Gastroenterology Flashcards
Achalasia associated with which cancer
SCC (10x risk compared to general population)
Achalasia barium swallow findings
Bird’s beak
Which subtype of achalasia is most severe?
Type 1
Progression from Type 3 to Type 1
Which subtype of achalasia has the best treatment outcome?
Type 2
Oral Tx options for achalasia
CCB
Isosorbide dinitrate
(effective in 50-60%)
Complication with Botox injection for achalasia
Causes submucosal fibrosis and unable to do subsequent definitive surgical treatment
Efficacy of Balloon dilatation in achalasia
60-90% effective
Risk of perforation in 1-6%
Recurrence in 2-3 years
Treatment of choice for achalasia
POEM (PerOral Endoscopic Myotomy)
- Success similar to Lap Myotomy, but less recovery ime
- SE: Reflux ++
Classic endoscopic features of eosinophilic oesophagitis
- Oedema
- Longitudinal furrows
- White exudates
- Concentric rings
- Strictures and mucosal tearing
Treatment of eosinophilic oesophagitis
- PPI
- Aerosolised steroids
- Diet: Elemental; Eliminate milk, wheat, gluten, eggs, nuts, shellfish, soy
- Dilatations for strictures
- Esperimental: Budesonide, montelukast
Mucosa change in Barret’s oesophagus
Strafed squamous epithelium replaced by cardiac type mucus secreting columnar epithelium +/- intestinal metaplasia
Medical treatment shown to slow/stop progression of Barrett’s to adenocarcinoma
PPI and aspirin therapy
- AspECT trial
- Surgical therapy is no more effective than PPI
Survival with Oesophageal Adenocarcinoma
5 year survival <20%
Mx recommendation for low grade dysplasia in Barrett’s
If LGD confirmed on 2 occasions 6 months apart by two pathologists, then endoscopic RFA is recommended OR close surveillence
-Risk of progression to HGD
Risk of HGD in Barrett’s to progress to Adenocarcinoma
~10%
Mx of HGD in Barrett’s
- Oesophagectomy vs endoscopic resection
- Then RFA to rest of Barrett’s due to risk of transformation
- Annual Gscope annually for 5 years
Risk of recurrence of Barrett’s post surgical excision/RFA
~10%
Greatest in first year
Features suggestive of malignant dysphagia
Shorter duration Solids > liquids Constant and progressive Older age Accompanying alarm symptoms
Mx of refractory GORD
Failed PPI BD trial for 3 months
- Check compliance and lifestyle modifcations
- Trial nocte H2 antagonist
- Repeat scope and perform pH testing
Location of most gastric ulcers and duodenal ulcers
Junction of fundus and antrum along the lesser curvature
DU are usually in the 1st or 2nd part
Evidence of PPI therapy in GI bleeding
No mortality benefit
Reduction in need for endoscopic therapy compared to placebo
Forrest Ia
Spurter
Forrest IIa
Non bleeding visible vessel
Forrest IIb
Clot at base
Forrest IIc
Dot
Forrest III
Clean Base
Evidence for post endoscopy PPI for GI bleeds
Reduces rebleeding significantly
-IB PPI infusion for 72 hours recommended post procedure
H pylori genes linked to carcinogenesis
cagA and vacA
Cancers associated with H. Pylori
Gastric cancer
MALT lymphoma
H pylori associated with a decreased risk of what cancer
Oesophageal adenocarcinoma
Treatment of H Pylori
Quad therapy:
PPI+Amoxy+Metro+Clarythromycin x 14 days
PPI+ Bismuth +Metro+Tetracycline x 14 days
Immune cell associated with MALT Lymphoma
Low grade B cell neoplasia
H Pylori association with ITP
H pylori eradication improves platelet counts in ~ 50% of ITP
When to do post H pylori eradication testing
> 4 weeks after completing treatment
Duration off ABx and PPI to investigate for H pylori
> 4 weeks ABx
>2 weeks PPI
Endoscopic features of malignant gastric ulcers
Irregular outline with necrotic or haemorrhagic base
Irregular raised margins
Prominent and oedematous rugal folds that usually do not extend to the margins
What INR is it safe to do a Gscope at
= 2.5
When to restart warfarin post UGIB
7-14 days post procedure
Histological Features of Coeliac Disease
Intra-epithelial lymphocytes
Crypt hyperplasia
Villous atrophy
Best initial testing for coeliac disease
Anti TTG IgA
High sensitivity and specificity
-If weakly positive, then do anti endomysial IgA
Non Responsive Coeliac Disease
- Compliance!
