L11: Hepatitis/Liver disease Flashcards
Most prevalent liver disease
Nonalcoholic fatty liver disease
Spectrum of AST or ALT values for liver disese
Shock liver/acetominophen (10,000) > Acute Hep A, B, C > ETOH> Chronic Hep B and C > Cirrhosis > normal (15-30)
Hepatocellular pattern
Increased liver transaminases: ALT + AST
+/- Elevated ALP
AST:ALT>2
Alcoholic liver disease
ALT>AST (AST:ALT<1)
NASH
Acute or chronic viral hepatitis
Cholestatic pattern
Elevated ALP and GGT
Fatty liver aka
hepatic steatosis
Non-alcoholic is defined as
<20 g ETOH/day (less than2-3 drinks/day)
Non-alcoholic steatohepatitis (NASH)
fatty liver with inflammation of liver with hepatocyte injury→ higher risk of fibrosis, cirrhosis→ worse prognosis, progression
Isolated steatohepatitis (NAFLD)
fatty liver without injury or fibrosis→ low risk of progression to cirrhosis (but still not considered benign)
Diagnosis of NASH
Biopsy is gold standard
but Fibroscan, MRI, MRE used more often
Presentation of NAFLD/NASH
Asymptomatic
Fatty infiltration incidentally seen on imaging→ exclude other causes, ETOH
NAFLD/NASH on liver biopsy
biopsy is not necessary, but you would see: steatosis, inflammation, +/- fibrosis
NAFLD/NASH labs
Hepatocellular pattern Mild Elevation ALT + AST <300 IU/ml Ferritin elevated (53-62%) → inflammation Hyperlipidemia Elevated fasting glucose ALP elevated in ⅓ GGT elevated \+/- Weakly positive autoimmune factors→ get bx to confirm Normal albumin, bilirubin and INR
NAFLD/NASH
Exclude all other causes of elevation of liver tests Order Fibroscan/calculate FIB- 4 Exercise + weight loss (DOC) Body weight reduction associated with histological improvement Minimize ETOH, Modify CVD risk factors Control diabetes and hyperlipidemia → compensated cirrhotic→ Statins Monitor LFT/liver tests Vaccinate for Hep A & Hep B
Liver bx→ confirm dx (before tx w/ meds), exclude concomitant liver disease, assess degree
DOC for NAFLD/NASH
Exercise + weight loss
Hereditary disorder of iron metabolism→ genetic mutation → increased GI absorption of iron → accumulation of iron in the liver, pancreas, heart, adrenals, testes, pituitary, skin, kidney
Hereditary Hemochromatosis
Bronze diabetes
Hereditary Hemochromatosis triad:
DM
Bronze pigmentation of skin
Cirrhosis
Hereditary Hemochromatosis presentation
Family history or incidental note ↑ AST + ALT (Northern Europeans)
Initially non-specific symptoms
Fatigue, malaise, RUQ discomfort
Hereditary Hemochromatosis labs
Elevated Liver tests AST, ALT, Alk Phos
Screen→ serum Fe + TIBC and ferritin
• Fe/TIBC = TS (transferrin saturation)
• TS > 45 and/or ferritin > 200 ng/mL (men) > 150 ng/mL (women) → GI- HFE* mutation analysis
Confirmed with genetic testing +/- liver biopsy
Hereditary Hemochromatosis management
Regular phlebotomy (hematologist )
Prevent cirrhosis from iron overload
Cirrhosis screen q 6 months (US +/- AFP)
Avoid Vit C, iron supplements, ETOH
Avoid uncooked shellfish (oysters) while iron testing
Hereditary Hemochromatosis screening guidelines
Genetic screen→ HFE genotype
Iron testing
Screen in pts with: Elevated Liver tests (AST/ALT) Abnormal iron studies First degree relative history Evidence of liver disease* Suggestive symptoms
Late Hereditary Hemochromatosis
4th-5th decade Hepatomegaly hepatic insufficiency cirrhosis (+/-complications) DM impotence, arthralgia (2nd/3rd MCP joints) bronze pigmentation of skin Cardiomegaly with or without CHF Bronze Diabetes
Very rare hereditary disorder of copper metabolism
Autosomal recessive mutation→ decreased excretion of copper into
bile→ accumulation of copper in liver→ liver capacity for copper exceeded→ released into bloodstream→ accumulates in brain, cornea, joints, kidney, heart, pancreas
Wilson’s Disease
Wilson’s disease presentation
Ages 3-55
Hepatic Symptoms
Neurologic/psychiatric symptoms→ tremor, dysarthria, incoordination/ataxia, parkinsonism personality/behavioral changes
Kayser-Fleischer ring→ fine pigmented brownish/gray-green granular deposits on cornea
→ detected by naked eye or ophthalmoscope
Wilson’s Disease treatment
Refer to GI with training in Hepatology
Chelating agents:
D-penicillamine
Trientine
Wilson’s Disease labs
Mildly Elevated AST/ALT
Alk phos→ normal or low
Reduced <5 ug/dl serum ceruloplasmin (initial screen)
→ plasma copper-carrying protein
Ophthalmologist eval.
