Clinical Aspects of Liver Diseases 39 Cardiovascular diseases and the liver

(1)

39 Cardiovascular diseases and the liver

Page:

1 Cardiocirculatory disorders of the liver 826

1.1 Acute heart insufficiency 827

1.1.1 Shock liver 827

1.1.2 Acute liver congestion 827

1.2 Chronic heart insufficiency 828

2 Disorders of the hepatic veins 829

2.1 Budd-Chiari syndrome 830

2.1.1 Definition 830

2.1.2 Aetiology 830

2.1.3 Morphology 830

2.1.4 Clinical features 830

2.1.5 Diagnosis 831

2.1.6 Treatment 832

2.2 Veno-occlusive disease 832

2.2.1 Definition 832

2.2.2 Aetiology 832

2.2.3 Morphology 833

2.2.4 Clinical features 833

2.2.5 Treatment 833

2.3 Endophlebitis obliterans hepatica 833

3 Disorders of the portal vein 833

3.1 Anomalies of the portal vein 833

3.1.1 Cavernous transformation 834

3.1.2 Cruveilhier-Baumgarten disease 834

3.1.3 Arterioportal venous fistula 834

3.2 Pylephlebitis 835

3.3 Portal vein thrombosis 835

3.4 Portal vein aneurysm 836

4 Disorders of the hepatic arteries 836

4.1 Aneurysm 836

4.1.1 Definition 836

4.1.2 Aetiology 837

4.1.3 Clinical features 837

4.1.4 Diagnosis 837

4.1.5 Treatment 837

4.2 Arterial occlusion 837

4.2.1 Aetiology 837

4.2.2 Clinical features 838

4.3 Nodular periarteritis 838

4.4 Arteriosclerosis 838

5 Hereditary haemorrhagic telangiectasia 838

앫 References (1⫺157) 839

(Figures 39.1 ⫺39.8; tables 39.1⫺39.5)

(2)

Due to its twofold vascular supply (portal vein, hepatic artery), the liver is closely integrated into the systemic circulation. The total blood flow through the liver is 1,500 ±300 ml/min. Oxygen consumption amounts to 6 ml/min/100g LWW. (s. pp 17, 244) The portal vein sup- plies about two-thirds of the hepatic flow volume and is thus responsible for 50% of the oxygen requirement of the liver. The ratio between portal and arterial perfusion is about 2 :1; this may, however, be reversed by compen- satory autoregulation in cirrhosis patients. Blood from the portal and arterial systems reaches the sinusoids, where both mixing and pressure compensation occur.

The hepatic blood flow is mainly regulated by inflow from the hepatic artery, which can be doubled when more oxygen is required. With continued demand for oxygen, the high capacity of the liver cell to extract oxy- gen (up to 95%) compensates for a limited blood flow.

The hepatic flow volume is about 20 ⫺25% of the cardiac output (CO). • In addition, the pressure in the lesser circulation is transferred directly to the pressure in the hepatic vein, so that the latter is almost equal to the pressure in the right atrium. The oxygen saturation of the arterioportal mixed blood in the sinusoids decreases continually with the flowing of the blood from the periportal zone to the central vein. The venous blood is then carried from the central veins and the venous branches into the inferior vena cava, usually through three (valveless) hepatic veins. • This anatom- ical proximity explains disturbances of the liver function as well as morphological damage resulting from shock situations, acute flow block in the hepatic veins and global heart failure. • Cardiovascular diseases may thus affect the heart or each of the three vascular systems:

1. Impaired cardiac function 2. Diseases of the hepatic vein 3. Diseases of the portal vein 4. Diseases of the hepatic artery

5. Hereditary haemorrhagic telangiectasia

1 Cardiocirculatory disorders of the liver

䉴 The functional relationship between the heart and the liver has been known since ancient times. In animal experiments con- ducted in 1914,

C. B olton

examined the effects of a ligation of the inferior vena cava on liver histology for the first time.

• N. J olliffe (1929)

detected clinically measurable changes of the hepatic function in congestive heart failure. (10)

•

Systematic investigations carried out by

S. S herlock (1951)

showed the con- sequences of passive liver congestion on hepatic morphology:

complete cirrhosis was observed in 25.5% and an increase in

reticular fibres in 27.5% of cases; the liver was without pathological findings in 47% of cases.

•

Autopsies carried out by

P. K otin (1951)

showed “cardiac cirrhosis” in 10% of patients suffering from right heart insufficiency. (13)

•

Subsequently, the effects of cardiocirculatory disturbances on various partial functions and on the morphology of the liver, including the effects of drug metabolism, were presented in numerous publi- cations.

Pathophysiology

䉴 The close functional relationship between the heart and the liver is based upon two physiologic facts:

(1.) The hepatic flow volume is 20 ⫺25% of the CO and is thus directly dependent on the cardiac ejection volume.

(2.) The pressure in the lesser circulation is transferred directly to the valveless hepatic veins and may thus also reach the central veins.

䉴 Even though the pathophysiology of hepatic changes during circulatory shock and in chronic liver congestion is very complex, two single mechanisms may be held jointly responsible for the impairment of metabolic and excretory liver functions:

(1.) Reduction in blood flow through the liver with hypoxia.

(2.) Increase in hepatic vein pressure with centrilobular hyperaemia.

䉴 Circulatory disturbances within the hepatic lobules are of central pathophysiological importance; three dif- ferent forms can be differentiated:

(1.) Disturbed outflow: the microscopic correlate is centrilobular hyperaemia; macroscopically, the liver is enlarged and has a dark red colour.

(2.) Disturbed inflow: hypoperfusion due to arterial, por- tovenous or combined oligaemia results in centrilobular necrosis or even anaemic liver infarction.

(3.) Disturbed flow: primarily, this occurs intralobularly as a result of various disorders (e. g. DIC, intrasinus- oidal fibrin precipitation, centrilobular increase in fibres).

The liver may be involved in numerous ways due to acute, short-term disturbances of the cardiocirculatory function or due to chronic, long-term heart failure:

Acute heart insufficiency Chronic heart insufficiency

1. Shock liver 1. Chronic liver congestion 2. Acute liver congestion 2. Congestive fibrosis

3. Cardiac cirrhosis

(3)

Heart insufficiency

Acute Chronic

CO↓ CVP↑

Hepatic blood flow↓ Hepatic vein

pressure↑ Hypoxia of liver cells Centrilobular

congestion

Liver cell necroses Atrophy of liver

cell trabeculae

Restitution Congestive fibrosis

Liver function ↓ Jaundice

Tab. 39.1: Pathophysiology of cardiocirculatory changes in the

liver

1.1 Acute heart insufficiency

Shock liver and acute liver congestion often display very similar histological changes, while the pathophysiologic features, such as laboratory findings, functional tests and drug metabolism, vary considerably. • Cardiogenic shock resulting from myocardial infarction is considered to be both a typical and frequent cause of shock liver, while acute liver congestion (acute right heart insuffi- ciency) is in most cases the consequence of pulmonary embolism. • During shock, the liver is involved in two ways: (1.) it is an important regulatory organ ( ⫽ liver in shock), and (2.) its function and morphology are com- promised by shock mechanisms ( ⫽ shock liver).

1.1.1 Shock liver

This condition is characterized by reduced hepatic blood flow (CO 앗) and hepatocellular hypoxia, result- ing in a loss of glycogen and the formation of hypoxic vacuoles in the hepatocytes; there are also coagulation necroses in acinar zone 3. It is a striking feature that the function of the liver is only mildly compromised and recovers quickly once the circulation is stabilized. Since the lattice fibre framework is generally intact, the centrolobular necroses do not leave behind any scars.

