Liver Transplantation

In the United States, cirrhosis and decompensated liver disease were the tenth highest cause of death for males. Liver transplantation (LT) is a life-saving surgery and a well-established treatment option for patients with acute and chronic end-stage liver disease. It restores regular health and wellbeing, as well as an approximately 15-year increase in lifetime. When all other medical options had been tried, liver transplantation was introduced as a last resort to treat a wide variety of liver disorders. Overall patient survival is high, according to the Scientific Registry of Transplant Recipients, with 90 percent at one year and 78 percent at five years following liver transplantation.

Since the first liver transplantation in the 1960s, there have been continual advancements and considerable changes in surgical technique, type of organ donation with the growth of the organ donation supply, and a big focus on the recipients' and donors' wellbeing. There are still significant obstacles, such as the scarcity of donor organs, the identification of liver transplantation candidates, and organ distribution.

What is Liver Transplantation?

A liver transplant is a medical process that involves removing a damaged or injured liver from one person and replacing it with a normal liver from another person, known as the donor.

In most circumstances, the healthy liver will come from a recently dead organ donor. A healthy person may occasionally donate a section of their liver. A member of the family could be a living donor. It could also be someone who isn't related to you yet shares your blood type. People who donate a portion of their liver can live a normal life with the remaining liver.

A transplanted section of the liver can regrow to normal size in a few months because the liver is the only organ in the human body that has the ability to regenerate or regrow. Transplanted livers are frequently from dead donors who were certified and registered donors. However, because the liver has remarkable regeneration abilities, a living person can give a portion of his or her liver to someone who needs a transplant.

Anatomy and Physiology

The liver is the biggest organ in the human body, and it lies beneath the right lowest four ribs. The right and left lobes, separated by the falciform ligament, the quadrate lobe, and the caudate lobe are the four anatomical lobes. The four lobes of the liver are not real functional lobes. The right and left lobes are separated by the Cantlie line and are the real functional hepatic lobes. As it travels through the gallbladder bed and the notch of the inferior vena cava, the Cantlie line splits the liver into nearly two portions. Each of these is divided into two segments, each of which is further broken into two subsegments depending on the hepatic artery and portal vein bloodstream, as well as biliary and hepatic venous outflow. The subsegments are numbered from one to eight, with the caudate lobe being subsegment one and the other subsegments are numbered clockwise.

The portal vein and hepatic artery provide a double blood supply to the liver, which comes from both the systemic and portal circulations. A hepatocyte is the primary component of the liver, and these hepatocytes are grouped into the following zones:

The periportal zone (zone 1), which receives the most oxygenated blood from the portal vein, has the best perfusion. Its primary function is metabolism, which involves oxidation.
The intermediate zone (zone 2), which is primarily affected by yellow fever.
Pericentral or centrilobular (zone 3), which is the furthest from the blood flow and so receives the least amount of perfusion. Biotransformation of drugs and toxins is one of its functions.

It's vital to remember that bile and blood circulate in opposing directions, thus bile made by the liver flows out and blood flows into the liver to nourish it. Most people's livers are made up of 60 percent right lobe and 40 percent left lobe, with the left lateral section accounting for 20 percent of the total capacity.

Liver Transplantation Indications

Patients are classified by the United Network for Organ Sharing using either the Model for End-Stage Liver Disease scoring system or the Pediatric End-Stage Liver Disease scoring system, depending on their age (if they are older or younger than 12 years). The Model for End-Stage Liver Disease or the Pediatric End-Stage Liver Disease scoring system score, or the designation of a status, determines the clinical priority for liver allocation. Patients with a life expectancy of fewer than 7 days without a liver transplant who are in the intensive care unit with severe clinical liver failure without underlying liver problems or with primary non-function of a donated liver within seven days of transplant are now prioritized.

