Liver Presentation PDF

The Liver Courtney Harris, PharmD Objectives  Describe how hepatitis A, B and C are contracted  Integrate their knowledge of the mechanisms of action, indications, contraindications and side effects of drugs used to treat hepatitis A, B, and C infections, in their appropriate use  Integrate th...

The Liver Courtney Harris, PharmD Objectives  Describe how hepatitis A, B and C are contracted  Integrate their knowledge of the mechanisms of action, indications, contraindications and side effects of drugs used to treat hepatitis A, B, and C infections, in their appropriate use  Integrate their knowledge of the mechanisms of action, indications, contraindications and side effects of drugs used to treat cirrhosis, in their appropriate use Objectives  Identify how the Child-Pugh score is utilized in prescribing to dose medication appropriately.  Apply a patient’s Child-Pugh score to appropriately dose medication. Hepatitis What is hepatitis?  Means inflammation of the liver  Hepatitis can be caused many different ways, but generally when we speak of hepatitis we are talking about viral hepatitis.  5 types of viral hepatitis: A, B, C, D, & E    A is a self-limiting disease that does not cause a chronic infection. B and C can cause both acute and chronic infection. D and E are uncommon in the United States. Vaccinations  Vaccinations exist for hepatitis A and B.  Those traveling to certain areas may receive the hepatitis A vaccine to prevent them from contracting the disease from contaminated food or water.  Hepatitis B vaccines are frequently given to everyone now, especially those in the healthcare profession.  No vaccination exists to prevent C, D, or E. Chronic Hepatitis B Infection 700,000-1.4 million persons in the US have chronic HBV.  An estimated 786,000 persons worldwide die from HBV-related liver disease each year.  Transmitted through activities that involve percutaneous or mucosal contact with infected blood or body fluids    NOT transmitted by breastfeeding HBV can survive at least 7 days outside of the body and can still be capable of causing infection Signs and Symptoms of HBV  Fever  Fatigue  Loss of appetite  Nausea  Vomiting  Dark Urine  Jaundice Jaundice Complications of Chronic HBV  Cirrhosis  Liver cancer  Risk for chronic infection is highest in young children.   Approximately 90% of infants and 25-50% of children 1-5 years will remain chronically infected. 95% of adults will recover completely from HBV. Who should be vaccinated?? Diagnosing HBV  Serologic tests that look at antibodies against HBV and presence for HBV surface antigens will determine whether a patient has had HBV, currently has HBV acutely, has HBV chronically, or has been vaccinated against HBV. Drugs Used in the Treatment of HBV        Interferon alfa Tenofovir Entecavir Telbivudine Lamivudine Adefovir Bolded treatments are preferred; the others are not preferred due to high rates of drug resistance. Interferon Alfa (Intron-A, Pegasys)  MOA: augments the body’s immune response  Side effects: chest pain, fatigue, headache, chills, rigors, depression, dizziness, irritability, pain, confusion, malaise, weight loss, alopecia, neutropenia  Dosing:   Intron-A: dosed daily or three times a week SQ Pegasys: dosed weekly SQ Tenofovir (Viread)  MOA: inhibits replication of HBV by inhibiting HBV polymerase  Dosed once daily for at least one year in appropriate patients  Side effects: insomnia, headache, pain, rash, increased cholesterol, nausea, diarrhea  Concerns: may cause renal toxicity, avoid with NSAIDs; do not give with adefovir Entecavir (Baraclude)  MOA: inhibits hepatitis B viral polymerase  Dosed once daily at least for one year  Dose adjust in renal impairment  Side effects: edema, ascites, fever, headache, fatigue Chronic Hepatitis C  Approximately 3.5 million persons in the US are estimated to have chronic HCV infection.  Approximately 15-25% of people can clear the virus from their bodies without treatment and do not develop chronic HCV.  