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Sunday, January 27, 2008

Special Issues

Cancer:

Liver transplant is not indicated for patients with liver cancer without liver cirrhosis. Primary and secondary liver cancers will recur rapidly in a transplanted liver. However patients with liver cirrhosis who develop primary liver cancer can undergo successful liver transplant. Even in this condition the disease should be confined to the liver without invading the blood vessels. There are definite criteria for accepting patients with cirrhosis and liver cancer in a transplant programme (contact the transplant center for further information). The survival after liver transplant in a patient with liver cancer will be lower than patients without any liver cancer if the tumour size is more than 5 cm. Most of these patients will also require additional chemotherapy before and after transplant. Cancers apart from hepatomas are seldom considered indications for liver transplantation. As high as 45 to 50 % five year survival has been reported among patients with primary liver cancer after liver transplant and adjuvant chemotherapy.

Hepatitis
Hepatitis C is notorious for recurrence after transplant. However Hepatitis C is now emerging as a leading indication for liver transplantation. Invariably all patients will have positive hepatitis C viral status after transplant and more than 50% will show evidence of varying degrees of chronic hepatitis and fibrosis within 5 years without antiviral therapy. Some patients are also known to develop a more aggressive form of recurrent hepatitis called fibrosing cholestatic hepatitis within a short period after transplant. The standard algorithm is to get a baseline viral load measured before transplant. Patients with very low viral loads have low incidence of recurrence. There are several strategies to counter hepatitis C. Reduction and ultimately elimination steroid therapy early is one of the most important steps. Use of Cellcept or Prograf in the antirejection therapy has a statistically lower incidence of recurrent hepatitis. Anti viral therapy with Ribavarin and Interferon can be started early after liver transplant. In the author's center the therapy is started within the first month of transplant in most patients. Early antiviral therapy decreases the severity of recurrences and delays graft destruction in most and eliminates the infection in some. Hepatitis C infection is now the commonest cause for transplant in the US. Since most patients have a slow progression of recurrent hepatitis and since aggressive therapy is likely to prolong the disease free interval down to two decades, liver transplantation is worth going in for.

Hepatitis-B until recently used to be considered a contraindication for liver transplant. However with usage of passive immunoprophylaxis (with hepatitis B immunoglobulins) it has now become possible to transplant even patients who are DNA positive for the virus. Since the viral load is maximum in the infected liver high dose of HBIG is given around the first 1 week of the transplant starting from the time the diseased liver is removed form the body. Following this it is crucial to maintain good titers of anti-hepatitis B antibody levels in the blood by weekly and then monthly administration of IV HBIG. This therapy is also combined with Lamivudine, a drug that is very effective in preventing proliferation of the hepatitis B virus. The regimens and dosages vary from center to center. The therapy is lifelong. The incidence of recurrence of hepatitis B is around 20% at five years with the combination high dose HBIG and Lamivudine. Short term recurrence is very low with single drug therapy (Lamivudine), however breakthrough viral recurrence is very common due to viral mutation in a large proportion of patients. The cost of IV HBIG therapy can be formidable - 30,000 USD for the first 3 months and 2 to 5,000 USD/ month thereafter.

Recurrence of primary disease
Hepatitis B and Hepatitis C are known to recur after transplant. Fulminant hepatitis B has lesser chance of recurrence. Primary biliary cirrhosis can recur in 2% of the patients. Idiopathic Autoimmune chronic active hepatitis (IACAH) rarely recurs after transplant, when it does it indicates lower immunosuppression state. Recurrence of Primary Sclerosing Cholangitis has been reported in the literature. Resumption of alcohol after liver transplant is known to hasten alcoholic hepatitis and liver failure.

Bloodless surgery
With advances in surgical techniques and instrumentation it is possible from time to time, perform liver teransplantaion without the usage of blood. Several centers use cellsavers during surgery to reduce the need for banked blood during a liver transplant. This is only possible in patients in whom the portal hypertension is not very advanced and in those who have not had any previous upper abdominal surgery. Some centers have carried out liver transplant in Jehova's witness patients.

New techniques and medicines
Living related liver donation amongst adult donors and recipients is the newest technical advance in liver transplant. Now over 800 liver transplants have been performed all over the world. In this procedure the right lobe (50-60%) of the living donor is removed surgically and transplanted into the recipient. This procedure is handy in countries where the cadaver organ donation rates are very low (Japan, Korea, India).

New device to preserve cadaver organs is being experimented. This machine circulates artificially oxygenated human blood through the organs removed from the human body and kept in sterile chamber for a long period of time. This innovation when becomes practical has the potential to reduce wastage of organs due to transportation logistics and in theory can keep an organ viable and functioning outside the human body until suitable recipient is found.

Activated factor VII is now available as a drug and is being used effectively (>80%) in patients with life threatening bleeding due to advanced coagulopathy.

Sirolimus (Rapamune) is a new immunosuppressive medication which is potent and has no toxic effect against the kidneys (unlike Cyclosporine and Tacrolimus). It is useful after transplant in patients with renal dysfunction along with liver failure.

Pegylated Interferon is a new depot preparation (once a week therapy) of Alpha Interferon used for treating hepatitis C after liver transplant. Studies so far have revealed that it is safe in post liver transplant status. It is expected to have better viral clearance and better tolerated.

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