The Model for End-Stage Liver Condition and the Pediatric End-Stage Liver Disease scores are meant to indicate the severity of the candidate's condition or the risk of three-month mortality without liver transplantation. However, these ratings do not always adequately indicate the probability of mortality in the absence of liver transplantation or the severity of liver disease sequelae. An exemption may be requested in these cases. The most prevalent diagnosis requiring a Model for End-Stage Liver Disease or Pediatric End-Stage Liver Disease score exception is hepatocellular carcinoma.

The following are some of the most common diagnoses that indicate a need for liver transplantation:

Non-cholestatic cirrhosis, such as hepatitis B or C post-necrotic cirrhosis or non-alcoholic steatohepatitis
Liver disorders caused by cholestasis (i.e., primary biliary cirrhosis or primary sclerosing cholangitis)
Acute hepatic failure, including hepatolenticular degeneration (Wilson disease) that is suddenly decompensated
Disorders of the metabolism (i.e., alpha-1-antitrypsin deficiency, tyrosinemia, glycogen storage disease type)
Benign lesions vs. malignant tumors (i.e., hepatocellular carcinoma, cholangiocarcinoma, polycystic liver disease, hepatic adenoma)

Liver Transplantation Contraindications

Because of improvements in liver transplant technology, the indications for liver transplantation have become wider, while the contraindications have become fewer. Still, there are several absolute and relative contraindications to liver transplantation.

Absolute Contraindications

A score of fewer than 15 on the Model of End-Stage Liver Disease
Cardiac or pulmonary disease that is severe and advanced.
Acquired immunodeficiency syndrome
Use of an alcoholic beverage or a banned drug
Hepatocellular carcinoma or perihilar cholangiocarcinoma that has migrated to other parts of the body
Septic shock or sepsis that has gone untreated
Anatomical defect that makes liver transplantation impossible.
Cholangiocarcinoma of the liver
Unless the patient has been tumor-free for more than two years and has a minimal risk of recurrence, extrahepatic malignancy should be avoided.
Hepatic fulminant dysfunction with sustained intracranial pressure greater than 50 mmHg or cerebral perfusion pressure lower than 40 mmHg.
Psychosocial assistance is lacking, and the patient is suffering from a serious psychological condition.
Significant pulmonary hypertension

Despite the fact that acquired immunodeficiency syndrome is an absolute contraindication to liver transplantation, several facilities are now considering patients who only have the human immunodeficiency virus as candidates.

Relative Contraindications

The following are some situations in which the doctor decides liver transplantation depending on risks and benefits:

General poor health
Continuous non-compliance
Elderly patients
Previous abdominal surgery that was extensive
Thrombosis of the portal vein or the mesenteric artery.

Personnel

An interdisciplinary team approach should be used to guarantee that the best possible patient care is provided.

Evaluation by a hepatologist, a transplant surgeon, and a transplant nurse coordinator is essential in the pre-transplant period to evaluate the patient, explain all required vaccinations, medications, lifestyle modifications, and types of surgeries, as well as have a thorough discussion about the post-transplant period, including immunosuppression and potential complications and results.

A psychological assessment by a transplant psychiatrist is required to treat any alcohol or substance misuse disorders, as well as to ensure that the patient understands the surgery and its potential implications.

Social workers play an important role in providing the patient's social welfare system, particularly during the post-transplant period and with home care and modifications. Medical insurance coverage for liver transplant surgery and immunosuppressive medications is assessed by a trained team.

Nutritionists are involved in both the pre-transplant and post-transplant periods to maintain sufficient nutritional health and to address dietary changes associated with chronic diseases such as diabetes mellitus, hypertension, and hyperlipidemia.

Preparation

Many essential features and health issues in liver transplantation candidates must be addressed during the pre-liver transplantation examination. To perform a full systematic assessment of patients and manage them appropriately, this assessment should involve a thorough, comprehensive history and physical exam, laboratory testing, and imaging scans.

