Lecture 5: Hepatitis Flashcards
Liver blood flow
Liver has double circulation with high o2 concentration – metabolic workshop, digests all nutrients, destroy toxin and metabolizes substances
Hepatocytes
metabolize proteins, lipids, carbs, produce bile, produce clotting factors and neutralize toxins. They are functional liver cells. When injured by inflammation or toxins they produce Transaminase – ALT, AST.
Bile
metabolizes lipids. Without then the lipids are not emulsified.
Cholangiocytes
cells of the inner membrane of the bile duct. If duct is obstructed, the cholangiocytes will produce alkaline phosphatase, another enzyme.
Unconjugated bilirubin
Liver metabolizes bilirubin. Bilirubin is produced by old red blood cells. 120 days is the lifespan of a RBC. Hemoglobin –> Haem –> Unconjugated bilirubin inside the spleen. This is indirect bilirubin, it is insoluble. Cannot be excreted by the body. Indirect and insoluble, cannot be excreted. –> Travels to the liver where it is conjugated and made soluble. Liver can get overwheled by too much hemolysis and the unconjugated bilirubin will back into the blood. Hemolysis –> Unconjugated hyperbilirubinemia (indirected hyperbilirubinemia)
Conjugated bilirubin
Travels to the liver where it is conjugated and made soluble. This is called direct bilirubin because it can be directly excreted by the body. This is excreted with bile into the stool. Which is why the stool is brown because of bilirubin. Due to direct bilirubin. Urine is yellow due to bilirubin when the kidneys excrete it
Bile duct obstruction (stones, tumors of the pancreatic head) cannot be drained, will
spill back conjugated
Hemolysis the problem is this type of bilirubinemia b/c liver is overwhelmed by the amount of bilirubin.
unconjugated
In obstruction of common bile duct via stone or tumor the problem is w drainage of this type of bilirubin
conjugated, because liver can conjugate but cannot excrete –> hyperbilirubinemia conjugated/direct.
LFTs for Injury
AST, ALT, Alkaline phosphatase. ALT and AST produced by hepatocytes, any injury regardless of etiology which cannot be determined which specific cause, will be a group of etiologies will indicate injury to hepatocytes. Alk phos is obstruction of bile flow/cholagiocytes
LFT Function
Albumin, PT/INR, Bilirubin
Hepatocellular
Injury to hepatocytes
ALT (Alanine aminotransferase)
AST (Aspartate aminotransferase)
Cholestatic
Obstruction of the bile flow (stasis of the bile)
Alkaline phosphatase
Hepatocellular caused by
Injury to hepatocytes Viral hepatitis Drugs affecting hepatocytes Alcohol liver disease Non-alcohol liver disease Autoimmune hepatitis Hereditary diseases (hereditary hemochromatosis, Wilson disease)
Cholestatic causes
Obstruction of the bile flow
Gall stones in common bile duct
Pancreatic/ hepatic mass
Drugs affecting bile flow
Drugs affecting the liver
Tylenol > 7.5 grams per day. TB drugs. Antiseizure drugs. Antifungals. Most commonly: acetaminophen, augmentin
ALT AST much higher than AP means what, and vice versa
Usually AST ALT <40.
ALT X 5 and alk phos x 2 then it is probably alcohol, or hepatitis, or fatty liver etc (hepatic)
Alk phos x 5 but alt x 2 –> cholestasis = stone, tumor –> next step: US
ALT > AST
in all hepatocellular conditions except conditions caused by alcohol
AST> ALT
in condition caused by alcohol (AST: ALT= 2:1)
AST > ALT (2:1) with AST in 100-200 u/L
Alcoholic liver disease
ALT > AST, with ALT in 1000 u/l
Acute viral hepatitis (A,B), acute drug induced injury, (acetaminophen >7.5 g/d). Work up: Hepatitis A, B panel, acetaminophen level
ALT > AST, with ALT in 100s u/l
Chronic viral hepatitis (B,C), drug-related injury (TB medications, antiepileptic, methotrexate, statins, amiodarone, acetaminophen, amoxicillin-clavulanate), non-alcoholic fatty liver disease, congestive liver disease, autoimmune hepatitis
ALT > AST, with ALT in 100s u/l – work up
Hepatitis B,C panel, autoantibodies (ANA), review medication history (obesity, T2DM, hyperlipidemia)
Why when AST ALT is lower in chronic
When liver is replaced by fibrous tissue there are no functional hepatocytes so nothing is producing ALT AST
Alkaline phosphatase (<120 u/L)
Marker of cholestatic injury (intrahepatic and extrahepatic)
Maybe slightly elevated in hepatocellular injury
Requires evaluation of biliary tree (US-initial test, MRCP is more accurate)
Elevated AP w/ ductal dilation
extrahepatic cholestasis. Choledocholithiasis (sharp pain) Pancreatic cancer (painless or dull pain)
Elevated AP w/ out ductal dilation
intrahepatic cholestasis. Metastatic disease (colon, prostate) Hepatocellular carcinoma
PT/INR (11-15 sec/1.0)
Most sensitive marker of synthetic function of the liver Most sensitive marker of acute liver injury. Marker of prognosis. Increase in PT/INR= decrease in the synthetic liver capacity. Albumin, Bilirubin, PT/INR = Liver Function
PT includes factor 7 half life of 6 hours only and is reflected in prolonged PT – more sensitive to acute changes than the PTT for liver injury but both will be abnormal. ACUTE changes reflected in PT. Not PTT.
