Hepatic occlusion

Portal hypertension is a consequence of increased resistance to blood flow through the portal vein. Increased resistance is usually due to restructuring of intrahepatic tissue (sinusoidal damage) but may also be caused by presinusoidal damage such as portal vein occlusion from trauma, malignancy, or thrombosis. A third (and the least common) mechanism is outflow obstruction of the hepatic vein. This latter damage is posthepatic, and normal liver structure is maintained. This chapter will focus on portal hypertension caused by intrahepatic damage from cirrhosis. 

Busulfan -alkylating agent -bone marrow suppression—can have prolonged nadir -ovarian suppression -seizures -hepatic veno-occlusive disease (VOD), particularly at BMT doses -interstitial pulmonary fibrosis -hyperpigmentation (particularly skin creases and nail beds)... 

Hepatic diseases do not change the serum levels of G-6-PDH (B15, K6, LI). In malignant occlusion jaundice, elevated levels of G-6-PDH have been reported (LI). 

Hepatic Effects. Severe cirrhosis of the liver was one of the primary systemic effects seen following injection of Thorotrast in humans (Baxter et al. 1980a, b Faber 1979 Kato and Kido 1987 Kato et al. 1983 Mori et al. 1979, 1983a, b Rao et al. 1986 Van Kaick et al. 1983). Cases of fibrosis, veno-occlusive disease, and blood-filled cavities were also found in the livers of Thorotrast patients (da Silva Horta 1967a Dejgaard et al. 1984). The latency period for the appearance of the cirrhosis was not clear, but was probably comparable to the latency period for liver tumors (25-30 years) since the two effects were often found together. 

Intravenous silymarin has been demonstrated to lower mortality from Amanita mushroom poisonings, but this formulation is available only in Europe. Animal studies have demonstrated hepatic protection against alcohol, acetaminophen, and mushroom toxins and protection against hepatic fibrosis with bile duct occlusion. There is also evidence of silybin protecting against cis-platin-induced nephrotoxicity in rats. It is not yet clear whether milk thistle extract offers any renal protection to humans. 

Cl) = 0.30 - 0.92] was offset by an increased risk of death in remission (OR = 2.22, 95% Cl = 1.20 - 4.14), mainly due to infections. Strikingly, 11% of patients in the 6-TG arm compared to less than 2% in the 6-MP arm developed non-fatal hepatic toxicity with features of veno-occlusive disease (VOD) characterized by symptoms including tender hepatomegaly, hyperbilirubinaemia with elevated aminotransferases, thrombocytopenia out of proportion to neutropenia, and portal hypertension. In 85% of affected 6-TG recipients, these symptoms were observed during maintenance or interim maintenance. Of interest, in patients randomized to 6-MP, hepatic toxicity was associated with intensification elements in which both treatment arms received exclusively 6-TG. 

Occasionally toxic compounds can directly damage the hepatic sinusoids and capillaries. One such toxic compound is monocrotaline, a naturally occurring pyrrolozidine alkaloid, found in certain plants (Heliotropium, Senecio, and Crotolaria species). Monocrotaline (Fig. 7.7) is metabolized to a reactive metabolite, which is directly cytotoxic to the sinusoidal and endothelial cells, causing damage and occlusion of the lumen. The blood flow in the liver is therefore reduced and ischemic damage to the hepatocytes ensues. Centrilobular necrosis results, and the venous return to the liver is blocked. Hence, this is known as veno-occlusive disease and results in extensive alteration in hepatic vasculature and function. Chronic exposure causes cirrhosis. 

The incidence of hepatic veno-occlusive disease in 249 consecutive women treated with norethisterone who... 

SPERL, W., STUPPNER, H., GASSNER, I., JUDMAIER, W., DEETZE, O., VOGEL, W., Reversible hepatic veno-occlusive disease in an infant after consumption of pyrrolizidine-containing herbal tea., Eta. J. Pediatr., 1995, 154, 112-116. 

ZUCKERMAN, M STEENKAMP, V., STEWART, M.J., Hepatic veno-occlusive disease as a result of a traditional remedy confirmation of toxic pyrrolizidine alkaloids as the cause, using an in vitro technique., J. Clin. Pathol., 2002, 55, 676-679. 