- Alterative associated issues: SIBO, Microscopic colitis, IBS
- Diet review
- Repeat Histo
- Colonic Bx - ?microscopic colitis
Refractory Coeliac Disease Type 1
Steroids +/- steroid sparing agent
Refractory Coeliac Disease Type 2
Poorer prognosis
Oligoclonal T cell expansion
High risk of transformation to enteropathy associated T cell lymphoma
PAS positive macrophages in sub mucosa on GI biopsies
Whipple’s Disease
Affect of omeprazole on Gastrin Level
Omeprazole increases Gastrin levels
Enterchromaffin cells
Stimulates gastric acid secretion
Responds to gastrin
Contains Histamine
Stains positive with silver
Hyperplasia of enterochromaffin cells in the gastric mucosa is associated with
Atrophic gastritis
Medication effective in preveting gastric ulceration with NSAID use
Misoprostol
Immunosuppressed and small discrete ulcers in the oesophagus - cause?
HSV
Immunosuppressed and giant ulcers in the oesophagus - cause?
CMV
CD117 (c-KIT)
GIST
Main mechanism of reflux in majority of episodes
Transient LOS relaxation due to vagal stimulation in setting of proximal gastric distension
Side effect of giving folic acid in B12 deficient patients
Causes severe neuropathy and worsening B12 deficiency because it will stimulate erythropoesis and further worsen B12
Side effect of giving glucose prior to thiamine in refeeding syndrome
Acute Beri Beri
Refeeding Syndrome - Glucose has what effect on insulin
Hyperinsulinaemia
- Which then results in Fluid and salt retention and intracellular K=/PO4 shift
- Results in dilutional hypoalbuminaemia
Factors which favour intestinal absorption in short bowel syndrome
-Length of remaining bowel (>60-90 cm of SB with colon OR >150 cm small bowel)
-Ileum>Jejunum
-Ileocecal valve present
-Absence of mucosal disease
-Presence of colon
-
Benefit of having a retained ileocecal valve in short bowel syndrome
Reduces risk of Small bowel bacterial overgrowth
What renal stones are associated with short gut
Oxalate
-Treat with calcium
Role of GLP2 in Short gut syndrome
Provides feedback to the upper intestine to optimise the nutrient and fluid absorption
- Mucosal growth
- Teduglutide
Target Hb for UGIB
70-90
-Reduces adverse events, further bleeding and improves 6 week survival
Evidence for IV PPI for 72 hours post endoscopy for UGIB
-Improved rate of rebleeding, blood transfusion requirement, duration of hospital stay
Evidence for Octreotide in variceal bleeding
Reduction in rebleeding and number of patients failing initial haemostasis
NO reduction in mortality
MOA Terlipressin
Synthetic vasopressin analogue
Avoid in significant CAD or PVD
Evidence for ABX in vleeding varices
Quinolones/3rd Gen Cephalosporins
- REduce all cause and infection mortality
- Reduced rebleeding rates
Evidence for ABX in vleeding varices
Quinolones/3rd Gen Cephalosporins
- REduce all cause and infection mortality
- Reduced rebleeding rates
Evidence for endoscopic rubber band ligation in acute oesophageal varices
Fewer side effects and more effective than sclerotherapy
Reduced mortality and rebleeding
Secondary prophylaxis for oesophageal varices
BB - Propanolol - start at Day 3-5 post acute bleed
-Reduce rebleeding and mortality
Further banding sessions 2-4 weeks a part until eradication (3-4 sessions)
NAFL Definition
Presence of steatosis without liver injury
Minimal risk of disease progression
NASH Definition
Hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. Can progress to cirrhosis, liver failure and cancer
NASH Cirrhosis Definition
Cirrhosis with current or previous evidence of NASH
Cryptogenic Cirrhosis
Cirrhosis with no obvious aetiology. Many have metabolic risk factors and likely to have NASH cirrhosis
What percent of Fatty liver progresses to NASH and cirrhosis
20% from fatty liver to NASH
4-8% NASH to cirrhosis
Tests used to screen for advanced liver fibrosis in NAFLD
- Presence of T2DM
- Decreased platelets
- AST:ALT >1
- NALFD Fibrosis score
Fibroscan result that correletes well with portal HTN
> 25
Most reliable test to rule out advanced hepatic fibrosis (High negative predictive value)
Fibroscan
Indications for Liver Bx for NAFLD
Abnormal ALT/GGT AND
- > /=3 features of metabolic syndrome (esp T2DM)
- NAFLD Fibrosis Score/Fibroscan 8-12
Benefits of weight loss in NAFLD