Obesity: Patients with a high BMI should be assessed because it raises perioperative complications and lowers long-term survival in liver transplantation patients. Obese patients with a BMI of 30 or higher should see a dietician, and a BMI of 40 or higher is regarded as a relative contraindication for liver transplantation.
Coronary Artery Disease: It's critical to identify your heart risk before surgery. Cardiovascular stress testing, either physical or pharmacological, should be performed on all patients. If the stenosis is discovered, coronary revascularization should be performed prior to liver transplant. Although the prognosis for liver transplantation in people over the age of 68 is not as excellent as it is in younger patients, higher age is not a contraindication to liver transplantation in patients without or with well-controlled diseases. It has recently been demonstrated that well-selected older liver transplant patients can benefit from liver transplantation and live longer than expected.
Portopulmonary hypertension: When the mean pulmonary artery pressure is more than or equal to 25 mmHg and is related to portal hypertension. Moderate to severe portopulmonary hypertension is linked to a greater mortality risk after liver transplant; if mean pulmonary artery pressure is above 50 mmHg, the mortality rate can exceed one hundred percent. Echocardiography is used to identify pulmonary hypertension, and right cardiac catheterization is used to confirm the diagnosis if it is severe. Vasodilators are used to manage this disease, and in patients who improve with vasodilator therapy and have a mean pulmonary artery pressure of less than 35 mmHg and a pulmonary vascular resistance of less than 400 dynes/s/cm, liver transplantation is recommended.
Hepatopulmonary Syndrome: It is a breathlessness and hypoxemia syndrome that affects patients with chronic liver problems, particularly those who have portal hypertension. This is due to intrapulmonary shunt caused by microvascular dilatation of the pulmonary vessels. Pulse oximetry should be used to evaluate patients before liver transplant. Based on the intensity of hepatopulmonary syndrome, patients may require a prolonged recovery time and long-term oxygen therapy after liver transplantation.
Renal Dysfunction: Patients with kidney impairment must be detected prior to receiving a liver transplant, as renal dysfunction raises mortality substantially. If a patient's glomerular filtration rate is less than 30 mL/min, suggesting chronic renal disease or acute renal failure, and dialysis is required for longer than eight weeks, combined liver and kidney transplantations are recommended.
Cigarette Smoking: It raises the risk of death from heart problems in liver transplantation recipients. It also raises the risk of clotting in the hepatic arteries. Smoking should be restricted, and many hospitals make quitting smoking a prerequisite for being considered for a liver transplant.
Extrahepatic Malignancy (malignancy outside the liver): Before receiving a liver transplant, patients should receive all age-appropriate screenings. If they have any heightened risk factors for particular cancer, they should be tested for that cancer type. Before undergoing a liver transplant, every patient who has been diagnosed with preceding cancer should be managed and cured.
Infectious Disorders: Before a liver transplant, any infectious diseases should be treated adequately. Viruses like hepatitis A and B, cytomegalovirus, Epstein-Barr virus, bacterial diseases like tuberculosis and syphilis, and fungal infections like Strongyloidiasis and coccidioidomycosis should all be tested for in the serum. All live attenuated virus vaccinations should be given before liver transplant because they are contraindicated after liver transplantation when immunosuppressive therapy is started.
Nutritional status: Prior to liver transplantation, patients should be assessed by a nutritionist, as it is necessary to resolve all nutritional deficits associated with chronic liver disease and fat malabsorption. Dietary control in relation to other diseases such as diabetes, hypertension, and hyperlipidemia should be emphasized.
Bone health: Before a liver transplant, all candidates should have their densitometry, vitamin D, and calcium levels checked. Osteoporosis is fairly prevalent in all individuals with chronic liver conditions, as a result of vitamin D malabsorption, and in patients of autoimmune hepatitis, as a result of corticosteroid use.
Human immunodeficiency virus: Affected persons with Human Immunodeficiency Viral I infection can only be eligible for a liver transplant if their CD4 levels are above 100 L and their viral load is undetectable before the procedure. Because of the availability of efficient antiretroviral medication, HIV is no longer regarded as a contraindication to liver transplants.
Psychological Evaluation: It's critical to check liver transplant patients for any psychiatric issues that could affect their outcome, medication adherence, or medical instructions. It's also crucial to assess social welfare systems and caregiver availability, particularly in encephalopathy patients. Patients with depressive symptoms, particularly in the immediate postoperative phase, have a poor prognosis following a liver transplant. Substance misuse should be assessed carefully.

