastrointestinal endoscopy that showed grade II oesophageal varices and measurement of portal pressures via transjugular approach showing increased hepatic venous pressure gradient (24 mmHg). We assume that portal hypertension was mainly related to these space occupying lesions.     

The extrahepatic uptake of198Au as an index of portal hypertension

A study was undertaken to determine if extrahepatic recticuloendothelial uptake of¹⁹⁸Au during hepatic scanning could be used as a measure of the portal venous pressure in patients with chronic diffuse liver disease. Twenty patients were studied by history, physical examination, liver function studies, liver biopsy, esophagoscopy,¹⁹⁸Au hepatic scan and wedged hepatic vein pressure measurements. Patients were separated into 2 groups: Group A—patients with neither spleen or lumbar vertebral bone marrow uptake of¹⁹⁸Au; Group B—patients with significant spleen and/or vertebral bone marrow uptake of isotope. Each of the 6 patients in Group A had a hepatic wedge pressure under 18 mmHg, and none had varices on esophagoscopy. All 14 patients in Group B had hepatic wedge pressures of 18 mmHg or more. Only 8 Group B patients had varices on esophagoscopy. These data suggest that the¹⁹⁸Au hepatic scan is a safe and valuable procedure for estimating the degree of portal venous hypertension in patients with diffuse chronic liver disease. In these 20 patients, if spleen or vertebral bone marrow uptake of isotope was present, the portal venous pressure was 18 mmHg or greater. If spleen and/or bone marrow uptake was lacking, then the portal venous pressure was below 18 mmHg.     

Cholestatic jaundice in two patients with primary amyloidosis: ultrastructural findings of the liver

Two patients with primary amyloidosis (amyloid light chain case) and severe cholestatic jaundice are described. Liver biopsy in the preterminal stage demonstrated amyloid deposits in the perisinusoidal space and in portal tracts, and hepatocytes were atrophic because of compression by amyloid fibrils. Ultrastructural findings showed amyloid fibrils not only in Disse's space but also in the sinusoids, and the hepatocyte microvilli facing the amyloid fibrils were spicular. There were aggregates of lysosomal granules in the vicinity of bile canaliculi and some bile canaliculi were dilated with loss of microvilli. Amyloid fibrils in the portal tract compressed bile ductules, causing wide intercellular space and separated basement membranes from their epitheliums. These findings suggested disturbance in transporting not only of essential materials from sinusoids to hepatocytes but also of secretory vesicles into bile canaliculi and leakage of bile juice from small bile ductules in preterminal stage of primary amyloidosis.     

Long-term favourable outcome of portal hypertension complicating primary systemic amyloidosis

Abstract: An unusual case of systemic amyloidosis complicated by portal hypertension is reported. In this condition, portal hypertension is a rare event associated with poor prognosis. In our patient, severe presymptomatic sinusoidal portal hypertension was demonstrated by hepatic vein catheterization and coincided with abundant perisinusoidal amyloid infiltration. Despite these features and the absence of objective response to 20 courses of melphalan and prednisone, the patient was still in good clinical condition 4 years after initial diagnosis. This observation suggests that in primary amyloidosis, the incidence of sinusoidal portal hypertension might be underestimated and also that it may be associated with a relatively good prognosis.     

Systemic and splanchnic hemodynamic changes in patients with hepatic schistosomiasis

Abstract: Although hepatic schistosomiasis is a common cause of portal hypertension, only a few hemodynamic studies, in humans, have been published on this subject. The aim of this study was to determine the systemic and splanchnic hemodynamic changes in hepatic schistosomiasis and to evaluate the influence of liver fibrosis on these changes. A retrospective analysis of a series of 13 patients with hepatic schistosomiasis who had undergone hemodynamic studies was performed. Portal or perisinusoidal fibrosis was present at liver biopsy in 8 patients. The control group included 22 patients with chronic hepatitis and normal hepatic venous pressure gradients. Patients with schistosomiasis exhibited high cardiac index (4.11±1.15 1 · min^-1 · m^-2 vs 2.99±0.85 1 · min^-1 · m^-2; p<0.05) and low systemic vascular resistance (1039±316 dyn · s · cm^-5 vs 1334±336 dyn · cm^-5; p<0.05). The hepatic venous pressure gradient and hepatic blood flow were normal. Azygos blood flow was markedly increased (0.90±0.66 1 · min^-1 vs 0.13±0.04 1 · min^-1; p<0.05). Hemodynamic values were not significantly different between patients with liver fibrosis and those without fibrosis at liver biopsy. In conclusion, patients with hepatic schistosomiasis had a hyperkinetic systemic and splanchnic circulation. In patients with esophageal varices, a normal hepatic venous pressure gradient confirmed presinusoidal portal hypertension. The presence of portal or perisinusoidal fibrosis did not influence hyperdynamic splanchnic state.     

