Gastroenterology Flashcards
Patient presents with red crusted lesions around mouth and finger pulps 3 months after SB resection for Crohns. What is the cause?
zinc deficiency.
Presents as “Acrodermatitis”
- peri-oral dermatitis
- acral involvement
- sometimes alopecia
What is the cell that is responsible for causing fibrosis in the liver?
STELLATE CELLS
What is the IL 28B genotype?
IL28B is a Genotype IN PATIENTS (NOT the virus!) that influences the viral kinetics in Hepatitis C.
IL28B has 2 main subsets: CC and TT
- “CC” is a GOOD/favourable genotype. (“Yum, these CC’s are good!”)
- “TT” is a BAD genotype (“Tsk Tsk! Don’t do that- That’s bad!”)
- CC is the commonest and is the best to treat, 80% respond to treatment
- TT mainly in Africans, responds very poorly to treatment
The favourable “CC” IL28B genotype is the single most important predictor of:
- TREATMENT RESPONSE with Peg-Riba
- SUSTAINED VIRAL CLEARANCE
- SPONTANEOUS Viral clearance
hence for CC –> treat immediately
TT –> no good data yet on best treatment regimen
What does it mean to have Hep C Genotype 1?
Genotypes 1-3 are the VIRAL GENOTYPES that influence response to treatment.
(genotype of the virus, not the patient)
Genotypes 2/3 are best to treat, but less common.
Genotype 1 is BAD.
Most prevalent worldwide.
TYPE 1A is worst»_space; 1B (“TYPE A personalities are the worst!”)
The new standard of care for Hep C Genotype 1’s are:
PEG-RIBA WITH PROTEASE INHIBITORS (TRIPLE THERAPY )
Options are: Peg-Riba-Telaprevir, or Peg-Riba-Boceprevir
What are the SIDE EFFECTS of using “Triple Therapy” for Hep C Genotype 1’s?
Triple therapy involves Peg-Riba PLUS a PROTEASE INHIBITOR.
Options are: Peg-Riba-Telaprevir or Peg-Riba-Boceprevir
SIDE EFFECTS of BOTH:
1. Myelosuppression
2. Riba –> severe HAEMOLYTIC ANAEMIA
(If resistant to one Prot inhibitor, you can not use the other. Resistance is a major problem)
SIDE EFFECTS of OF TELAPREVIR:
- “Fire-a-rrhoea” (Telaprevir is excreted in bile –> diarrhoea and anal pain)
- Rash in 6%
(“if you watch TELAvision all day, your ass will hurt!”)
SIDE EFFECTS OF BOCEPRREVIR:
- Dysgeusia (bad taste)
- nausea
(“This BOCCONCINI Cheese left a bad taste in my mouth- it’s “dysguesting”!!”)
What is the duration of treatment for Hep C Triple therapy?
Trick question.
Duration of therapy is determined by “Response guided therapy”
That is, we monitor HCV RNA at the 8-week mark.
If HCV RNA UNDETECTABLE at 8 weeks, then the TRIPLE THERAPY DURATION IS 24 WEEKS (6 months)
If HCV is DETECTABLE, then treatment duration is 48 WEEKS (approx 12 months)
Note:
- New treatment is Sofosbovir and Ledipasvir (“SOFT-LED”) for 12 WEEKS ONLY.
- 90% effective for ALL Genotypes, and good toxicity profile.
What is Sofosbovir?
What are the other new agents?
NEW drug treatment for Hep C Genotype 1.
(“If nothing else works for HepC, just hit them over the head with “SOFT-LEAD”) ie. SOF-LED.
SOFosvobir is a POLYMERASE INHIBITOR - a new Direct Antiviral agent.
“SOFOSBOVIR-LEDIPASVIR” is the NEW gold-standard treatment of ALL Genotypes.
Sofosbovir plus Ledipasvir combination for 12 WEEKS ONLY.
Good toxicity profile.
Available in Australia on compassionate grounds only.
But readily available in America.
(Also new drugs being trialled are other Protease Inhibitors:
Ritonavir (used in HIV)
simepravir (less s/e)
And another target is IFN LAMBDA)
What are the PHASES of Hep B infection, and what do these following tests correspond to?
- sAg positive, eAg positive, core IgM +/-, core IgG positive, HBV DNA positive, sAb neg, eAb neg.
- sAg positive, eAg negative, core IgM positive, core IgG positive, HBV DNA positive, sAb neg, eAb positive.
- sAg positive, eAg negative, core IgM negative, core IgG positive, HBV DNA negative, sAb negative, eAb negative.
Phases of Hep B:
Phase I - Immunotolerant (NO liver disease, occurs in 80%)
Phase II - acute infection (either acute 1st episode or acute flare of chronic hep)
Phase III - latent disease
Phase IV - pre-core mutant infection (when the host directs a lot of immune pressure towards the eAg (eAg is only present in wild type virus) –> results in neg eAg and positive eAb –> however patient is still susceptible to a flare up of hepatitis from a pre-core mutant, hence core IgM positive.
Note that eAg only indicates infection with the wild type virus.
sAg indicates infection with any type of virus (wild or mutant)
- Acute flare of a chronic infection (phase II) - active hepatitis
- Pre-core mutant infection (phase IV) - active hepatitis
- Latent disease (phase III)
What is the standard of care for Hep B?
- In YOUNG patients or those with Hep D co infection –> PEG (pegylated IFN) “single”-agent therapy for 48 weeks (approx 1 year)
(“BE (B) quick!! You need to PEG the SINGLE YOUNG guy!)