During this phase, we only detected slightly delayed indocyanine green (ICG) elimination, while galactose elimination capacity and theophylline clearance were slightly inhibited.

(18)

This means that essential partial functions of the liver are relatively independent of the blood flow and that short-term hypoxia can be compen- sated by increased extraction of oxygen. By contrast, we also found greatly increased GOT and GPT values similar to those present in “hepatitis”, with low-grade cholestasis and jaundice. The terms ischaemic hepatitis,

hypoxic hepatitis or acute hepatic infarction are alterna- tive definitions.

(4⫺6, 11, 25, 29)

In shock liver, there is therefore a marked discrepancy between a relatively slight reduction in excretory and metabolic functions and considerable liver cell damage detectable by enzyme analysis. • The hepatic blood flow is decreased due to shock-induced hyperperfusion of the heart and brain with simultaneous vasoconstriction in the splanchnic nerve area ( ⫽ centralization of circulation). However, liver cell damage often develops or intensifies as a result of subsequent reperfusion, whereby the substances that are introduced in increased amounts at this point (endo- toxins, cytokines, biogenic amines, degradation pro- ducts, etc.) are probably the main cause of such liver cell damage.

(26)

The damage occurring in shock liver and acute liver congestion may thus be due to ischaemia and/or ischaemic-toxic factors.

(2, 3, 27)

(s. fig. 39.1) 1.1.2 Acute liver congestion

In our investigations, patients suffering from acute right heart insufficiency showed considerable delays in ICG half-times. In an earlier study, we were able to demon- strate a close correlation with right-sided atrial pressure.

Theophylline clearance was likewise greatly delayed.

Standard enzymes showed only slightly increased or even normal values; hyperbilirubinuria, which is consid- ered to be the most sensitive laboratory value in liver congestion, was generally present. Thus there is also a discrepancy between “liver function” and “cell damage”

in this context ⫺ albeit exactly the reverse of that found in shock liver.

(16, 18)

Patients suffering from acute liver congestion have considerably impaired metabolic and excretory functions, even after clinical recompensation.

Perisinusoidal oedema resulting from elevated hepatic vein pressure is of the utmost pathogenetic significance in acute liver congestion because it lengthens the transit route. In acute congestion, the liver is capable of taking up blood equivalent to 70% of its own weight (approx.

1.0 ⫺1.5 l), so that both circulatory overload and tachy- cardia are reduced.

Morphology: Within the first day following the onset of acute liver congestion, massive sinusoidal hyperaemia and perivenous cell necroses occur due to the fact that centrilobular oxygen saturation is lower than that of the lobular periphery. The reticular fibre framework usually remains intact. In addition, venous stasis may occur, especially in acute congestion, including dilatation of the central veins and sinusoids with blood pooling, resulting in hepatomegaly. Macroscopically, the liver appears heavy and dark red. Microthrombi may be pre- sent due to disseminated intravascular coagulation (DIC). They can form the basis of later diffuse calcifica- tion. This might be related to the disturbance of intra- cellular calcium homoeostasis due to ischaemia.

(27)

After recompensation, numerous granulocytes and pig-

ment-loaded macrophages subsequently appear, fol-

lowed by proliferating epithelial cells. The necrotized

(4)

Fig. 39.1: Centroacinar shock necrosis and acute haemostasis in

the liver (HE)

Fig. 39.2: Acute blood stasis with centrilobular congestion and

centricentral congestion paths

cells and erythrocytes are phagocytized by the Kupffer cells. Morphological repair starts after about 5 days and is completed within 3 ⫺4 weeks.

(1, 16, 19)

(s. tab. 39.1) (s. figs. 39.1, 39.2)

Drug metabolism: According to present knowledge, there is a delay in the elimination of certain drugs in patients with acute heart insufficiency. Thus, a dose reduction may have to be considered in some cases. In particular, these drugs include quinidine, cumarin/war- farin, digoxin, hydrochlorothiazide, lidocaine, mexilet- ine, procainamide and theophylline.

(16, 18)

• Our studies demonstrated a 30% reduction in the elimination rate of flow-limited ( ⫽ ICG) and capacity-limited (⫽ galactose, theophylline) substances. We found a normal glucuro- nidization capacity for 4-methylumbelliferone, but a sig- nificant delay in the biliary excretion of 4-MU-monoglu- curonide.

(15)

These findings are considered to be the cause of conjugated hyperbilirubinaemia, which is com- mon in patients suffering from a congested liver.

Clinical features: Acute liver congestion results in upper abdominal pain due to stretching of the capsule caused by liver enlargement; this might even mimic an acute

abdomen. There have also been courses with fulminant liver failure, particularly with existing chronic heart insufficiency.

(8, 20, 24, 26)

In addition to the laboratory findings given above, it is worth mentioning the increase in GDH, mainly localized in the centrilobular cells. The ratio (GOT ⫹ GPT) : GDH is <10. (s. tab. 5.6) In gene- ral, LDH is markedly elevated. Mild jaundice is often in evidence; hyperglycaemia and renal impairment may occur. A decrease in Quick’s value may point to DIC.

An increase in transaminases due to ischaemia (with bioptic detection of centrilobular cell necroses) was observed even in cases of severe hypoxaemia caused by sleep apnoea in patients with considerable obesity (with- out cardiac or respiratory dysfunction!).

(5)

Imaging procedures show hepatomegaly and dilated hepatic veins. • Treatment consists of stabilizing the circulation and eliminating the causes.

1.2 Chronic heart insufficiency

The hepatic blood flow is decreased in chronic heart insufficiency, and there is disturbed venous outflow, i. e.

cardiac output is diminished. There is also a pressure increase in the splanchnic nerve area with subsequent blood pooling as a result of the rise in CVP. The mark- edly reduced hepatic blood flow at first evokes an increase in oxygen extraction, but after its elimination, hypoxia with centrilobular cell necroses follows. The ele- vated CVP extends as far as the central veins, so that dilatation and hyperaemia of the sinusoids occur. Peri- central atrophy in the liver cell trabeculae develops at a later stage. (s. tab. 39.1) (s. fig. 39.3)

Fig. 39.3: Chronic passive congestion with centroacinar paren-

chymal atrophy and fibrosis (HE)

Chronic congestion leads to an enlarged and plump liver

with a dark red (purplish) colour. The central veins are

dilated. In continued congestion, stasis paths develop

between the central veins, resulting in the formation of

confluent stasis areas. Various degrees of fatty changes in

the liver cells as well as pigment deposits (lipofuscin, cer-

oid) appear. In the course of time, fibrosis of sinusoidal

reticular fibres takes place; fibroses can also be observed

(5)

along the stasis paths. In about 15% of cases, periodic acid-Schiff positive and diastase-resistant hyaline glob- ules can be found. They are typically located directly around the zones of centrilobular congestion in hepato- cytes. These globules range in size from 3 to 20 µm; they occur either as one or two large globules or as clusters of smaller inclusion bodies.

(12)

The extent of the congestive fibrosis depends largely upon the degree of cardiac con- gestion. (s. fig. 39.3) In 147 patients with chronic pulmo- nary heart disease, it was possible to demonstrate conges- tive fibrosis by autopsy in 14 ⫺42% of cases (depending on the degree of severity and the duration of disease).