Liver Transplantation Procedure

There are two parts to any liver transplant operation: the donor and the recipient.

The native liver of the patient is removed in its entirety after the separation of the hepatic ligamentous connections and hilar structures. To provide proper blood management, the inferior vena cava should be ringed. Donors can be either dead or living.

Whole liver transplantation is more prevalent than dead donor liver transplantation. The donor's liver is normally prepared on a different table from the recipient's body, and once the patient's body is ready, the donor's liver is transported to the table, and anastomoses are started. The suprahepatic inferior vena cava is attached first, followed by the infrahepatic inferior vena cava, and finally the portal vein. The clamps are released when these stages are completed, and blood begins to flow into the portal vein, perfusing the liver.

The recipient's and donor's hepatic vessels are joined around the gastroduodenal artery anastomoses, and the bile duct is then repaired. In 2003, the first separated graft was attempted, in which the dead donor liver is split for transplantation into two recipients: the right lobe is used as an allograft without the middle hepatic vein, equivalent to the modified procedure used in the live donor liver transplant right lobe graft, and the left part of the liver with the inferior vena cava and the common hepatic artery. Living Donor Liver Transplantation: Previously, living donors were primarily employed in child liver transplant cases. Living donors are also employed in adults due to the growing number of patients requiring a liver transplant and the scarcity of deceased donors. Living donor liver transplant is more complicated and necessitates meticulous dissection. A partial graft from a living donor is different from a total graft from a dead donor. Because a living donor graft has a visibly smaller hepatic artery, hepatic vein, and portal vein to implantation, the most important step is to make enough area for the arterial hepatic, portal, and biliary reconstruction by puncturing the hepatic vein along the sidewalls.

The hepatic vein is anastomosed first, which requires a sufficient length for union, then the portal vein, and lastly the hepatic artery, which is challenging to anastomose due to many short branches. Finally, a duct-to-duct suture for the bile duct is done. The left lateral sector, which makes up 20 percent of the overall liver volume, the left lobe, which makes up 40 percent of the volume, and the right lobe, which makes up the remaining 60 percent of the liver volume, are all grafted from a living donor. Dual grafts, in which two left lobes from two donors are transplanted in one recipient, are sometimes employed.

The rectus muscle on both sides is protected because all donors having hepatectomy have a distinctive cut in the right subcostal area that continues into the midline. Before wound repair, the left hepatic lobe should be connected to the anterior abdominal wall in instances of right hepatic lobe transplantation.

Liver Transplantation Complications

Early or late complications can occur following a liver transplant:

Early Complications

Non-function of liver allograft
Thrombosis of the hepatic artery
Acute cellular rejection
complications of the biliary system
Infection

The abnormal liver enzymes normally return to normal during the first week, and the liver graft begins to recover.

The primary non-function of the allograft is the most significant complication following liver transplantation. The lack of bile synthesis or the formation of clear bile, as well as increased liver enzymes and bilirubin, are indications of this acute consequence. For the patient to survive this immediate problem, a new graft is required.

Abnormal liver tests commonly appear two to three days after a liver transplant, indicating graft damage induced by cold and warm ischemia during extraction and implantation into the recipient. However, a Doppler ultrasonography should be performed to rule out hepatic artery thrombosis after liver donation. Hepatic artery thrombosis normally develops early after a liver transplant; however, it can sometimes develop later. Patients may be asymptomatic or have a fever and elevated liver enzymes, depending on the clinical manifestation. Hepatic ischemia, necrosis, and ischemic cholangiopathy can all result from this. Patients may need a re-transplant depending on the seriousness of graft malfunction, especially if it occurs within the first week after liver transplant.