Idiopathic portal hypertension (perisinusoidal fibrosis) after renal transplantation.

We report the cases of two renal transplant recipients suffering from idopathic portal hypertension, a condition characterised by increased portal venous pressure in the absence of both histological lesion of the liver and obstruction of the portal vein. In these two patients, perisnusoidal fibrosis, invisible by light microscopy, was demonstrated by electron microscopy; it is suggested that partial obstruction of hepatic sinusoids by perisinusoidal fibrosis could be the mechanism for increased portal venous pressure in all the patients with idiopathic portal hypertension. In these two patients, who received 6-mercaptopurine and azathioprine, perisinusoidal fibrosis might be the consequence of prolonged administration of these drugs.     

Portal hypertension and ascites in acute hepatitis: clinical, hemodynamic and histological correlations

We attempted to ascertain the mechanism of portal hypertension and ascites complicating acute hepatitis in 66 patients who underwent transvenous liver biopsy and measurement of hepatic venous pressure gradient. Increase in hepatic venous pressure gradient was related to the severity of acute hepatitis, as indicated by the significant correlation between the values for hepatic venous pressure gradient and serum bilirubin, serum albumin or coagulation factor V, and by its higher value in patients with, than in patients without, encephalopathy. Hepatic venous pressure gradient was higher in patients with, than in patients without, ascites (12.5 +/- 3.4 vs. 8.4 +/- 3.6 mmHg, respectively; p less than 0.001). No ascites was clinically detectable in the patients in whom hepatic venous pressure gradient was below 6 mmHg. We tested the hypothesis that sinusoidal collapse due to liver cell dropout was a major factor in portal hypertension. Semiautomatic determination of the fractional area of sinusoidal collapse on chromotrope-stained sections and automatic measurement of Sirius red-stained collagen fiber density were performed. Hepatic venous pressure gradient significantly correlated with fractional sinusoidal collapse area (r = 0.61, p less than 0.001) and with Sirius red-stained collagen fiber density (r = 0.43, p less than 0.01). We conclude that portal hypertension in the course of acute hepatitis is related to the severity of liver damage and is a major factor in the development of ascites. Portal hypertension is mainly determined by intrahepatic vascular space being reduced by the collapse of sinusoids.     

Relationship between degree of portal hypertension and liver histologic lesions in patients with alcoholic cirrhosis

The relationship between the degree of portal hypertension and histologic liver lesions was studied in a group of 84 patients with histologically proven alcoholic cirrhosis. The degree of portal hypertension was evaluated by the gradient between wedged and free hepatic venous pressures. Five histologic lesions were quantified: liver cell necrosis, Mallory bodies, neutrophilic infiltrate, fibrosis, and fatty infiltration. The gradient between wedged and free hepatic venous pressures was significantly correlated with the degree of liver cell necrosis and the degree of neutrophilic infiltrate. The stepwise regression analysis showed that only liver cell necrosis has a significant and independent correlation for the degree of portal hypertension. The value for the gradient between wedged and free hepatic venous pressures was significantly higher in patients with (N=48) than in those without (N=36) acute alcoholic hepatitis (19.4±0.8 and 16.5±0.7 mmHg, respectively). Thus, histologic liver lesions observed in acute alcoholic hepatitis may play a role in the risk of complications of portal hypertension in patients with alcoholic cirrhosis.     

Functional liver imaging with asialoglycoprotein receptors and serum hyaluronate in a patient with amyloidosis

A 47-year-old man with primary amyloidosis was admitted with abdominal pain. A new radionuclide liver imaging technique using Technetium-99 m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was performed and the serum hyaluronate concentration was measured. Although ordinary laboratory tests revealed only slight abnormalities, the uptake of the radiolabelled ligand for hepatocyte asialo-glycoprotein receptors was dereased, and marked hepatomegaly was revealed. Furthermore, the serum hyaluronate level was elevated. Histological examination of a hepatic needle biopsy specimen revealed a marked deposition of amyloid in the hepatic perisinusoidal spaces. These results indicate, that this new radionuclide liver imaging technique (using Technetium-99 m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin) and the measurement of serum hyaluronate may be useful supplementary tools for identifying amyloid deposition in the hepatic perisinusoidal spaces in patients with amyloidosis.     

