Midgut Flashcards
Monitoring test in fulminant hepatic failure
PT/INR the best lab to monitor status (up to four times per day)
- Extensive and complete lab evaluation
- Doppler ultrasonography of the liver
Transplant criteria for fulminant hepatic failure
Acetaminophen induced liver failure
* Arterial pH <7.30
OR
* Grade 3 or 4 encephalopathy with PT>100seconds and Cr>340 mg/L
Non-acetaminophen induced liver failure
* PT>100 seconds
OR
* Any three of :
* Age <10 or >40 years
* Non-A and non-B viral hepatitis, idiosyncratic drug reaction, Wilson
* Jaundice >7 days prior to encephalopathy
* PT>50 seconds
* Bilirubin >180 mg/L
Reservoir for Hep A
only in humans
hep A % -> fulminant liver failure?
< 1% (usually if already have liver disease)
hep B % -> fulminant liver failure?
0.1-0.5% -due to massive immune-mediated lysis of infected hepatocytes (often DNA negative)
HBV extra-hepatic manifestations
in 20%
* Polyarteritis nodosa
* Glomerular disease (membranous nephropathy, MPGN, nephrotic syndrome)
* Serum sickness (arthritis, rash)
HBV treatment criteria
- Anyone with cirrhosis
- Immune active chronic HBV
Maybe (guidelines changing)
* HBV DNA >2000 IU/ml (HBeAg neg) with ALT 2x ULN
* HBV DNA >20,000 IU/ml (HBeAg pos) with ALT 2x ULN
HBV that doesn’t need treatment
- Immune tolerant phase (HBeAg positive, High DNA, normal transaminases)
- Inactive carrier phase (low or no DNA, normal transaminases)
- Latent HBV infection (DNA without HBsAg)
Which HBV treatment safe if preggers?
Lamivudine
HCV viral halflife?
~ 45 mins
Percent of acute HCV -> Chronic -> Cirrhosis
60-85% to chronic
20-30% with chronic to cirrhosis (over 20-30 years)
Extra-hep manifestations HCV
Cognitive impairment independent of liver disease stage
Lichen planus
* 19% with lichen planus will have HCV
* Six fold rise in risk for HCV in persons with lichen planus
* a T-cell mediated autoimmune disorder in which inflammatory cells attack an unknown protein within the skin and mucosal keratinocytes.
Essential Mixed Cryoglobulinemia
- Half of persons with HCV will have cryoglobulins
- Leukocytoclastic vasculitis
- Arthralgias
- Membranoproliferative glomerulonephritis
- Neurologic disease, peripheral neuropathy
Porphyria Cutanea Tarda
(a rare disorder characterized by painful, blistering skin lesions that develop on sun-exposed skin (photosensitivity))
Porphyria Cutanea Tarda
* Decreased activity of uroporphyrinogen decarboxylase
* May be inherited or acquired
* Sun exposed skin changes
* Elevated urine uroporphyrin levels
* 50% of those with PCT have HCV
HEV transmisison
- RNA virus transmitted in water/feces
- Highest incidence in Asia, Africa, Middle East, and Central America
- Animal reservoir (rodents, deer, boar)
- Acute disease in nonimmunocompromized patients
- Chronic disease in those with transplants
Fulminant HEV?
- Fulminant hepatic failure in 15-25 % in women who are pregnant
Most common meds -> DILD?