Increased 24 hour urinary copper
Confirmed with liver biopsy +/- molecular testing*
First degree relative screening→ genetic analysis
Pathognomonic for Wilson’s Disease
Kayser-Fleischer ring + neuro manifestations
D-penicillamine
Copper chelating agent
Trientine
Copper chelating agent
Severe alpha-1 antitrypsin deficiency
Severe→ < 11 umol/L
alpha-1 antitrypsin deficiency presentation
non-smoker with emphysema at a young age (<45 years)
neonatal cholestasis
childhood cirrhosis
alpha-1 antitrypsin deficiency screening
Emphysema in :
• Young patient (<45 yo)
• Non-smoker or minimal smoker
• Predominant basilar changes on CXR
Adult onset asthma
• Persistent airflow obstructive pattern on post bronchodilator spirometry testing
Clinical findings or history of unexplained chronic liver disease
• Current or prior elevation of liver tests
• Patient with cirrhosis +/- portal HTN (nodular small liver, splenomegaly, low platelets)
Family hx of emphysema and/or liver disease
History of panniculitis (skin)
alpha-1 antitrypsin deficiency labs
Mild elevation of AST/ALT
Decreased serum alpha-1 antitrypsin
Alpha-1 antitrypsin genotype (MM=wildtype)
Rule out other causes
+/- Liver biopsy
alpha-1 antitrypsin deficiency treatment
Liver transplant
Genetic counseling
Autoimmune hepatitis presentation
Variable
Asymptomatic w/ elevated liver enzymes
Cirrhosis
Non-specific symptoms→ Fatigue, Malaise, Anorexia, Pruritus, Abdominal Pain, Arthritis
Acute severe liver disease→ Acute hepatitis +/- liver failure (⅓)
→ Hepatosplenomegaly
→ Jaundice, Fever
Labs for autoimmune hepatitis
- Antinuclear antibodies (ANA) (10%)
- Anti-smooth muscle antibodies (ASMA) (90%)
- +/- Liver kidney microsomal antibody (LKMA)
- antibody to liver cytosol (LKC-1 (30-50%)
- Anti-soluble Liver Antigen (SLA) → children
- Anti-liver pancreas antigen (LPA) → children
- Elevated bilirubin
- Elevated ALP→ 3x ULN
- Elevated PT/INR
- Albumin (decreased)
- AST/ALT→ 7-10x ULD
- High IgG titer
Autoimmune hepatitis management
Refer to Gastroenterologist/ hepatologist
Depends on disease activity
Prednisone +/- Azothioprine (Imuran)
• Continue until remission (normalization of LFT)
• Watch for side effects from steroids/Imuran with labs and follow-up
• Maintain on lowest dose of Imuran for continued remission
• Monitor bone density (DEXA)
Liver transplant→ fulminant liver failure
Vaccinate for Hep A and Hep B
Prednisone +/- Azothioprine (Imuran)
mainstay of tx for Autoimmune hepatitis
Acute hepatitis
Hep A, E
Fecal-oral hepatitis
Hep A, E
Vaccines for hepatitis
Hep A, B
Hepatitis that’s fatal in pregnancy
Hep E
Hep A background/transmission
Inadequate sanitation/clean water
Endemic→ Asia + Africa
Recent homeless outbreaks
Fecal-oral, person to person (oral-anal sex), contaminated food or water
Hep A presentation
Acute Children <6 years asymptomatic Adults symptomatic Incubation→ 15-50 days (avg 28) Prodrome Flu-like→ fever, N/V/A, malaise, RUQ pain Icteric phase Jaundice→ 1 week after symptom onset *Hepatomegaly*, dark urine, pruritus, light colored stool
Hep A labs
Increased AST/ALT (>1000 or 15x ULN)
Increase bilirubin + ALP
(+) IgM anti-HAV→ acute
(4 months)
(+) IgG anti-HAV→ immunity
Hep A management
Supportive→ fluids, rest→ recovery in 6 months
