Liver Transplant For Autoimmune Hepatitis

The Transplant Evaluation Process

If your provider thinks you may be a good candidate for a liver transplant,he or she will refer you to a transplant center for evaluation. Transplantcenters are located in certain hospitals throughout the U.S.

You will have a variety of tests done by the transplant center team. Theywill decide whether to place your name on a national transplant waitinglist. The transplant center team will include:

• A transplant surgeon

• Other team members such as a dietitian, a chaplain, or an anesthesiologist

The transplant evaluation process includes:

• Psychological and social evaluation . Many different issues are assessed. They include stress, financial concerns, and whether you will have support from family or friends after your surgery.

• Blood tests . These tests are done to help find a good donor match and assess your priority on the waiting list. They can also help improve the chances that your body wont reject the donor liver.

• Diagnostic tests . Tests may be done to check your liver and your general health. These tests may include X-rays, ultrasounds, a liver biopsy, heart and lung tests, colonoscopy, and dental exams. Women may also have a Pap test, gynecology exam, and a mammogram.

The transplant center team will review all of your information. Eachtransplant center has rules about who can have a liver transplant.

You may not be able to have a transplant if you:

What Is A Living Donor Liver Transplantation

During a living donor liver transplant, a portion of a healthy persons liver is removed and transplanted into another person to replace their unhealthy liver. Both the donors and recipients livers will regrow over the next few months. Receiving a living donor transplant reduces the amount of time a person needs to wait on the national transplant waiting list.

Getting On The Waiting List

If you are accepted as a transplant candidate, your name will be placed ona national transplant waiting list. People who most urgently need a newliver are put at the top of the list. Many people have to wait a long timefor a new liver.

You will be notified when an organ is available because a donor has died.You will have to go to the hospital right away to get ready for surgery.

If a living person is donating a part of their liver to you, the surgerywill be planned in advance. You and your donor will have surgery at thesame time. The donor must be in good health and have a blood type that is agood match with yours. The donor will also take a psychological test. Thisis to be sure he or she is comfortable with this decision.

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Indication Of Liver Transplantation For Chronic And Acute Liver Failure Due To Autoimmune Hepatitis

The majority of patients with AIH are presented with chronic disease . Its diagnostic criteria have been standardized and validated by the International Autoimmune Hepatitis Group and is widely used . On the other hand, although several useful prognostic models are proposed in other autoimmune liver diseases such as primary biliary cirrhosis and primary sclerosing cholangitis , there are no useful prognostic tools available in AIH. Thus, the indication for LT based on the prognosis of the native liver in the AIH setting should be evaluated similarly as other non-autoimmune liver diseases LT is usually indicated in patients with chronic decompensated liver disease with a Model for End-Stage Liver Disease score of 15 . Complications of hepatopulmonary syndrome, portopulmonary hypertension and hepatocellular carcinoma with or without an elevated Child-Pugh score can be other factors in consideration for the timing of LT and a MELD exceptional point .

Researching Autoimmune Liver Disease

The focus of our research at Mount Sinai has been to identify ways to slow the progression of autoimmune liver diseases. We evaluate the genetic and environmental influences of liver disease. We also research treatments with minimal side effects. Our studies have led to several clinical trials and global collaborations.

Our research teams dedication means you have access to comprehensive, groundbreaking care. We have made strides in diagnosis to post-transplantation care. Our team also supports patient-directed self-help groups for those with autoimmune diseases.

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Prophylaxis With Alternative Dosing Schedules Of Hbig

The high economic cost of prophylaxis schedules combining HBIG plus oral antivirals, together with the high efficacy and safety of the more recent oral antivirals , have led to the study of different prophylactic strategies aimed at lowering or eliminating HBIG in order to reduce costs and the inconveniences associated with its administration.

Additionally, other possible routes of administration of HBIG have been assessed. Several studies have shown that low-dose intra-muscular administration of HBIG when combined with NAs is a cost-effective alternative to its intravenous administration. Recently the subcutaneous administration of HBIG has been found equally effective, well-tolerated, and accepted by patients.

These studies, therefore, show that IV administration of high doses of HBIG is neither necessary nor cost-effective when given together with oral antivirals and also highlight the importance of pretransplant levels of HBV-DNA as a predictive factor for recurrence.

Withdrawal of HBIG after combined prophylaxis: Studies of this strategy vary greatly in design, type of antiviral agent used, and time from LT to HBIG withdrawal. In addition, most of the studies are observational and from a single center, with just three randomized studies. The overall rates of recurrence in these studies ranged from 0% to 17%.

No studies are yet available concerning the combined use of two ANs as prophylaxis without HBIG.

Symptoms Of Autoimmune Hepatitis

Symptoms of autoimmune hepatitis may include jaundice , fatigue, nausea, vomiting, loss of appetite, an enlarged liver, skin rashes, abdominal discomfort, dark-colored urine, light-colored stools, joint pain, and spider veins on the skin. Patients with advanced disease are more likely to have ascites or encephalopathy , which result from chronic liver dysfunction. Women with autoimmune hepatitis may stop having menstrual periods.

