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End Stage Liver Disease & Disease-Specific Indications For End Stage Liver Disease & Disease-Specific Indications for Liver Transplant Sherona Bau, NP The Pfleger Liver Institute 200 UCLA Medical Plaza, Suite 214 Los Angeles, CA 90095 July 31st, 2018 Objectives End stage Liver Disease Indications for liver transplant Disease specific indications leading to liver transplant Ultimate goal of liver transplant End Stage Liver Disease The term “end-stage liver disease” is synonymous with ◦ Advanced liver disease ◦ Liver failure ◦ Decompensated cirrhosis - irreversible Liver transplantation can be a definitive and potentially curative treatment for irreversible liver disease Orthotopic Liver Transplantation Initially attempted in 1963 ◦ 1-year survival rate of 30% Since the early1980’s, improved immunosuppression (ie. Tacrolimus, cyclosporine), organ preservation, surgical techniques, and peri-operative care have led to increased patient survival rates ◦ 1-year survival of 86% ◦ 4-year survival of 73% 5.5 Million with Liver Failure in the U.S. Hepatitis C 42% Hepatitis C/ETOH 22% NASH 10% ETOH 8% Hepatitis B 4% Others 14% Indications for liver transplant Cirrhosis + ◦ MELD-Na > 15 ◦ and/or ◦ Liver decompensation ◦ and/or ◦ Exception ◦ Hepatopulmonary syndrome ◦ Portopulmonary hypertension ◦ Hepatocellular carcinoma ◦ Cholangiocarcinoma MELD-Na Calculation INR Total bilirubin Serum Creatinine Serum Sodium Dialysis x 2 within week Child-Pugh Class Three-month mortality in chronic liver disease patients 0.6 0.5 0.4 0.3 Probability 0.2 0.1 0 1 ABC Child-Pugh Score 0.8 0.6 0.4 Probability 0.2 0 -10 0 10 20 30 40 MELD Score Disease Specific Indications for Liver Transplant Acute liver failure Alcoholic liver disease Autoimmune hepatitis Cholestatic liver diseases – Primary biliary cholangitis (PBC), Primary sclerosing cholangitis (PSC) Viral hepatitis - Hepatitis C, Hepatitis B Primary liver malignancies: Hepatocecullar Carcinoma Metabolic disorder: Wilson disease Cryptogenic/ Non alchoholic steatohepatitis Other Survival by Indication for Liver Transplantation 100% 80% 60% 40% Bil Atresia HBV 20% PBC HCV Patient Survival PSC Fulminant ALD Malignancy 0% 0 102030405060708090100110120 Months Acute Liver Failure Acute liver failure refers to -Encephalopathy -Impaired synthetic function (INR of ≥1.5) in a patient without cirrhosis or preexisting liver disease. -Previously undiagnosed Wilson disease, vertically acquired hepatitis B virus, or autoimmune hepatitis, in whom underlying cirrhosis may be present, provided the disease has been recognized for <26 weeks. Acute Liver Failure Acute Liver Failure Acetaminophen toxicity accounts for approximately 50% of all causes of ALF in the U.S. Acute Liver Failure Acetaminophen, acute hepatitis A, pregnancy-related liver disease, and shock liver - the highest likelihood of spontaneous survival. ALF patients are eligible for UNOS Status 1a- gives them preference in organ allocation over all forms of chronic liver disease as well as broader UNOS regional sharing. Acute Liver Failure Criteria for status 1 listing ◦ Ventilator dependence ◦ Renal replacement therapy with hemodialysis or hemofiltration ◦ INR > 2 with onset of hepatic encephalopathy within 8 weeks of initial symptoms of liver disease Acute Liver Failure Patients with ALF require immediate referral to a liver transplant center Patients with acetaminophen overdose should be evaluated for and meet reasonable expectations for adherence to medical directives and mental health stability as determined by the psychosocial evaluation. Alcoholic Liver Disease The second most common indication for liver transplant. Ninety five percent are not referred for evaluation although referral criteria are met. Most patients with ALD have the comorbid psychiatric diagnosis of alcohol dependence with a relapsing, remitting course. Alcoholic Liver Disease Require evaluation by clinicians skilled in mental health in order to establish the correct psychiatric diagnoses and adequate treatment plan. A 6-month minimum period of abstinence is commonly enforced. In acute alcoholic hepatitis patients, before 6 months abstinence has been demonstrated to improve survival, but remains controversial. Alcoholic Liver Disease Six months sobriety without assessment or treatment does not therapeutically address a potential addictive disorder. Abstinence alone may not meet the listing criteria for liver transplant. Ongoing monitoring