Who Needs a Liver Transplant?
Vinay Kumaran, MBBS, MS, M Ch
Liver Transplant, Hepatobiliary and Pancreatic Surgeon
The liver is remarkable among our organs in many ways. It performs so many functions that we’re far from even attempting to replace it artificially. Unlike the kidney, there is no substitute for dialysis for the liver. However, it does have a remarkable reserve. We can remove up to 75% of a normal liver and the remaining 25% will keep the patient alive. An even more amazing property of the liver is the capacity of the liver to regenerate. If we remove part of the liver or if the liver gets damaged due to some reason, it will grow back rapidly (within a few weeks). However, there are situations in which the capacity to regenerate and the reserve are overcome, and the liver fails. In these situations, death is inevitable unless the liver is replaced. The replacement of a diseased liver with a normal one is called a liver transplant. The causes of liver failure could be chronic (ongoing damage over an extended period) or acute (sudden and severe damage). The liver may also need to be removed for severe injuries as a life saving measure or for cancer of the liver. We will review these various scenarios separately.
Chronic Liver Disease
Liver cirrhosis is the result of damage to the liver over an extended period. Taking alcohol again and again is one cause but it can also be caused by unsuspected viral infections (hepatitis B and C) or even due to progression of a fatty liver caused by diabetes, being overweight, having a bad lipid profile or simply an unhealthy diet and lack of exercise. Since the cause of liver damage is constant over a period of many years, the liver keeps trying to repair the damage. The result is areas of scarring and areas of regeneration. Eventually the scarring replaces so much of the liver that regeneration is no longer possible. The liver becomes shrunken, nodular and hard. At this point, we call the condition liver cirrhosis. However, the diagnosis of liver cirrhosis does not, by itself, mean that a liver transplant is required. If the cause of liver damage can be treated (for instance if a patient of alcoholic liver disease stops taking alcohol or if a patient with cirrhosis due to hepatitis B or C is treated with antivirals) then it may still be possible to manage the condition medically. However, there are signs and symptoms which suggest that the cirrhosis has decompensated, and then liver transplant is the only way to save the patients life. Features of decompensation include:
Ascites: this is collection of fluid in the abdomen. It is partly due to portal hypertension (high pressure in the veins of the stomach and intestine because of resistance to blood flow through the liver) and partly because the liver is not making enough protein (albumin) leading to a reduction in the osmotic gradient in the blood vessels and collection of water in the tissues (the legs also swell up). In the initial stages, ascites can be managed by diuretics (medicines which increase the urine output) but eventually it collects despite these medicines or these medicines begin having side effects such as deterioration in kidney function (an increase in serum creatinine) or deranged serum electrolytes (levels of sodium and potassium in blood). Once ascites is not easily controlled, it is time for a transplant. Infection of the fluid in the abdomen is called SBP (Spontaneous Bacterial Peritonitis). This is a life-threatening complication of cirrhosis and anyone who has had even one episode of SBP should have a transplant.
Gastrointestinal bleeding: the portal hypertension (increased pressure in the veins in the stomach and lower oesophagus) results in engorged blood vessels (varices) which can burst and bleed profusely. This manifests as vomiting of blood or passing blood with stools. The bleeding can be massive and fatal. Bleeding varices can normally be managed endoscopically (they put bands on the varices to stop or prevent bleeding) and medically (using medicines to try and reduce the pressure) but bleeding does mean it’s time to plan for transplant.
Coagulopathy: the proteins in the blood which cause blood clotting (essential to stop bleeding when there is an injury) are made by the liver. In liver failure, two things happen. The congestion of the spleen due to the portal hypertension results in an increase in the size of the spleen. The large spleen removes platelets and other blood cells from the blood faster than normal and the platelet count, haemoglobin and white cell count drop. The lack of clotting proteins results in slow and disordered blood clotting. This can be measured by doing a test called the prothrombin time. The more prolonged the prothrombin time is, the more urgent the transplant is.
Jaundice: it is the job of the liver to remove the breakdown products of old red blood cells (bilirubin) from the blood. When the liver is not working well, the bilirubin level rises, making the urine a darker yellow than usual and giving a yellowish tint to the sclera (the white area of the eye).
