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Hepatic Disease Keynote
 

Hepatic Disease Keynote

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  • Energy metabolism- carbohydrates, lipid and protein\nglucose production\ncholesterol synthesis\nProtein synthetic functions\nplasma proteins (albumin, clotting factors – not VII, angiotensinogen\nSolubilization, transport, and storage\ndrug and poison detoxification\nsolubilization of fats and fat-soluble vitamins\nsynthesis of VLDL, HDL, LDL, Various binding proteins\nuptake and storage of Vit A, D, B12 and Folate\nProtective and clearance functionsdetox of ammonia\ndetox of drugs\nclearance of damaged cells and proteins, hormones, drugs and clotting factors\nclearance of bacteria and antigens \n\n
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  • Hepatocyte function - absorption\nInability to conjugate – glucuronide transferase deficiency\nProblems transfer/excretion - bilirubin glucuronide into the biliary canaliculi \n** biliary obstruction – Gallstones \n
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  • The course of chronic viral hepatitis is unpredictale\n40-50% of HBV pts with cirrhosis die\nHBC is often subgclinical cirrhosis and hepatocullular CA \n
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  • The course of chronic viral hepatitis is unpredictale\n40-50% of HBV pts with cirrhosis die\nHBC is often subgclinical cirrhosis and hepatocullular CA \n
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  • The clinical presentation is a spectrum of enlarged liver critically ill who dies. \n\nSigns (pathopneumonic)\n\nPossible signs\n
  • The clinical presentation is a spectrum of enlarged liver critically ill who dies. \n\nSigns (pathopneumonic)\n\nPossible signs\n
  • The clinical presentation is a spectrum of enlarged liver critically ill who dies. \n\nSigns (pathopneumonic)\n\nPossible signs\n
  • The clinical presentation is a spectrum of enlarged liver critically ill who dies. \n\nSigns (pathopneumonic)\n\nPossible signs\n
  • The clinical presentation is a spectrum of enlarged liver critically ill who dies. \n\nSigns (pathopneumonic)\n\nPossible signs\n
  • The clinical presentation is a spectrum of enlarged liver critically ill who dies. \n\nSigns (pathopneumonic)\n\nPossible signs\n
  • B1 (thiamine) should be given in conjunction with glucose\nPrednisone is considered for mortality reduction\n
  • B1 (thiamine) should be given in conjunction with glucose\nPrednisone is considered for mortality reduction\n
  • B1 (thiamine) should be given in conjunction with glucose\nPrednisone is considered for mortality reduction\n
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Hepatic Disease Keynote Hepatic Disease Keynote Presentation Transcript

  • Hepatic Disease Clinical Medicine I Patrick Carter MPAS, PA-C February 14, 2011
  • Objectives Discuss the major metabolic functions of the liver. Identify the categories of viral agents that cause hepatitis. For each of the following, describe the etiology, risk factors, transmission, clinical features, diagnostic findings, treatment, and prophylaxis: ◦ HAV ◦ HBV ◦ HCV ◦ HDV ◦ HEV ◦ HGV Discuss the possible complications of viral hepatitis.
  • Objectives Differentiate between toxic and drug induced injury of the hepatic system. Define autoimmune chronic active hepatitis. Identify the typical clinical presentation of alcoholic liver disease. Identify the pathophysiologic mechanisms of alcohol injury to the liver.
  • Objectives Identify the typical treatment options for alcoholic liver disease including pharmacological, dietary, and life style treatments Discuss the association between alcoholic liver disease and portal hypertension. State the major complications of alcoholic liver disease including presentation, laboratory findings, and treatment of: spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy Indicate the prognosis for alcoholic liver disease.