(7)

• Chronically indurated nutmeg liver

^{(F. K}iernan, 1833)

develops gradually; the cut surface of such a diseased liver shows sunken, dark red centrilobular zones and slightly raised bulging, yellowish to pale brown (depend- ing on the degree of fatty changes) peripheral areas of the lobules. • Cardiac cirrhosis was mentioned in older studies in up to 10% of cases.

(13)

Our own studies did not yield a single case of cardiac cirrhosis.

(7)

This clinical picture must be considered rare and is most likely in cases of con- strictive pericarditis or in long-standing tricuspid valve insufficiency. It is assumed that the development of cardiac cirrhosis originates in sinusoidal thrombosing processes which extend to the vascular bed of the hepatic veins.

(23, 30)

Distinct regenerative nodes are not found in cardiac cirrhosis; this condition generally does not lead to extrahepatic cirrhosis-related complications.

Clinical features: With regard to the main findings of chronic heart insufficiency, the liver is symptom-free, apart from tenderness upon pressure in the right upper abdomen corresponding to hepatomegaly. On palpation, the liver is hard and has a smooth surface. Splenomegaly is detected in about 20% of patients.

In this condition, hepato-jugular reflux is positive if the venous channels between the hepatic and jugular veins are patent (i. e. long-standing pressure below the right costal arch accelerates the filling of the jugular veins, since the insufficient right ventricle is incapable of trans- porting the rising amount of blood supplied by the liver). • When the result is negative, the free passage between the hepatic veins and the jugular vein is interrupted. This sign is useful for diagnosing tricuspid regurgitation.

According to our own investigations, P-III-P concentra- tion is the most important laboratory parameter

⁽¹⁷⁾

: it is significantly higher in patients suffering from chronic liver congestion (due to the activity of fibrogenesis).

There was also a correlation with the pressure in the right atrium. Moreover, the P-III-P value allowed a fol- low-up of chronic liver congestion or chronic congestive fibrosis. No correlation with hepatic biochemical stand- ard values was found ⫺ these were normal or only mar- ginally elevated.

(14, 16, 17)

Only the serum bilirubin was slightly increased in most cases. ICG elimination and the galactose elimination capacity were significantly

Fig. 39.4: Sonographic image of chronic liver congestion with

dilated hepatic veins and inferior vena cava

reduced. Severe jaundice may occur in heart failure

(22)

, in some cases with massive liver cell necroses.

Hepato(spleno)megaly is detected by sonography. The liver margin is rounded, the reflex pattern is dense and inhomogeneous. The hepatic veins are enlarged (at the confluence > 12 mm). (s. fig. 39.4) The inferior vena cava presents a rather rigid wall without respiratory- dependent lumen fluctuations. Smaller amounts of asci- tes are frequently detectable. Echocardiography and col- our-encoded Doppler sonography are among the most important diagnostic and monitoring methods.

(9)

CT may yield additional findings of chronic liver conges- tion.

(21)

2 Disorders of the hepatic veins

䉴 The hepatic venous blood flow begins in the central veins of the lobules (so-called terminal hepatic vein), drains into the sublobular

veins (

⫽ intercalated veins), from there into the collecting veins and then into the truncal veins. Perivenous connective tissue increases with the diameter of the vein. Venous blood reaches the inferior

vena cava via three (valveless) hepatic veins; the confluence is below

or within the diaphragm. From the

caudate lobe, 1⫺2 small veins

open directly into the inferior vena cava, as do a few small veins from the posterior segment of the right lobe of liver. (s. p. 17)

•

There are generally no

anastomoses between the hepatic veins and

the portal vein, except in liver cirrhosis. Similarly, no anastomoses are present between the hepatic veins and arteries either in a heal- thy liver or in a cirrhotic liver.

•

Normal

hepatic vein pressure is

about 6 mm Hg.

Oxygen saturation of the hepatic veins amounts

to approx. 67%.

With regard to the main diseases of the hepatic venous system, three types worthy of mention can be distin- guished:

1. Budd-Chiari syndrome 2. Veno-occlusive disease

3. Endophlebitis obliterans hepatica

(6)

2.1 Budd-Chiari syndrome 2.1.1 Definition

The Budd-Chiari syndrome (BCS) is defined as par- tial or complete obstruction of the hepatic veins due to thrombosis. This may affect the whole hepatic venous system from the central vein to the large hepatic veins, even as far as the opening of the in- ferior vena cava into the right atrium. However, the obstruction can simply occur in individual branches of the hepatic veins and thus affect only certain areas of the liver. The syndrome may have an acute onset or begin insidiously and take a chronic course. The clinical picture is usually characterized by the Chiari triad: hepatomegaly, abdominal pain and ascites.

䉴

^R eynaud (1829)

was the first to report thrombosis in the vena cava with involvement of hepatic veins and the development of collateral circulation. In 1842

E. L ambron

described inflammation of the hepatic veins concomitant with a liver abscess.

•

In 1845 the English internist

G. B udd

reported three further cases:

in two of them, hepatic vein thrombosis was likewise caused by liver abscesses, whereas no cause was evident in the third case although membranes were detected in the hepatic veins.

•

In 1899 the German pathologist

H. C hiari

, who was working in Prague at that time, gave an account of two of his own patients and assessed the 8 cases which were known to him from the literature. However, more than 25 cases of veno-occlusive disease had already been reported prior to Chiari’s publication.

•

The above-mentioned clinical picture with unclarified aetiology was defined by

H. C hiari (1899)

as primary phlebitis of the large hepatic veins with secondary thrombosis, which he regarded as a separate entity. This gave rise to the term endophlebitis obliter-

ans hepatica (s. p. 833), also called Chiari’s disease.

2.1.2 Aetiology

Aetiologically, BCS is characterized by an extremely heterogeneous clinical picture, even though it is initially possible to categorize the majority of causes into four groups: (1.) hypercoagulopathies, (2.) infections, (3.) malignant diseases, and (4.) endotheliotoxic substances.

In 80 ⫺90% of patients, BCS can be attributed to a spe- cific cause. The disease has often been detected during pregnancy as well. The observation that women con- tract the disease twice as often as men following the introduction of oral contraceptives supports the aetio- logical theory that it is linked to an increase in the oestrogen/progesterone level. The discovery of new genetic defects causing hypercoagulability can also explain some cases of BCS.

(56)

• A membranous obstruc- tion, especially close to the opening of the middle and left hepatic veins into the inferior vena cava, is considered to be an aetiological peculiarity. Such a “web” varies from a thin membrane to a thick fibrous band.

(73)

This unusual phenomenon is often encountered in India, Japan and South Africa (congenital?, phytotoxins?). A chronic course develops. (s. tabs. 14.5; 39.2) (s. pp 249, 548)

Fig. 39.5: Budd-Chiari syndrome due to essential thrombocythaemia.

Long-standing thrombotic occlusion of a liver vein (van Gieson) (s.

fig. 29.9)

2.1.3 Morphology

Laparoscopy: The liver is enlarged and displays a dark reddish cyanotic surface with a rounded margin. Con- gested veins and collaterals in the abdominal region sug- gest portal hypertension. Transformational processes may occur in a chronic course (in 30 ⫺40% of cases) or when the liver is only partially affected, so that even the picture of a cirrhosis has been observed. Ascites, occasionally also in its sanguinolent form, is detected in most patients.

