Liver Failure: The Basics PDF

Liver Failure: The Basics Chelsea Wernsdorfer, MSN, AG-ACNP-BC Some basic terms ► Hepatitis: is just another word for liver inflammation. ► Fibrosis: scarring, possibly reversible. ► Cirrhosis: scarred non-functional tissue – will not regenerate. ► Failure: The organ is non-functional...

Liver Failure: The Basics Chelsea Wernsdorfer, MSN, AG-ACNP-BC Some basic terms ► Hepatitis: is just another word for liver inflammation. ► Fibrosis: scarring, possibly reversible. ► Cirrhosis: scarred non-functional tissue – will not regenerate. ► Failure: The organ is non-functional. Liver Failure – Some Basics ► Many causes Toxic agents: ETOH, acetaminophen, meds, mushrooms, dietary supplements Infectious: Hepatitis A – E, CMV, HSV, EBV, parasites Mechanical: injury, obstruction, thrombosis, Budd-Chiari, (HCC) Anyone know what Autoimmune: Wilson’s, PSC, PBC, PFIC we are looking at in this picture? Even pregnancy! More Terminology Acute or Fulminant Liver Failure Chronic ► Develops in days to ► Develops over greater weeks than 6 months ► Hyper-acute over several ► Often due to prolonged days exposure to cause ► Acute – any timeframe up (ETOH, untreated to 6 months infection, AIH) Some Common Causes Acute Liver Failure Chronic Liver Failure Medications: Tylenol*, Antibiotics, ETOH herbal supplements NAFLD/NASH Toxins: exposure to chemical agents Chronic Viral Hepatitis (B, C) Hepatitis A, B, E AIH/Congenital: PSC, PBC, Wilson’s ETOH alpha-1 antitrypsin Budd-Chiari Cancer Cancer Medications/drugs: methotrexate, Auto-immune isoniazid, Tylenol Rhabdomyolysis Cryptogenic Prevalence Hep C Chronic Liver Disease in the US: 4.5 million NASH/NAFLD ETOH Hepatitis B Hepatitis A Other – auto-immune, congenital, cryptogenic Hepatitis C ETOH NASH Hepatitis B Hepatitis A Other Data from CDC, American Liver Foundation 2023 The effects of recent history… Increase in alcohol related deaths (all- cause) What world event happened? From CDC https://www.cdc.gov/nchs/products/databriefs/db448.htm Causative Diseases ► NAFLD/NASH ► ETOH ► Hepatitides ► Auto-immune: Wilson’s, PSC, PBC, alpha-1 antitrypsin, cryptogenic, hemochromatosis, pregnancy, Budd-Chiari ► Hepatocellular Carcinoma NASH/NAFLD/ETOH NAFLD/NASH ETOH ► More common in ages ► More common in men, 40-65 but incidence in women ► More common in women, rising and people of Latinx or ► Women more at risk for Asian ancestry harm secondary to ► Associated with metabolic alcohol misuse syndrome The Hepatitides ► Not a Greek Island! ► Hepatitis A, B, C, D, E If it’s a vowel, it’s fecal/oral If it’s a consonant, it’s bloodborne Worldwide causes of ESLD ► An old slide (2014), but a good one to demonstrate variance in causes of ESLD ► What shifts do you think we’ll see next? National Vital Stats The Hepatitides Hepatitis A/E Hepatitis B/D Hepatitis C Fecal/Oral transmission Bloodborne Bloodborne Most spontaneously 95% clear D if 15-25% will clear clear coinfected at same time spontaneously Vaccine: yes for A Vaccine for B No vaccine but now curable A more common in Cannot get D without B, Multiple genotypes developed Western B very common in Asia Frequently chronic, countries, E in Middle Frequently Chronic especially in Baby Boomer and Far East. generation Can be reactivated Rarely chronic Can be reactivated or Once it’s gone, it’s gone reacquires From CDC: Hepatitis  Hepatitis B: the 200 pound Gorilla ► Serologies of Hepatitis B are complex HBsAg: the individual is infectious! Anti-HBs: indicates recovery and immunity Total HBc: previous or ongoing HBV infection IgM anti-HBc: recent, acute infection Hepatitis B e antigen (HBeAg): active replication of virus, suggests high levels of HBV HBV DNA: direct quantification of virus ► Prophylaxis and Treatment Vaccinations Suppressive medications – entecavir, tenofovir, lamivudine ► Hepatitis B can survive outside the body for up to 7 days! From