1883份肝穿刺活检组织标本病理分析

目的：分析肝穿活检组织病理检查结果,加深对各种肝病的认识。方法B型超声引导下采用快速穿刺法取肝组织,对肝穿组织进行HE染色、网状纤维染色及胶原纤维染色,用免疫组织化学法检测肝组织中HBsAg、HBcAg、HCV,根据需要加做其他免疫组织化学及特殊染色,如刚果红、PAS、铜、铁等。结果所有病理诊断中,肝炎1234例,占65．53％,其中乙型肝炎856例,占45．46％。有573例临床诊断为不明原因的肝损伤,病理诊断203例为肝炎,占35．43％,其中乙型肝炎8例,占1．40％,乙型肝炎临床诊断与病理诊断的符合率为95．50％。自身免疫性肝病177例,占30．89％。Dubin-Johnson综合征6例,占0．32％,HE染色中央静脉周围肝细胞见较多粗大深棕色色素颗粒;肝淀粉样变5例,占0．27％,淀粉样蛋白主要沉积于肝窦周围隙,刚果红染色呈桔红色;血色病5例,占0．27％,含铁血黄素在肝小叶弥漫分布,普鲁士蓝染色呈蓝色。肝糖原贮积症有2例,占0．11％,细胞质内有大量糖原沉积,PAS染色呈红色。结论临床资料对病理诊断意义重大,肝穿刺活检对各种肝病诊断具有重要的价值。     

Hepatic familial amyloidosis caused by a new mutation in the apolipoprotein AI gene: clinical and pathological features

OBJECTIVE: Recently, we reported a nondescribed deletion/insertion mutation in the apolipoprotein AI gene as the cause of hereditary amyloidosis with hepatic presentation. We describe the clinical and pathological features of this type of amyloidosis in one affected family. METHODS: Demographic, clinical, and biochemical data were obtained from 33 members of the family in whom the apolipoprotein AI gene was studied. Diagnosis was based on the detection of the apolipoprotein AI gene mutation, scintigraphy using radioionated serum amyloid P component, and histological and immunohistochemical studies. RESULTS: Eight members with the mutation had hepatic involvement. Six patients were practically asymptomatic, presented with an elevation of alkaline phosphatase and gamma-glutamyl transpeptidase, and remained stable during follow-up (7.6 +/- 4.9 yr). One patient had jaundice, developed ascites and encephalopathy, and died of hepatorenal syndrome a few months after diagnosis. Jaundice and portal hypertension appeared in the remaining patient, who died 4 yr later. CONCLUSION: This form of familial amyloidosis is characterized by elevation in serum alkaline phosphatase and gamma-glutamyl transpeptidase secondary to amyloid deposits in the portal tracts. Patients remain stable and asymptomatic for many years, but portal hypertension and liver failure can develop later in life and lead to death. Thus, patients should be observed regularly and liver transplantation should be indicated when progression is detected.     

Hepatic venous pressure gradient measurement: Time to learn!

Portal hypertension is a clinical syndrome defined by a pathological increase in portal pressure. The development of cirrhosis of the liver is characterized by clinical manifestations related to portal hypertension like esophageal varices, ascites, bleeding, and encephalopathy. Direct measurement of portal pressure is invasive, inconvenient, and clinically impractical. Currently, the most commonly used parameter is the Hepatic Venous Pressure Gradient (HVPG), i.e., the difference between the wedged (WHVP) and the free hepatic venous pressures. HVPG represents the gradient between pressures in the portal vein and the intra-abdominal portion of inferior vena cava. When blood flow in a hepatic vein is stopped by a wedged catheter, the proximal static column of blood transmits the pressure from the preceding communicated vascular territory (hepatic sinusoids) to the catheter. Thus, WHVP reflects hepatic sinusoidal pressure and not the portal pressure itself. In the normal liver, due to pressure equilibration through interconnected sinusoids, wedged pressure is slightly lower than portal pressure, though this difference is clinically insignificant. In liver cirrhosis, the static column created by balloon inflation cannot be decompressed at the sinusoidal level due to disruption of the normal intersinusoidal communications; therefore, WHVP gives an accurate estimation of portal pressure in cirrhosis. The normal HVPG value is between 1 to 5 mmHg. Pressure higher than this defines the presence of portal hypertension, regardless of clinical evidence. HVPG >/= 10 mmHg (termed clinically significant portal hypertension) is predictive of the development of complications of cirrhosis, including death. HVPG above 12 mmHg is the threshold pressure for variceal rupture. The main advantages of HVPG are its simplicity, reproducibility, and safety. This review summarizes the technique of the HVPG measurement.     

Massive vitamin A intoxication with ascites and pleural effusion

Vitamin A intoxication was diagnosed in a 14-year-old girl who presented with massive exudative ascites and right pleural effusion, impaired liver enzymes, and hypertriglyceridemia. Electron microscopy of liver biopsy material demonstrated numerous perisinusoidal lipid-filled Ito cells. The patient had taken 100-200,000 I.U. vitamin A per day for 15 months. Serum vitamin A level remained elevated for 4 months after vitamin discontinuation. The unusual severity of portal hypertension was documented by a high wedged hepatic vein pressure level. The ascites occurred 2 months after vitamin A had been discontinued, probably owing to particularly slow mobilization of large hepatic stores of vitamin A. Portal hypertension disappeared after a 6-month low vitamin A diet, but the liver biopsy failed to demonstrate any decrease in number or size of Ito cells, suggesting that lipid venous obstruction is unlikely to be the only mechanism responsible for portal hypertension in vitamin A-induced liver disease.     