Albumin (3.5-5.3 g/dl)
Marker of synthetic function of the liver. Decrease in albumin = decrease in the synthetic liver capacity. Albumin is not specific for the liver( decrease in albumin in nephrotic syndrome or malnutrition) Maybe normal in acute injury. Albumin half life is 20 days. Synthetic liver function, does not indicate acute changes. Nephrotic syndrome lose the protein in urine where albumin will also be depleted but not due to liver, same with malnutrition.
Total bilirubin (0.5 -1.0 mg/dL)
Marker of synthetic function
Indicator of severity of disease
Jaundice if bili >
2
Elevated bilirubin : caused by
hemolytic and obstructive
Hemolytic
increased destruction of red blood cells, overwhelmed liver is unable to conjugate all unconjugated bilirubin (increase in indirect/unconjugated bilirubin)
Obstructive
obstruction of the bile ducts or damage to the hepatocytes so that the usual amount of conjugated bilirubin cannot be excreted into GI tract (increase in direct bilirubin)
Elevated total bilirubin w/ normal direct bilirubin etiology
hemolysis need reticulocyte count, anemia, normal liver enzymes, (-) urine bilirubin
Elevated total bilirubin w/ elevated direct bilirubin etiology
Liver disease (cholestatic or hepatocellular). Abnormal liver enzymes, (+) urine bilirubin
Hepatocellular disease labs
AST/ALT very high, AP normal to high, total and direct bili normal to high, INR and Albumin usually normal unless severe cirrhosis
Cholestastatic disease
AST/ALT normal to high, AP very high, total and direct bili normal to high, INR and Albumin usually normal unless severe cirrhosis
Hep A
Fecal oral transmission, Traveling to endemic areas (fecal contamination of water, food) Only acute form; self-limiting. Fulminant hepatitis is rare
Hep B
Blood Unprotected sex Mother-baby transmission, at risk Unprotected sex IVD users, Acute and chronic . Chronic in 90% of infected infants and only 5% of infected adults. Cirrhosis (in 20% of chronically infected 20 years after exposure) Hepatocellular carcinoma (HCC 2% risk per year)
Hep C
Blood Unprotected sex (very rare) transmission, at risk IVD users Healthcare workers, 85% of infected individuals will have chronic infection. Cirhosis (in 20% of patients 20 years after exposure). Hepatocellular carcinoma (HCC 2% risk per year)
Hep D
Coexist w B, all the same as B
Hep E
fecal oral, same as A
Clinical manifestations of acute hepatitis (regardless of etiology)
Maybe completely asymptomatic in severe cases : Fatigue, Anorexia Weight loss Nausea, +/- vomiting Abdominal discomfort Low grade fever (+/-) arthralgia Signs: Jaundice, scleral icterus, dark urine, pale stool, liver tenderness, hepatomegaly
Clinical manifestations of chronic hepatitis
Asymptomatic (discovered by abnormal liver enzymes/ abnormal US imaging) or Mild symptoms (fatigue, abdominal discomfort “ fullness”, anorexia) or Symptoms of decompensated cirrhosis (ascites…)
Cirrhosis leads to reduced albumin which causes
decreased oncotic pressure and transudation of fluid –> ascites
physical exam for ascites includes what?
Bulging flunks (observation), fluid wave (palpation), shifting dullness (percussion)
Chronic liver disease stigmata
“Spider” angioma, Palmar erythema, Gynecomastia
Portal hypertension leads to?
distention of abdominal veins aka Caput medusae
Hepatic encephalopathy results from ?
hyperammonemia
Workup for suspected hepatitis includes?
Consider travel history, risk factors, alcohol consumption, medications review, history of diabetes, obesity, hyperlipidemia
LFTs and bilirubin (increased direct bilirubin, increased ALT more than AST, minor elevation of Alk phosphatase)
Viral hepatitis serology (A,B,C)
Consider CMV serology (CMV IgM), EB (EB IgM)
HBs Ag is?