Can lead to cirrhosis and liver cancer How is HCV spread?  Injection drug use (most common in US)  Receipt of donated blood, blood products, and organs before blood screening started in 1992  Needlestick injuries  Birth to HCV-infected mother How is HCV spread?  HCV is infrequently spread through sex with an HCV-infected person because it is an inefficient means of transmission. Who is at highest risk for HCV infection? Symptoms of HCV  Acute         Fever Fatigue Dark urine Abdominal pain Loss of appetite Nausea Vomiting Jaundice  Chronic  Most are asymptomatic and are only diagnosed with HCV after they try to give blood or have elevated LFTs on a routine blood draw. HCV and Genotypes  At least 6 different genotypes existing of HCV with 50 different subtypes.  In the US, genotype 1 is the most common. Medications Used to Treat Acute or Chronic HCV Interferon alfa  Ribavirin  Boceprevir  Telaprevir  Sofosbuvir  Sofosbuvir+ledipasvir  Glecaprevir + pibrentasvir  Daclatasvir  Ombitasvir, Paritaprevir, Ritonavir,and Dasabuvir  Ombitasvir, paritaprevir, and ritonavir  Simeprevir  Elbasvir+grazoprevir  Sofosbuvir+velpatasvir  Sofosbuvir, velpatasvir, and voxilaprevir  Simplified Treatment: Used for adults with chronic hep C (any geneotype) without cirrhosis or previous hep C treatment  Sofosbuvir + velpatasvir (12 weeks)  Glecaprevir + pibrentasvir (8 weeks) Ribavirin  MOA: inhibits viral replication  Side effects: fatigue, insomnia, headache, nausea, anorexia, fever, depression, neutropenia  Dose adjust in renal and hepatic impairment  Concerns: CANNOT be used in females who are pregnant or may become pregnant or in males whose female partners are pregnant; 2 forms of contraceptive must be used during and for 6 months post treatment Sofosbuvir + ledipasvir (Harvoni)  MOA: ledipasvir – inhibits HCV NS5A protein necessary for viral replication; sofosbuvir – inhibits NS5B RNA-dependent RNA polymerase and acts as a chain terminator  Side effects: fatigue, headache, insomnia, nausea, diarrhea  Concerns: reactivation of Hep B; bradycardia when given with amiodarone  Cost: $37,800 for one month Glecaprevir + Pibrentasvir (Mavyret)  MOA: glecaprevir – inhibitor of HCV NS3/4A protease; pibrentasvir – inhibitor of HCV NS5A  Side effects: headache, fatigue, nausea, diarrhea, increased serum bilirubin  Concerns: reactivation of Hep B; not recommend for Child-Pugh class B and contraindicated in class C  Cost: $15,840 for one month Sofosbuvir + velpatasvir (Epclusa) **generic available**  MOA: velpatasvir – inhibits HCV NS5A protein needed for viral replication; sofosbuvir – inhibits NS5B RNA-dependent RNA polymerase and acts as a chain terminator  Side effects: headache, fatigue, nausea  Concerns: reactivation of Hep B; bradycardia when given with amiodarone Cirrhosis What is cirrhosis?  Late stage of fibrosis of the liver  Can be caused by hepatitis or chronic alcohol abuse  If caught early and the source of damage is treated, cirrhosis damage can be further limited, but the current damage cannot be undone.  Fibrosis and scarring of the liver will prevent it from doing its job. Cirrhosis Symptoms  Signs and symptoms often do not appear until the damage is extensive.  Fatigue, bleeding or bruising easily, itchy skin, jaundice, ascites, loss of appetite, nausea, edema in extremities, weight loss, hepatic encephalopathy Two Common Cirrhosis Complications  Ascites  Varices Ascites Ascites  Build up of fluid between the lining of the abdomen and abdominal organs  Results from portal hypertension and low levels of albumin  Management of ascites includes watching sodium and fluid intake, medications, paracentesis, or insertion of a shunt (TIPS). Ascites: What to Avoid  Drugs  Certain blood pressure medications   to Avoid Beta blockers, ACEi, ARBs Pain medications  NSAIDs  Products  Alcohol to avoid Management with Medications Spironolactone (Aldactone)  MOA: aldosterone antagonist/potassiumsparing diuretic - prevents retention of sodium and fluid  Side Effects: hyperkalemia, hypotension, gynocomastia  Contraindications: hyperkalemia Furosemide (Lasix)  MOA: block Na+ and Cl- reabsorption in kidneys  Side Effects: hypotension, photosensitivity, ototoxicity, hypokalemia, hypocalcemia, hyperuricemia  Contraindications: allergy (sulfonamide) Paracentesis A procedure to take out fluid that had collected in the belly  This fluid can be analyzed to find the cause of the fluid build up.  