  • Assessment Parameters Acute or chronic Focal or diffuse Mild or severe Reversible or irreversible Fulminant – development of hepatic encephalopathy within 8 weeks Sub-fulminant -- development of hepatic encephalopathy at 8 weeks – 6 months
  • Definitions Jaundice (Icterus) ◦ Yellow pigmentation of skin & sclera secondary to increased serum bilirubin Bilirubin ◦ Yellow breakdown product of normal heme catabolism Unconjugated (Indirect) bilirubin ◦ Heme is turned into unconjugated bilirubin in the reticuloendothelial cells of the spleen. It is then bound to albumin and sent to the liver. Conjugated (Direct) bilirubin ◦ In the liver bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase. Much of it goes into the bile and thus out into the small intestine Hepatitis ◦ Inflammation of the liver Cirrhosis ◦ Scarring and fibrosis of liver secondary to chronic liver disease
  • Hepatic Physiology Energy metabolism ◦ carbohydrates, lipid and protein ◦ glucose production ◦ cholesterol synthesis Protein synthesis functions ◦ plasma proteins (albumin, clotting factors)
  • Hepatic Physiology Solubilization, transport, and storage ◦ drug and poison detoxification ◦ solubilization of fats and fat-soluble vitamins ◦ synthesis of VLDL, HDL, LDL ◦ uptake and storage of Vit A, D, B12 and Folate
  • Hepatic Physiology Protective and clearance functions ◦ detox of ammonia ◦ detox of drugs ◦ clearance of damaged cells and proteins, hormones, drugs and clotting factors ◦ clearance of bacteria and antigens
  • Etiology of Hepatic Disease Cholelithiasis Excessive alcohol intake Inherited disorders Viruses/bacterial Infection Medications Cirrhosis Cancer
  • Jaundice (Icterus)
  • Causes of Jaundice CMDT 2011 Chapter 16
  • JaundicePathology Smart Charts, Groysman; McGraw-Hill. 2001
  • Acute Hepatic Failure Fulminant ◦ Hepatic encephalopathy within 8 weeks after onset of acute Liver Disease Subfulminant ◦ Hepatic encephalopathy between 8 weeks and 6 months after onset of acute Liver Disease
  • Acute Hepatic Failure Causes ◦ Acetaminophen toxicity is most common accounting for at least 45% ◦ Idiosyncratic drug reactions 2nd most common ◦ Viral Hepatitis (only 12% of all cases) ◦ Poisonous mushrooms ◦ Shock ◦ Hyperthermia / Hypothermia ◦ Budd-Chiari syndrome ◦ Malignancies ◦ Wilson disease
  • Acute Hepatic Failure Risk of acute hepatic failure is increased in patients with diabetes Outcome is worsened by obesity Symptoms & Signs ◦ Gastrointestinal ◦ SIRS ◦ Hemorrhagic phenomena ◦ Adrenal insufficiency ◦ Subclnical myhocardial injury
  • Acute Hepatic Failure Labs ◦ Serum aminotransferase levels are elevated (>5000 in acetaminophen tox) ◦ Bilirubin may be normal or minimally elevated initially then elevates as progresses ◦ Serum ammonia elevated – correlates with encephalopathy & intracranial hypertension
  • Acute Hepatic Failure Treatment ◦ Correct coagulation defects ◦ Correct electrolyte defects ◦ Correct acid-base disturbances ◦ Correct hypoglycemia ◦ Correct encephalopathy (lactulose) ◦ Prophylactic antibiotics not routinely recommended (only Sepsis) ◦ Steroids are uncertain in value ◦ Stress gastrophathy prophylaxis
  • Acute Hepatic Failure Treatment ◦ Treat intracranial hypertension (Mannitol) ◦ Administer acetylcysteine for acetaminophen toxicity ◦ EARLY transfer to liver transplantation center is crucial
  • Acute Hepatic Failure Prognosis ◦ Mortality up to 80% - except acetaminophen toxicity ◦ Acetaminophen toxicity up to 65% transplant free survival ◦ Be familiar with poor prognostic indicators for acetaminophen and non-acetaminophen hepatotoxicity in CMDT (page 608)
