How to treat and prevent bleeding in cirrhosis ??? - What does American association of study of liver diseases says ??

How to manage Cirrhosis Complications?? Part 1- gastrointestinal bleeding.

We have discussed about when liver transplantation is required for cirrhosis.

Now I will try to describe how to tackle various complication of cirrhosis wither without transplant or if you are in the waiting list for transplant.

Today I will take on gastrointestinal bleeding.

Why gastrointestinal bleeding occurs in cirrhosis?

Blood from gastrointestinal tract first goes to liver because nutrients absorbed from intestines needs to be digested to release energy and harmful substance from it needs to be removed. Liver does both the functions. Now in cirrhosis due to microscopic changes there is increase resistance to this blood so there are backpressure on the vessels so these blood vessels gets dilated. Mostly it is seen in lower end of esophagus. (Esophageal varices)When pressure increase beyond certain level these blood vessels burst and cause bleeding which can be life threatening.

Remember if you have survived one episode of bleeding chances of re bleeding is as high as 60%.

So if you are encountering these bleeding repeated time only definitive therapy is remove that resistance and most definitive therapy for it is change the diseased liver. i.e Transplantaion.

But there are other ways to tackle it particularly if rests of the liver functions are good or you are waiting for transplant.

These varices (dilated vessels in esophagus etc is generally managed by durgs like Inderal, endoscopic banding, Tranjugular Intrahepatic Porto systemic Shunts or (TIPS OR TIPSS).

But How to use them in different situation is described wonderfully by American Association of Study of Liver Diseases.

I will mention guidelines given by American Association of study of Liver diseases for managing these cases.

A.    PATIENTS WITH CIRRHOSIS AND NO VARICES:

1.     In patients with cirrhosis who do not have esophageal varices, nonselective β -blockers (medical drugs like Inderal etc.) cannot be recommended to prevent their development.

2.     In patients who have compensated cirrhosis (Preserved Liver function )and no varices on the initial endoscopy, it should be repeated in 3 years. If there is evidence of hepatic decompensation, (abnormal liver function )EGD should be done at that time and repeated annually.

B.    PATIENTS WITH CIRRHOSIS AND SMALL VARICES THAT HAVE NOT

BLED

1.  In patients with cirrhosis and small varices that have not bled but have criteria for increased risk of hemorrhage (Child B/C or presence of red wale marks on varices),

nonselective β -blockers (Inderal) should be used for the prevention of first variceal hemorrhage.

2. In patients with cirrhosis and small varices that have not bled and have no criteria for increased risk of bleeding, β -blockers can be used, although their long-term benefi t

has not been established.

3. In patients with small varices that have not bled and who are not receiving β -blockers, endoscopy should be repeated in2 years. If there is evidence of hepatic decompensation, EGD should be done at that time and repeated annually (Class I, Level C). In patients withsmall varices who receive β -blockers, a follow-up EGD is not necessary.

C.   PATIENTS WITH CIRRHOSIS AND MEDIUM/LARGE VARICES THAT HAVE NOT BLED.

1.  In patients with medium/large varices that have not bled but have a high risk of hemorrhage (Child B/C

or variceal red wale markings on endoscopy), nonselective β -blockers (inderal) or endoscopic banding may be recommended for the prevention of first variceal hemorrhage.

2.  In patients with medium/large varices that have not bled and are not at the highest risk of hemorrhage (Child A patients and no red signs), nonselective β –blockers (Inderal etc.) are preferred and banding should be considered in patients with contraindications or intolerance or non-compliance to β –blockers (Inderal etc.)

3. If a patient is placed on a nonselective β -blocker, it should be adjusted to the maximal tolerated dose;

follow-up surveillance endoscopy is unnecessary. If a patient is treated with banding, endoscopy should be repeated every 1– 2 weeks until obliteration with the first surveillance, endoscopy performed 1– 3 months after obliteration and then every 6– 12 months to check for variceal recurrence.

D.   PATIENTS WITH CIRRHOSIS AND AN ACUTE(emergency, sudden) EPISODE OF VARICEAL HEMORRHAGE

1.  Acute bleeding in a patient with cirrhosis is an emergency that requires prompt attention with intravascular volume support and blood transfusions, being careful to maintain a hemoglobin of ∼ 8 g/dL .

2. Short-term (maximum 7 days) antibiotic prophylaxis should be instituted in any patient with cirrhosis and  bleeding.

3. Medical treatment (somatostatin or its analogues

octreotide and vapreotide; terlipressin) shouldbe initiated as soon as variceal hemorrhage is suspected

and continued for 3– 5 days after diagnosis is confirmed

4. Endoscopy, performed within 12 hours, should be used to make the diagnosis and to treat variceal hemorrhage, either with banding or sclerotherapy.