Liver biopsy: Histology reveals pronounced centrilobu- lar congestion as well as sinus ectasia, necroses and thrombi in the central veins, which are either fresh or are already organized. Parenchymal atrophies and nodal transformational processes can be observed after a longer period of time. (s. figs. 29.9; 39.5)

2.1.4 Clinical features

BCS is a rare disease and responsible for about 5% of all cases of portal hypertension. The highest incidence is observed in 3

^rd

and 4

^th

decades. Frequency varies con- siderably in different countries and regions depending on its aetiology. • The clinical picture is determined by the course of disease and therefore there is great vari- ability in findings. In chronic BCS, abdominal pain is mild, and hepatomegaly develops only gradually.

Splenomegaly, diarrhoea and ascites, including oedema in the legs, are occasionally in evidence. Oesophageal varices may develop as a result of postsinusoidal portal hypertension. Non-characteristic symptoms (fatigue, inappetence, weakness, meteorism) are present in most cases. All laboratory parameters may remain in the nor- mal range for a long time. • A far smaller percentage of patients suffer from acute BCS with severe pain in the upper abdomen, nausea, vomiting and malaise. Jaun- dice is often present. Hepatomegaly develops rapidly.

Acute BCS can present clinically as acute liver failure.

(60)

The caudate lobe is enlarged as it has efferent

(7)

hepatic veins of its own, which circumvent the main branches of the hepatic vein and lead directly to the inferior vena cava.

(33)

As a rule, in an enlarged caudate lobe, which may also compress the inferior vena cava, it is technically impossible to apply a portacaval shunt. In cases of severe parenchymal deterioration, there is a risk of hepatic encephalopathy and hepatorenal syndrome.

The prognosis of acute BCS is very poor; the dramatic course of the disease rapidly leads to liver failure.

(38, 40, 50, 51, 54, 60, 69)

1.

Hypercoagulopathies

Antiphospholipid syndrome (59) Antithrombin III deficiency Essential thrombocytosis Factor V mutation (39) Lupus anticoagulant

Myeloproliferative disease (31) Paroxysmal nocturnal haemoglobinuria Polycythaemia vera

Protein C deficiency (68) Protein S deficiency Sickle-cell anaemia 2.

Infections

Amoebic liver abscess Aspergillosis

Crohn’s disease Echinococcosis Hepatic abscess Schistosomiasis Syphilis Tuberculosis 3.

Malignant diseases

Adrenal carcinoma Bronchogenic carcinoma Fibrolamellar carcinoma Hepatocellular carcinoma Leiomyosarcoma Leukaemia

Renal cell carcinoma Rhabdomyosarcoma 4.

Endotheliotoxic substances

Cytostatics (63) Azathioprine Phytotoxins 5.

Hormonal factors

Oral contraceptives (56) Pregnancy (46) 6.

Immunological factors

Behc¸et’s disease (34) Hypereosinophilia Sarcoidosis (64) Sjögren’s syndrome (53) 7.

Other aetiological observations

Abdominal trauma

Laparoscopic cholecystectomy Membranous obstruction (73) Polycystic liver disease (35) Retroperitoneal neurilemmoma (65) Tumour in the right atrium (42) 8.

Cryptogenic

Tab. 39.2: Possible causes of the Budd-Chiari syndrome (including

some references) (s. figs. 29.9; 39.5)

2.1.5 Diagnosis

Laboratory parameters are irrelevant for diagnosis!

Transaminases, LDH, GDG and alkaline phosphatase are in general moderately increased, and hyperbilirubin- aemia can be detected in 20 ⫺25% of cases. The albumin level is usually reduced; hypoproteinaemia may be caused by protein-losing enteropathy. Evidence of disturbances in blood coagulation, with regard to both hypercoagulopathic status and haemorrhagic diathesis, is of significance. P-III-P serum values rise in chronic courses with increasing fibrosis. Liver function tests, however, generally show normal results.

Sonography shows hepatomegaly and inhomogeneous, hypoechoic zones. The hepatic veins are invisible or pre- sent as narrow structures only. The caudate lobe is enlarged and often causes an hourglass-like constriction of the inferior vena cava. Ascites is confirmed. Colour- encoded duplex (or Doppler) sonography is a valuable additional means of examination. The diagnosis proves to be correct in 85 ⫺90% of cases; the results are further improved by CT angiography or MR angiography.

(23, 37, 45, 54, 69)

Computer tomography, especially when coupled with a contrast medium and in the form of CTAP, is an excel- lent tool for analyzing the venous blood flow and detecting any disturbances in inflow or outflow. Throm- bosed hepatic veins are not visible; the parenchyma is characterized by an inhomogeneous, patch-like en- hancement. (s. fig. 39.6) • MRI provides reliable evalua- tion by means of multiphase, contrast-enhanced, three- dimensional MR angiography.

Angiography, coupled with cavography and venography of the liver, is the most reliable examination method:

venous obstructions can easily be localized, and the residual venous blood circulation always displays a spider web-like picture. • In some 20% of cases, the por- tal vein is also thrombosed, indicating arteriography in the form of indirect splenoportography. In addition, angiography also offers the therapeutic possibilities of interventional radiology.

(36, 43)

Histology: In cases where histological evidence is

required, samples should be taken from both liver lobes,

since the expressivity of the histological picture can vary

greatly in different sections of the liver in BCS. The best

technique in this connection is laparoscopy (possibly

combined with targeted biopsy). Although the risk of

haemorrhage is generally high in biopsy, intense bleed-

ing or delayed coagulation can be effectively reduced

and more easily controlled under laparoscopy. As a rule,

however, the laparoscopic image of BCS is impressive

enough per se ⫺ especially if supported by imaging pro-

cedures ⫺ so that biopsy and the accompanying risks

can indeed be avoided altogether.

(8)

Fig. 39.6: Budd-Chiari syndrome: pronounced collateral circula-

tion resulting from thrombotic occlusion of the right hepatic vein.

• Re-opening of the vessel and rapid reduction of the collateral vessels following successful balloon dilatation

2.1.6 Treatment

There are very few reports of spontaneous remission even in partial BCS. • The therapeutic principle in all cases is to remove liver congestion, limit and lyse any thrombo- ses as well as eliminate ascites.

(40, 51, 69)

• Medication includes immediate lysis treatment followed by heparini- zation. Despite initial success, frequent complications have been reported (e. g. pulmonary embolism, re-occlu- sion, intraperitoneal bleeding).

(66)

• Percutaneous bal- loon angioplasty was first used by

^{S. E}guchi et al.

in 1974 in membranous obstruction of the inferior vena cava and was subsequently applied in BCS.

(73)

(s. fig. 39.6) In some cases, a stent implantation proved to be success- ful.

(49, 70, 71, 72)

The significance of percutaneous trans- luminal angioplasty is not only based on its long-term therapeutic effect, but also on its combination with operative shunts or other surgical techniques.

(36, 43)

This method was improved by laser assistance

(S. Furui et al., 1988)

• To date, a total of 23 different surgical tech- niques have been reported

(32, 47, 50, 54, 58, 69)

, consisting mainly of shunt placements, preferably the mesocaval

shunt, bypass operations, resections, thrombectomies and liver transplantation. Even though it is technically difficult, dorsocranial liver resection with direct hepa- toatrial anastomosis successfully corrects the venous perfusions of the liver physiologically. Meanwhile, the transjugular intrahepatic portosystemic stent shunt (TIPS) has proved effective.

