Liver Disease
Definition:
Liver disease is classified according to the duration of abnormalities as either acute (< 6 months) or chronic (>6 months). Liver disease is common in the tropics from widespread consumption of alcohol and since the organ is in effect a filter of blood coming from the portal circulation, it is far more frequently exposed to bacteria, viruses, parasites and toxins.
Laboratory Evaluation:
Aminotransferases: (AST, ALT), intracellular enzymes released secondary to necrosis/inflammation. ALT more specific for liver than is AST (also found in heart, skeletal muscle). ALT > AST more likely viral hepatitis or fatty liver. AST: ALT ratio is > 2:1, this is suggestive of alcoholic hepatitis. Increased LDH is suggestive of ischemic or toxic hepatitis
Alkaline phosphatase: enzyme bound in hepatic canicular membrane. Besides liver, found in bone, intestines. Confirm it is liver in origin by check gamma glutamyltranspeptidase (will also be increased). Increased levels seen in biliary obstruction or intrahepatic cholestasis.
Albumin: marker for liver protein synthesis. Decreases in chronic liver disease
Prothrobmin Time (PT): depends on synthesis of coagulation factors. Increased levels found in severe acute injury or chronic injury.
Bilirubin: product of heme metabolism in liver. Direct or conjugated bilirubin is increased in obstruction.
Imaging:
Abdominal ultrasound: important for assessing portal and hepatic veins, degree of injury
Patterns of Liver Injury
Hepatocellular: markedincrease in AST and ALT +/- increased bilirubin in severe forms. AST and ALT > 1,000 is indicative of severe viral hepatitis, acetominophen toxicity or ischemic hepatitis
Cholestasis: increased alkaline phosphatase and direct bilirubin +/- mild increases in AST and ALT
Jaundice: a clinical sign when bilirubin levels are high > 2.5 mg/dl, if hyperbilirubinemia is conjugated, should see increase in urine bilirubin
Fulminant liver failure: increases in AST/ALT and alkaline phosphtase/bilirubin, need to also see increased in PT/INR and hepatic encephalopathy
Clinical Presenation:
Jaundice and/or hepatomegaly are almost always encountered with liver disease.
Other signs of liver disease: clubbing, palmer erythema, bruising, asterixis, spider nevi, gynecomastia, loss of body hair, splenomegaly, ascites, testicular atrophy, edema, muscle wasting
Types of Liver Injury:
Prehepatic causes:
Falciparm malaria, HUS, sepsis, pneumococcal pneumonia, sickle cell disease
Hepatic causes:
Viral Hepatitis: acute clinical syndrome ranges from asymptomatic infection to fulminant liver failure. Some progress to subclinical persistent infections and progress to chronic liver disease with cirrhosis +/- hepatocellular carcinoma.
-Pathophysiology: panlobular infiltration with mononuclear cells, hepatic cell necrosis, variable degress of cholestasis
-Signs/symptoms: anorexia, malaise, nausea, vomiting, fatigue, myalgias, headache, low grade fevers, RUQ pain, jaundice in 2 weeks, dark urine/pale stools. Increased AST/ALT first, bilirubin rises later in disease course. Prolonged PT = severe disease.
-Hepatitis A: fecal oral transmission, serologies: acutely anti HAV IgM, past infection is IgG. Can be a mild illness in children. No chronic carrier state. Treatment is supportive.
-Hepatitis B: **most common in tanzania, parenteral and perinatal -transmission.
-Serologies: hep B surface antigen positive = infection. Hep B surface antibody positive: immune to infection. Hep B E antigen positive: high infectivity rate.
-Pathophysiology: liver damage is mediated by host cellular immune response to infected hepatocytes
-Hep B infected patients have a high rate of progression to hepatoma (cancer). -Treatment: supportive, interferon, lamivudine, adefovir, tenofovir
-Can have co-infection with Hep D (hep D needs hep B in order for infection)
-Hepatitis C: parenteral transmission (particularly IV drug abuse). Serology: anti Hep C antibody positive. Treatment: pegylated interferon, ribaviron
-Hepatitis E: fecal oral transmission. More common in southeast asia. Increased mortality in pregnancy. Serology: IgM anti HEV
-EBV, CMV can also cause viral hepatitis
Alcoholic Hepatitis: usually an acute exacerbation of symptoms in a patient with chronic and excessive alchohol ingestion.
