HEPATOCELLULAR CARCINOMA

Liver transplantation was originally conceived as an ideal therapy for advanced hepatic malignancy because it eliminates the primary liver tumor and the potential for recurrence in the liver remnant, compared with standard hepatic resection. Several attempts to implement this strategy in the 1960s, 1970s, and 1980s led to poor results, and as such transplantation for both primary and metastatic tumors was largely abandoned. In 1996, Mazzaferro and colleagues reported a novel strategy for surgical treatment of hepatocellular carcinoma—performing liver transplants in cirrhotic patients with early-stage malignancy. In their study, liver transplantation was evaluated in 48 patients with HCC, apparently meeting the preset criteria of either one tumor <5 cm or up to three tumors <3 cm, the now called Milan criteria. This approach has markedly changed organ allocation and established standardized indications for transplant, with excellent long-term results. More than 60 percent of liver transplant patients with advanced liver cancer are still alive after five years, compared to nearly zero survival for those patients who did not undergo transplant, In addition to the favorable five-year survival rates, the survival rates have increased steadily over the last decade, suggesting that criteria for patient selection established by other experts may assist physicians in selecting those patients most likely to respond well to the procedure.

The survival rate following transplantation is both significantly better than with hepatic resection and comparable with the survival rate following liver transplantation for other indications. Milan criteria is most commonly used to determine the candidature of a patient with HCC for performing liver transplant. Detection of HCC in the cirrhotic liver provides a seemingly highly appropriate indication for LDLT. Since hepatic dysfunction in these individuals is typically modest, the transplant can be planned as a semi-elective procedure, yet more expeditiously than is usually possible with deceased-donor transplantation. LDLT appeared to provide a distinct advantage over deceased-donor liver transplantation. Survival rates for patients undergoing LDLT versus deceased-donor liver transplantation were 86% and 71% (at 1 year) and 68% and 42% (at 5 years), respectively.

It is a common perception that the Milan criteria may be too stringent and may be excluding some patients who might benefit from the procedure from consideration for transplantation. Several other guidelines are available, more popular amongst these are the UCSF guidelines. UCSF criteria (one tumor ≤6.5 cm, three or fewer nodules with the largest lesion ≤4.5 cm and total diameter ≤8 cm) has shown results comparable with that in the patients undergoing transplantation based on the Milan criteria. 

Initial experience in patients undergoing Liver Transplantation for Cholangiocarcinoma was unsatisfactory due to early disease recurrence and poor long term survival. Treatment of patients with hilar Cholangiocarcinoma by liver transplantation has gained attention in recent years. Neoadjuvant chemo radiation in combination with liver transplantation for highly selected patients with hilar Cholangiocarcinoma has shown impressive results with 5-year survival rates of approximately 76% to 82%. This is similar to other standard indications for liver transplantation, including hepatocellular carcinoma. The Mayo Clinic has published data on the largest series of patients with hilar Cholangiocarcinoma to have undergone liver transplantation. Rigorous diagnostic criteria have been implemented to ensure the best outcome including tumor size less than 3 cm in radius, the findings of a malignant-appearing stricture confirmed by biopsy or cytology, an elevated CA 19-9 level more than 100 IU/mL, or evidence of aneuploidy in tissue samples. Unresectability is predicated based on technical considerations or the presence of intrinsic underlying liver disease.  Exclusion of regional lymph node and peritoneal involvement is required by operative staging after completion of Neoadjuvant therapy. The protocol includes pretransplant external-beam irradiation followed by transcatheter irradiation and 5-fluorouracil (5-FU) followed by oral Capecitabine. An exploratory laparotomy is performed to exclude extrahilar lymph node disease, following which the patient is activated on the waiting list. 

Epitheloid hemangioendothelioma is a disease affecting mainly younger females and resulting from a malignant transformation of vascular endothelium. An association with oral contraceptives has been suggested but not completely established. Clinical presentation may be with abdominal pain, but more frequently the lesion is an incidental finding. Since the tumor is often widespread within the parenchyma, complete resection may not be possible, even in the non-cirrhotic liver. The results after liver transplantation are quite acceptable, being comparable with those after OLT for viral-induced cirrhosis.

Hepatoblastoma is the most common malignant tumor of the liver in the pediatric population, affecting mostly young boys age less than 3 years and accounting for 75% of primary liver tumors in childhood. Diagnosis is usually at a late stage. The introduction of chemotherapy with cisplatin and doxorubicin has changed the treatment success of hepatoblastoma substantially, and despite a large tumor mass at presentation, a combined surgical and chemotherapeutic approach has yielded a 5-year survival rate of approximately 80%. Liver transplantation plays a role in those patients whose tumors cannot be completely resected after appropriate chemotherapy. The most complete report of liver transplantation was published by Otte et al. who reviewed the results of 147 patients from several European pediatric centers. The overall survival rate at 6 years post-transplantation was 82% in patients who had not undergone pretransplant-attempted liver resections, versus 30% at 6 years for patients who underwent liver transplantations after failed resections.