Improves biochemical profile, histo, decreases steatosis, reduces inflammation, decreases fibrosis
HCC surveillance in cirrhosis
6 monthly USS in NASH cirrhosis
Haemochromatosis Histo
Grade 3 hepatocyte iron accumulation with an acinar distribution pattern
Stains with Perl’s prussian blue
Hereditary Haemachromatosis genetics
Autosomal recessive
HFE on chromosome 6
-C282Y mutation
TF Saturation in haemachromatosis
> 45%
Classic triad of haemachromatosis
Bronze skin
Cirrhosis
Diabetes
Most sensitive screening tool for haemachromatosis
Fasting morning transferrin saturation
Hepatitis B in pregnancy - Risk with normal delivery and breast milk
No protective effect of C-section
No increased risk with breast milk
Hepatitis E Antigen
Correlates with infectivity (marker of active replication) Higher viral load
Anti-HbE important sign of serovconversion of eAg and beginning of clearance
HbsAg -
Anti HBc +
Anti HBs -
- Most often: Distant resolved infection wit hloss of HBsAb
- Recovering from acute infection before sAb is detected
- False positive
- PAssive transfer of maternal anti HBc in children up to 3
- Occult Hep B
CHECK viral load!
Occult Hepatitis B
Presence of HBV DNA without detectable surface antigen
Still at risk of cirrhosis and HCC
Hep B Pre core mutant or Basal core promoter mutant
Downregulates HBeAg production: HBeAg negative/Ab positive
Increased rates of advanced disease
Escaping immune control
Risk of death with chronic Hep B
15-25% chance of death associated with virus
Chronic Hep B:
Immune Tolerance
High HBV DNA
Normal LFTs
HBeAg Positive
Children usually remain in this phase until 20s to 30s
Mx: Monitor 6-12 months
Chronic Hep B:
Immune Clearance
Body begins to recognise Hep B and attacks
Viral load begins to drop
Derranged LFTs
Usually HBeAg seroconversion
At risk of progression to cirrhosis and HCC at this stage
Mx: Medications
Chronic Hep B:
Immune Control
Inactive virus
Lower HBV DNA
Normal LFTs
HBeAg negative and Ab positive
Mx: Monitor 6-12 months
At this stage: 3 things can happen
- Clear virus (rare)
- Remain in immune control long term
- Immune escape
Chronic Hep B:
Immune escape
High HBV DNA
Derranged LFTs
HBeAg negative and Ab positive
At risk of cirrhosis and HCC
Hep B Surveillance
6 monthly Liver USS and AFP
Fibroscan 2 yearly
Patient groups:
- Cirrhosis
- Family or PHx of HCC
- HBV Asian men over 40 or women over 50
- HBV africans over 20
- HBV >40 years age with Increased HBV DNA and Increased ALT
Treatment of Chronic Hep B:
Polymerase inhibitors
TDF Entecavir Lamivudine Adefovir TAF
Benefit:
- Suppress HBV DNA
- HBeAg seroconversion 10-20%
- No resistance with Entec and TDF/TAF
- Safe in deco,pensated disease
Downside:
-Indefinite therapy
Treatment of Chronic Hep B:
Immunomodulator
Peg Interferon
Benefit:
- Higher rate of HBeAg loss in 1 year
- Finite course
- No resistance
CI:
-Cirrhosis, pregnancy, acute Hep B, immunosuppressed, psych instability
What is the normal ULN for ALT
25 in females
35 in males
HBeAg Positive + non cirrhotic
When to treat?
ALT >/= 2xULN
HBV DNA >20,000
If HBV DNA <20,000 and persists for 6 months, then treat
HBeAg Negative + non cirrhotic
ALT >/= 2xULN
HBV DNA >2,000
Choice of Hep B treatment if known previous Lamivudine resistance
TDF/TAF
Likely to have Entecavir resistance
Choice of Hep B Tx in decompensated cirrhosis
- Entecavir perferred
2. TDF/TAF
Choice of Hep B Tx in Renal insufficiency
Entecavir preferred
Choice of Hep B Tx in Pregnancy/child bearing age
Tenofovir
Choice of Hep B Tx in women of child bearing age wishing to eradicate virus prior to pregnancy
Peg Interferon alfa 2a or 2b
Choice of Hep B Tx in HIV coinfection
Tenofovir +Emtricitabine or Lamivudine
Pregnant woman + Hep B Viral load in 2nd trimester <10^5 -?Mx
Monitor
Infant: HBIG +vaccine at birth w/i 12 hours of birth (efficacy 95%)
Pregnant woman + Hep B Viral load in 2nd trimester >10^5
Tenofovir at 28-32 weeks
Infant: HBIG +vaccine at birth within 12 hours of birth
Hepatitis D
Most aggressive Hepatitis
Needs HBsAg to replicate
Treatment Peg interferon for 2 years (30% efficacy)
Check for it if ALT not improving with Hep B treatment
Commonest cause for liver transplat
Hepatitis C
High levels of mutation in Hep C due to what?