(44, 55, 57, 62)

It is relatively quick and easy to apply, has proved to be a low-risk procedure and can be carried out before resorting to other invasive or surgical techniques. Thus it is possible to bridge the time required for planning any surgical intervention or liver transplantation. The latter is urgently indicated in an acute course. Continuous long- term anticoagulation is necessary even after transplan- tation, as is also invariably the case with all of the above-mentioned treatment measures.

(44, 48, 61, 67)

Constrictive pericarditis: The clinical picture and hepatic changes of the liver are similar to those of the Budd- Chiari syndrome. Considerable thickening of the liver capsule may resemble sugar icing. The liver is enlarged and firm. Tense ascites is present. Histologically, the changes resemble those of cardiac cirrhosis.

2.2 Veno-occlusive disease 2.2.1 Definition

Veno-occlusive disease (VOD) is characterized by thrombosis of the central and small (sublobular) hepatic veins. It is also known as the radicular form of the Budd-Chiari syndrome or as the Stuart-Bras syndrome. (s. tab. 14.5)

(75, 92, 93)

2.2.2 Aetiology

Toxic substances or physical impact cause direct damage to the centrilobular veins as well as to the small branches of the hepatic veins, resulting in subsequent thrombosis. • The first reports were published simultan- eously in South Africa

(G. Selzer et al.)

and Jamaica

(K. R.

Hill)

in 1951. This disease of the small branches of the hepatic veins is due to chronic intoxication with pyrroli- zidine alkaloids, which can be found in plants such as genera Senecio, Crotalaria, Heliotropium and Cyno- glossum. Intake occurs by drinking medicinal tea or through consumption of contaminated pulses and cer- eals. In 1974 and 1978, epidemic-like outbreaks of VOD were observed in Afghanistan and India after local in- habitants had eaten cereals contaminated with pyrro- lizidine alkaloids. The real toxicity of these alkaloids is based upon their transformation into alkylating pyrrole derivatives, which are toxic to endothelial cells and hepatocytes. • Other important causes of VOD include cytostatics, immunosuppressives, radiotherapy (> 30 Gy), immunological reactions and alcoholic hepatitis. (s.

tab. 39.3) (s. pp 548, 570)

(9)

1. Alcoholic hepatitis

2. Allogeneic bone-marrow transplantation

(80, 84, 85, 87)

3. Cytostatics

(76, 78, 79, 86, 88)

4. Immunosuppressives 5. Lupus erythematosus

(90)

6. Oral contraceptives

(94)

7. Pyrrolizidine alkaloids

(89, 91, 94)

8. Radiotherapy

9. Stem-cell transplantation

(83)

Tab. 39.3: Possible causes of veno-occlusive disease (VOD) (includ-

ing some references) (s. fig. 29.10)

2.2.3 Morphology

Histology provides useful diagnostic evidence. Sinus- oidal endothelial damage can be found, including extra- vascular accumulation of erythrocytes in Disse’s spaces as well as subendothelial oedema and cellulation. After 2 to 3 days, delicate fibres appear within the central and sublobular veins, occasionally also in the medium-sized hepatic veins, ultimately resulting in occlusion of the lumen. Fibrotic thickening of the vessel walls occurs.

Stenosis and thrombosis of the small hepatic veins cause extensive sinusoidal congestion. The liver cells become necrotic or atrophic. • Micronodular cirrhosis develops in a chronic course. (s. fig. 29.10)

2.2.4 Clinical features

The clinical symptomatology is similar to that of chronic Budd-Chiari syndrome. About 10% of cases dis- play an asymptomatic clinical picture over an extended period of time. • Spontaneous reversibility of VOD has been observed following administration of pyrrolizidine.

(91)

However, the disease may also progress rapidly to liver failure. A chronic course generally leads to liver cirrhosis with postsinusoidal portal hypertension. • La- boratory values reveal a slight increase in transaminases and occasionally in alkaline phosphatase as well as thrombocytopenia with a rapid decrease in haemo- globin. A rise in P-III-P is also significant in VOD, both for early diagnosis and monitoring purposes.

(80)

• The wedged hepatic vein pressure is increased. Due to its localization in the small hepatic veins, VOD cannot be diagnosed by means of imaging techniques. However, these techniques, particularly CEDS and CTAP, provide reliable evidence of gradually developing portal hyper- tension as well as the reduction or reversal of the portal blood flow during normal flow in the hepatic veins and the inferior vena cava.

(81, 82)

• Histology makes it pos- sible to achieve a reliable diagnosis. (s. fig. 29.10) 2.2.5 Treatment

Once the cause of VOD has been determined, it must be eliminated (if possible). Treatment is symptom- oriented and primarily directed towards the conse-

quences of portal hypertension. In order to reduce portal hypertension, medication (spironolactone, molsi- domin, beta blockers) and the application of TIPS are recommended.

(77)

Ultimately, indications for liver transplantation have to be considered.

(87)

2.3 Endophlebitis obliterans hepatica

This is also called

Chiari’s disease (1899) and defined as a truncal form of the Budd-Chiari syndrome (1899). (s. p. 830) •

It consists of primary, independent phlebitis of the large hepatic veins. (s. tab.

14.5) • Fibrinoid swelling of the intima with inflammatory, granu- lating processes, luminal obstruction and secondary thrombosis are characteristic findings. The large hepatic veins are affected with varying intensity and at different stages. This development is typical of the clinical picture. It is mainly caused by inflammatory processes of the immediate neighbouring structures or rheumatoid and paraneoplastic diseases. Total obstruction of the hepatic veins is infaust. Partial occlusion results in posthepatic portal hypertension and its sequelae.

3 Disorders of the portal vein

䉴 The portal vein is formed by the retropancreatic union of the right and left gastric veins, the pyloric vein, the superior and inferior mesenteric veins and the splenic vein. Its trunk runs inside the

hepatoduodenal ligament to the liver. Within the porta hepatis, the

portal vein divides into a

right branch (which also receives the cys-

tic vein) and a

left branch (into which the paraumbilical veins con-

tained in the round ligament and the ventroflexus ramus from the left sagittal fossa open). • The rami of the portal vein branch out and reach the portal fields where they become

interlobular veins,

which generally fork into

two interlobular venules (⫽ leading veins).

The latter transport the blood into distributory veins which con- tinue in Y-form into the

afferent venules (final ramifications) and

transport portal blood into the

sinusoids. • The portal vein is 5⫺8

cm in length and has a diameter of 1.2±0.2 cm. The normal portal

pressure is 3

⫺6 (⫺8) mmHg. (s. fig. 2.6) The portal blood flow amounts to 1150⫺1300 ml/min. (s. pp 17, 244)

Portal vein diseases may be congenital or acquired, or arise as a sequela of portal hypertension: (1.) portal vein anomalies, (2.) pylephlebitis, and (3.) portal vein thrombosis.

3.1 Anomalies of the portal vein

Congenital anomalies of the portal vein are very rare. This also applies to accessory portal veins with their indi- vidually varying patterns.

䉴 Accessory portal veins are small veins at the surface of the hepatic serosa and in the surrounding peritoneal folds which nor- mally originate in the diaphragm and the stomach. They can either open into the portal vein or enter the liver parenchyma indepen- dently.

• Anomalous accessory portal veins may sometimes originate

in the area of the portal veins around the gall bladder, the porta hepatis, the omentum, the interior surface of the abdominal wall or the hepatorenal ligament, etc.