Neuroendocrine tumors are usually hormone producing (serotonin, insulin, gastrin, glucagon, etc.), but also may present as a nonfunctioning mass lesion. The clinical presentation is diverse, depending upon the hormone secreted. These tumors typically metastasize to the liver, and some patients note pain, resulting from capsule distention, as a first symptom. Even after metastasizing, these tumors often remain slow growing so that approximately one-third of the patients survive for 5 years after the development of liver metastases. Because of the somewhat indolent nature of their liver metastases, these patients are considered appropriate candidates for liver transplantation. Liver resection resulted in a 5-year survival rate of 67%, but a disease-free survival rate of only 29%. Liver transplantation resulted in a 5-year survival rate of 70% and recurrence-free survival rate of 53%. Patients with hepatic metastases from neuroendocrine tumors may have prolonged survival, especially under the ideal selection criteria: age less than 46 years, limited liver tumor burden with favorable histology, and no extra hepatic disease. Such patients often have good overall survival and quality of life.

Transplantation for metastatic liver disease secondary to colorectal metastasis is currently a controversial subject. In the pilot study from the Oslo Transplant Center, Hagness et al reported their experience with liver transplantation in 21 patients performed over a 4.5-year time interval. The 5-year overall survival rate was 60%, with a 1-year disease-free survival rate of 35% and no patients had long-term disease-free survival. The status of Liver Transplantation for Colorectal metastasis to the Liver at this time is investigational.

RGCI is a Government certified liver transplant center and it successfully started its liver transplant program in September 2019. Patient was a case of CLD (HCV related) with portal hypertension with HCC with tumor thrombus in right portal vein, diagnosed 2 years back . Initially he had undergone TACE at RGCI 2 years back and was on sorafenib. Lately for 6months he was having signs of liver decompensation, so liver transplant was planned. His daughter agreed to donate his part of liver and he underwent right lobe living donor liver transplant on 26 september 2019. Both donor and recipients recovery was uneventful and they are doing well. Show Less

About the Liver

Liver is the largest abdominal organ. Liver weighs about 1200 - 1500 grams in an average roughly 2% of body weight. Liver, though a single organ, broadly it can be divided into two parts - right and left liver and 8 independent segments (each having its own blood supply and biliary drainage) functioning as a single organ. Liver as a whole has a hepatic artery supplying oxygenated blood, a portal vein carrying blood from intestines to liver and bile ducts draining bile formed in the liver to intestines. Blood from liver is delivered-to-heart-via-three-hepatic-veins.

Liver produces bile which is drained by biliary tree. Gall bladder is a reservoir for the bile lies on the liver bed, and is attached to bile duct. It regulates delivery of bile into intestines. Liver is endowed with remarkable capacity to regenerate after division into parts. This is the basis of Live Related Liver Transplants, and the reason why live related liver transplant is possible.

Functions of Liver

The liver is in the right upper abdomen. The liver serves many functions, including the detoxification of substances delivered to it from the intestines, and the synthesis of many proteins.

• Liver is the powerhouse of body. It is the main organ of metabolism i.e. it involves, series of breaking down and making up of chemical reactive and generation of energy
• Liver converts food into chemicals necessary for life and growth
• Liver processes and removes drugs, alcohol and other substances generated in body that may be harmful
• Liver produces elements necessary for the absorption of fats and vitamins
• Liver manufactures important proteins that are necessary for normal blood clotting and building muscle
• Liver maintains the hormonal balances
• Liver stores important vitamins

Who requires a Liver Transplant?

Liver transplant may be necessary for patients who suffer from:

• liver damage due to alcoholism (Alcoholic cirrhosis)
• Malignancies involving liver: Hepatocellular carcinoma, Hepatoblastoma, Hilar Cholangiocarcinoma, etc
• primary biliary cirrhosis
• long-term (chronic) active infection (hepatitis B or C)
• liver (hepatic) vein clot (thrombosis)
• birth defects of the liver or bile ducts (biliary atresia)
• metabolic disorders associated with liver failure (e.g., Wilsons disease)

Patients require hospital care for one to four weeks after liver transplant, depending on the degree of illness. After liver transplantation, patients must take immunosuppressive medications for the rest of their lives-to-prevent-immune-rejection-of-the-transplanted-organ.

What is liver transplant?

Liver transplant means removing a whole or part of liver from a deceasedor living donor, placing and attaching in a patient after removing whole of the diseased liver.

What are types of liver transplant?

Liver is obtained from a Deceased donor or Live Related donor.

Deceased Donor (Cadaver)

Liver is obtained from patients who are brain dead. (They are actually dead for from legal, ethical, spiritual and clinical point of view). Once a brain dead patient is identified, and is deemed as a potential donor, the blood supply to his body is maintained artificially. This is the principle of deceased organ donation. Patients who die of head trauma, brain hemorrhage or other causes of sudden-death-are-the-donors-suitable-for-organ-donation.