https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm#general  Antibody and Antigen Biomarkers for Hepatitis B Infection Clinical state HBsAg Total Anti-HBs Total anti-HBc Action Chronic infection Positive Negative Positive Link to hepatitis B-directed care Acute Positive Negative Positive Link to hepatitis (IgM anti-HBc) B-directed care Resolved infection Negative Positive Positive Counseling, reassurance Immune (immunization) Negative Positive Negative Reassurance Susceptible Negative Negative Negative Vaccinate (never infected and no evidence of immunization) *Isolated core antibody Negative Negative Positive Depends on situation From https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm#general  Hepatitis C: the 500 lb. Gorilla ► 2.4 million Americans, now recommended to screen adults for Hep C. Of every 100 individuals infected with HCV, approximately: 75-85 will go on to develop chronic infection, 10-20 will go on to develop cirrhosis over a period of 20-30 years ► Among patients with cirrhosis, there is: 1-5% annual risk of hepatocellular carcinoma, 3-6% annual risk of decompensation, for which the risk of death in the following year is 15- 20% Rates of progression to cirrhosis are increased in the presence of a variety of factors: males > female, age > 50 years, alcohol, nonalcoholic fatty liver disease, HBV or HIV coinfection, immunosuppressive therapy https://www.cdc.gov/hepatitis/index.htm and https://www.hepatitisc.uw.edu/page/treatment/drugs  Hepatitis C: the 500 lb. Gorilla ► Labs to send HCV antibody HCV PCR and genotype ► Treatment 1st: wait and retest 2nd: multiple new therapies available, efficacy varies by genotype – some examples: Harvoni, Mavyret, Zepatier, Epclusa, Vosevi – these have replaced the PEG/Interferon and ribavirin of old. 90-95% will have SVR with 8-12 weeks of treatment https://www.cdc.gov/hepatitis/index.htm and https://www.hepatitisc.uw.edu/page/treatment/drugs Viral Prodrome ► Malaise, myalgia, arthralgia & fatigue ► Anorexia, nausea & vomiting common ► Diarrhea or constipation ► Rash, arthritis or serum sickness in early HBV ► Fevers (as high as 104° F or 39.5° C) ► Mild, constant RUQ or epigastric abdominal pain ► Increased with exertion Icteric Phase ► Dark urine & clay-colored stool ► Jaundice at onset or within 10 days ► Intensified prodromal symptoms BUT – some patients asymptomatic ► Tender hepatomegaly ► Splenomegaly ► Posterior cervical lymphadenopathy can occur, but rare BUT – some patients have normal exam Physical Findings Grimace Grimace-like habitus The “Grimace” body Physical Findings Jaundice in dark and light skinned people Physical Findings Ascites, vascular cephalization, caput medusae, jaundice Other findings… Palmar erythema Asterixis https://youtu.be/pAOWjYo- sX4 aka Liver Flap Other Hepatic Findings Encephalopathy Graded I-IV Incidence or worsening can be provoked by: ► GI bleed ► Overuse of diuretics ► Electrolyte abnormalities ► Psych meds ► Dehydration ► Constipation ► Poor diet Wasserman, 2019 Other ROS/PE findings ► Dark, cola-colored urine ► Pale, clay-colored stools ► Bruising, petechiae ► Complaints of nosebleeds ► Fetor Hepaticus ► Hepatomegaly, splenomegaly Common Diagnostic Labs and Findings ► Elevated liver tests – Bilirubin, liver associated enzymes ► Elevated INR ► Decreased platelets ► Hypoglycemia ► Increased creatinine ► Hypoalbuminemia ► Hyponatremia ► Azotemia ► Elevated serum ammonia Associated Pathophysiology ► CV: hypotension, pulmonary hypertension, varices, arrhythmias – due to electrolyte disturbances ► Respiratory: dyspnea, hepatic hydrothorax, aspiration ► Infectious: spontaneous bacterial peritonitis (SBP), cholangitis, sepsis ► GI: anorexia, constipation, GI bleeds – varices ► Renal: hepato-renal syndrome, hyponatremia ► Hematology: thrombocytopenia, coagulopathy, anemia ► Oncology: hepatocellular carcinoma ► Endocrine: hypoglycemia, sick