Cirrhosis liver transplantation

Shresta, R., McKinley, C., Showalter, R., Wilner, K., Marsano, L., Vivian, B.R., Everson, G.T. Quantitative liver function tests define the functional severity of liver disease in early stage cirrhosis. Liver Transplant. Surg. 1997 3 166-173... 

As stated at the beginning of this article, the liver is the most intensively studied animal tissue in biochemistry. In the context of the role of free radicals in human diseases, the liver is not obviously at centre stage, since heart disease and cancer are more important in the industrialized world than, for example, cirrhosis. Free-radical biochemistry of the liver will remain a fertile area of work, however, not least because so many original ideas and techniques are developed there and then applied to the study of other tissues. The increasing use of liver transplantation, following the acceptance of kidney and heart transplants as almost routine, will surely increase the interest in the study of ischaemia-reperfusion injury in... 

Decompensated liver disease is complicated by jaundice, refractory ascites, bacterial peritonitis, coagulopathy, and variceal bleeding and may require liver transplantation. The number of liver transplants for decompensated cirrhosis doubled from 1990 to 2004, when 5845 cadaveric (orthotopic) liver transplants were performed (65). 

The main indications for liver transplantation include chronic hepatitis C, alcoholic liver disease, nonalcoholic fatty liver disease, and cryptogenic cirrhosis. 

Unlabeled Uses Prophylaxis of liver transplant rejection, treatment of alcoholic cirrhosis, biliary atresia, chronic hepatitis, gallstone formation, sclerosing cholangitis... 

Liver disease is the most common medical complication of alcohol abuse an estimated 15-30% of chronic heavy drinkers eventually develop severe liver disease. Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. In the United States, chronic alcohol abuse is the leading cause of liver cirrhosis and of the need for liver transplantation. The risk of developing liver disease is related both to the average amount of daily consumption and to the duration of alcohol abuse. Women appear to be more susceptible to alcohol hepatotoxicity than men. Concurrent infection with hepatitis or C virus increases the risk of severe liver disease. 

Peliosis hepatis has been described in association with contraceptive-induced hepatic tumors and has sometimes developed in isolation, perhaps as a herald of more serious changes to follow, for example cirrhosis and portal hypertension one such case ultimately required an orthotopic liver transplant (219). 

It should be realized, however, that therapeutic interference with only one cell type may not be enough to treat liver cirrhosis, because all hepatic cell types contribute to some extent to the development of the disease. Therefore, a combination of drug-targeting preparations to stellate cells, KC, endothelial cells, and/ or hepatocytes might improve the pharmacological therapies and compete with the liver transplantation technique. In addition to therapeutic applications, modified albumins may also be used for diagnostic purposes (an issue that will be addressed in section VI.C.4). 

Recent reports from European health authorities have linked kava to at least 25 cases of liver toxicity, including hepatitis, cirrhosis, and liver failure. The FDA is currently (2002) investigating the health risks of the herbal supplement. Under review are 38 Americans, including a liver transplant recipient, with medical problems associated with kava use. As of February 2002, sales have been halted in Switzerland and are suspended in Britain, Germany is acting to make kava a prescription product and the FDA recommends avoiding kava until safety questions are answered. 

Jaundice and pruritus were observed at age 6 weeks and resolved spontaneously after approximately 2 months. He was hospitalized for pneumonia at age 20 months, and an enlarged liver was noted. A percutaneous needle biopsy specimen from the liver was interpreted to show postnecrotic cirrhosis, although reevaluation of the biopsy specimen showed the presence of globules that were periodic acid-Schiff (PAS) positive, diastase resistant (Fig. 4-1). He was then referred to our institution at age 2.5 years for liver transplantation. 

Eastell R, Dickson ER, Hodgson SF, etal. (1991) Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis. Hepatology 14 296-300. 

Hepatic cirrhosis is typically the end stage of liver disease. Cirrhosis describes an irreversible change (Treinen-Moslen, 2001) characterized by accumulation of excessive collagen deposition in the form of bridging fibrosis which disrupts the hepatic architecture. Cirrhosis may be micronodular or macronodular depending on the amount of fibrosis and tissue regeneration. Liver transplantation is the only solution to restore adequate liver fimction in human medicine. 