Hospitalize→ elderly, multiple comorbidities, underlying liver disease, fulminant liver failure
Infection precautions→ hand washing, food handling, food prep/cook temp >185 F, chlorine/bleach for cleaning
Notify local health department
Non immune contacts→ HAV IgG and/or vaccination
Prevention→ vaccination
Hep A patients who get hospitalized
Elderly
multiple comorbidities
underlying liver disease
fulminant liver failure
Nonimmune contacts can get ____ as Hep A prophylaxis
HAV IgG
Vaccine
Hep B transmission
DNA virus
Blood/blood derived body fluid, sexual, parenteral contact (needle sharing), perinatal transmission during delivery
Hep B is a ____ virus, Hep C is a ____ virus
Hep B: DNA virus
Hep C: RNA virus
This means Chronic Hep C can be cured/cleared from the body because it doesn’t have DNA intermediates. Chronic Hep B has no cure.
Hep B presentation
Incubation→ 45-160 days Symptomatic (30%)→ N/V, RUQ pain, jaundice, malaise, arthralgias, fever. Increased bilirubin, ALP Increased ALT >15x Subclinical (70% adults, 90% children) Chronic→ <5% adults, most infants Fulminant hepatic failure (rare)
Leading cause of cirrhosis + hepatocellular carcinoma
Chronic Hep B
Hep B management
Supportive→ 95% of adults recover with immunity
+/- antiviral therapy→ acute liver failure or protracted course
Hospitalize these patients with Hep B
Underlying liver disease
Multiple comorbidities
Older/Elderly→ more severe in age >60 years
Signs of liver failure→ transfer to liver transplant center (rare)
Who most commonly gets chronic hepatitis B?
Children <5 years
Immunocompromised
HBsAg
(+) active disease→ acute or chronic
(+) >6 months→ chronic
1st detectable marker of infection→ 1-9 weeks after exposure→ before onset of symptoms
Hallmark of active infection
Anti-HBs/HBsAb
(+) immune→ vaccine or resolved infection
Appears after disappearance of HBsAG→ indicates end of acute infection phase→ recovery & immunity
Hep B vaccine→ exposure to HBsAg→ (+)
Anti-HBc
(+) IgM→ acute
(+) IgG→ previous
(+) Total→ previous
IgM→ shortly after HBsAg detected, or HBsAg cleared but Anti-HBs not yet detected
Acute/recent infection→ 4 months
IgG→ prior or resolving infection→ forever
Total= IgM + IgG → prior exposure
HBeAg
(+) → high viral load, actively replicating
(-) → low viral load
Marker of infection→ higher levels of HBV DNA
Anti-HBe
(+) → predictor of long term clearance
(+) anti-HBe + (-) HBeAg→ lower levels of HBV DNA
HBsAg (-)
Total anti HBc (-)
Anti-HBs (-)
Susceptible to HBV infection
HBsAg (-)
Total anti HBc (+)
Anti-HBs (+)
Immune to HBV by natural infection
HBsAg (+)
Total anti HBc (+)
Anti-HBs (-)
IgM anti-HBc (+)
Acute infection with HBV
HBsAg (+)
Total anti HBc (+)
Anti-HBs (-)
IgM anti-HBc (-)
Chronic infection with HBV
HBsAg (-)
Total anti HBc (+)
Anti-HBs (-)
Interpretation unclear:
-
1. Resolved infection (most common)*
2. False (+) anti-HBc→ susceptible
3. Low level chronic infection
4. Resolving acute infection
HBsAg (-)
Total anti HBc (-)
Anti-HBs (+)
Immune to HBV by vaccination
most common cause of liver transplantation with hepatocellular carcinoma
Hep C
Hep C
RNA virus
Blood/blood derived body fluid transmission
Most develop chronic infection