Gastrointestinal GI hypersensitivity reaction, nausea, vomiting, pancreatitis, hepatotoxicity, hepatic veno-occlusive disease... 

The hepatic vessels may be visualised by conventional angiography or venography. These are invasive techniques requiring the injection of contrast media into the artery or vein via catheters during radiographic screening. Stenoses or occlusions are identified, e.g. occlusion of the hepatic veins in Budd-Chiari syndrome. 

Herbal medicines are becoming more and more popular, and indeed some herbal products may be considered to benefit people with liver disease, e.g. Silybum marianum (milk thistle), Picrorhiza kurroa, Phyllanthus, etc. Herbal hepatotoxicity is increasingly being recognised, for example, with kava kava, black cohosh, and many traditional Chinese remedies. The range of liver injury includes minor transaminase elevations, acute and chronic hepatitis, steatosis, cholestasis, zonal or diffuse hepatic necrosis, veno-occlusive disease and acute liver failure. In addition to the potential for hepatotoxicity, herb-drug interactions may affect the safety and efficacy of concurrent medical therapy [15]. 

Busulfan Nausea and vomiting rarely diarrhoea Bone marrow depression pulmonary infiltrates and fibrosis alopecia gynaccomasiia ovarian failure hyperpigmentation azoospermia leukaemia chromosome aberrations cataracts hepatitis seizures and veno-occlusive disease with high doses... 

Adverse effects include constipation, dry mouth and insonmia which occur in > 10% of users. Less commonly, nausea, tachycardia, palpitations, raised blood pressure, anxiety, sweating and altered taste may occur. Blood pressure should be monitored closely throughout its use (twice weekly in the first 3 months). Contraindications include severe h3q>er-tension, peripheral occlusive arterial or coronary heart disease, cardiac arrhythmia, prostatic hypertrophy and those with severe hepatic or renal impairment. It should not be used to treat obesity of endocrine origin or those with a history of major eating disorder or psychiatric disease. Concomitant use with tricyclic antidepressants should be avoided (CNS toxicity). 

Collateral hepatic circulation (cirrhosis, portal vein thrombosis, occlusion of hepatic vein, etc)... 

Magnetic resonance imaging in the staging of hepatic veno-occlusive disease. Eur. J. Gastroenterol. Hepatol. 1994 6 453-456... 

Scintigraphic proof of cirrhosis is based on (i.) enlarged rectangular liver, (2.) reduced and patchy uptake of radioactivity by the hepatic RES ( mottled liver ), (3.) shift in the maximum activity from the right to the left lobe of liver, and (4.) increased uptake by the spleen and bone RES. The recorded scintigraphic findings permit assessment of the course of liver cirrhosis and provide information on focal complications such as .) occlusion of the branches of the portal vein with locally impaired perfusion and (2.) development of hepatocellular carcinoma. 

Tc-DTPA Arterial perfusion accounts for 20%-40% of the circulation in portal hypertension, cirrhosis causes arterial perfusion to increase to over 60%. In portal vein thrombosis, only an arterial curve is visible. Liver metastasis usually displays relatively high arterial perfusion. In (rare) occlusions of the hepatic artery, only a portal venous curve is visible. When a bolus injection of 400 MBq "Tc-diethylenetriamine pentaacetic acid (DTPA) is applied, scintigraphy is able to reveal a bi-phasic time-activity curve. The initial increase of activity is produced by the arterial influence and the second peak by the portal venous inflow. Both curves can be evaluated quantitatively. (36) Perfusion scintigraphy may be useful in the case of liver trauma, TIPS, hyper-vascularized hepatic tumours and partial liver resection as well as after liver transplantation. 

An increase in blood both in the sinusoids and in Disse s spaces culminates in hepatomegaly. This can be witnessed particularly in cases of right heart failure, constrictive pericarditis, veno-occlusive disease and the Budd-Chiari syndrome. Inflammation-related hyper-aemia also occurs in acute viral hepatitis. 

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