Liver Transplantation

Progression to cirrhosis or hepatocellular carcinoma is a major cause of morbidity and the most frequent indication of liver transplantation in adults in united states.

Ref: Kliegman, Behrman, Jenson, Stanton (2008), “Nelson Textbook of Pediatrics”, Chapter 355, “Viral Hepatitis”, Volume 2, Page 1687; Harrison’s Principles of Internal Medicine, 17th Edition, Pages 1939, 1963, 1984; Current Gastroenterology, 2nd Edition, Page 556

We are presently undergoing a hidden epidemic of hepatitis C infection in this country.

While many individuals may have very slowly progressive courses with good health for decades, some develop cirrhosis relatively earlier in their disease process. These individuals are increasingly becoming candidates for liver transplantation, although the number of available livers is far less than the number of people with end-stage hepatitis C infection who might use one.

Hepatitis C can recur in the new liver, but often does not become a serious problem.

Instead, chronic rejection turns out to more often limit the longevity of the transplant.

Chronic rejection of any solid organ entails cellular injury to endothelial cells, resulting in intimal proliferation, fibrosis, and eventually, ischemic injury to the graft. Immunosuppressive therapy is directed at controlling lymphocyte activity and minimizing cellular rejection.

“Because of multicentricity, bilobar involvement, portal vein invasion, and lymphatic metastasis only 15-20% of hepatocellular carcinoma are resectable”

Ans. is ‘b’i.e., Most common indication for liver transplantation 

.               The most common indication for liver transplantation crrently is cirrhosis due to chronic hepatitis’C’ infection. About other options

.               HCV is a RNA virus; the only hepatitis virus which has DNA is HBV.

.               HCV can cause liver carcinoma.

.                       HCV may cause coinfection with HBV and coinfection of HCV with HBV increases the rate of development of cirrhosis and the risk of HCC compared with infection with either virus alone.

                Ans. is (c) i.e. Over 80% tumours are surgically resectable

Sabiston 18/e p1500 (17/e, p1548); C.S.D.T 13/e p520, 1206 (11/e p.573, 1349)]

“Because of multicentricity, bilobar involvement, portal vein invasion, and lymphatic metastasis only 15-20% of hepatocellular carcinomas are resectable”

About other options

• Option a :  “The highest incidence of disease (>10-20 per 100,000) is found in Southeast Asia and tropical Africa, and the lowest incidence (1-3 per 100,000) is found in Australia, North America, and Europe. “- Sabiston I8/e
• Option b :  “The geographic distribution of HCC is clearly related to the incidence of hepatitis B virus (HBV) infection.”

-Sabiston 18/e

• Option ‘d’

Treatment options for unresectable disease are limited. The liver cannot tolerate high doses of radiations and the disease is not responsive to chemotherapy. Investigative immunotherapy and gene therapy techniques have not yet been successful.

Liver transplantation offers the only chance of cure for unresectable disease.

Other important points about HCC

• HCC is more common in males (about 4 times)
• 75-85% arise in cirrhotic liver

Ans. is ‘c’ i.e. Hepatitis A 

Liver transplantation is indicated for those children and adults, who in the absence of contraindications suffer from severe, irreversible liver disease for which alternative medical or surgical treatments have been exhausted or are unavailable.

• Most common indication

in children ________  Biliary atresia

in adults  –> Cirrhosis

Harrison 17/e writes- “Currently, chronic hepatitis C and alcoholic liver disease are the most common indications for liver transplantation, accounting for over 40% of all adult candidates who undergo the procedure.”

Ans. is ‘c’ ie. Orthoptic liver transplantation

• Child-Pugh’s classification is used to assess the status of pt. of liver cirrhosis.
• A liver cirrhotic pt. having variceal bleeding or ascites can be controlled by shunt surgery only if he falls in Child­Pugh’s ‘A’ class (or some pts. of B class). Moderate to severe grade liver insufficiency can only be managed by liver transplantation.

Ans is ‘c’ i.e. Anastomose donor bile duct with recipient bile duct or Roux-en-Y choledochojejunostomy

“Caval, portal vein, hepatic artery, and bile duct anastomoses are performed in succession, the last by end-to-end suturing of the donor and recipient common bile ducts or by choledochojejunostomy to a Roux-en- Y loop if the recipient common bile duct cannot be used for reconstruction (e.g., in sclerosing cholangitis).”- Harrison 17/e p

Bile duct anastomosis in orthotopic liver transplant is done by

1. Choledochocholedochostomy or
2. Roux-en-Y choledochojejunostomy

Choledochocholedochostomy

end to end anastomosis between donor CBD and the recipient CBD

used when the recipient bile duct is not diseased

preferred method of bile duct anastomoses

Roux-en-Y choledochojejunostomy

alternative bile duct anastomosis when choledochocholedocostomy is not possible, that is when recipient extrahepatic bile duct is diseased (eg. sclerosing cholangitis), or small or when there is significant recipient donor duct size mismatch.

Ans is d i.e.; Biliary atresia

Ans. is ‘a’ i.e., Starzl 

The first human liver transplant was performed in 1963 by Dr. Thomas Starzl.

Answer is C (In advanced stages of cirrhosis major blood supply to liver comes from Hepatic vein)

Answer is B (Autoimmune hepatitis):

Amongst the options provided, recurrence of primary disease in the liver following liver transplantation is most common with auto immune hepatitis.

‘Autoimmune hepatitis has been recognized to recur in upto 40% of transplanted livers as immuno supression is reduced.’ – CMDT’ 2006 / 663

Answer is D All (All of the above) :

Biliary atresia is an indication for Liver transplantation in children while primary Biliary Cirrhosis, Sclerosing cholangitis and Hematochromatosis an established indications for Liver transplantation in adults

Indication for Liver Transplantation:

Children

• Biliary atresia
• Neonatal hepatitis
• Congenital hepatic fibrosis
• Alagille’s disease”
• Byler’s disease
• a 1 -Antitrypsin deficiency
• Inherited disorders of metabolism
• Wilson’s disease
• Tyrosinemia
• Glycogen storage diseases
• Lysosomal storage diseases
• Protoporphyria
• Crigler-Najjar disease type I
• Familial hypercholesterolemia
• Primary hyperoxaluria type I
• Hemophilia

Aduts

• Primary biliary cirrhosis
• Secondary biliary cirrhosis
• Primary sclerosing cholangitis
• Autoimmune hepatitis
• Carob’s disease’
• Cryptogenic cirrhosis
• Chronic hepatitis with cirrhosis
• Hepatic vein thrombosis
• Fulminant hepatitis
• Alcoholic cirrhosis
• Chronic viral hepatitis
• Primary hepatocellular malignancies
• Hepatic adenomas
• Nonalcoholic steatohepatitis
• Familial amyloid polyneuropathy

“Arteriohepatic dysplasia, with paucity of bile ducts, and congenital malformations, including pulmonary stenosis.

^“Intrahepatic cholestasis, progressive liver failure, mental and growth retardation

`Multiple cystic dilatations of the intrahepatic biliary tree.

Hematochromatosis is also an indication for Liver Transplantation

‘Among genetic and metabolic conditions, Hematachroatosis is the most common reason for Liver Transplantation’