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What Happens During A Liver Transplant

Liver transplant surgery requires a hospital stay. Procedures may varydepending on your condition and your providers practices.

Generally, a liver transplant follows this process:

Autoimmune Liver Diseases And The Risk Of Hepatocellular Carcinoma

Hepatocellular carcinoma is the sixth most common malignancy worldwide and the third most common cause of cancer-related death. The majority of HCC develops in the setting of cirrhosis or liver inflammation. The incidence of HCC is believed to vary depending on the underlying cause of liver disease. In one meta-analysis examining the development of HCC in various etiologies of cirrhosis, chronic hepatitis B , hepatitis C , and alcohol-related liver disease were found to have the highest risk for HCC compared to other causes, including AILDs. A single center study in Toronto, Canada found similar results, with incidence per 1000 person years of 26.2, 21.8, and 18.4 for HBV, HCV, and ALD cirrhosis, respectively. Furthermore, in keeping with the changing landscape of cirrhosis etiology, a recent study identified nonalcoholic fatty liver disease as the fastest growing cause for HCC development among patients listed for liver transplant in the United States.

According to a recent meta-analysis, the incidence of HCC in AIH is 3.06 per 1000 person-years . Cirrhosis is the predominant risk factor for the development of HCC, with an incidence rate of 10.07 per 1000 person-years in patients with AIH cirrhosis. Other risk factors associated are older age, increased frequency of relapses, concurrent alcohol consumption, and a trend for male sex. Asian populations are also observed to have an increased incidence of HCC, suggesting an influence of genetic and environmental factors.

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Our Approach To Autoimmune Hepatitis

UCSF offers the most advanced diagnostic and treatment options for patients with autoimmune hepatitis. We generally begin with a high dose of prednisone to stop or slow the immune system’s attack on the liver. We then taper the dose and may supplement the regimen with additional immune-suppressing medications to manage the condition long term.

Autoimmune hepatitis can lead to severe liver damage or failure. In these cases, a liver transplant may be necessary. Our liver transplant program, designated a center of excellence by the U.S. Department of Health and Human Services, is known for outstanding outcomes and for helping pioneer techniques that have made transplants safer and more successful. We perform more than 100 transplants each year, and our survival statistics are among the best in the country.

Tregs And Chronic Liver Disease

Tregs are known to be actively involved in the immune response within both secondary lymphoid tissue and peripheral organs . The frequency of Tregs within the liver, known as liver infiltrating Tregs , is higher in livers from patients with autoimmune, alcoholic and viral related liver diseases in comparison to healthy livers . TregsLIT have demonstrated the ability to suppress T-cell activation in the setting of chronic liver disease, however they have also been associated with reduced matrix metalloproteinases and inhibiting the clearance of fibrosis . In addition, the suppressive effects TregLIT have on CD8+ T-cell responses has been proposed to contribute to reduced clearance of hepatotrophic viruses . Therefore, therapeutic intervention that aims to increase TregsLIT frequency or function must balance these opposing effects. In chronic liver disease, the impact Tregs have on inflammation, fibrosis, antigen clearance and oncogenesis must be considered .

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How Is Autoimmune Hepatitis Diagnosed

A health care provider will make a diagnosis of autoimmune hepatitis based on symptoms, a physical exam, blood tests, and a liver biopsy.

A health care provider performs a physical exam and reviews the person’s health history, including the use of alcohol and medications that can harm the liver. A person usually needs blood tests for an exact diagnosis because a person with autoimmune hepatitis can have the same symptoms as those of other liver diseases or metabolic disorders.

Blood tests. A blood test involves drawing blood at a health care provider’s office or a commercial facility and sending the sample to a lab for analysis. A person will need blood tests for autoantibodies to help distinguish autoimmune hepatitis from other liver diseases that have similar symptoms, such as viral hepatitis, primary biliary cirrhosis, steatohepatitis, or Wilson disease.

Liver biopsy. A liver biopsy is a procedure that involves taking a piece of liver tissue for examination with a microscope for signs of damage or disease. The health care provider may ask the patient to temporarily stop taking certain medications before the liver biopsy. He or she may also ask the patient to fast for 8 hours before the procedure.

Indications For Liver Transplantation For Patients With Autoimmune Hepatitis

Liver transplantation may be indicated for patients with autoimmune hepatitis if one of the following conditions are present: Acute liver failure Decompensated cirrhosis or Hepatocellular carcinoma. Liver transplantation may be required if there is a failure to diagnose and treat autoimmune hepatitis, inadequate response or intolerance to immunosuppressive therapy, or if the patients are not compliant with the treatment. Ultimately, 10%-20% of patients with autoimmune hepatitis eventually need liver transplantation.

Autoimmune hepatitis accounts for approximately 5% and 2%-3% of liver transplants in the United States and Europe, respectively. The frequency of acute and chronic rejection after liver trans-plantation for autoimmune hepatitis is more frequent compared to other liver diseases. Five-year patient and graft survivals for autoimmune hepatitis are reported to be 80%-90% and 72%-74%, respectively.