Living Donor

Liver has the capacity to regenerate if a part of normal healthy liver is removed. Hence we can divide part of liver from a live donor and implant it into another patient. In a live donor liver transplant, a portion of the liver is surgically removed from a live donor and transplanted into a recipient immediately after the recipient’s liver has been entirely removed.
Donor safety is the first objective of whole process. Utmost care is taken while selecting and operating live donors. The risk of serious morbidities following a living donor liver resection is 10%.The risk of death in the donor is 0.02to 0.5%. Live donor liver transplantation is possible because the liver (unlike any other organ in the body) has the ability to grow back to its original size. The regeneration of liver following surgery is complete by 4 to 8 weeks.

Who can donate?

Selecting the correct donor for a live donor liver transplant requires experience, skill and technical expertise on the part of the many doctors, transplant coordinator and other health care professionals who make up the Live Donor Team.
Potential live liver donors are carefully evaluated. The health and safety of the donor is the most important concern during the evaluation. Only donors in good health are considered.

A potential donor should:

• Be either a relative or spouse,
• Have a compatible blood type
• Be in good overall health and physical condition
• Be older than 18 years of age and younger than 55 years of age
• Have-a-near-normal-body-mass-index-(not-obese)

A donor must be free from:

• History of Hepatitis B or C
• HIV infection
• Active alcoholism or frequent heavy alcohol use
• Any drug addiction.
• Psychiatric illness currently under treatment
• A-recent-history-of-cancer

The donor should be having the same or compatible blood group.

Blood group compatibility chart

Note: The Rh factor (+/-) of blood type is not important in compatibility

What are the positive aspects of living donation?

• The gift of an organ can save the life of a transplant candidate.
• Donors have reported positive emotional experiences, including feeling good about giving life to dying person.
• Transplants can greatly improve recipients’ health and quality of life, allowing them to return to normal activities.
• Transplant candidates generally have better results when they receive organs from living donors as compared to organs from deceased donors.
• Better genetic matches between living donor and candidates may decrease risk of organ rejection.
• A living donor makes it possible to schedule the transplant at a time that is convenient both for the donor and the transplant candidate.

How long I will take to recover after liver donation?

As a liver donor, you may stay in the hospital up to 10 days or longer in some cases. The liver typically regenerates in two months. Most liver donor returns to works and normal activities in one month, although some may need more time. Please talk to transplant team members to understand what to expect, although the surgery and recovery process can differ among living donors. Consider talking with other donors and contacting the organizations. Attend follow-up visits to clinic regularly as advised and do blood or other investigations to make sure that you are recovering well.

What are the risks of liver transplant?

The biggest risks associated with liver transplants are rejection and infection..Rejection occurs when the body’s immune system attacks the new liver as an unwanted foreign substance; just as it would attack a virus. To prevent rejection, transplant patients must take drugs to suppress the immune system. However, because the immune system is weakened, it is harder for liver transplant patients to fight other kinds of infections. Fortunately, most infections can be treated with other medicines.

What medicines do I have to take?

• Anti-rejection-drugs
• For the first-three months after transplantation you need to take the following medicines.
• Antibiotics–to-reduce-the-risk-of infections
• Antifungal-liquid-to-reduce-the-risk-of-fungal-infection
• Antacid–to-reduce-the-risk-of-stomach-ulcers-and-heartburn
• Any other medicines that you have to take will be prescribed for you depending on your Symptoms.

Why are Anti Rejection Drugs (Immunosuppressant Drugs) needed?

Ones body doesnt accept other’s organ. It is bodys defense system to try to attack and destroy others organ. Anti rejection drugs makes defense mechanism weak against donors organ and allow liver graft to sustain and work normally.

What-precautions-should-I-take-after-my-liver-transplant?

Communication, cooperation and coordination between the transplant team, local physician, pharmacist, Liver Transplant Coordinator or Liver Transplant Consultant and the patient is essential for well-being of the Liver Transplanted recipient. It is important to follow the instructions that will help prevent or lessen complications.
One of a patients most important jobs is to ensure that family physician, local pharmacist, and his family members are aware of the transplant, the medications he takes each day, and the precautions he must follow to stay healthy. Each of his family members should have the telephone number of his Liver Transplant-Coordinator-or-Liver-Transplant-Consultant. The patient and his family members must be fully aware about the precautions to be taken after a successful Liver Transplant. Nothing can be taken for granted after this operation. A rigorous session with Liver Transplant Coordinator or Liver Transplant Consultant is recommended for the patient and his family members to understand the Life after Liver Transplant and precautions to be taken.

How long will my transplanted liver last?

Liver transplant has excellent outcomes. Recipients have been known to have a normal life for over 30 years after the operation. The five year survival rate for liver transplant patients is about 75 percent. Show Less