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Gastroenterology Lecture: Hepatitis



SSL starts with his song:
There must be 50 Ways to Clog Your Liver
(to the tune of Fifty Ways to Leave Your Lover, music by Paul Simon)
(from his CD: Talkin'bout Degeneration)

I started life out with a liver oh so clean,
Since then I've do so much to make it turn dark green
Now that I've got it back to functioning again,
There must be fifty ways to clog your liver:
Pierce a body part Bart, Have a one night stand Fran
Eat the wrong shrooms June, Just listen to me
Get diabetes Regis, Don't need to percuss much,
Drink a slow gin fizz Liz, and get your Hep C

Now patients come to me complaining of the same,
I say you've got to learn the hepatic cleansing game
That means you won't be doing anything tonight,
There must be fifty ways to clog your liver:
Eat it deep fried Clyde,
You'll have to get mad Thad,
Take ERT Lee, just listen to me
Gonna have to rush Gus
Don't need to percuss much,
Just guzzle the beer dear, and get your hep C

Why don't the both of us just sleep on it tonight and
I believe in the morning you'll begin to see the light
I'd like to help your P450 system work
There must be fifty ways to clog your liver:
Suppress your joy Roy
Forget to breathe, Steve
Hydrogenated oil, Doyle, just listen to me
Get a tattoo drew, don't need to percuss much
Just snort up some coke, bloke, and get your hep C

***************************************************************************
HEPATITIS AND STEATOHEPATITIS

ETIO
viral
alcohol, toxins
drugs (HMG CoA reductase inhibitors, etc)
primary sclerosing cholangitis
Wilson's dz
NASH
hemochromatosis
primary biliary cirrhosis

TESTS TO ORDER
HEP A
order IgM anti-HAV
HEP B
several tests
anti-HBs for past infx or vacinations
HBsAg for present infx
HBeAg marks infectivity
anti-HBe marks low infectivity
Hep B viral DNA high levels show active infx, low levels show dormant
HEP C
anti-HCV Ab

CHRONIC HEP C
in chronic infx still can have normal transaminases (they fluctuate)
transaminases fluctuate
viral load fluctuates
what's unique about hep c? SSL: virus is good at changing its genome
so it shifts to different subtypes and immune system doesn't recognize it for a while
then when immune system figures out it's still there but changed, new flare
KW had pt on SSL shift, he was a partier, drinker, coke, was always tired
his transaminases were fine but they never checked for hep C Ab
coke: sharing straws, spoons, mucosa is friable when doing coke, shares fluids
**anyone who snorts coke and is tired: check for hep C antibody
risk factors: transfusion before 19990, IV drug use, intranasal cocaine, nonsterile tatoos and piercings, sex partners + for HCV
sx: chronic fatigue
most imp tx: abstinence from alcohol
SSL's saying "alcohol is like lighter fluid on the backyard barbecue of hep C"
tx: abstention for alcohol does more than all the rest
tx: supplements
tx: pegylated interferon and ribarivin
sx of tx: flu like, N, hair loss, emot, skin, depress, organ damage, blood conditions incl thrombocytopenia
tx: silybum marianum (milk thistle) (anti-inflam, antiviral)
tx: oral and IV antioxidants (high dose vit C now popular)
tx: vit C, E, alphalipoic acid

study 2007 "inhibition of T-cell inflam cytockines ....by standardized silymarin
inhibs TNF alpha-->lowers liver inflam, prophylactic vs HCV infx
works well with interferon alpha, better than either alone

another study: silymarin can decr transaminases but doesn't lower viral load or improve liver histology (another study disagrees, does help histology)

study 2007: 100 chronic HCV pts who failed interferon tx, gave combined oral and IV anti-ox therapy, IV and oral worked much better than just oral, lowered ALT and improved histology in 48%, used: vit C, E, ala, silybum, glycyrrhiza, selenium, beta carotene, schizandra, L-glutathione 1x daily for 24 wks, IV was glycyrrhiza, ascorbate, L-glutathione and B complex 2x weekly, improvements held longer than without IV

GLYCYRRHIZA
antiviral
in every single Chinese liver formula, directs other herbs to liver
long term may prevent cancer in pts with hep c
lowers liver enzymes
SE: HTN, decr K, headache, sluggishness, ascites
may interact with drugs incl diuretics

NASH RISK FACTORS
obesity
DM
insulin resistance
hyperlipidemia
females > males
aspirin
SURGical procedures that cause rapid weight loss: jejunoileal bypass (not commonly done), small bowel resection, gastroplasty, biliopancreatic diversion, starvation, IV glucose
DRUGS: Ca channel blockers, tamoxifen, corticosteroids, synthetic est, ASA, methotrexate, valproic acid, cocaine, AZT, amoidarone
METAbolic conditions: rapid wt loss, TPN, acute starvation, Weber-Christian dz, Wilson's dz, abetalipoproteinemia, small bowel diverticulosis