䉴 Anomalies are described as a missing portal vein and intrahepa- tic branches with simultaneous hyperplasia of the hepatic artery.

•

The portal vein and its branches may also be located in front of the duodenum and the pancreatic head. Sometimes, even a

(10)

multitude of small vessels can be found instead of a single portal vein. Another anomaly has been described as a faulty opening of the portal vein into the renal vein, with the enlarged hepatic artery taking over the entire blood supply to the liver.

•

Moreover, there may be anomalous anastomoses between the portal vein and the branches of the greater circulation.

•

Besides aplasia or obliteration of the portal vein, congenital arterioportal fistulas (s. tab.

14.2) (s. p. 245) or portal vein stenoses also cause portal hyperten- sion with subsequent phlebosclerosis.

In addition to the congenital anomalies, other clinical features may be responsible for disorders of the portal vein system:

1. Anomalous accessory portal veins 2. Aplasia

3. Arterioportal fistula 4. Cavernous transformation

5. Cruveilhier-Baumgarten syndrome 6. Faulty openings of the portal vein 7. Displacement

8. Obliteration 9. Portal vein stenosis

3.1.1 Cavernous transformation

This condition is primary angiomatosis of the portal vein: a spongy convolution of venous vessels branching in a tendril-like manner has formed instead of a trunk

⫺ predominantly in the area of the hepatoduodenal ligament.

(95, 96)

Prehepatic portal hypertension develops as a result of the disturbed outflow from the splanchnic nerve area.

However, both liver function and histology are normal.

Occasionally, considerable mechanical jaundice has been observed. Clinical symptoms include abdominal pain, splenomegaly, haematemesis and oesophageal var- ices. The internal pressure in the spleen is increased, while the wedged hepatic vein pressure remains in the normal range. Successful diagnosis is based upon imaging techniques and colour-encoded duplex Doppler sonography.

(97)

(s. tab. 14.2) (s. p. 245)

3.1.2 Cruveilhier-Baumgarten disease

In the absence of physiological postnatal closure of the umbilical vein, an anastomosis will form between the portal vein and the abdominal wall. Hypoplasia of the portal system and liver can be observed at the same time. Prehepatic portal hypertension develops with vis- ible and palpable venectasia in the abdominal skin, also known as Medusa’s head

(M. A. Severino, 1632)

. (s. p. 87) (s. fig. 14.13) A venous murmur (so-called venous hum) can often be heard periumbilically, generally in the centre of the Medusa’s head. Splenomegaly causes splenogenous maturation arrest. The diagnosis is con- firmed by imaging techniques. (s. p. 246!)

Cruveilhier-Baumgarten syndrome: This is a secondary syndrome observed in liver cirrhosis with pronounced

portal hypertension. Recanalization of the umbilical vein and of the paraumbilical veins develops. (s. fig.

39.7) • Clinical symptoms include splenomegaly, Medu- sa’s head, periumbilical vascular murmur and ascites.

Fig. 39.7: I: Re-opened umbilical vein (VU) due to pronounced

portal hypertension in haemochromatotic cirrhosis (VP⫽ umbilical branch of the left portal vein) • II: Hepatofugal blood flow in the umbilical vein (VU) depicted by colour-encoded duplex sonography

Acquired causes may also be responsible for some of the congenital anomalies described above. Mention should be made of (1.) arterioportal fistulas, (2.) cavernous transformation of the portal vein (in portal vein throm- bosis), (3.) fibrous obliteration of the portal vein, and (4.) cicatricial portal vein stenosis. These may also cause prehepatic hypertension. (s. tab. 14.2) (s. p. 246!) 3.1.3 Arterioportal venous fistula

Arterioportal venous fistulas

(R. Sachs, 1892)

between the

arterial and portal system may occur perihepatically

(11)

following puncture, trauma, invasive surgery and tumour growth. Congenital arterioportal fistula is very rare. Only about 12 cases have been reported to date.

(98)

Clinical symptoms include prehepatic portal hyper- tension

(102, 103)

, vascular murmur in the right hypo- chondrium, abdominal pain

(103)

and signs of hyper- dynamic circulation. Sonography shows dilation of both the hepatic artery and the intrahepatic portal vein branches. Calcification of a liver biopsy-related fistula may occur.

(100)

The diagnosis is generally made by duplex Doppler sonography and confirmed by angio- graphy, with the possibility of simultaneous emboliza- tion of the fistula. In the case of treatment failure, selec- tive resection of the fistula is indicated.

(99, 101)

There is usually no change in portal hypertension after the development of hepatoportal sclerosis. (s. p. 246)

3.2 Pylephlebitis

Purulent inflammation of the branches of the portal vein is usually accompanied by subsequent portal vein thrombosis. Aetiologically, intrahepatic and extrahepa- tic purulent pylephlebitis share certain similarities. • Portal vein infections have their origin in inflammatory processes of neighbouring structures such as appendi- citis, cholecystitis, liver abscesses (as was already pos- tulated by

H. Chiari

in the first cases published) (s. p.

830), suppurative hydatid cysts, colitis, diverticulitis, infected haemorrhoids, covered perforations (gall blad- der, gastric ulcer) and malignant tumours (gall bladder, pancreas). • Clinical symptoms include fever, chills, abdominal pain, meteorism, enlarged and tender liver as well as splenomegaly. In most cases, inflammation parameters are clearly pathological. (s. tab. 37.6) Bacteriological haemocultures only yield positive results when the defence mechanisms of the liver RES have been overwhelmed. The clinical picture of septic portal vein thrombosis can often be observed. Treatment with local fibrinolysis and TIPS has proved successful.

3.3 Portal vein thrombosis

Thromboses in the vessels of the portal system consti- tute the most common cause of prehepatic portal hyper- tension. • Even in the postpartal phase, portal vein thrombosis may occur due to the obliteration of the umbilical vein spreading to the portal vein or due to an infection of the umbilical vein with subsequent pyle- phlebitis. • In the adult, this clinical picture is most com- monly observed in liver diseases that cause the portal blood flow to slow down (or even reverse). All diseases which are accompanied by hypercoagulopathies also have a strong tendency to cause portal vein thrombosis.

(106, 110, 112, 119, 121)

Patients with liver cell carcinoma due to cirrhosis quite often develop thrombosis. Septic processes (such as appendicitis, diverticulitis, colitis) are a further common cause, particularly in immuno-

compromised patients. In addition, inflammatory tissue, tumours, lymphomas or fibrosis may narrow the lumen of the portal vein and trigger thrombosis. Thrombosis of the portal vein may also result from progressive thrombosis of the splenic vein. (s. tab. 14.2) Portal vein thrombosis can hence be caused by many factors.

(107, 108, 119, 121⫺123)

(s. tab. 39.4) (s. fig. 39.8)

Fig. 39.8: Thrombosis of the portal vein (

⇐) and splenic vein (씮):

contrast medium-free, hypodense structure; evidence of ascites

The severity of the clinical picture depends upon how rapidly and to what extent the portal vein obstruction develops. • Haemorrhagic infarction of the intestine, due to sudden thrombotic occlusion, causes severe abdom- inal pain, haematemesis and melaena, circulatory shock and, ultimately, the death of the patient. • In gradual obstruction, splenomegaly and hypersplenism develop, accompanied by collateral vessels in the form of a sponge-like venous network ( ⫽ cavernous transforma- tion), which makes partial compensation possible. Gall- bladder varices, even with rupture and bleeding, have also been observed.