Hepatolenticular degeneration (Wilson s disease) is caused by a genetic failure to eliminate copper absorbed from food so that it accumulates in the liver, brain, cornea and kidneys. Chelating copper in the gut with penicillamine (p. 293) or trientine can establish a negative copper balance (with some clinical improvement if treatment is started early). The patients may also develop cirrhosis, and the best treatment for both may be orthotopic liver transplantation. 

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. 

Xanthomas are found in the form of small nodular foci or as nodu-lations, mainly symmetrical, on the buttocks, elbows, knees, fingers, feet and toes, neck, tendons, and below the breast. They are reddish-brown to yellow in colour. These depositions of cholesterol are reversible - particularly with a marked reduction in the cholesterol level due to liver cirrhosis. Following transplantation of the liver, they generally disappear after one or two years, (s. p. 85) (s. figs. 4.14-4.16)... 

Liver transplantation not only removes the continued risk of variceal bleeding, but also eliminates the underlying liver disease causing portal hypertension. However, due to the scarcity of liver donors, limited financial resources and the life-long immunosuppression required, this major surgical intervention can only rarely be considered - perhaps in cases where a previous shunt operation or the creation of a TIPS was not possible. The survival rate for transplantation is higher than when recurrent bleeding is treated by repeated sclerotherapy (73% versus 17% after 4 years). The indication for transplantation (e. g. cirrhosis Child B or C) should be set as early as possible, (s. p. 872)... 

Hypoxaemia (Pa02 < 70 mm Hg) is observed in 45-69% of patients suffering from cirrhosis or liver insufficiency. Only rarely has severe hypoxaemia been demonstrated (Pa02 < 50 mm Hg). (6, 32, 51, 52, 56) Intrapulmonary vasodilations could be ascertained in 13-47% of liver transplant candidates. (27) In about 50% of all cirrhotic patients, a decline in the diffusion capacity for carbon monoxide was detected. (24) About 30% of cirrhotic patients showed no (physiological) reduction in pulmonary vasoconstriction under conditions of hypoxia. The prevalence of HPS in cirrhotic patients varies between 4% and 19%. It occurs more... 

This clinical picture was described for the first time in 1951 by F. Mantz et al. (65) and confirmed in 1983 by P.J. McDonnell et al. Portopulmonary hypertension (PPH) is defined as a secondary form of pulmonary hypertension with portal hypertension. Frequency in patients with cirrhosis is given as 2-4%, in patients in an advanced stage of cirrhosis (e.g. presenting for liver transplantation) as 5-10% of cases, (s. pp 258, 735)... 

Eriksson, L.S., Sdderman, C., Ericzon, B.-G., Eleborg, L., Wahren, J., Hedenstierna, G. Normalization of ventilation perfusion relationship after liver transplantation in patients with decompensated cirrhosis evidence for an hepatopulmonary syndrome. Hepatology 1990 12 1350-1357... 

Patients suffering from alcoholic liver cirrhosis in the Child-Pugh C stage may well have a chance of liver transplantation. However, prerequisites are (I.) a minimum period of 6 months and (predictable) continued abstention, (2.) emotional stability, (2.) stable socio-economic situation, (4.) no other alcohol-induced organ damage, and (5.) subsequent psychotherapeutic support. Treatment results are no worse than in non-alcoholic patients the five-year survival rate is about 70% in both groups, the alcohol relapse rate is about 10%. Without liver transplantation, the survival rate with continued alcohol consumption was 40% after 5 years, and when abstention was maintained, it was 63%. (42, 79, 103, 111, 113, 141)... 

Liver transplantation may be indicated in patients with considerable cirrhosis-related complications. However, NASH can also reoccur in the transplanted liver. (45, 63) This observation points to a systemic disorder of the lipid metabolism. 

Occasionally, the liver is also involved slight increases in the transaminases and bilirubin, and possibly impaired excretory functions as well. Initially the hepatocytes reveal ultrastructural changes, and later slight steatosis and siderosis. The liver bioptate shows no signs of red fluorescence. In AIR, there is a high risk of cirrhosis and liver cell carcinoma developing. (266, 269, 294) In some patients suffering from such conditions, liver transplantation has proved successful. 

---