Nuclear medicine dynamic investigations of diffuse chronic liver diseases and portal hypertension

Radio-isotopic techniques may be useful in diagnosis and staging of chronic diffuse liver diseases. Liver angioscintigraphy (LAS) and per-rectal portal scintigraphy (PRPS) are at well discriminating portal hypertension (PHT), very early cirrhosis hemodynamic failure and compensatory arterialisation of liver perfusion. Supplied information is related to PHT, liver morphology and mesenchimal activity in liver, spleen and bone marrow. Correlation of LAS and PRPS may diagnose installing of PHT earlier than any actual morphologic imagistic method. Our experience (after more than 300 PRPS and 500 LAS) suggests that PHT and portal-cave shunts (PCS) may be classified in five functional stages. These five patterns (types) are characteristic for portal dynamics, supporting disease staging and follow-up of evolution to cirrhosis. All five dynamics may be assessed by PRPS and LAS. Scintigraphic techniques also explore portal thromboses, perfusion differences between the lobes of cirrhotic liver, betablockers effect in PHT, earliest stages of PHT, malignant tumours occurring on cirrhosis, the different characteristics of alcoholic liver comparing to viral etiology.     

Nuclear medicine dynamic investigations in the diagnosis of Budd-Chiari syndrome

AIM:To investigate the hepatic hemodynamics in the Budd-Chiari syndrome(BCS) using per-rectal portal scintigraphy(PRPS) and liver angioscintigraphy(LAS).METHODS:Fourteen consecutive patients with BCS were evaluated by PRPS between 2003 and 2012.Ten of them underwent LAS and liver scan(LS) with Tc-99m colloid.Eleven patients had clinical manifestations and three were asymptomatic,incidentally diagnosed at PRPS.The control group included 15 healthy subjects.We used new parameters at PRPS,the liver transit time of portal inflow and the blood circulation time between the right heart and liver.PRPS offered information on the hepatic areas missing venous outflow or portal inflow,length and extent of the lesions,open portosystemic shunts(PSS),involvement of the caudate lobe(CL) as an intrahepatic shunt and flow reversal in the splenic vein.LAS was useful in the differential diagnosis between the BCS and portal obstructions,highlightingthe hepatic artery buffer response and reversed portal flow.LS offered complementary data,especially on the CL.RESULTS:We described three hemodynamic categories of the BCS with several subtypes and stages,based on the finding that perfusion changes depend on the initial number and succession in time of the hepatic veins(HVs) obstructions.Obstruction of one hepatic vein(HV) did not cause opening of PSS.The BCS debuted by common obstruction of two HVs had different hemodynamic aspects in acute and chronic stages after subsequent obstruction of the third HV.In chronic stages,obstruction of two HVs resulted in opening of PSS.The BCS,determined by thrombosis of the terminal part of the inferior vena cava,presented in the acute stage with open PSS with low speed flow.At least several weeks are required in the obstructions of two or three HVs for the spontaneous opening of dynamically efficient PSS.The CL seems to have only a transient important role of intrahepatic shunt in several types of the BCS.CONCLUSION:Dynamic nuclear medicine investigations assess the extent and length of hepatic venous obstructions,open collaterals,areas without portal inflow,hemodynamic function of the CL and reverse venous flow.     

Liver angioscintigraphy: clinical applications

Liver angioscintigraphy (LAS) is a radio-isotope method for the investigation of liver perfusion and its alteration in various hepatic diseases. It measures the arterial and portal venous fractions of total liver blood flow. The percentage of liver blood flow supplied by hepatic artery is estimated mathematically by the hepatic perfusion index (HPI), normally between 25 % and 40 %. The decrease of portal blood flow in liver cirrhosis is compensated ("buffer" mechanisms) by increased arterial supply, with higher HPI value. For a patient with chronic liver disease, HPI over 50% suggests arterialization of hepatic perfusion, guiding the diagnose to liver cirrhosis. Splenic curve is completing the diagnostic information of the hepatic curve. Corroborated with per rectal scintigraphy and liver SPECT, LAS offers a good hemodynamic staging of chronic inflammatory liver diseases. Malignant tumors (primitive or metastases) increase the arterial supply of the liver and decrease the portal flow, HPI being over 50% (currently 65 % - 90 %). Benign tumors do not change portal/arterial liver blood flow ratio. SPECT or non-scintigraphic morphological investigations increase the diagnostic value of LAS for primitive liver tumors. Liver cancer occurring on cirrhosis is a limitative factor for LAS. Hepatic metastases increase the arterial perfusion (and HPI value) very quickly, before their size allows morphologic imaging diagnosis. LAS is therefore an early method to diagnose liver metastases being especially used in colorectal cancer. Other clinical applications of LAS are: follow up of liver toxicity of drugs, evaluation of portal vein permeability, post surgery follow up of the liver tumor patients.     