5. TIPS is indicated in patients in whom hemorrhage from esophageal varices cannot be controlled or in whom bleeding occurs again despite combined pharmacological and endoscopic therapy

E.    PATIENTS WITH CIRRHOSIS WHO HAVE RECOVERED FROM ACUTE VARICEAL HEMORRHAGE:

Remember chances of rebleeding as as high as 60% once you have upper gastrointestinal bleeding with chances of death are as high as 33 % due to bleeding.

1. Patients with cirrhosis who survive an episode of active variceal bleeding should receive therapy to prevent recurrence of variceal bleeding (secondary prophylaxis)

2. Combination of nonselective β -blockers plus banding is the best option for secondary prophylaxis of variceal hemorrhage (Class I, Level A).

3. The nonselective β -blocker should be adjusted to the maximal tolerated dose. EVL should be repeated every 1– 2 weeks until obliteration with the first surveillance

endoscopy performed 1– 3 months after obliteration and then  every 6– 12 months to check for variceal recurrence.

4. TIPS should be considered in patients who are Child A or B who experience recurrent variceal hemorrhage despite combination pharmacological and endoscopic

therapy. In centers where the expertise is available, surgical shunt can be considered in Child A patients.

5. Patients who are otherwise transplant candidates should be referred to a transplant center for evaluation.

As you can see mentioned in last guideline last option is transplant but before that they mention tips.

Now what is TIPS?

It is an radiological procedure where radiologist creat a communication between vessels that are carrying the blood to liver and vessels which are coming out of the liver so that practically hey bypass liver.

So that resistance is gone and bleeding can be prevented. Only disadvantage of this procedure is liver is bypassed so that liver can no longer remove harmful substance from the blood that also contains toxic substance from the blood. These substances can reach to brain and cause mental status changes known as encephalopathy.

These joining of blood vessels can also be done by various surgical options. But in the era of transplant they are less preferred as they can difficult in subsequent transplantation. If transplant is not the option and any how you have to manage bleeding then there are few surgical procedures but they should be considered as a last option.

 Trans jugular intrahepatic porto systemic shunt or (TIPS)

Cirrhosis – When to think about Liver Transplantation???

Cirrhotic Liver

Signs and Symptoms of Liver Cirrhosis

Yes, I was about to write about chemoembolization and radio embolization for primary liver cancer today but I got a few patients queries that forced me to write this.

There can be various causes of liver cirrhosis- hepatitis c, alchoholic , hepatitis b ,non alcoholic fatty liver disease, Autoimmune or some times you do not know cause at all. I will try to explain details about every disease but that part later.

OK you got liver cirrhosis now what to do???

Remember once you have got liver cirrhosis there is no medical cure.

Medicines at the most delay the inevitable that is end stage liver disease and liver failure.

Only treatment for liver cirrhosis is liver transplantation.

Should every body who has got liver cirrhosis should under go transplantation immediately????

Answer is no.

Then what is the way out??

Broadly there are 3 stages of liver cirrhosis (medically it is known has child A, Child B and child c)

I will point out theses stages without going in to technical details, mostly It is summarized as below.

Child A: liver is cirrhotic but still can carry out its function reasonably well. Chances of your living for another one year are 80-90%. (You are not required to under go transplant at this stage.

Child B: Liver functions started deteriorating and liver can not function optimally now but still it has not completely failed. Chances of your living for another year are 60 -80 %. (you can take your time to think about transplant but yes you need to start thinking and in country like India where brain death donors are not available at lease list your self for transplant)

Child C: Liver has failed and is no longer able to carry out its normal functions. Chances of your living one more year are just 30%. You need liver transplant as soon as possible. (in country like India with no brain dead donors, you have to find donor from your relatives who is willing to donate and decide about live donor liver transplant. You do not have luxury to wait for brain dead organ now.

So , always ask your gastroenterologist at what stage my liver disease is. For that he will require simple liver function tests.

Usually liver transplant is required in broad terms to

1.     Increase the quantity of life.

2.     Increase the quality of life.

If you have stage 3 or child c disease that liver transplant is absolutely necessary to increase your life. You cannot survive without it.

If you have stage 2 disease but your life is miserable i.e. repeated hospital admissions due to accumulation of water inside the abdomen, repeated intestinal bleeding etc. then liver transplant is necessary to increase your quality of life.