Percutaneous transhepatic measurement of the pressure gradient between the portal and hepatic veins

Abstract Background: Knowledge of the portal pressure may be of value in the assessment of patients with chronic liver disease but its measurement is problematic. Aims: To evaluate the ease and safety of percutaneous transhepatic measurement of the pressure gradient between the portal and hepatic veins and to determine directly the need for an internal zero. Methods: Sixty-one patients undergoing liver biopsy for suspected liver disease had pressures in branches of portal and hepatic veins measured using a flexible 22G (Chiba) needle. Results: The procedure was successful in all patients, took less than ten minutes in most, and was associated with minimal discomfort. Post-procedure morbidity was similar to that of liver biopsy. Portal pressure using an external zero (either puncture site or sternal angle) was inaccurate compared with pressures obtained using the generally accepted gold standard internal zero, hepatic venous pressure, and led to incorrect classification of the presence or absence of portal hypertension in at least 10% of patients. Variations in hepatic venous pressure were not predictable on clinical grounds. The only histopathological feature predictive of portal hypertension was cirrhosis, 20 of 25 patients with and four of 36 patients without cirrhosis having portal hypertension. Of routine biochemical and haematological tests, only plasma albumin and platelet count jointly (and negatively) predicted hepatic venous pressure gradient on multiple regression analysis (R²= 0.40). Conclusions: The use of an internal zero is essential for accurate measurement of portal pressure and this can be achieved safely using the percutaneous, transhepatic route in patients with well compensated liver disease.     

Comparison between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related cirrhosis

Portal vein pressure and wedged hepatic vein pressure were measured simultaneously in 21 patients with hepatitis B-related cirrhosis of the liver and were compared to pressure measured in six patients with idiopathic portal hypertension. No significant difference in the portal venous pressure gradient was found between patients with cirrhosis and those with idiopathic portal hypertension (17.3 +/- 4.3 mmHg (mean +/- S.D.) vs. 19.7 +/- 3.1 mmHg, P greater than 0.05). However, the difference between the portal and the hepatic venous pressure gradient was significantly smaller in patients with cirrhosis than in idiopathic portal hypertension patients (1.3 +/- 1.7 vs. 10.8 +/- 2.1 mmHg, P less than 0.001). An excellent correlation was found between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related cirrhosis (r = 0.94, P less than 0.001). There was no linear relationship between the portal venous pressure gradient and varix size or bleeding episodes. We concluded that a close agreement existed between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related liver cirrhosis. Therefore, measurement of wedged hepatic vein pressure reliably reflects portal vein pressure in these patients.     

Measurement of portal vascular resistance in patients with portal hypertension

Portal vascular resistance was measured percutaneously in 60 patients with chronic liver disease and in 5 control subjects. The portal vascular resistance (PVR) was calculated, using the following equation, from the portal blood flow (QPV), portal venous pressure (PPV), and hepatic venous pressure (PHV): PVR = (PPV - PHV)/QPV. The portal blood flow was measured using an ultrasonic Doppler duplex system, and the portal venous and hepatic venous pressures were measured using percutaneous transhepatic catheterization and venous catheterization, respectively. The wedged hepatic venous pressure was measured by occluding the hepatic venous branch using a balloon catheter. The portal vascular resistance was 0.25 +/- 0.13 mmHg X ml-1 X min X kg body weight (mean +/- SD, n = 5) in the control group, 0.64 +/- 0.29 mmHg X ml-1 X min X kg body wt (n = 13) in the chronic active hepatitis group, 1.34 +/- 0.79 mmHg X ml-1 X min X kg body wt (n = 30) in the cirrhosis group, and 0.85 +/- 0.69 mmHg X ml-1 X min X kg body wt (n = 13) in the idiopathic portal hypertension group.     

Portal hypertension and hemorrhoids. Cause effect relationship?

The aim of this study was to compare the prevalence and the size of hemorrhoids with the degree of portal hypertension; 101 patients with intrahepatic portal hypertension documented by measuring wedged and free hepatic venous pressures before performing transjugular liver biopsy and 67 patients free of liver disease were investigated by proctoscopy. Portal hypertension was associated with a higher prevalence of hemorrhoids (93 p. 100 vs 76 p. 100); there was no relation between portal pressure and the size of haemorrhoids; no relation was found between the size of hemorrhoids and the grade of esophageal varices.