Long-term follow-up study of adult patients with non-cirrhotic obstruction of the portal system: comparison with cirrhotic patients.

Thirty-two patients with non-cirrhotic portal system obstruction and oesophageal varices of non-malignant etiology were recruited over 13 years. Diagnosis was based on the presence of oesophageal varices at endoscopy, minor alterations in liver function tests and liver histology, a low hepatic venous pressure gradient, and pertinent angiographic patterns. Twenty-three had portal vein thrombosis, nine had splenic vein thrombosis. Twenty-one had idiopathic portal vein obstruction, 11 had secondary obstruction. The outcome was compared with a group of 32 patients with cirrhosis and portal hypertension, matched for age, Child-Pugh class, previous history of gastrointestinal bleeding, and size of oesophageal varices. Patients with non-cirrhotic obstruction of the portal system were followed for up to 171 months (mean 94 months). During follow-up ten patients had gastrointestinal bleeding, and eight died (five of gastrointestinal bleeding). After 6 years of follow-up, the cumulative risk of gastrointestinal bleeding was 24%, the cumulative risk of death was 17%, and the cumulative risk of death from gastrointestinal bleeding was 14%. Cumulative probability of death by any cause and the probability of gastrointestinal bleeding were significantly lower in patients with non-cirrhotic obstruction of the portal system than in patients with cirrhosis comparable for liver function and portal hypertension (p = 0.04 for both). The cumulative probability of death by gastrointestinal bleeding was not significantly different. In conclusion, the prognosis for non-cirrhotic obstruction of the portal system is significantly better than for patients with cirrhosis with comparable levels of liver function impairment and severity of portal hypertension.     

Non-cirrhotic portal fibrosis related end stage liver disease in adults: evaluation from a study on living donor liver transplant recipients

Background  

That non-cirrhotic portal fibrosis (NCPF) can lead to end stage chronic liver disease (CLD) has been convincingly demonstrated only recently after the study of explant livers from clinically cirrhosis cases.     

Pulmonary hypertension associated with primary biliary cirrhosis in the absence of portal hypertension: a case report.

Pulmonary hypertension is well described in association with portal hypertension of any cause including end stage primary biliary cirrhosis (PBC). The essential feature of this association is the presence of portosystemic shunting, including surgically created shunts. A patient with primary pulmonary hypertension and PBC without portal hypertension is reported. This suggests that primary pulmonary hypertension may be associated with PBC in the absence of portal hypertension. Decisions regarding appropriate organ transplantation may depend on whether pulmonary hypertension is primary or secondary to portal hypertension.     

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.     

Cruveilhier-Baumgarten syndrome: An efficient spontaneous portosystemic collateral preventing oesophageal varices bleeding

The protective role of large spontaeous portosystemic shunts in oesophageal varices bleeding due to portal hypertension in liver cirrhosis is still debated. A series of 20 consecutive patients with haemodynamically efficient collaterals involving the para-umbilical-epigastric venous route (evaluated by Echo-Doppler flowmetry) is reported. All patients presented absent or mild oesophageal varices at endoscopy. During a mean follow-up period of 23.5 months, no patient developed large varices or experienced variceal bleeding. Hepatic encephalopathy was present in 35% of patients. Haemodynamically efficient spontaneous portosystemic shunts may protect cirrhotic patients from the risk of oesophageal varices forming and bleeding. The diversion of large amounts of blood from portal to systemic circulation correlates with the higher trend of hepatic encephalopathy in these patients.     

Portal-systemic encephalopathy due to a congenital extrahepatic portosystemic shunt: three cases and literature review

Extrahepatic portal-systemic encephalopathy due to congenital extrahepatic portosystemic shunt has so far been rarely reported in the literature. We herein report 3 such cases without liver cirrhosis or portal hypertension which were presented with the chief complaint being disturbance of consciousness and abnormal behavior. In all cases the brain computed tomography scan revealed no pathological findings, while electroencephalogram showed a diffuse slow activity with triphasic waves. The laboratory data revealed a high serum ammonia level. Percutaneous transhepatic portography demonstrated portosystemic shunts. After these shunts were surgically occluded, the serum ammonia level reached a normal range and encephalopathy disappeared. A liver biopsy also revealed neither fibrosis nor cirrhosis in any of the cases. The 23 previously reported cases are also discussed.     