  • Acute Viral Hepatitis
  • Viral Hepatitis Essentials of diagnosis ◦ Prodrome of anorexia, nausea/vomiting, malaise, aversion to smoking ◦ Fever, enlarged and tender liver, jaundice ◦ Normal to low WBCs, markedly elevated aminotransferases early in the course ◦ Liver biopsy rarely indicated, but might show hepatocellular necrosis
  • Acute Viral Hepatitis Symptoms ◦ Icteric phase – jaundice after 5-10 days ◦ Convalescent phase – gradual disappearance of symptoms Signs ◦ Hepatomegaly ◦ Liver tenderness ◦ Splenomegaly in about 15% of cases
  • Hepatitis A Virus (HAV) Fecal/oral transmission Poor sanitation or crowded living situations Contaminated water & food ~ 30 days incubation Low level of mortality Fulminant cases are rare Never chronic
  • Hepatitis B Virus (HBV) Blood and blood products Sexual transmission Maternal-fetal transmission Prevalent in homosexuals and IV drug users Incidence has decreased by 75% since the 1980’s Onset is more insidious than HAV
  • Hepatitis B Virus (HBV) 6 week – 6 month incubation Aminotransferase levels higher than in HAV Risk of fulminant hepatitis is less than 1% but has a 60% mortality rate Infection persists in 1-2%, higher in immunocompromised
  • Hepatitis B Virus (HBV) Patients with chronic HBV have substantial risk of cirrhosis and hepatocellular carcinoma (up to 40%) HBsAg – first evidence of infection Anti-HBs – signals recovery from HBV infection and immunity Vaccination exists
  • Hepatitis B Virus (HBV) CMDT 2011 Chapter 16
  • Hepatitis C Virus (HCV) Transmission ◦ IV drug use ◦ Body piercings ◦ Blood transfusion Low risk of transmission ◦ Sexual ◦ Maternal/fetal
  • Hepatitis C Virus (HCV) 30 – 50% of HIV patients are coinfected with HCV ◦ Faster progression of chronic HCV to cirrhosis Incubation period is 6-7 weeks Clinical illness is generally mild or asymptomatic 80% will become chronic
  • Hepatitis C Virus (HCV) Screening to detect HCV antibodies Confirmation by an assay for HCV RNA About 20% of patients infected with HCV will clear the infection No vaccination available Treatment exists with varying results
  • Hepatitis D (Delta agent) Defective RNA virus that causes hepatitis ONLY in association with HBV Usually percutaneous exposure As superinfection with HBV, may cause fulminant hepatitis or severe chronic hepatitis In US, occurs mainly in IV drug users 3 x risk of hepatocellular carcinoma
  • Hepatitis E (HEV) Rare in the US Endemic areas are India, Burma, Afghanistan, Algeria and Mexico Waterborne Illness is self-limited Mortality rate of 10-20% in pregnant women
  • Hepatitis G (HGV) Percutaneously transmitted and associated with chronic viremia lasting at least 10 years Has been detected in ◦ 1.5% of blood donors ◦ 50% of IV drug users ◦ 30% of hemodialysis patients ◦ 20% of hemophiliacs ◦ 15% of patients with chronic hepatitis B or C
  • Hepatitis G (HGV) Does not cause important liver disease Does not affect the response of patients with chronic hepatitis B or C to antiviral therapy HGV coinfection may improve survival in patients with HIV infection
  • Viral Hepatitis Symptoms ◦ Prodromal phase  General malaise, myalgia, arthralgia, fatigue and anorexia  Distaste for smoking  Nausea/vomiting  Serum sickness in HBV  Fever, usually low-grade  RUQ or epigastric pain, usually mild
  • Acute Viral Hepatitis Prevention ◦ Thorough handwashing ◦ Universal precautions ◦ Screening of blood supply ◦ Vaccinations  HAV – close contacts of infected patients, persons traveling to endemic areas  HBV – universal vaccination of infants and children, healthcare workers