Risk: IVDU, tattoos, piercings Transfusion <1992 Received clotting factors <1987 Know exposure (needle stick) Children born to HVC (+) mother (rare) Sexual contact (rare, >MSM)
Acute Hep C infection
14-180 days post exposure Asymptomatic (most) Symptomatic→ jaundice, fatigue, fever, nausea, vomiting, RUQ discomfort (10-20%) AST/ALT→ elevated, <300 IU/l ) Bilirubin elevated
(-) Hep C Ab with (+) RNA viral load
OR
(+) Hep C Ab prior had (-) Hep C Ab
Chronic Hep C
Most asymptomatic and diagnosed by ↑LFT/liver tests→ AST + ALT <100
+/-fatigue, wt. loss, anorexia, nausea, RUQ discomfort
Cirrhosis w/in 20-30 years (10-20%) → watch for complications
Many present in 20s due to IVDU
Screening for Hep C
Born 1945-1965 w/o prior assessment of risk
Received a blood transfusion or organ transplant before July 1992 or clotting factor concentrates before 1987
Injected/intra-nasal illegal drugs
Long term dialysis
Children born to HCV positive women
Healthcare workers and public safety workers after needle sticks, sharps or mucosal exposure to HCV (+) blood
Evidence of chronic liver disease (PE or labs)
IVDU→ annually
Pregnant women
Unregulated Tattoo or body piercings
Past incarceration
HIV infection (annually if they have unprotected sex)
Sexually active persons about to start PEP (post exposure prophylaxis)
Hep C labs
Varying ALT patterns: Normal→ Chronic Acute→ 100s Cirrhosis→ AST>ALT LFTs can rise and fall
Hep C management: lifestyle
Screen for HAV + HBV→ not immune→ Vaccinate
Non-infected sexual partner testing→ Sexual transmission risk low(<2%, higher MSM)
Avoid ETOH intake
Don’t donate blood, organs, share toothbrushes, nail clippers, razors
Cover open cuts on skin
Hep C management: preventing complications/cure
Monitor signs/complications of cirrhosis
Check for co-infection with HBV (HBsAg and HB core Ab), other causes of liver disease, HIV
Refer to GI for treatment→ Cure of Hepatitis C does not preclude re-infection
Direct-acting antiviral agents→ oral, 8-16 weeks
Regime based on: genotype, treatment (naïve or experienced), cirrhotic and non-cirrhotic +/- viral load
Treatable and curable in most patients
Resistance Associated Variant Analysis sometimes needed prior to treatment
HVC→ no known intracellular reserves, no DNA intermediates→ impact viral replication→ clearance→ cure
Hep C serology basics
Hep C Ab takes 8-12 weeks to develop
RNA viral load develops 2-4 weeks after infection
(-) Hep C Ab with (+) RNA viral load
Acute Hep C infection
(+) Hep C Ab prior had (-) Hep C Ab
Acute Hep C infection
(+) Hep C ab (-) RNA viral load
resolved (treated) Hep C
Hepatitis D
Acute hepatitis symptoms
Seen only in conjunction with Hep B→ Associated with more severe course
Always test Hep B pts
Management→ Eradicate Hepatitis B (refer to GI/hepatology)
Hep D serology
Delta virus RNA with +HBsAg
Used to diagnose Hep D in Hep B pts
Hep E
Transmission→ Fecal-oral
Presentation→ Acute hepatitis symptoms
similar to Hep A.
Travel to developing countries in last 1-2 months (highest in East + South Asia).
Fatal in approx 20% of infected pregnant women, <1% otherwise
More severe and greater mortality in 2nd in 3rd trimester
Management→ Supportive
Hep E serology
Hepatitis E RNA
Metabolic syndrome criteria
3 of the 5: Obesity HTN DM Hyperlipidemia Hypertriglyceridemia
big risk for NASH/NAFLD