Varicose bleeding after liver transplantation in a patient with severe portosystemic shunts

Recipients for liver transplantation often have portosystemic shunts due to portal hypertension. It is an important problem whether such shunts should be ligated during operations. Ligating the shunts seems of benefit for increasing portal blood flow to the liver, but it is sometimes difficult technically, and it is invasive to the patient. We experienced a recipient with huge portosystemic shunts and no esophageal varices before living-related liver transplantation. Some shunts were ligated during operation to increase portal blood flow to the graft. Unfortunately, the patient suffered severe bleeding from esophagogastric varices after he underwent retransplantation owing to accidental liver failure. Based on our experience, extreme care should be exercised to avoid varicose bleeding after ligating the portosystemic shunts of liver transplantation patients.     

Effect of the development of portosystemic shunts in the maintenance of portal hypertension in rats

We studied the role of portosystemic shunt development in the maintenance of portal hypertension in a prehepatic portal hypertension rat model. A first group was studied two days after partial portal vein ligation. When portosystemic shunts were negligible; the second group was studied 3 weeks after the partial portal vein ligation, when large portosystemic shunts were present. Portal pressure was significantly higher in the first group than in the second group (19.9 +/- 0.8 mmHg (mean +/- 1 SD) and 12.8 +/- 2.3 mmHg, respectively; p less than 0.001). When compared with sham operated rats: a) portal tributary blood flow (measured with the radioactive microspheres method) was decreased in the first group (- 34 p. 100; p less than 0.01) and increased in the second group (+ 32 p. 100; p less than 0.02); b) portal system vascular resistance was markedly increased in the first group (+ 269 p. 100; p less than 0.001) and did not significantly change in the second group (+ 30 p. 100). These results suggest that portosystemic shunt development decreases portal pressure but not to normal value because portal tributary blood flow is increased. Moreover the increase in portal system vascular resistance and in portal tributary blood flow play different roles in the maintenance of portal hypertension depending on the stage of evolution of portal hypertension.     

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.     

Comparison between ultrasonographic signs and the degree of portal hypertension in patients with cirrhosis

The sensitivity of ultrasonography (US) for the diagnosis of portal hypertension was assessed in 48 patients with known cirrhosis. These results were compared to the hemodynamic values obtained on the same day by hepatic vein catheterization. The sensitivity of US in detecting portal hypertension was about 40% considering either a greater than 13 mm diameter of the portal vein, or the lack of mild caliber variation of the superior mesenteric vein. The sensitivity was more than 80% considering the presence of portosystemic venous collaterals. Presence of numerous portosystemic shunts was significantly associated with high hepatic venous pressure gradients which reflected the severity of portal hypertension.     

Adult-to-adult living donor liver transplantation in severe portosystemic shunt cases

To date, the need for spontaneous portosystemic shunt division during adult-to-adult living donor liver transplantation (LDLT) remains unknown. This study reports 2 patients with large portosystemic shunts who required LDLT. The first patient was a 40-year-old male with liver cirrhosis due to hepatitis C. The angiogram showed splenosystemic shunts with hepatopetal flow. Shunt occlusion was not performed after implanting a small-size graft because sufficient portal blood flow was observed. On the first postoperative day, portal blood flow was not detected; therefore shunt occlusion was per formed and the portal blood flow was restored. The second patient was a 51-year-old female with primary biliary cirrhosis. Marked collateral circulation with hepatofugal flow was observed. Shunt occlusion was performed after implanting a medium-size graft. Postsurgery, hepatopetal portal blood flow was observed and the postoperative course was satisfactory. These cases demonstrate that large portosystemic shunts should be ligated to maintain adequate portal blood flow that corresponds to the graft volume.     

Vitamin A abuse: development of cirrhosis despite cessation of vitamin A. A six-year clinical and histopathologic follow-up

ABSTRACT— We report the case of a 35-year-old man who contracted vitamin A-induced liver cirrhosis. Five years before, he had been investigated for vitamin A-induced non-cirrhotic portal hypertension. In this case, the clinical and histopathologic evolution from non-cirrhotic portal hypertension to cirrhosis was documented. In spite of the cessation of pharmaceutical vitamin A intake, the disease progressed. Therapy with colchicine and phenobarbital apparently did not influence evolution to cirrhosis. This suggests that vitamin A can trigger largely unknown mechanisms of liver fibrosis which seem to be self-perpetuating.     