  • Chronic Viral Hepatitis
  • Chronic Hepatitis Defined as chronic inflammatory reaction of the liver of more than 3-6 months duration HBV +/- HDV, HCV, autoimmune hepatitis, Wilson’s disease, etc. Traditionally classified as chronic active or chronic persistent
  • Chronic Hepatitis B Affects 1.25 million people in the US Males > females Coinfection with HIV is associated with increased frequency of cirrhosis Treatment ◦ Interferon alpha-2b for 4 months for active stage ◦ Lamivudine 100 mg po qd – better tolerated
  • Chronic Hepatitis C Diagnosed by detection of HCV RNA in the blood About 20% will progress to cirrhosis in 20 years EtOH use more than 50 g/day increases risk of cirrhosis
  • Chronic Hepatitis C Treatment ◦ Most effective for genotypes 2 and 3 ◦ Combination therapy with pegylated interferon and ribavirin 600 mg po BID ◦ Response rates up to 55% ◦ Treatment is for 48 weeks ◦ May reduce the risk of hepatocellular carcinoma
  • Autoimmune Hepatitis Usually a disease of young women Onset is usually insidious May have multiple spider nevi, striae, acne, hirsutism and hepatomegaly Serum gamma globulin levels are usually elevated Liver biopsy is indicated
  • Autoimmune Hepatitis Treatment ◦ Prednisone with or without azathioprine  Prednisone 30 mg daily tapered down to maintenance dose of 10 mg daily  Azathioprine 50 mg daily ◦ Response rate to therapy is 80% ◦ Cirrhosis does not reverse with therapy ◦ Liver transplant may be required for treatment failures, may recur in 1/3 of patients
  • Hepatic Injury Direct hepatic toxins ◦ Dose related severity ◦ Latent period following exposure ◦ Susceptibility in all individuals ◦ Examples  Acetaminophen, EtOH, carbon tetrachloride, chloroform, heavy metals, mercaptopurine (6-MP), tetracycline, vitamin A
  • Hepatic Injury Drug induced idiosyncratic reactions ◦ Sporadic ◦ Not dose associated ◦ Features suggest allergic reaction (fever and eosinophilia) ◦ Examples  Amiodarone, ASA, carbamazepine, chloramphenicol, diclofenac, halothane, isoniazid, ketoconazole, phenytoin, etc.
  • Alcoholic Hepatitis Acute or chronic inflammation and parenchymal necrosis of the liver induced by EtOH Often reversible Most common cause of cirrhosis in the US 4-5 times more common cause of death as HCV which is the second most common
  • Alcoholic Hepatitis Frequency estimated at 10-15% of daily drinkers (more than 50 g) for over 10 years 50 g = 4 drinks (4 oz. 100 proof whiskey, 15 oz. wine or 48 oz. beer) Women > men Concurrent HBV or HCV increases risk
  • Alcoholic Hepatitis Signs and symptoms ◦ Enlarged liver ◦ Anorexia and nausea ◦ Hepatomegaly and jaundice ◦ Abdominal pain ◦ Splenomegaly ◦ Ascites ◦ Fever ◦ Encephalopathy
  • Abdominal pain
  • RecentHeavy Abdominal painDrinking SplenomegalyAnorexia AscitesNausea FeverHepatomegaly EncephalopathyJaundice
  • Treatment Strict EtOH abstinence - ESSENTIAL Caloric supplement and nutritional support Vitamin supplement – folic acid and thiamine Glucose administration increases Vitamin B1 needs and can precipitate Wernicke- Korsakoff syndrome – must co-administer thiamine
  • Treatment Prednisone 32 mg/day for 1 month ◦ May reduce short-term mortality for patients with alcoholic hepatitis and encephalopathy or greatly elevated bilirubin Experimental therapy with pentoxifylline 400 mg TID for 4 weeks may decrease risk of hepatorenal syndrome