Acute cellular rejection is prevalent after liver transplant, with up to 50 percent of patients experiencing it. The majority of occurrences occur within the first two months after a liver transplant, and the majority of patients respond well to corticosteroids. Anti-thymocyte globulin is required in the case of corticosteroid-resistant rejections. For a definite diagnosis, a liver biopsy should be conducted. Long-term results are promising.

Biliary strictures are most commonly found at the biliary anastomosis. Endoscopic dilation, stenting, or surgical correction are all options for treating this. Hepatic artery thrombosis, ABO incompatibility, prolonged graft ischemia time, or grafts donated after cardiac death can all cause non-anastomotic or ischemic strictures.

Immunosuppressive therapy after transplant raises the risk of opportunistic infections such as CMV, Candida infections, Pneumocystis carinii, Aspergillus, and Nocardia. Tacrolimus and cyclosporine usage can cause neurological and kidney impairment, as well as the development of hyperglycemia.

Late Complications

Immunosuppression-related complications
After a liver transplant, a recurrent disease can develop.
Malignancy

The harmful effects of immunosuppressive medications are primarily to blame for late problems. Chronic kidney disease, hypertension, diabetes, and dyslipidemia are the most frequent. Calcineurin inhibitors, when combined with pre-transplant chronic kidney disease and hypertension, influence the development of kidney failure after liver transplant. This is treated by lowering blood pressure and reducing or stopping calcineurin inhibitors.

Immunosuppressive medications raise the risk of cardiovascular disease by increasing risk factors such as diabetes, high blood pressure, obesity, and dyslipidemia. This, combined with a high-risk lifestyle, causes a significant increase in atherosclerosis.

Protracted use of corticosteroids, as well as malnutrition and vitamin D insufficiency linked to liver dysfunction, raise the risk of osteoporosis. This consequence has recently been minimized as a result of effective bisphosphonate medications and reduced corticosteroid doses. Calcineurin inhibitors cause neurologic problems, most notably tremors, as well as sleeplessness and paresthesia.

Recurrent hepatitis C or B infections are examples of recurrent infections after a liver transplant. Both of these conditions can be well-managed after a liver transplant. Non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, AIH, and hepatocellular carcinoma are examples of chronic liver diseases that can occur. Malignancies develop spontaneously and are a leading cause of death in liver transplant recipients over time.

Liver Transplantation Prognosis

Liver transplantation is a tried-and-true treatment for end-stage liver disease that should be made available to anybody who qualifies. By carefully selecting both contributors and recipients, you can get the most out of your money. This necessitates a multidisciplinary team of medical professionals, which is usually based at a transplantation facility. One solution to the donor scarcity could be living-related liver transplantation.

Approximately 75 percent of those who have liver transplantation live for at least five years. People receiving a liver from a living donor have a higher chance of surviving in the near term than those who receive a liver from a dead donor. Long-term outcomes are difficult to compare since persons who receive a liver from a living donor usually have a shorter wait for transplantation and aren't as unwell as those who have received a liver from a dead donor.

Survival statistics for liver transplantation recipients vary per transplant center in the United States, according to the Scientific Registry of Transplant Recipients.

Conclusion

The treatment of acute and chronic liver problems has been transformed by liver transplantation. The scarcity of donor organs continues to be a barrier to their usage. Over the last few years, the donor supply has grown significantly as the use of expanded criteria organs has grown. In East Asia, live donor liver transplantation has proven to be a good substitute for deceased donor liver transplantation regardless of disease severity, and the results are presently comparable. With improving survival rates in most transplant hospitals, more attention should be paid to long-term consequences.