by clinicians and toxicology screening is necessary while patients are on waitlist. Alcoholic Liver Disease Early referral of ALD patients for initiation of liver transplant evaluation facilitates psychosocial assessment and setting addiction treatment goals Ongoing monitoring is an important part of a comprehensive treatment plan Alcoholic Liver Disease Authority Standard Advice Men Advice Women unit in the g/day g/day U.S. Department 14g No more 28 g No more 14 g of than two than one Agriculture/ drinks per drink per Department day day of Health and Human Services Alcoholic Liver Disease Daily alcohol consumption of 50 g or greater was associated with a 34 percent increase in the rate of fibrosis progression A standard drink contains 12 g of alcohol and is equivalent to 360 mL (12 oz) of beer, 150 mL (5 oz) of wine, or 45 mL (1.5 oz) of whiskey or other 80 proof distilled spirits. Other risk factors – NASH or HCV in addition to ALD is associated with higher fibrosis progression. Autoimmune Hepatitis Autoimmune hepatitis may result in the development of cirrhosis and hepatocellular failure although around 80% of autoimmune hepatitis patients respond well to immunosuppressive regimens. Long-term outcomes after liver transplant are excellent with 5 to 10-year survival rates of ~ 75% Autoimmune Hepatitis Factors associated with poor outcome include ◦ Delayed aminotransferase response to therapy ◦ Young age ◦ Greater acuity at presentation ◦ MELD score > 12 ◦ Multiple relapses Autoimmune Hepatitis Acute liver failure due to autoimmune hepatitis is not fully defined ◦ Central zone perivenular inflammation on biopsy, but not typically seen in chronic autoimmune hepatitis B. Some plasma cells around a central vein. E. Perivenular necroinflammatory activity Autoimmune Hepatitis Corticosteroid use in acute liver failure due to autoimmune hepatitis is controversial It is best reserved for less severe disease (MELD < 28) Corticosteroid use in severe disease can increase risk of sepsis Autoimmune Hepatitis Liver transplant should be considered in patients with decompensated autoimmune hepatitis who do not respond corticosteroid-based immunosuppressive regimens. Liver transplant should be indicated in acute liver failure phase if recovery is unlikely. Cholestatic Liver Diseases Primary biliary cholangitis (PBC) Primary sclerosing cholangitis (PSC) Primary Biliary Cholangitis Chronic liver disease resulting from progressive destruction of the bile ducts in the liver – intrahepatic bile ducts damage Primary Biliary Cholangitis Therapy with ursodeoxycholic acid has improved outcomes in PBC – decrease in the number of patients with PBC requiring liver transplant. Indications for liver transplant in PBC include ◦ Refractory PBC ◦ Severe portal hypertension ◦ Refractory pruritus Transplant outcomes are excellent, with 5-year survival rates of 80-85% Primary Sclerosing Cholangitis Characterized by inflammation and fibrosis of both intrahepatic and extrahepatic bile ducts formation of multifocal bile duct strictures. Primary Sclerosing Cholangitis Primary Sclerosing Cholangitis Primary Sclerosing Cholangitis No effective medical therapy is available for PSC, which is associated with an increased risk of cholangiocarcinoma and gallbladder carcinoma as well as colon cancer in patients with associated inflammatory bowel disease (IBD). Indications for liver transplant in PSC patients ◦ Decompensated liver cirrhosis ◦ Recurrent bacterial cholangitis may be eligible for MELD exception ◦ Cholangiocarcinoma may be eligible for MELD exception Primary Sclerosing Cholangitis Liver transplant outcomes for PSC are excellent, with 5-year survival rated of ~ 90% The presence of active IBD prior to liver transplant appears to worsen post-transplant outcomes. Colonoscopy surveillance for PSC patients with IBD both prior to and following liver transplant due to an increased risk of colorectal cancer. Ultimate Goal of Liver Transplant Improve quality of life Increase overall survival Conclusion Purpose of liver transplant is to improve patient survival and improve quality of life Indications for liver transplant -> MELD-Na > 15, decompensated liver cirrhosis, with MELD exception HPS, POPH, HCC, Cholangiocarcinoma Diseases specific indications for liver transplant -> viral hepatitis, AIH, ALF, ALD, Cholestatic liver diseases, NASH, Wilson, HCC Outcomes and prognosis are mostly very good after liver transplant .
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