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How Do I Get Ready For A Liver Transplant

• Your healthcare provider will explain the procedure to you. Ask him or her any questions you have about the surgery.

• You may be asked to sign a consent form that gives permission to do the surgery. Read the form carefully and ask questions if anything is not clear.

• For a planned living transplant, you should not eat for 8 hours before the surgery. This often means not having any food or drink after midnight. If your liver is from a donor who has just died, you should not eat or drink once you are told a liver is available.

• You may be given medicine to help you relax before the surgery.

Your healthcare provider may have other instructions for you based on yourmedical condition.

Psc And Liver Transplantation

Transplantation is required for patients with PSC with life-threatening complications of cirrhosis or recurrent cholangitis. In highly selected cases, LT is considered for selected patients with cholangiocarcinoma in conjunction with neoadjuvant chemotherapy. On a prognostic level, patients with serum alkaline phosphatase levels greater than or equal to 2.4 times the upper limit of normal are at increased risk of LT. The post-LT survival for PSC is excellent with 1-year, 3-year, 5-year, and 10-year post-LT survival rates of 93.4%, 89.7%, 87.4%, and 83.2%, respectively, in the United States.

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Treatments For Liver Failure

Treatment for acute liver failure depends on the underlying cause. Treatments may include:

• Activated charcoal: This reduces the amount of acetaminophen absorbed into your digestive tract.
• N-Acetyl Cysteine: Taken orally or intravenously, this drug can help in cases of acetaminophen overdose and other causes of acute liver failure.
• Lamivudine: This type of drug stops the hepatitis virus from replicating.
• Steroids: These drugs treat autoimmune hepatitis.
• Liver transplant: If the other treatments do not work, you may be a candidate for a liver transplant.

Treatment In Decompensated Cirrhosis And On Transplant Wait List

In those patients for whom liver transplantation becomes necessary, viral suppression ideally to undetectable levels remains important in preventing HBV recurrence in the graft. Studies have shown a direct correlation between viral load at time of transplant and rate of recurrence.19 This, in conjunction with post-transplant prophylaxis, which will be discussed later in this review, has resulted in HBV recurrence rates falling from 70% to 100% to < 10%.20

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What Is Autoimmune Hepatitis

Autoimmune hepatitis is a chronicor long lastingdisease in which the body’s immune system attacks the normal components, or cells, of the liver and causes inflammation and liver damage. The immune system normally protects people from infection by identifying and destroying bacteria, viruses, and other potentially harmful foreign substances.

Autoimmune hepatitis is a serious condition that may worsen over time if not treated. Autoimmune hepatitis can lead to cirrhosis and liver failure. Cirrhosis occurs when scar tissue replaces healthy liver tissue and blocks the normal flow of blood through the liver. Liver failure occurs when the liver stops working properly.

Management And Outcomes Of Aih Recurrence

Graft failure occurs in 13% to 50% of patients with rAIH. Compared to other liver diseases, rAIH is associated with a higher risk of graft loss and an increased risk of death from liver failure. Re-transplantation is performed for pediatric and young adult patients with progressive liver failure from rAIH. Treatment of AIH recurrence depends on the clinical presentation and severity of the disease. In most cases, optimizing immunosuppression with corticosteroid and/or azathioprine can induce and maintain disease remission . In treatment failure, other immunosuppressive agents, such as mycophenolate mofetil , or sirolimus are found to have some benefit in rAIH management. The role of preventative corticosteroid use is controversial because a meta-analysis failed to demonstrate a benefit of continuous steroids on graft survival, rejection rates, rAIH, and patient survival. Accordingly, the current AASLD guidelines suggest discontinuing corticosteroids post LT and monitoring for rAIH.

Figure 1. Prevention and treatment of AILD recurrence post LT. AZA: Azathioprine IBD: inflammatory bowel disease MMF: mycophenolate mofetil OCA: obeticholic acid UDCA: ursodeoxycholic acid.

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E Chronic Vs Fulminant Presentation Of Aih

AIH patients were classified by transplant for complications of chronic disease or by fulminant presentation . No significant differences were observed overall between chronic and fulminant presentation for age, ethnicity, weight, and blood type, degree of cholestasis, type of donor organ, hospitalization status or risk of for rejection. The calculated PELD of the chronic group was 10.8±1.7. A fulminant presentation was more common in males than in females , p=0.042. Fulminant AIH patients had higher height z-scores. Cyclosporine appeared to be used less often for fulminant AIH but care is needed in interpreting these data as information was missing in 8/45 fulminant vs. 5/68 chronic. While no differences in 4 year patient or graft survival were observed, all deaths in the fulminant group occurred within the first year .

AIH and non-AIH patients with a fulminant presentation were also compared . At transplant, fulminant non-AIH patients were younger and appeared more ill as suggested by a lower weight and a higher serum bilirubin and INR. Patient and graft survival in AIH fulminant patients was similar to the non-AIH fulminant and the chronic AIH group .