ABETALIPOPROTEINEMIA
http://en.wikipedia.org/wiki/Abetalipoproteinemia
aka Bassen-Kornzweig syndrome
rare autosomal recessive disorder: must have 2 copies of mutated gene to have dz
mutation in the microsomal triglyceride transfer protein (MTTP)
essential for creating beta-lipoproteins
interferes with the normal absorption of fat and fat-soluble vitamins from foodnot to be confused with familial dysbetalipoproteinemia
tx: lots of vit E
sx sim to those in Apolipoprotein B deficiency, related: def of apolipoprotein B

TWO HIT THEORY
1) IR, hepatocytes fill with fat, incr fatty acid syn, decr lysis, incr mitochondiral oxidation of fatty acids, incr TGs exiting hepatocytes, hepatic insulin resistance
2) mitochondrial ROS, increased oxidative stress-->rancid fat, lipid peroxidation



************************************************************
CASE
male 35 270 lbs 6foot1
chronic sx: legs sensitive, some numb, pins/needles in feet, shins, sometimes upper legs, sometimes hands (peripheral neuropathies!), also sciatica
cc: sharp pain with deep inspiration, loc under ribs on R, feels like lump
fatigue, energy 5/10
constipated, dark stool, small amounts
takes lactase to prevent diarrhea with dairy
used to take ibu daily for back/muscle pain (hyperperm?)
indigestion, epigastric sx x5 yrs
sleeps well up to 10 hours, wakes tired, snores
chiro tx helped leg sx some
kneeling-->numbness
anatomically short R leg
lumbar disc degen shown in old xray
no tatoos, piercings, coke hx
drinks 3+ 6packs/week (SSL says 2 drinks/day is social drinking)
urine freq normal
PE
abd exam: BS4Q ok, tender RUq
liver 13-14 cm mid-costal, smooth border
chapman's hh pt: 2
desc colon pt 2
colon pt 1
peripheral neuro exam

LABS: want fasting comp metabolic with lipid panel
(listing only abnormals)
AST 25
ALT 78 high (alt>ast-->prob nash not alc)
chol 190
TGs 258 vhigh
VLDL 52 high
HDL 33 low
fasting glucose 89
fasting insulin 27.1 high (tells you the IR story long before glucose goes up)
(over 10 is too high, ideal is 3-4)(separate test, not cheap)
negative for Hep C ab
RBC and HCT high-->polycythemia: dehydrated? sleep apnea
Magnesium 1.8
ASI: am & noon cortisol are depressed, afternoon top of normal, elevated at midnight
this pattern suggests blood sugar problems or gluten intolerance to SSL

SLEEP APNEA (an aside)
sleep apnea-->make more RBCs dt chronic hypoxia
also-->arrhythmias, HTN, may have screaming headache in am
TX: wt loss
TX for obstructive sleep apnea: nasal specific, avoid allergens
TX for central sleep apnea: neurofeedback

WORKING DX for this case: NASH dt transaminases with ALT higher
(some say over 2 drinks/day can't call it NASH)
(if AST passes ALT then blame it on the booze)
also insulin resistant: want to serially test post prandial glucose
(IR pts don't have to drink alcohol, they make their own:
eat sugar + SIBO-->gut bugs make methane, hydrogen, and alcohol)
IR is 25-40% of disease in this country, must know how to recognize/tx it

TX
exercise: walking min 30 mins/day
avoid alcohol
(1 drink/day improves IR in healty pts but SSL not recommend w/ steatohepatitis)
diet: low glycemic, avoid fried, increase fiber, veg
weight loss, gradual
choleretics
betaine
NAC
alpha lipoic acid
Vit e
lipotropics: methionine, cysteine, inositol

FOLLOWUP
RUQ stopped hurting after 7-10 days
could and did stop drinking except for occasional party
did walk 2 days/week, changed his diet
sciatica went away-->more walking

RECOMMENDS BOOK: 7 WEEKS TO SOBRIETY
(I have it on shelf, will read one of these days)
Joan Matthews-Larson
6 different types, looks like this may be the source for his next lecture

************************************************************

ON THE LIVER LABS
Both AST and ALT are serine proteases.

AST = aspartate aminotransferase
marker of diffuse cell necrosis (eg viral hep)
mitochondrial enzyme preferentially increased in alcohol-induced liver dz

ALT = alanine aminotransferase
marker of diffuse liver cell necrosis (eg viral hep)
more specific for liver cell necrosis than AST

OTHER ENZYMES

CK-MB = creatine kinase
isoenzyme increased in acute MI or myocarditis
now troponin also used

Amylase and Lipase
markers for acute pancreatitis
lipase more specific for pancreatitis
amylase also increased in salivary gland inflam (eg mumps)

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