RNA polymerase can’t proof read
Most common genotypes in Australia for Hepatitis C
1 and 3
Definition of Quasispecies in Hep C
Different strains within a host
Importnat in viral persistance, lack of response to IFN based therapy and leads to difficulties in vaccine development
How to test for Hepatitis C
ELISA
Window period of 6 weeks (ranging 2-26 weeks)
If indeterminate response - Do HCV RNA
Most specific test for Hep C
HCV RNA (PCR) -Can pick up active infection earlier with this
Qualitative: Diagnosis of infection
Quantitative: Viral burden and duration of Tx with IFN
Hep C Point of care testing
HCV ab mouth swab or fingerprick
HCV viral load in 105 mins
Same day result
What are the perinatal transmission risks for Hep C
2-8% risk of vertical transmission if RNA + (Higher if HIV +)
No increased risk of transmission with breast feeding
No evidence for CS
Baby: Can only check HCV ab after 15-18 months due to passive transfer from mum
Factors related to spontaneous clearance of Hep C
Younger age
Female
MHC genes, IL28B
Extrahepatic Manifestations of Hepatitis C
- Rh Factor postive
- T2DM 11x increase risk
- Cryo
- Membranoproliferative GN 7x risk
- PCT
- Lichen planus
- Lymphoma
- Keratoconjunctivitis sicca
APRI Test
Used to assess for Fibrosis
- AST to Platelet Ratio Index
- > 1 result is suggestive of cirrhosis
Equation: AST/ULN AST all divided by platelet count x100
SVR -Sustained virological response in Hep C definition
HCV RNA negative 12 weeks after completion of treatment
Direct Acting Antivirals MOA
Target specific non structural proteins of HCV to disrupt viral replication
-4 classes
Nucleoside NS5B polymerase inhibitors
- Buvirs
- Sofosbuvir
Non Nucleoside NS5B polymerase inhibitors
-Dasabuvir
NS3/4 Serine protease inhibitors
-Previrs
NS5A replication inhibitors
-Asvirs
Pangenotypic Hep C treatment
Sofosbuvir/Velpatasvir
-Add ribavirin for Child pugh B and C
Hep C treatment duration
Varies with regimes and if cirrhotic
- Cirrhosis: 12 weeks
- Sometimes less if non cirrhotic
Hep C Treatment Adverse effects
Fatigue/Insomnia
Headache
GI Sx
Can Reactivate Hep B!
Drug interactions with Hep C treatments
Statins
Omeprazole - Reduces absorption
Amiodarone (Bradycardia)
Potent P-gp inducers (rifampicin, St. Johns wort)
MELD scores for HEP C treatment guidance
MELD < 15 -treat
MELD 15-20/25 - Treat cautiously
MELD >20/25 -Defe Tx until post Transplant - If not a transplant candidate - discuss with patient as may worsen liver failure
HCC screening after SVR in Hep C
Mild fibrosis - none
F3-F4 fibrosis: USS and AFP 6 monthly
MOA of Cirrhosis
- Primarily due to activation of hepatic stellate cells (liver macrophages)
- Involved in healing and repair after biliary or hepatocellular injury
- Chronic activation results in increased collagen & extracellular matrix
Fibroscan Scores
F0-1: <7.5 = absent/mild disease
F2-3: 7.5-13 = unclear
F4: >13 = Cirrhosis
Factors assessed in Child Pugh Score
- Encephalopathy
- Ascites
- INR
- Albumin
- Bilirubin
MOA of cirrhotic portal HTN
-Increased vascular resistance due to structure (liver vasc architecture by fibrosis) and Dynamic (increased hepatic vascular tone due to endothelial dysfunction and decreased NO bioavailability
Ascites
- Reflects renal Na+ and H2O retention via activation of RAAS
- Portal HTN is primary driver, not hypoalbuminaemia
SAAG Score
Serum Albumin - Ascites albumin
> 11 suggestive of portal HTN
SBP Leucs and PMN in ascitic fluid
Leucs >500
PMN >250
If significantly higher leucs and polys, may need to consider alternative cause - ?perforation
SBP Mx
- 3g Ceftriaxone for 5-7 days
(Tazocin if on norflox/bactrim)