  • Treatment Liver transplant ◦ Usually requires abstinence for 6 months prior to transplant ◦ Absolute contraindications  Malignancy, advanced cardiopulmonary disease and sepsis ◦ Relative contraindications  Age > 70, HIV infection, portal vein thrombosis, active substance abuse, severe malnutrition
  • Cirrhosis 12th Leading Cause of Death in U.S. Hepatocellular injury that leads to: ◦ Fibrosis ◦ Nodular Regeneration Risk Factors ◦ Chronic Viral Hepatitis ◦ Alcoholic Hepatitis ◦ Drug Toxicity ◦ Autoimmune Hepatitis
  • Cirrhosis Clinical Features are Secondary to: ◦ Portal HTN ◦ Hepatic Cell Dysfunction ◦ Portosystemic Shunting
  • Portal HypertensionPathology Smart Charts, Groysman; McGraw-Hill. 2001
  • Signs of Portal HTN
  • Major Complications Ascites ◦ Diagnostic paracentesis indicated for new ascites  Cell count and culture  Albumin level ◦ Restriction of dietary sodium and fluid intake ◦ Diuretics – spironolactone +/- Lasix ◦ Large-volume paracentesis (4-6 L) ◦ TIPS (transjugular intrahepatic portosystemic shunt
  • Major Complications Spontaneous bacterial peritonitis ◦ Abdominal pain, increasing ascites, fever and progressive encephalopathy ◦ Paracentesis shows high WBC count ◦ Cultures are usually positive – most common E. coli or pneumococci
  • Major Complications Spontaneous bacterial peritonitis ◦ Treatment with IV cefotaxime 2 g q 8-12 hours for 5 days ◦ Overall mortality rate is up to 70% in 1 year Hepatorenal syndrome ◦ Azotemia in the absence of shock or significant proteinuria in a patient with end- stage liver disease
  • Major Complications Hepatorenal syndrome ◦ Does not improve with IV isotonic saline ◦ Oliguria and hyponatremia ◦ Diagnosis of exclusion ◦ Cause is unknown ◦ Treatment is generally ineffective ◦ Mortality is high without liver transplant ◦ TIPS procedure may buy time until transplant
  • Major Complications Hepatic encephalopathy ◦ Disordered CNS function due to failure of the liver to detoxify noxious agents originating in the gut ◦ Ammonia is most readily identified ◦ Dietary protein withheld during acute episodes ◦ Lactulose to acidify colon contents NH4+ NH3 + H+
  • Major Complications Hepatic encephalopathy ◦ NH4+ is not absorbable ◦ Lactulose should be dosed at 30 mL 3 or 4 times daily ◦ Avoid opioids and sedatives that are metabolized or excreted by the liver ◦ Zinc deficiency should be corrected if present
  • Prognosis Points Class One year survival Two year survival 5-6 A 100% 85% 7-9 B 81% 57% 10-15 C 45% 35%
  • Non-Alcoholic Fatty Liver Disease(NAFLD) Up to 30% US population Etiology ◦ Obesity ◦ Diabetes ◦ Hypertriglycerides ◦ Corticosteroids Physical Activity protects against NAFLD Don’t worry about NASH
  • Non-Alcoholic Fatty Liver Disease(NAFLD) Signs & Symptoms ◦ Asymptomatic ◦ Mild Right Upper Quadrant Pain ◦ Hepatomegaly (up to 75%) Chronic Liver Disease uncommon
  • Non-Alcoholic Fatty Liver Disease(NAFLD) Laboratory Findings ◦ Mild elevated Aminotransaminases & Alkaline Phosphatase levels ◦ Ratio ALT to AST > 1 (opposite ETOH) ◦ Ratio does decrease if fibrosis/cirrhosis develop Imaging ◦ CT/MRI/US demonstrate fatty liver ◦ Does not distinguish hepatitis
  • Non-Alcoholic Fatty Liver Disease(NAFLD) Liver Biopsy ◦ Percutaneous ◦ Diagnostic & “Standard Approach” ◦ Assess degree of inflammation & fibrosis BARD Score used to predict advanced fibrosis
  • Non-Alcoholic Fatty Liver Disease(NAFLD) Treatment ◦ Remove offending factors ◦ Weight Loss ◦ Exercise ◦ Fat Restriction ◦ Gastric Bypass with BMI > 35 Statins are NOT contraindicated
  • Questions?