(104, 109)

The size of the liver is nor- mal, as are the wedged hepatic vein pressure (with increased intrasplenic pressure) and histology. Impair- ment of liver function only occurs at a later stage

(118)

, and hepatoportal sclerosis develops. • The diagnosis is mainly established by colour Doppler sonography (sen- sitivity > 90%)

(114)

, CT (s. fig. 39.8) and angiography (e. g. CTAP). Angiographic findings are also useful for deciding on the respective therapy: thrombolysis with subsequent anticoagulant treatment (if possible!)

(105, 113, 116)

, percutaneous transhepatic angioplasty and thrombectomy (both procedures can only be applied in the early stages of disease), TIPS (possibly, with local thrombolysis) or a shunt operation. The prognosis is poor.

Zahn’s infarct: This well-demarcated hyperaemic area in

the liver was first described by

F.W. Zahn

in 1897. He

called the phenomenon “atrophic red liver infarction”,

but without necrosis. Such a form of infarct is an oddity.

(12)

1.

Hypercoagulopathy

Antiphospholipid sydrome Oral contraceptives Antithrombin III deficiency Protein C deficiency Factor V mutation Protein S deficiency Factor VIII elevation Pregnancy

Hyperhomocysteinaemia Thromboembolism Myeloproliferative diseases

2.

Inflammatory processes

Appendicitis Crohn’s disease

Behc¸et’s disease Diverticulitis

Cholangitis Pancreatitis

Cholecystitis PSC

Collagenoses Ulcerative colitis

3.

Infections

Actinomycosis Schistosomiasis

Candida albicans Tuberculosis

Echinococcus 4.

Invasive treatment

Abdominal surgery Liver transplantation

Alcohol injection Portography

Chemoembolization Sclerotherapy

Dialysis Splenectomy

Islet-cell injection TIPS

Liver resection

5.

Delayed portal blood flow

Congenital fibrosis Liver cirrhosis Lymphoma

Nodular regenerative hyperplasia Retroperitoneal fibrosis

Stenoses/strictures

6.

Progressive splenic vein thrombosis

Pancreatitis

Pancreatic carcinoma Splenectomy 7.

Malignant processes

Cholangiocarcinoma Cystic carcinoma Hepatocellular carcinoma

Pancreatic tumour (⫽ thrombophlebitis migrans) 8.

Intoxications

Arsenic Cytostatics Radiation

9.

Haematologic diseases

Paroxysmal nocturnal haemoglobinuria Sickle cell anaemia

10.

Cardiovascular diseases

Constrictive pericarditis

Obstruction of inferior vena cava Pylephlebitis

Tricuspid insufficiency Tumour of the right atrium Umbilical vein infection Veno-occlusive disease 11.

Trauma

12.

Cryptogenic

Tab. 39.4: Possible causes of portal vein thrombosis

(111, 117)

Intrahepatic occlusion of hepatic vein branches results in a narrowing and atrophy of the liver cell tra- beculae and consecutive dilation of the associated sinus-

oids. A dark bluish red area of the liver appears, which is most clearly visible when the liver is simultaneously congested. (Despite the term “infarct”, no necrosis can be observed!) Zahn’s infarct may also be found in the area surrounding liver metastases due to compression of the portal vein branches by tumourous tissue.

3.4 Portal vein aneurysm

Aneurysms of the portal vein are very rare. However, since the introduction of imaging procedures, this gen- erally asymptomatic finding has been detected more fre- quently, in most cases by chance. In intrahepatic local- ization (first reported by

^{H. S. V}ine et al., 1979

), the aneurysms are mainly situated in the right lobe and reach a size of up to 4 cm in diameter. The cause is not clear. Congenital malformation with subsequent portal hypertension has been postulated, as has acquired vessel wall weakness (e. g. in pancreatitis). The diagnosis is made by sonography and MRI.

(124, 125)

Caroli’s syn- drome has to be ruled out by differential diagnosis.

Spontaneous rupture of such an aneurysm has been reported.

(127)

Treatment is not primarily required, but regular monitoring is necessary. In portal hypertension, however, the application of a shunt (surgically, trans- jugal-portacavally) may be indicated.

(126)

4 Disorders of the hepatic arteries

䉴 The common hepatic artery, a branch of the coeliac artery, runs in a retroperitoneal direction above the pancreas into the hepatoduodenal ligament. It continues as the

proper hepatic artery, which

branches into the

right hepatic artery (with the cystic artery) and

the

left hepatic artery to supply the two liver lobes. Ramification

of the hepatic artery varies greatly.

•

The branches of the hepatic artery accompany the bile ducts and the portal vein as far as the portal fields. Radicular branches subsequently fork off forming the

peribiliary plexus within the connective tissue of the portal paths.

The peripheral, medial and central areas of the hepatic lobules are supplied by

intralobular arterioles. •

A small percentage of the arterial blood supply is also guaranteed by influx from the superior mesenteric, inferior pancreatic-duodenal and supraduodenal arteries.

•

Only 40⫺50% of the oxygen requirement and 35% of the blood volume of the liver (350⫺500 ml/min.) are supplied by the hepatic artery. Hence, the clinical picture of diseased liver arteries is usually relatively mild, apart from bleeding caused by ruptures.

(s. p. 16)

The most important clinical disorders of the hepatic artery are:

1. Aneurysm 3. Nodular periarteritis 2. Occlusion 4. Arteriosclerosis

4.1 Aneurysm 4.1.1 Definition

While aneurysms of the hepatic arteries are in them-

selves rare, they nevertheless constitute 20% of all an-

(13)

eurysms of the splanchnic arteries. They are located extrahepatically in 80% and intrahepatically in 20% of cases. At 60%, the common hepatic artery is most fre- quently involved, followed by the right hepatic artery, which is affected in 30% of cases. A rupture (up to 80%

of cases) constitutes a great risk to the afflicted, but often symptom-free patients. After confirmation of the diagnosis, treatment should begin immediately.

4.1.2 Aetiology

Congenital anomalies and aneurysms in the hepatic arteries are very rare.

(129)

Acquired aneurysms are the result of vessel wall damage, injuries or inflammatory processes.

(131, 133, 136)

• Pseudoaneurysms may occur after acute pancreatitis and the formation of pseudo- cysts.

(135)

(s. tab. 39.5)

1.

Congenital aneurysms

5.

Infections

Endocarditis 2.

Vascular wall degeneration

Mycosis Arteriosclerosis

Pancreatitis Fibromuscular dysplasia

Syphilis Media degeneration

Tuberculosis 3.

Abdominal traumas

6.

Vasculitis

4.

Iatrogenic causes

Periarteritis nodosa Bile-duct surgery

Vasculitis Intra-arterial chemotherapy

Liver biopsy 7.

Multiple preg-

Transhepatic interventions

nancies Tab. 39.5: Possible causes of hepatic artery aneurysm

4.1.3 Clinical features

Symptomatology depends on the extent and localization of the aneurysm, which can vary considerably in size, ranging from the diameter of a millet seed to that of a walnut (there have been cases where aneurysms as big as a grapefruit were observed). Small aneurysms do not cause any symptoms and are only discovered inciden- tally during imaging procedures or surgery. In most cases, patients complain of uncharacteristic abdominal pain, which may precede a rupture by several months.

Large aneurysms are characterized by a continuous murmur.

(132)

After perforation (60⫺80% of patients), an aneurysm becomes manifest in the form of abdominal pain, which can be very severe.