-IV Conc Albumin load and >2 bottles/day for >3 days
-Repeat tap 48 hours post tratment
Hepatic Hydrothorax
Ascitic fluid leaking into pleural space, usually right sided
Ascites Mx
- Spiro 100mg
- Frusemide 20 mg
- Aim 1 kg weight loss/day
- Restrict salt to 5 g/day (more important than fluid restriction)
- AVOID Normal Saline, leads to salt retention and worsening ascites
Albumin with paracentesis
20% conc albumin 100 ml over 1/24 for each 2L ascites drained
- Colloid osmotic effect 4x that of plasma
- Prevents large plasma volume drainage - renal failure/hypotension
Ascites refractory to diuretics
- Weekly Albumin infusion shown to improve mortality
- TIPS; Terlipressin infusions as outpatient
- Transplant consideration
Hepatic Encephalopathy
West Haven Criteria
Grade 1: Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction
Grade 2: Lethargy or apathy; minimal disorientation for time/place; personality change, inappropriate behavior
Grade 3: somnloence to semistupor but responsive to verbal stimuli; confusion; gross disorientation
Grade 4: Coma
Hepatic encephalopathy Mx
Lactulose
Rifaximin add on
-Reduced recurrence of HE, not mortality
Mx of VAriceal bleeding
- SBP >90
- Hb >70
- Blood/ albumin preferable - avoid saline
- IV thiamine if drinker
- Blood cultures and empical IV Ceftriaxone
- Terlipressin
- Scope
TIPS Indications
- Variceal bleeding unable to be treated endoscopically
- Diuretic refractory ascites or hepatic hydrothorax
- Budd Chiari
TIPS Contrindications
Increased Risk of HE!
RHF
Type 1 HRS
- Acute deterioration
- Poor outcome if untreated (50% survival at 11 days)
- Mx: Terlipressin infusion and Albumin, and ultimately need transplant or will ide
Type 2 HRS
- Slow progression
- A/W refractory ascites
- 6 month transplant free survival 40-50%
HCC CT Quad phase finding
Arterial enhancement, portal vein washout
HCC Mx (BCLC Staging) -Single HCC <2 cm, normal Portal pressure
Resection
HCC Mx (BCLC staging) -Single HCC <2 cm, Increased Portal pressure
Transplant
HCC Mx (BCLC staging) -3 nodules <3 cm and no associated diseases
Transplant
HCC Mx (BCLC staging) Early stage -3 nodules <3 cm and no associated diseases
RFA
HCC Mx (BCLC staging) Intermediate -Multinodular and no portal HTN
TACE (palliative)
- Transarterial chemo embolisation
- Can decompensated CLD if portal HTN is present
HCC Mx (BCLC staging) Advanced -Portal invasion, metastatic disease
Sorafenib (palliative) -Multi kinase inhibitor (VEGF and platelet derived growth factor receptors), RAF -Only suitable for compensated cirrhosis -ECOG 0-1
SE: Palmar-plantar erythrodysesthesia, Fatigue, fevers, diarrhea, increased bleeding risk (so banding prior)
- Lenvatinib (non inferior and also first line)
- Can change between the two if there is intolerance
HCC Mx (BCLC staging) -Child Pugh C
Terminal, symptomatic
SBP Prophylaxis indication
low protein (<10g/L) or Bilirubin >50 with impaired renal function -Norflox 400 mg daily or Bactrim reduces mortality and SBP
Variceal screening frequency if small varices
annual
Variceal screening frequency if no varices
2 yearly
Calculating Hepatic Venous Pressure Gradient (HVPG)
HVPG = WHVP - FHVP
WHVP = Wedged Hepatic Venous Pressure
FHVP = Free Hepatic Venous pressure
HVPG suggesting Portal HTN
> 5
If >10, then increased likelihood of varices, decompensation and HCC
Gives you pressure over the sinusoids
MOA of propanolol with varices
Reduction in cardiac output and splanchnic blood flow
Allow unopposed alpha-1 adrenergic receptor activity which results in splanchnic vasoconstriction and reduction in portal pressure