euthyroid, hypogonadism ► Neurology: encephalopathy, RUQ pain ► Dermatology: pruritis ► Regarding Imaging – US, CT, MRI: hepatomegaly and “scalloped edges” of organ indicative of cirrhosis Diagnosis, Treatment and Monitoring Labs: CBC, CMP, INR, Hepatitis serologies, liver biopsy Imaging: Ultrasound, MRI, CT liver protocol Healthy, Fatty, Cirrhotic – Images courtesy American Liver Foundation Diagnosis and Treatment ► Supportive/Monitoring INR, CBC, Bili and LFTs o Real LFTs: hypoglycemia, hypoalbuminemia and elevated INR Encephalopathy: limit oral protein and give lactulose Hypoglycemia: 10% glucose infusion Coagulopathy: vitamin K, FFP Hyponatremia: free water restriction Ascites: low Na+ diet, diuretics PRN, careful paracentesis (significant loss of albumin) Antibiotic prophylaxis for spontaneous bacterial peritonitis (SBP) Medications ► Lactulose – hepatic encephalopathy ► Rifaximin – hepatic encephalopathy ► Diuretics such as furosemide, spironolactone ► Midodrine – for hypotension ► Propranolol – hypertension, portal hypertension ► Octreotide – varices? ► Pantoprazole – GI prophylaxis ► Cipro or other antibiotics – spontaneous bacterial peritonitis (SBP) prophylaxis Diagnosis and Treatment ► Remove offending agent, treat cause and give supportive care. The patient will either:  Recover or  Develop Chronic Liver Failure Medical Management, Transplant, Palliative Care Diagnosis and Treatment ► Remove offending agent, treat cause and give supportive care ► The patient will either: Recover Or Develop chronic liver failure ► Treatment Medical management to control/reduce symptoms Transplant for life sustaining therapy Palliative care if transplant not appropriate Common Procedures ► Paracentesis – why? ► Thoracentesis – why? ► TIPS ► ERCP/EGD ► Biopsy ► Transplant TIPS Paracentesis ► Risks Bleeding Puncture of other organs ► Benefits Increased ease of breathing, comfort of patient ► Therapeutic vs Diagnostic Thoracentesis Thoracentesis ERCP and EGD Left side is ERCP, Right side is view of EGD with clipping of varix Transplant Destination therapy Lifelong immunosuppression Surgical Recovery Need Cancer Screening Cardiac Clearance Living Donor Transplant From Mayo Clinic References American Association for the Study of Liver Diseases–Infectious Diseases Society of America. (2019). Hepatitis C Guidance 2019 Update: Recommendations for testing, managing, and treating Hepatitis C iirus Infection. AASLD-IDSA Hepatitis C Practice Guideline from https://www.aasld.org/publications/practice-guidelines Bernal, W., & Wendon, J. (2013). Acute liver failure. The New England Journal of Medicine. Retrieved from https://www.nejm.org/doi/full/10.1056/nejmra1208937 Centers for Disease Control and Prevention. (2023, March) Viral Hepatitis. Retrieved from https://www.cdc.gov/hepatitis/index.htm Kwong, A. J., et al. (2021). OPTN/SRTR 2021 Annual Data Report: Liver. American Journal of Transplant. Suppl 1:178- 263, retrieved from https://amjtransplant.org/article/S1600-6135(23)00253-8/fulltext Mayo Clinic, (2022) https://www.mayoclinic.org/diseases-conditions/liver-problems/symptoms-causes/syc-20374502 National Vital Statistics System. (2017). QuickStats: Death rates for chronic liver disease and cirrhosis, by sex and age Group, 2000 and 2015. Morbidity and Mortality Weekly Report DOI: http://dx.doi.org/10.15585/mmwr.mm6638a9External Terrault, N., et al. (2018). AASLD PRACTICE GUIDLINE update on prevention, diagnosis, and treatment of chronic Hepatitis B. AASLD, Hepatitis B. Guidance from https://www.aasld.org/publications/practice-guidelines University of Washington. Hepatitis C Online. Retrieved on 4/2/2023 from https://www.hepatitisc.uw.edu/ Vilstrup, H., et al. (2016). Hepatic encephalopathy in chronic liver disease. 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Retrieved 3/11/2020 from https://www.aasld.org/publications/practice-guidelines