Wake up call

It is refreshing to see that governments are finally recognising the problem.

Times of India Pune Edition 31st Aug 2012

Will state governments all over the country follow suit?

Cadaver organ donations in India have been at an embarrassingly low level of 0.02 per million as opposed to between 5-30 per million in the western world. More appropriately called 'deceased' organ donation has been allowed in India since 1995 when the Transplantation of Human Organs Act of 1994 was passed by parliament and ratified by most state assemblies.

Since health is a subject on the concurrent list of the Indian constitution, any changes or rules under this act can be applicable only when the concerned state takes the initiative to frame these rules.

Repeated and persistent efforts by doctors, patient groups and NGOs to get states to frame rules to simplify and facilitate process of organ donation for all concerned have until now fallen on deaf ears. The state of Tamil Nadu has been the obvious exception with rules having been simplified paving the way for a spurt in donation and transplantation of hundreds of livers, kidneys as well as some heart and pancreata. Other states until recently haven't followed suit.

The above article from the Times of India, Mumbai on 22nd August is a welcome move but one can't help thinking the state has woken up from its slumber after the recent much publicised death of a prominent leader from that state. Whatever has been behind this, this effort if taken to its meaningful conclusion will benefit thousands of people with end stage organ failure waiting expectantly for organs that more often than not did not come in time to be of use.

Let us hope more states are awakened by this movement.

Partial or whole liver transplant

Improvement in outcomes in the 1980s led to increased acceptance and widening of indications for liver transplantation across the western world.
The demand for organs persistently exceeded the supply of organs leading to death of patients while waiting for an organ.
Advances in liver surgery by the late 1980s made it possible to divide the liver into functionally independent viable parts along specific planes. This sowed the seed of partial grafting. Almost concurrently this concept was applied to splitting whole livers from deceased donors either in vivo or ex vivo and to living donors. European surgeons who had access to deceased organs could split organs to benefit two patients usually an adult and a child . In Asia, partial grafts from
Living donors were used initially in children and subsequently into adults as well. In US and Europe progress in splitting also was extended to doing a full right-left split of the deceased donor liver.
There is no doubt that a whole liver graft is the gold standard for adult liver recipients. Partial grafts from deceased and split donors have been used over three decades and in almost all situations with equivalent results. As long as liver cell quality is good,hepatocyte mass is adequate and ischemia time is kept low, partial liver transplant in an experienced center provides results equivalent to whole liver transplant .

Liver transplantation for children: no child's play

Children when they need liver transplantation present challenges different from adults.

Common causes for end stage liver disease in children depend on age but biliary cirrhosis due to extrahepatic biliary atresia, metabolic disorders like Wilson disease, liver resident enzyme defects and autoimmune disorders are more common than viral hepatitis. Almost one fifth of those who need transplantation have acute liver failure.

Most deceased donors being adults, children are rarely able to receive a whole organ. Partial grafts obtained by reducing or splitting a deceased donor organ or a living donor are usually the only grafts available.

Liver disease has a profound impact on physical, psychosocial and intellectual development in children. If liver transplantation is needed it should be performed as early as possible to take advantage of catch-up growth and avoid interference with schooling.
Parents have to be extremely motivated to work in conjunction with the transplant teams to ensure compliance with instruction particularly as the child grows and the baton of responsibility passes on from parents to the child.

Liver transplantation for hepatitis C: the hidden truth

Hepatitis C related chronic liver disease is an important cause of decompensated cirrhosis in patients who need liver transplantation in south-east asia, europe, africa and north america. Although anti-viral treatment for hepatitis C in the form of Pegylated interferon and ribavarin are fairly effective in achieving virological response in those who do not have genotype 1 of the virus, patients who already have liver dysfunction at the time of diagnosis or those that have ascites or severe hypersplenism are unable to complete the course of therapy or need dose reductions. Even those who attain virological response may relapse.
Patients with HCV related cirrhosis who undergo liver transplantation usually have significant viral loads at the time of transplant and treating them with interferons to reduce this level is often impractical and can be poorly tolerated. Unlike for hepatitis B there is no effective vaccination or immunoglobulin to protect against recurrence of HCV infection in the transplanted liver. As of now patients with HCV should clearly understand that HCV infection will recur in all the transplanted livers. In fact, HCV virus can be identified in the liver within hours of transplantation. The timing and outcome of HCV related damage to the liver after transplantation is different and is related to factors in the following cartoon.

Patients with concurrent obesity and significant alcohol intake or HIV infection are at a higher risk of accelerated HCV recurrence and damage. 

Active surveillance and protocol liver biopsy to detect early HCV related inflammation in the transplanted liver cells followed by supervised therapy is the only way to mitigate the progression to fibrosis in the transplanted liver. The transplanted liver cells are more susceptible to viral damage due to the immune-suppressive state. While some studies have suggested that cyclosporine has anti HCV action as compared to tacrolimus among the immune-suppressive agents, this has not been proven conclusively. Undetected and inappropriately treated, HCV recurrence can lead to cirrhosis and end stage liver disease within months to a few years. Despite adequate treatment, sustained virological response may not be achieved in all patients and these may develop recurrent cirrhosis and become candidates for a re-transplant after a variable period of 5-20 years. In fact ,most re-transplantations across the western world are performed for this indication.

Patients with HCV therefore should bear in mind the following before undergoing liver transplants

1. Unless there is concurrent liver tumor within the liver, kidney dysfunction or other life-threatening complication, liver transplant should be delayed as far as possible.
2. HCV patients should abstain from alcohol and keep their weight in check
3. Immunosuppression should be tightly monitored as excessive or pulse therapies can accelerate recurrence and hepatocyte damage
4. They should discuss with their transplant centres and preferably not accept deceased organs from older donors (>65 years) that are fatty or have cold ischemia of more than 6 hours 
5. After transplantation, they have to be extremely compliant with follow-up for early detection of recurrence
6. Re-transplantation may be required in a significant proportion of patients after 5-20 years 

Whole deceased liver transplant...classical

The classical whole deceased donor liver transplant is a time honored surgical technique from the early days of liver transplantation. Although most centers around the world have all but abandoned this technique in favour of the more recent 'piggyback' technique, it is worth mentioning here for the sake of  the non physician readers.
In the classical technique after the division of the blood vessels that take blood into the diseased liver of the patient ( hepatic artery and portal vein), the inferior vena cava below and above the liver is clamped and the diseased liver is removed along with the retrohepatic inferior vena cava. The whole donor liver is then sewn in the following sequence: supra hepatic vena cava-donor suprahepatic vena cava, infra-hepatic vena cava-donor infrahepatic vena cava, portal vein to donor portal vein and hepatic artery to donor hepatic artery.

Stages of liver damage