Paracentesis should be performed on all patients with new-onset ascites to determine the cause.  Diurectics should be used to reduce the fluid volume in the belly instead of serial paracenteses, but refractory cases of ascites may require frequent paracenteses.  Paracentesis  If a large volume of fluid is to be removed via paracentesis, a patient may require an infusion of albumin to reduce mortality.  Usual dosing is to give 6-8 grams of albumin for every liter of ascitic fluid removed. Albumin  Available   in 5% and 25% solution 5% is used in hypovolemic patients or intravascularlydepleted patients 25% is used in patients in whom fluid and sodium intake is restricted  MOA: provides increase in intravascular oncotic pressure and causes mobilization of fluids from interstitial into intravascular space  Side effects: chills, headache, edema, allergic reactions (hives, rash, itching, anaphylaxis) Complications of Ascites  Ascites puts a patient at risk for spontaneous bacterial peritonitis (SBP).  SBP is when bacteria are present within the ascitic fluid and cause infection.  SBP is treated with antibiotics, and anyone who survives one episode of SBP should be placed on SBP prophylaxis. Treatment of SBP Treatment of SBP = w/o recent b-lactam in community-acquired setting 3 rd Gen Cephalosporin Treatment of SBP Treatment of SBP with recent b-lactam and/or nosocomial setting = Depends on patient and local data New SBP Treatment Recommendations 3rd Generation Cephalosporins  Cefotaxime  MOA: (Claforan) & Ceftriaxone (Rocephin) inhibits bacterial cell wall synthesis by binding one or more PBPs  Side effects: injection site reactions, diarrhea, rash  Cefotaxime: requires dose adjustment in renal impairment  Ceftriaxone: do NOT use in neonates (≦28 days) SBP Prophylaxis Not available in the US Norfloxacin  Fluoroquinolone abx  MOA: DNA gyrase inhibitor  Side effects: dizziness, headache, nausea, tendonitis  Concerns: take on an empty stomach, and separate it from divalent cations (Ca, Mg, Fe) by two hours; avoid in children Sulfamethoxazole/Trimethoprim (Bactrim/Septra)  Sulfa abx  MOA: sequential inhibition of enzymes of the folic acid pathway  Dose adjust in renal impairment  Side effects: rash, photosensitivity, diarrhea, nausea, hyperkalemia (high doses)  Concerns: do NOT given to neonates (≦28 days) Varices Varices  Enlarged veins of the esophagus and stomach that result from portal hypertension  Medication can be used to prevent varices from bleeding, and multiple procedures exist to prevent variceal bleeding.  Nonselective beta blockers are used to help prevent varices from developing and prevent variceal bleeding. Nonselective Beta Blockers  nadolol (Corgard), propranolol (Inderal)  MOA: reduces portal pressure by producing splanchnic vasoconstriction and reducing portal blood flow  Side effects: bradycardia, hypotension, depression, dizziness, fatigue, sedation  Concerns: titrate to the maximal tolerated dose Child-Pugh Score Also known as Child-Turcotte-Pugh Score  This was developed to assess the prognosis of chronic liver disease (specifically cirrhosis).  It uses total bilirubin, serum albumin, prothrombin time, and the presence of ascites or hepatic encephalopathy to judge a patient’s degree of liver dysfunction.  It was originally made to predict mortality during surgery but is now mainly used to determine prognosis, treatment, and necessity of liver transplantation.  The Scoring System Resources  CDC Website on Hepatitis  AASLD Chronic Hepatitis B Treatment Guidelines  AASLD/IDSA/IAS-USE Hepatitis C Guidance  AASLD Varices Treatment Guidelines  AASLD Ascites Treatment Guidelines