Virtual Rounds Session 12: Liver Pathology (Premed Shadowing)

Throughout each premed virtual shadowing session, you will actively participate by answering and asking questions about the week’s proposed case. Like an in-person shadowing experience, we strive to stimulate students intellectually and ultimately reaffirm their interest in medicine.

Introduction – Liver Pathology

The liver is important for production of bile, excretion of bilirubin/cholesterol, and metabolism of fats, carbohydrates, and proteins. The liver is also responsible for production of clotting factors responsible for successful fibrin clot formation. Due to the fact that the liver is the site of excretion of drugs, alcohol, and hormones, it can suffer damage in the way of increased fat deposition (steatosis) or scarring (cirrhosis).

Case Highlights 

A 47 y/o M with a PMH significant for HTN presents to the ED with a three day history of shortness of breath. He describes shortness of breath at rest of which is exacerbated by ambulation. His spouse is present and also states that the patient “has been more yellow than usual” and disoriented. He describes intermittent episodes of N/V, occasionally with blood but denies syncope, CP, or LOC. The patient is a daily drinker of alcohol and consumes approximately 1 six-pack of beer per day for “as long as I can remember.” History is also positive for fatigue, diffuse abdominal pain with bloating, and weakness. No previous similar episodes. The patient takes lisinopril for hypertension but denies other medications. 

Pathology 

1. DEFINITION
   1. Fibrosis of the liver is the result of recurrent insult to the hepatocytes and normal liver architecture of which is often irreversible. 
   2. Historically, cirrhosis has been classified as:
      1. Micronodular (<3mm) 
      2. Macronodular (>3mm) 
      3. Mixed
      4. Usually macronodular → micronodular in end stages of cirrhosis.
2. ETIOLOGY 
   1. Consider the following causes of cirrhosis:
      1. Alcoholic cirrhosis 
         1. Substance abuse 
      2. Hepatitis (viral)
         1. IVDA, risky sexual behavior 
      3. Hemochromatosis 
         1. Genetic, HFE gene
      4. NAFLD
         1. Poor diet (western diet)
      5. Autoimmune hepatitis 
         1. Genetic, anti-smooth muscle Ab
      6. Wilson’s Disease 
         1. Copper transport, genetic 
      7. Alpha-1-antitrypsin Disease
         1. Genetic 
      8. Veno-occlusive Disease (Budd-Chiari)
         1. Hypercoagulable states
      9. Medications 
         1. MTX, INH
3. DIAGNOSIS / EVALUATION
   1. On physical exam, you may find the following:
      1. Jaundice 
      2. Gynecomastia, palmar erythema
         1. Increased estrogen 
      3. Spider angiomata
      4. Asterixis 
      5. Fetor hepaticus 
      6. Hepatosplenomegaly
      7. Caput medusae 
      8. Varices 
         1. Rectal, esophageal → GI bleeding
      9. AMS, encephalopathy 
      10. Ascites
   2. In order to diagnose cirrhosis, lab values might show:
      1. ↑ AST / ALT (liver enzymes)
         • AST > ALT in alcoholic cirrhosis 
      2. ↑ ALP, GGT
      3. ↑ Bilirubin 
         • May be normal in compensated cirrhosis, though increase as disease progresses
      4. ↓ Albumin (may lead to fluid shifts and ascites)
      5. ↑ PT (loss of clotting factors produced by the liver)
      6. Thrombocytopenia, anemia, leukopenia
      7. ANA, Anti-Smooth muscle Antibody (AI hepatitis)
   3. Furthermore, you might order the following imaging / diagnostic testing in order to confirm the diagnosis:
      • US (first-line) 
      • CT
      • MRI 
      • Biopsy (gold-standard, see below for biopsy of liver cirrhosis.
4. COMPLICATIONS
   1. Complications of cirrhosis include:
      1. Portal hypertension
      2. Ascites
      3. Spontaneous bacterial peritonitis (SBP) 
      4. Hepatic encephalopathy 
      5. Hepatorenal syndrome
      6. Bleeding
      7. Hepatocellular carcinoma 
      8. Increased risk of infection 
      9. Death 
5. TREATMENT
   1. Treatment of cirrhosis ultimately depends on the underlying cause:
      1. Viral Hepatitis (B, C) = anti-virals 
      2. Hemochromatosis = phlebotomy 
      3. Wilson’s Disease = penicillamine
      4. Alcoholic = drinking cessation, avoid/manage complications of cirrhosis. 
      5. Medications = stop offending agent 
      6. Veno-occlusive disease = anticoagulation
      7. Autoimmune hepatitis = prednisone, azathioprine

 Take home points

1. 1. Liver pathology can cause significant morbidity and mortality given the multitude of functions that the liver has, including production of bile, excretion of drugs, and production of clotting factors.
   2. There are many causes of liver cirrhosis of which must be determined in order to implement the correct treatment. 
   3. A combination of physical exam findings, labs, and imaging/diagnostic testing can help diagnose and potentially pinpoint the etiology of cirrhosis. 
   4. Since cirrhosis is often irreversible, treatment can be directed toward not only the cause itself but managing or preventing complications of cirrhosis.