-Pathophysiology: hepatocyte injury, necrosis, polymorphonuclear infiltration
-Signs/Symptoms: RUQ pain, nausea, vomiting, low grade fever, jaundice, leukocytosis, AST: ALT ratio > 2:1, tender hepatomegaly
-Treatment: stop alcohol, supportive. If severe injury with hepatic encephalopathy, can treat with steroids x 1 month with taper
Vascular Hepatitis:
-Ischemic hepatitis: “shock liver” from severe hypotension (low cardiac output state) from septic shock, cardiogenic shock, AST/ALT > 1000
-Congestive hepatitis: from any cause of right sided heart failure -> passive congestion leading to ischemia and necrosis of liver
-Budd-Chiari Syndrome: occlusion (thrombosis) of the hepatic veins leading to sinusoidal congestion and portal hypertension -> passive congestion and ischemia of liver, necrosis of hepatocytes
Toxin induced Hepatitis:
-Acetominophen: usually ingestion > 10 grams to cause clinical syndrome but can occur at 2-6 grams in malnourished and alcoholics. 4-12 hours after ingestion: nausea, vomiting,diarrhea, abdominal pain, shock. Treatment: n-acetylcysteine
-Isoniazid, rifampin, fluconazole, phenytoin
-HIV medications: zidovudine, didanosine, nevirapine
-All statins for hyperlipidemia (stop drug is AST/ALT reaches 3-4 x upper limit)
Autoimmune Hepatitis:
-Pathophysiology: cell mediated immunological attack on liver cells
-Type 1: most common
-Signs/Symptoms:. Nausea/vomiting, fatigue, arthritis, anorexia, rashes, anemia.
-serology: anti smooth muscle antibody, + ANA. Treatment: steroids
Genetic Causes of Liver disease:
-Hemochromatosis: iron overload with deposition in liver, heart, pancreas. Signs/symptoms: bronze skin coloring, arthritis, CCF, hepatomegaly, cirrhosis. Diagnosis: increased iron saturation (iron/TIBC x 100% > 45%), increased ferriton.
-Wilson’s Disease: copper overload. Signs/symptoms: neurological manifestatinos (copper toxicity in brain), movement disorder, psychiatric, Kayser-Fleischer rings (copper deposits in cornea). Diagnosis: low serum ceruloplasmin.
Biliary origin:
-Primary biliary cirrhosis: autoimmune destruction of intrahepatic ducts
-Primary sclerosing cholangitis: cholestasis with fibrosis, stricturing of intra and extra hepatic ducts
Liver Disease Clinical Cases
Case 1
38 yo male with no past medical history presents to hospital with 2 week history of malaise, fatigue, nausea, RUQ pain and a 3 day history of dark urine and pale stools. His blood pressure on admission is 130/80 and heart rate 74. He is afebrile.
1. What disease process is he describing?
a. Acute liver injury with hepatic insufficiency
2. What laboratory tests and/or images do you want to order?
a. LFTs, US abdomen, EtOH level, Hepatitis Panel, Coags, FBP
3. What kinds of questions do you want to ask him to get a better history?
a. Recent exposures, etoh history, meds, sick contacts, new foods, contact with lake victoria
You order liver function tests and an abdominal ultrasound. His AST/ALT come back moderately high and his bilirubin is mildly high. Ultrasound is still pending. His RUQ pain is dull, achy and does not radiate. He does tell you that he is regularly involved with prostitutes. He does not drink alcohol excessively and he does not take any medications.
1. What is the most likely etiology of his liver disease?
a. Hepatitis B
2. What serologies do you want to order and which ones may come back positive?
a. Hepatitis panel with HbsAg, HbsAb, HBcAb, HBeAb specifically
i. Would also want to know IDS status!
3. What treatment can you offer him?
a. Oral therapy is thought to be as effective as Ifn, without the often intolerable side effects, So could start with lamivudine, adefovir, or tenofovir.
Case 2
40 yo male who is HIV positive (CD4 count of 300) presents with 2 month history of abdominal pain, nausea, vomiting and fatigue. He just started his antiretrovirals about 6 months ago and takes them daily. His abdominal pain is described as RUQ and dull with no radiation. He has not noticed any discoloration of his skin, urine or stool. His blood pressure on admission is 120/78 and his heart rate is 72. He is afebrile.
1. What laboratory tests and/or imaging do you want to order?
a. LFTs, US abdomen, EtOH level, Hepatitis Panel, Coags, FBP
2. What are you looking for in those laboratory tests?
a. Transaminase pattern and level, coagulopathy, liver texture, hepatitis serologies, and for signs of thrombocytopenia/anemia
3. What other questions do you want to ask?
a. Beyond the things mentioned above, with this patient on ARVs knowing which medications is quite important!
You order liver function tests and an abdominal ultrasound. The tests come back showing an elevated AST and ALT but normal alkaline phosphatase and bilirubin. His abdominal ultrasound shows patent hepatic and portal veins and mild hepatomegaly, no splenomegaly. His portal pressure on the abdominal ultrasound is normal. He tells you that his medications include nevirapine
1. What is the most likely etiology of his liver disease?
a. Acute hepatocellular damage 2/2 nevirapine.
2. How to do you want to treat this patient?
a. Change ARV regimen!