= PEG Single agent in hep B
- there is a risk of decompensated liver disease
- 1/3 of patients get a sustained viral response
- (“You can “be” L.A.T.E. For OLDER guys”)
L - Lamivudine - but problems with resistance
A - Adefovir
T - Tenofovir - renal side effects
E - Entecavir
All of these are Nucleoside Analogue Reverse Transcriptase inhibitors –> prevents viral replication in cells
Indefinite duration of therapy Almost all (95-100%) patients get viral suppression but only a sustained response in 6% Not much risk of decompensated liver disease
What is the treatment for Hep B reactivation in pregnancy?
There is a 10% risk of vertical transmission if untreated!
hence treat mum with LAMIVUDINE And TELBIVUDINE (Lam-Telbi)
At 32 weeks to decrease vertical transmission
12hrs prior to delivery –> Hep B Immunoglobulin
What percentage of people with Hep B develop cirrhosis?
What is the most important risk factor for cirrhosis?
20%
Hep B DNA Viral load!!
Treatment for HCC
Stage A:
Small SINGLE tumours resect and laser RFA ablation
Stage B:
Multinodular –> TACE /chemoembolisation
(Chemo with anthracyclines Doxo or Epirubicin, plus Lipiodol and Gelfoam –> into hepatic artery as blood supply to HCC is from hepatic artery not portal vein)
Stage C:
** SORAFENIB = VEGF inhibitor. Inhibits angiogenesis.
S/E rash, hand-foot reaction (good signs)
Middle-aged patient presents with fatigue and arthralgias in the 2nd and 3rd MCP joints for the last 3 years. He has bronzed skin, newly diagnosed Diabetes. He drinks moderate alcohol. On examination there is hepatomegaly. What is the diagnosis?
Hereditary Haemochromatosis. Autosomal recessive. Carrier status 1:8 Due to homozygosity in C282Y (H63D also causes HH- less commonly) 48% have Diabetes at diagnosis.
–> Increased Fe absorption AND
Inceased Fe release from MACROPHAGES in erythrophagocytosis
–> leads to Fe deposition in LIVER (cirrhosis due to Fe accumulation in peri portal hepatocytes), HEART (cardiomyopathy- do a TTE), PITUITARY (hypogonadism, check FSH), PANCREAS (diabetes), JOINTS (2nd/3rd MCP)
CRITERIA IS:
Tsats high >45%
Ferritin high >674 in men and >449 in women
CRP normal (need to exclude acute infection)
Which of these does NOT cause Pancreatitis? A. statins B. fibrates C. triglycerides D. thiazides E. Ercp
List all the things that cause Pancreatitis (name at least 8)
Answer is A.
New evidence that STATINS are PROTECTIVE against pancreatitis
but
FIBRATES INCREASE RISK OF PANCREATITIS.
Causes of Pancreatitis: Alcohol, gallstones ERCP (2% mortality) --> hence give NSAIDS/Indomethacin suppository prior to ERCP *** FIBRATES *** THIAZIDES! Triglycerides
SPINK1 mutation –> HEREDITARY, Auto DOM, chronic pancreatitis
Autoimmune causes: related to Sjogrens, Primary Biliary Cirrhosis, RA
–> treat with steroids
Necrotising pancreatitis = cx mgt
What genes are associated with Crohn’s disease?
NOD2 and CARD 15.
- part of the innate immune system
- NOD recognises a PAMP called Muramyl Dipeptide which is on bacterial peptidoglycan cell wall
NOD 2 positivity is bad!!
- predicts a higher need for bowel resection in Crohns
- predicts MORE OPERATIONS a
What are “high risk” features in Crohn’s disease?
STRICTURES (worst feature) Weight loss (also bad) Steroids at time of diagnosis Smoking (increases risk by 90%, increases risk perianal fistulae) Perianal disease ASCA positive - in 40% of Crohns Deep ulcers in colon Upper GI disease NOD 2 positivity Female Young age < 40
(Ken says worst feature is strictures and weight loss)
What is the management for Crohns Disease?
Use a “Step Up” approach.
- Quit smoking (as effective as starting a patient on Infliximab!)
- ASA’s for DISTAL disease
- reasonable to try ASAs but not amazing evidence
- PR plus PO combination is more effective than single agent - Steroids
- Thiopurines - AZA –> 6MP
- ** Early therapy reduced risk for surgery! **
- Test thiopurine metabolites if patient not responding:
the higher the level of 6-TGN, the better the response
(6MMPR = hepatotoxicity) - MTX
- Anti-TNFs - INFLIXIMAB, Adalimumab (Biologics)
- more effective when combined with AZA
- need to qualify for this! - Monitor for mucosal healing (repeat scope)
- Surgery
- options - seton, or Ileocolic resection
Side effects of 5-ASAs
Stephen Johnsons Syndrome in Sulfazalazine! (Sulfa drug)
Interstitial nephritis
Diarrhoea
Pancreatitis
Patient with Crohns is not responding to AZA.
Thiopurine metabolites show a low TGN and high 6MMPR.
What is the next step in management?
Add on ALLOPURINOL to increase TGN levels.
–> clinical improvement.
What are the side effects of Thiopurines AZA / 6MP?
LYMPHOMAS (2x increased risk!) Skin cancers BM suppression Hepatitis Pancreatitis Flu-like symptoms
What is the criteria for qualifying for anti-TNF therapy in Crohns?
To qualify for Biologics, must have:
FISTULISING CROHNS,
OR
No response to Thiopurines/Methotrexate for 3 MONTHS, and
Steroids for 6 MONTHS.
Also need to DEMONSTRATE a response to Biologics with the “CDAI” (“Crohns Disease Activity Index”) to continue therapy. CDAI >300.