(129)

When an intrahepatic haema- toma reaches the bile ducts, haemobilia may result (about 40% of cases)

(133)

, just as compression of the excretory bile ducts may lead to the development of jaundice (in some 50% of cases).

(134, 138)

Heavy bleeding into the free abdominal cavity constitutes an acute abdomen with signs of circulatory shock. Bleeding into the intestinal tract or into the portal vein is less frequent. Lethality due to rupture is 30 ⫺50%; the prognosis for massive bleeding with haemoperitoneum is even poorer.

4.1.4 Diagnosis

Laboratory findings are normal. However, alkaline phosphatase (and LAP) and possibly also bilirubin may be increased in biliary stasis.

With unclarified abdominal pain, sonography is usually the diagnostic procedure of choice. An aneurysm appears as a round or oval focus either intrahepatically or extrahepatically between the portal hilum and the pancreas. The hypoechoic, cystic focus may contain hyperechoic, thrombotic material. Occasionally, there is a connection to an afferent vessel.

(128)

A suspected aneurysm can be confirmed by colour Doppler sonogra- phy, with the possibility of distinguishing blood flow and arterial blood. An echo-free aneurysm provides a typical arterial sphygmogram.

CT scanning reveals a hypodense to hyperdense focal space-occupying lesion, with the hyperdense parts cor- responding to the thrombotic structures within the aneurysm. Diagnostic accuracy is considerably im- proved by using contrast-medium CT.

Angiographic scanning of the hepatic artery confirms the diagnosis as well as giving an indication of the most appropriate therapeutic measures. • Due to the develop- ment of modern MRI techniques, invasive angiography is no longer necessary in most cases.

4.1.5 Treatment

Once detected, an aneurysm of the hepatic artery requires immediate treatment. Up to a certain size, intrahepatic aneurysms are treated by angiographic embolization. Coagulation by means of direct thrombin injection has also been described.

(130)

Larger an- eurysms are treated by vascular surgery (ligation, vascu- lar reconstruction, resection).

(132, 137)

4.2 Arterial occlusion

Occlusion of the hepatic artery is responsible for a 50%

reduction in oxygen supply. Even if an unimpaired oxy- gen supply via the portal vein is guaranteed, arterial occlusion usually causes ischaemic infarction. The clin- ical and morphological pictures are characterized (1.) by the speed with which an occlusion develops and (2.) by the presence of variants that can be used as a bypass or of collaterals that have already been established in gradual vascular occlusion. This results in a broad clin- ical spectrum, which may range from a symptom-free condition to liver hypoxia, including infarction up to hepatic coma.

4.2.1 Aetiology

Causes of occlusion are as follows: (1.) primary vascular

diseases (nodular periarteritis, giant-cell arteritis, etc.),

(2.) iatrogenic measures (intra-arterial catheterization,

(14)

i.v. cytostatic infusions, surgical interventions, etc.), (3.) traumas (dissections), (4.) embolisms (bacterial endo- carditis, severe arteriosclerosis, mitral valve defect), and (5.) fibromuscular hyperplasia.

4.2.2 Clinical features

In acute occlusion with infarction, there is dull upper abdominal pain, often coupled with shock symptoms;

the liver is tender upon pressure. Fever, jaundice and leucocytosis rapidly develop; Quick value decreases, and haemorrhages develop. Transaminase and alkaline phosphatase levels rise. Liver failure is imminent. Apart from possibly detecting hypoechoic foci, sonography provides no diagnostic information. Contrast-medium CT reveals hypodense regions with mostly blurred boundaries. In MRI, the infarct is low T

1

-weighted, with a high signal intensity in the T

₂

image. The diagno- sis is confirmed by arteriography, which should be car- ried out without delay if there is suspicion of acute occlusion. • Treatment is symptomatic and aimed at sta- bilizing the liver function in order to allow time for the formation of collaterals (within a few days). A lethal course must be anticipated if the openings of the gastric and gastroduodenal arteries are involved in the occlu- sion. The prognosis for distal occlusions in the area of the right or left hepatic artery is more favourable.

Ischaemic infarction: Ischaemic infarction with haemor- rhagic marginal zones not only occurs after occlusion

(139⫺141)

, but also without vascular obstruction, e. g. in shock, diabetic ketoacidosis, pre-eclampsia or lupus ery- thematosus. Small infarctions have also been described as complications following liver biopsy. • Morpholog- ically, fresh anaemic infarctions appear as coagulation necroses. Large infarctions may cause “bile lakes” with evidence of air. From the second day, a wall of leuco- cytes forms at the infarction margins, and pigment- loaded macrophages can be observed. The reticular fibre structures collapse, and the granulation tissue is vascularized. Ultimately, indrawn scars develop.

4.3 Nodular periarteritis

This primary vascular disease is a febrile systemic auto- immune reaction, presumably caused by excessive immune activities. In this process, immune complexes are deposited in the walls of vascular arterioles as well as in the larger arteries, giving rise to a progressive inflammatory reaction with round-cell infiltrates, pearl string-like thickening and proliferations of the intima.

The narrowing of the lumen results in ischaemic necro- ses, which are also present in the liver in up to 65% of patients. Non-specific reactive inflammation in the por- tal fields may also be observed. As a rule, the gall blad- der is involved just as frequently. Nodular periarteritis often leads to the development of aneurysms. • Clin- ically, there are highly pathological inflammation

parameters. (s. tab. 39.2) Marked increases in BSR and alkaline phosphatase are characteristic. Various pains in the abdomen, joints and renal areas occur; weight loss adds to a distinct feeling of being ill. If the liver is affected, transaminase values may be slightly increased.

• Treatment consists of prednisolone and azathioprine, unless active viral hepatitis is present.

4.4 Arteriosclerosis

Arteriosclerosis affects the extrahepatic liver arteries with the same frequency as the mesenteric arteries, but less frequently than the splenic artery. • The intrahepatic branches of the hepatic artery are usually only involved in pronounced arterial hypertension. In these patients, thickening of the media can be found in the small ar- teries of the portal fields.

5 Hereditary haemorrhagic telangiectasia

This dysvascular state, also known as Osler’s disease or Rendu-Osler-Weber disease, was first observed by the Canadian internist

W. Osler

in 1901.

(152)

It is a rare autosomal dominant hereditary disease (1 : 100,000) with high penetrance (almost 100%). The homozygous presence of the affected allele is a lethal factor. All types of vessels are affected by these vascular malformations.

Thus, for example, arteriovenous fistulas, aneurysms and telangiectasias of the arterial and venous terminal vessels as well as phlebectasias are found. The liver is involved in 40 ⫺70% of cases. Star-shaped vascular ecta- sias can be found on the liver surface. Polymorphism of these angiodysplasias is caused by genetically deter- mined damage to fibroelastic fibres within the vascular walls and the perivascular tissue. There is no evidence of any mesenchymal reaction or inflammatory activity.

(142, 145, 146, 148, 154, 155, 157)

• Osler’s disease usually progresses through three phases: the asymptomatic latent period extends from childhood into puberty: the subsequent haemorrhagic phase is generally charac- terized by recurrent nasal bleeding; manifest angio- matosis has its onset in the 3

^rd

or 4

^th

decade. Various clinical features can be witnessed, including post- haemorrhagic anaemia, hyperdynamic circulatory prob- lems due to arteriovenous fistulas with cardiac insuffi- ciency, signs of portal hypertension with hepatomegaly