Angiogenesis and portal-systemic collaterals in portal hypertension

In patients with advanced liver disease with portal hypertension, portal-systemic collaterals contribute to circulatory disturbance, gastrointestinal hemorrhage, hepatic encephalopathy, ascites, hepatopulmonary syndrome and portopulmonary hypertension. Angiogenesis has a pivotal role in the formation of portal-systemic shunts. Recent research has defined many of the mediators and mechanisms involved in this angiogenic process, linking the central roles of hepatic stellate cells and endothelial cells. Studies of animal models have demonstrated the potential therapeutic impact of drugs to inhibit angiogenesis in cirrhosis. For example, inhibition of VEGF reduces portal pressure, hyperdynamic splanchnic circulation, portosystemic collateralization and liver fibrosis. An improved understanding of the role of other angiogenic factors provides hope for a novel targeted therapy for portal hypertension with a tolerable adverse effect profile.     

Spontaneous porto-systemic shunts in liver cirrhosis: Clinical and therapeutical aspects

Spontaneous porto-systemic shunts(SPSS) are frequent in liver cirrhosis and their prevalence increases as liver function deteriorates, probably as a consequence of worsening portal hypertension, but without achieving an effective protection against cirrhosis' complications. Several types of SPSS have been described in the literature, each one associated with different clinical manifestations. In particular,recurrent or persistent hepatic encephalopathy is more frequent in patients with splenorenal shunt, while the presence of gastric varices and consequently the incidence of variceal bleeding is more common in gastrorenal shunt. In the advanced stage, the presence of large SPSS can lead to the so called"portosystemic shunt syndrome", characterized by a progressive deterioration of hepatic function, hepatic encephalopathy and, sometimes, portal vein thrombosis. The detection of SPSS in patients with liver cirrhosis is recommended in order to prevent or treat recurrent hepatic encephalopathy or variceal bleeding.     

Vitamin A abuse: development of cirrhosis despite cessation of vitamin A. A six-year clinical and histopathologic follow-up.

We report the case of a 35-year-old man who contracted vitamin A-induced liver cirrhosis. Five years before, he had been investigated for vitamin A-induced non-cirrhotic portal hypertension. In this case, the clinical and histopathologic evolution from non-cirrhotic portal hypertension to cirrhosis was documented. In spite of the cessation of pharmaceutical vitamin A intake, the disease progressed. Therapy with colchicine and phenobarbital apparently did not influence evolution to cirrhosis. This suggests that vitamin A can trigger largely unknown mechanisms of liver fibrosis which seem to be self-perpetuating.     

Varizenblutung bei Patienten mit Leberzirrhose

In patients with cirrhosis, portal hypertension induces the development of portosystemic collaterals. Bleeding from these collateral vessels, however, only develops if the portosystemic pressure gradient is below 12 mmHg. Portal hypertension in cirrhosis is mediated by an increased intrahepatic resistance of the liver on the one hand and by an increase in the portal tributary blood flow on the other. Consequently, therapy can aim to reduce intrahepatic resistance or mesenteric blood flow (shunts, pharmacologic therapy) or can act locally on the source of bleeding itself (endoscopic therapy). Four aims can be defined: (1) inhibition of the development of varices, (2) prevention of the first bleeding episode when varices already exist, (3) therapy of the acute bleeding episode, and (4) prevention of recurrent bleeding.     

64层螺旋CT门静脉造影对门静脉高压侧支循环的临床应用研究

目的评价64层螺旋CT门静脉造影对肝硬化门静脉高压侧支循环的临床应用价值。方法肝硬化患者27例,行64层螺旋CT门静脉造影检查,容积数据经采用最大强度投影法（MIP）、容积再现法（VR）及多平面重组法（MPR）三维重建,观察其侧支循环的影像学特征,并结合术中探查结果进行对比、分析。结果 64层螺旋CT门静脉造影能准确显示侧支循环血管分布范围并能初步评估病变程度;对21例患者施行手术,术中探查所见与术前影像学诊断完全相符。结论 64层螺旋CT门静脉造影能够多角度、立体观察门静脉高压侧支循环情况,对外科手术方案的制定具有重要的指导意义。