- Paracetamol / acetaminophen most common
- Amoxacillin/clavulanate most common antibiotic
Treatment for DILD
Drug withdrawal
Specific therapies
* N-acetylcysteine for paracetamol
* L-carnitine for valproic acid overdose
Glucocorticoids - may have a role in hypersensitivity reactions
Transplant if needed
Treatment in alcoholic hepatitis
Rule out other stuff
Prednisone
- 40 mg daily for 28 days, followed by a 16 day taper
- Lille score can be used to determine response to tx
Pentoxifylline
- 400 mg three times per day as an alternative
Inhibitor of TNF (Controversial) Discontinue nonselective beta-blockers
Risk scores in Alc Hep
Maddrey Discriminant Function
* DF= (4.6 x PT elevation)+ bilirubin mg/dl
* If >= 32, high short-term mortality, consider steroids
MELD
* If >11, high mortality
Glasgow alcoholic hepatitis score
Type 1 vs type 2 AI hepatitis
Type 1 AIH
* SMA and ANA
* Sens 43%, Spec 99%
* Anti-actin Ab
Type 2 AIH
* Anti-LKM1
* Spec 99%
Simplified diagnostic criteria for AI hep
Autoimmune hepatitis treatment
- Treatment not required in asymptomatic patients with normal or minimally elevated transaminases and gamma globulin levels and minimal necroinflammatory activity on biopsy
- Monotherapy
- prednisone 60, 40, 30, 30, 20 indefinitely
- Combination
- Prednisone 30, 20, 15,15,10, … 5…..?
- Azathioprine 50 mg daily (or 1-2 mg/kg/day)
Investigational
* Budesonide (9mg/day) and azathioprine an option if no cirrhosis
Haemachromatosis genes
C282Y or H63D
- C282Y homozygosity in 1 in 250 white northern European descendents
- Compound heterozygotes (C282Y/H63D) in 10%
what upregulates hepcidin?
Interleukin-6 upregulates Hepcidin Ç Anemia of chronic disease
Hepcidin main actions
- reducing transfer across the basolateral membrane of enterocytes by binding ferroportin
- induces macrophages to store iron
Haemachromatosis diagnostic criteria
- Transferrin saturation >45%
- Ferritin >200 ng/ml in men or >150 ng/ml in women
- Liver biopsy is only needed in select cases
Haemachromatosis extra-hepatic manifestations
No Improvement with phlebotomy
* Diabetes in 50%
* Arthropathy (pseudogout, chondrocalcinosis) Second and Third MCP
Improvement
* Cardiomyopathy
* Hypogonadism (secondary)
ceruloplasmin in Wilson’s disease
- Low serum ceruloplasmin - due to instability from lack of Cu incorporation
- Binds and transports the copper from the cytoplasm to the late endosomal lumen
Clinical manifestations Wilson’s disease
Liver disease – 18-84%
* Steatosis, fulminant hepatic failure with Coombs-negative hemolytic anemia, cirrhosis
* Acute liver failure – alkaline phosphatase is typically normal or subnormal
* Only 50% have Kayser-Fleischer rings
Eye signs
Neurologic Disease – 18-73%
* Behavior deterioration, difficulty writing, tremor, speech change, Parkinsonlike, dysarthria, dystonia, ataxia, drooling
* MR may show basal ganglia hyperintensity on T2-weighted images
* 98% will have Kayser-Fleischer rings, Sunflower cataracts
* Elevated copper in CSF
Psychiatric – 10-100%
* psychosis, depression, anxiety
Most diagnosed between 5 and 35 years
Treatment for Wilson’s?
Copper removal
1. Chelators - usually 6 -12 months to remove the excess copper
* D-penicillamine – 30% cannot tolerate
* Trientine – Lower AE, expensive
2. Tetrathiomolybdate – Being studied
Low Copper diet
– Avoid liver, kidney, shellfish, nuts, dried fruits or beans, peas, unprocessed wheat, chocolate, cocoa, and mushrooms
- Oral Zinc- interferes with Cu absorption
Which patients should D-penicillamine not be used in
– Not ideal for neurologic disease – may worsen neuro symptoms
in general ~ 30% cannot tolerate
What is the number one cause of death in individuals with nonalcoholic steatoheapatitis (NASH)?
Cardiovascular disease
MELD score needed for liver transplant
15 and above are approaching it
Leading cause of death in a person who has had a liver transplant?
Infection
Liver transplantation complications?
Infection
- leading cause for mortality after transplant
- Highest risk in the first three months
CMV (arthralgias, leukopenia, recent treatment for rejection)
Biliary obstruction or hepatic artery thrombus if cholestatic
Hypertension
- develops in approximately 70% post-transplant
Diabetes
Dyslipidemia
Metabolic bone disease
Malignancy