Encephalopathy: in the presence of cirrhosis, collateral veins (veins which bypass the liver) develop and carry blood from the intestines directly into the circulation. Normally the liver removes ammonia and other toxins from the blood before it reaches the rest of the body. When this process is disrupted, the raised ammonia levels and likely other toxins affect the brain causing drowsiness, confusion and eventually unconsciousness (liver coma). Encephalopathy indicates advanced cirrhosis and is an indication for transplant. The earliest sign of encephalopathy is a change in the sleep pattern. The patient feels sleepy during the day and has difficulty sleeping at night. Even with early encephalopathy, reflexes and judgement are impaired. Like a drunk person, a patient with encephalopathy should not drive, operate heavy machinery or make crucial decisions at work.
Effect on other organs: when the liver fails, it affects other organs as well. It can affect the kidneys directly (hepatorenal syndrome) or indirectly as a side effect of medicines used to treat ascites. It can affect the heart in many ways. Cirrhotic cardiomyopathy causes a decrease in the function of the heart. Pulmonary hypertension increases the pressure in the blood vessels in the lungs. Hepatopulmonary syndrome is due to opening of small abnormal blood vessels in the lungs which lead to blood bypassing the alveoli leading to a drop in oxygen levels in blood. All of these are indications for transplant, but they are quite late features and they increase the risk of transplant too. It is best to do a transplant before these complications occur.
MELD score: a simple score based on the serum bilirubin, prothrombin time and serum creatinine is used to objectively measure how bad the cirrhosis is. There are many free apps for calculation of the MELD score. The lowest score is 6 in which everything is normal. The highest is 40 (it is possible for the calculated score to be higher than 40 but at that point the patient is so sick that it does not make any difference, so the score is capped at 40). A patient with cirrhosis and a MELD score more than 15 needs a liver transplant.
Acute Liver Failure
Sometimes damage to the liver happens quickly. Causes include acute viral hepatitis (typically due to hepatitis A and E), reactions to some drugs (often those used to treat tuberculosis), overdoses of some drugs such as paracetamol or certain types of poisons (yellow phosphorus, some mushrooms).
In most cases the liver recovers because of its reserve and regenerative capacity but sometimes this capacity is overcome. In such cases (fulminant hepatic failure), the jaundice rises progressively, the prothrombin time becomes very prolonged and swelling of the brain produces irritability, drowsiness and eventually coma.
Patients with acute liver failure can deteriorate very quickly and die in a matter of a few days. However, they also recover very quickly if a liver transplant can be done in time. These patients should be managed at a centre where liver transplant is available. By the time they deteriorate, it may be too late to transfer them safely.
Most patients with liver cancer have underlying chronic liver disease. Similarly, patients with liver cirrhosis are at increased risk of developing liver cancer and should be screened for it every 6 months. Liver cancer does not produce any symptoms in the initial stages and is often detected too late to do anything about it.
When liver cancer develops in a patient with a normal liver and if it is detected before it spreads to other organs, it can usually be removed surgically. However, if the patient has cirrhosis then surgery to remove part of the liver may cause liver failure and a liver transplant may be the only way to save the patient’s life.
The risk of recurrence (cancer coming back after transplant) can be estimated from the size and number of tumours and the level of AFP (alpha-fetoprotein, a tumour marker). If there is only one tumour less than 5 cm in size or if there are up to 3 tumour and none of them is more than 3 cm in size, then there is a 75% chance that the patient will be cured by a transplant.
Liver transplants are sometimes done for genetic (Wilson’s Disease, Hemochromatosis etc) or developmental disorders (biliary atresia). These are the usual causes of liver transplantation in children. However, children can also get acute liver failure, liver cirrhosis or liver cancer requiring transplant.
Very rarely a liver may be so badly injured that it must be removed to control bleeding to save the patient’s life. In these situations, an emergency liver transplant is required.
1. Liver failure (beyond the capacity of the liver to recover) is invariably fatal. There is no effective medical treatment of liver failure.
2. Sometimes liver cancer in a patient with liver cirrhosis can only be cured by removing the entire liver and doing a transplant.
3. A timely liver transplant can be done safely with excellent long-term outcomes.
Dr Vinay Kumaran, MBBS, MS, M Ch (Gastrointestinal Surgery) is a liver transplant, hepatobiliary and pancreatic surgeon, formerly head of the liver transplant unit at Kokilaben Dhirubhai Ambani Hospital, Mumbai and before that Director, Liver Transplant at Sir Ganga Ram Hospital, New Delhi, he is presently setting up a liver transplant unit at Shalby Hospital, Ahmedabad.
I have a blog on which I write about medical and other matters. You can read it at https://vinaykumaran1.blogspot.in/