Remember one thing Liver transplant is a major and long duration surgery and you will require immunity lowering drugs after that so for optimal success of the liver transplantation you body should be in perfect shape.

i.e. your kidneys should be ok, your heart and lung should able to with stand such a massive surgical stress.

One should always remember that aim of liver transplant is to cure the patient and not just replace diseased liver with healthy liver and then telling the patient that liver is working fine but other organ were diseased from before and we can not do anything about it.

So yes, liver transplantation done in child b gives much better success rates then child c. But still in child C also success rates are 70-80% worldwide that is far better then 30% without liver transplant.

What to select cadaver liver transplant or live donor?

 In present scenario in countries like India you do not have choice. You have to select both. Once you are advised liver transplantation you need to immediately register your self for cadaver liver transplant because cadaver liver transplant is like a lottery. You never know when you are lucky and spare your dear one from risky surgery.

Another reason for listing in cadaver liver transplant is, in India by law only relatives can donate liver, that donor should be willing, should be fit for the surgery and his/her liver should be suitable for transplantation to avoid risk to the donor and recipient.

If you are child c, chances that you will find the cadaver liver in time in India are very less so think about live donor.

Cirrhosis can be cured if you and your doctor take right decision at right time.

Liver Transplantation for primary liver cancer part 2 (Living donor Liver transplant)

We have discussed about criteria and indications for cadaveric or brain death liver transplantation.

In countries like India and other Asian countries where organs from brain dead donor are available rarely, we must think of living donor liver transplants.

As we have seen in the previous post that living donation is a personal gift particularly for India where only relatives can donate the organ. For unrelated to give organs it requires huge legal work and mostly not possible, It becomes more of a family affair.

So can we deny when a person has willing donor and ready to take all the risk if he does not fulfill the criteria and cancer has not spread to any other organ. Well there is ongoing debate about this.

In other Asian countries some follow strict criteria like UCSF or some have their own criteria.

But mostly if cancer is too many in number or huge in size, success of liver transplant is not that much. I.e. most patients will come back with recurrent. So Huge cost of liver transplant is wasted and a healthy person undergoes unnecessary major surgery.

So decision for living donor liver transplant has to be taken on patient-to-patient bases, keeping in mind logistics also. Generally it is believed that if surgeon feels that after transplant there are 50% chance of surviving more than 5 years then a transplant is a feasible option.

One way is assess tumor biology either by biopsy or time of tumor progression etc if tumor biology is good and person has willing donor one can go ahead with living donor transplant with keeping in mind risks involved.

But in countries like India where brain dead donors are rarely available, and person fulfills the criteria mention in previous post, person should immediately think about living donor liver transplant.

Living Donor Liver Transplantation

When Primary Liver Cancer should be Transplanted?? Part 1

We have dicussed about liver resection in case of primary liver cancer and limitation due to underlying liver disease.

So when should primary liver cancer transplanted??

Idea behind liver transplantation for hepatocellular carcinoma is that it is believed that hepatocellular carcinoma or primary liver cancer most commonly occurs due to underlying liver disease.So if diseased liver is changed with healthy liver before liver cancer is spread to any other part of the body chances of recurrence of cancer are low.

However for transplantation some one has to donate. This donated liver comes from either brain dead donor and living donor.

Brain dead donations are believed to be gift to the society so it is given to the patient who is most benefitted from the transplantation. Because lots of patients who have end stage liver disease but not liver cancer are also wating for special gift called organ.

So After years of research scientists have concluded that patients are most benefited from transplant if tumor burden is not exceeding a certain limit.

So they defined crteria. If patients fulfills that criteria than he is suitable for transplantaion.

There are mainly two criteria accepted around the world for liver transplantation.

·      Milan criteria :

o   One lesion smaller than 5 cm

o   Up to 3 lesion with each lesion smaller than 3 cm

o   No spread outside liver

o   No liver blood vessel involvement

·      University of california San Fransisco criteria or UCSF criteria.

o   No Single lesion greater than 6.5 cm

o   Up to 3 lesion none greater than 4.5 cm

o   Totoal tumor size should not be more than 8 cm

Reason for defining these criteria is that it shown that if size and number and liver cancer increase there is increase chance of early recurrence of the cancer and that means whole activitiy of transplant becomes futile and one prescious gift to society (donated liver) is wasted.

And if we can transplant the disesed liver with HCC within these criteria then chances of cure of liver cancer are increased dramatically with more than 70-80% of the patients live more than 5 years.

Brain death liver transplantation

How underlying disease can lead to primary liver cancer??

Living donation is the personal gift as donor is giving his organ to a particular person and not to the society so there is dilema weather to stic to these criteria in living donation or not. That  I will discuss in part 2.