Surface antigen. Rises first and indicates active infection. Triggers production of surface antibodies (Anti HBs)
Anti HBs is?
Antibodies for surface antigen, indicates resolution of active infection and immunity (and successful vaccination)
HBc Ag is?
Core antigen. NOT detected in blood. Triggers production of surface antibodies ( IgM Anti-HBc, IgG-Anti HBc)
IgM Anti HBc is?
Antibodies to core antigen. Indicates acute infection
IgG Anti-HBc is?
Antibodies to core antigen. Indicates resolution of infection
HBe Ag
E antigen. Indicates high level of infectivity ( correlates with high viral load)
Anti- HBe
Antibody to e antigen. Indicates low level of infectivity
acute hep B serology?
HBs Ag, IgM anti-HBc
Resolution of acute Hepatitis B serology?
anti-HBs, IgG anti-HBc
Chronic Hepatitis B serology?
HBs Ag, IgG anti-HBc
Interpret: (-) HBsAg, (-) anti-HBc, (-) anti-HBsAg
nothing. should be vaccinated.
Interpret: (-) HBsAg, (+) anti-HBc, (+) anti-HBsAg
previous infection that has been resolved. not infected now
Interpret: -) HBsAg, (-) anti-HBc, (+) anti-HBsAg
pt was successfully vaccinated (core is negative)
Interpret: (+) HBsAg, (+) anti-HBc, (+) anti- HBc IgM,
(-) anti-HBsAg
acute active infection because + surface antigen, -antibody; Igm+ so acute
Interpret: (+) HBsAg, (+) anti-HBc, (-) anti- HBc IgM,
(-) anti-HBsAg
infected, chronic because IgM is negative
Interpret: (-) anti-HCV
no hep c
Interpret: (+) anti-HCV , followed by (+) HCV RNA
active infection (chronic hep c)
Interpret: (+) anti-HCV , followed by (-) HCV RNA
resolved spontaneously or treated and cured
Treatment of acute viral hepatitis (A and B)
- Supportive (anti-emetics, adequate hydration, adequate nutrition)
- AVOID alcohol (not limit- avoid)
- Steroids, high-carbohydrate and low-protein diets are not recommended (small frequent meals)
Treatment of chronic hepatitis B
Oral direct antiviral therapy monotherapy , 20-25% achieve suppression of viral load
Only patients with significant viral activity (HBeAg and high viral load should be treated
Goal is suppression Hep B replication (low viral load -HBV DNA) and HBeAg seroconversion
Long-term therapy is necessary (4-5 years and more)
Treatment of chronic hepatitis C
Oral direct antiviral therapy (one pill once a day), >90% patients achieve cure
Goal is to achieve undetectable HCV RNA for at least 6 months after cessation of therapy (= cure)
The treatment and the duration is based on Hepatitis C genotype (genotype 1 accounts for 70%), usually 12-24 weeks
All patients with active HCV infection would benefit, with the exception of those with life expectancy less than 12 months
Treatment of compensated cirrhosis
Surveillance of HCC every 6-12 months (ultrasound)
Screening for esophageal varices (endoscopy)
Avoidance alcohol (no safe level !)
HAV, HBV, pneumococcal pneumonia, and influenza immunizations
Statins can be safely used
Acetaminophen may be used in persons with cirrhosis in doses of up to 2 g daily
Aspirin and other NSAIDs should be avoided- because can cause kidney damage and also because these pts are predisposed to bleeding
High-caloric small meals
Treatment of decompensated cirrhosis
Esophageal varices – non-selective beta-blockers ( decrease portal flow)
Ascites – diuretics (Spironolactone) and sodium restriction diet
Hepatic encephalopathy- lactulose (decrease absorption of ammonia)
who should we screen for hep c?
Individuals borne 1945-1965 regardless of risk factors IV drug users HD patients HIV infected individuals MSM Abnormal liver enzymes
who should we screen for hep b?
All pregnant women (each pregnancy) IV drug users HD patients HIV infected individuals MSM Abnormal liver enzymes
who should get vaccinated for hep a? (2 doses)
Travellers to endemic areas
MSM
Drug users (poor housing conditions, high prevalence of hepatitis C)
Patients with chronic liver disease
who should get vaccinated for hep b? (3 doses)
IV drug users Multiple sexual partners MSM Healthcare/ public safety workers Patients with chronic liver conditions Patients on HD Patients with DM 19-59 y. (sharing needles, finger stick devises, syringes ,needles)