Kings college criteria for ALF (paracetamol Induced)
- pH <7.3 OR all of the following:
- INR >6.5
- Cr >300 micromol/L
- Grade 3 or 4 HE
Kings college criteria for ALF (non paracetamol induced)
- INR >6.5 OR 3 out of 5 of the following:
- Age <11 or >40
- Bilirubin >300 micromol/L
- Jaundice to coma time >7 days
- INR >3.5
- Drug toxicity
MELD Score for Transplantation
> 15
Early (<3/12) Liver Tx morbidity/mortality
Graft failure (rare)
Infection
Biliary stricture
Renal/diabetes/cosmetic
Findings of acute Rejection in Liver Transplant and time period
- Portal Based inflammation (cholestatic LFTs)
- Usually at days 7-10
- Occurs in 1/3
- No chronic sequelae
- Mx: Bolus steroids
Findings of chronic Rejection in Liver Transplant
Rare
- Vanishing bile duct syndrome (cholestatic LFTs)
- Increase Tacrolimus dose for Mx
Milan Criteria for HCC Transplantation
Single lesion ≤ 5cm, and/or Up to 3 separate lesions, all < 3cm No evidence of gross vascular invasion No evidence of regional nodal or distal metastases
UCFS Criteria for HCC Transplantation
A single nodule ≤ 6.5cm, or
Up to 3 nodules, the largest of which is ≤ 4.5cm
Cumulative tumoursize (sum of all diameters) ≤ 8cm
Most specific LFT parameter for liver
ALT
LFTs in Pregnancy:
Hyperemesis Gravidarum
1st Trimester
Vomiting and weight loss
ALT/AST Increase
LFTs in Pregnancy:
HELLP
2nd/3rd Trimester/Postpartum
HTN, RUQ/epigastric pain, N+V, Headache, visual changes
AST >2x ULN; Plt <100,000; LDH >600; Pr:Cr >0.3 mg
Mx - Delivery
LFTs in Pregnancy:
Preeclampsia
2nd/3rd Trimester/Postpartum
HTN, Headache, visual change, RUQ/epigastric pain
AST/ALT >2xULN, Plt <100,000
Mx - antihypertensives, MgSO4
LFTs in Pregnancy:
Intrahepatic Cholestasis
2nd/3rd trimester
Pruritis, steatorrhea, RUQ pain
Usually AST/ALT <2xULN
Mx - Ursodeoxycholic acid or cholestyramine
LFTs in Pregnancy:
Acute Fatty Liver in Pregnancy
3rd Trimester
N+V, abdo pain, acute liver failure
AST and ALT elevations up to 500
Mx- Delivery
Cause of Increased AST:ALT
Alcoholic hepatitis
NASH
Chronic HCV cirrhosis
Wilson’s disease
Role for Maddrey Score
In Alcoholic Hepatitis
Prognostication
Uses PT and Bilirubin
Score >32 suggests poor prognosis and may benefit from steroids
Drug of choice for agitation in patients with hepatic encephalopathy
Haloperidol
PBC Histo
shows periportal inflammation, periductal granulomas, and biliary inflammation and necrosis
What percent of the liver blood supply is from the hepatic portal vein
75%
New Mx in IBS
IBS-D
- Ondans - 65% Sx relief
- Rifaximin - 40% Sx relief
- Eluxadoline
IBS - C
-Linaclotide - guanylate cyclase c receptor
Chronic constipation
- Elobixibat - inhibitor of bile acid transporter
- Tanapenor - increases intestinal fluid and improves transit
Eluxadoline MOA and SE
For IBS-D
29% effective
Peripherally acting mixed mu-opioid receptor agonist, gamma opioid receptor antagonist, Kappa opiod receptor agonist
SE: Rare sphincter of Oddi Spasm, pancreatitis
CAPS - Centrally mediated abdominal pain syndrome
Severe continuous abdominal pain, impacting daily function, chronic, usually associated with psych issues
Favorable factor in Hep C treatment
-Genotype 1 (IL-28B polymorphism)
USe of amiodarone when starting Hep C Treatment
NEed 3 months off amiodarone as it can precipitate heart block
Tx of Hep C genotype 3 and decompensated liver disease
Add riboviran to increase treatment success from 50% to 85%
HEp C treatment in pregnacy
Contraindicated in pregnancy
If on ribviran therapy, need to wait 6 months before getting pregnant
Sofosbuvir CI
egfr <30
Hep C regime for renal impairment
ombitasvir
paritaprevir
Ritonivir
Hep C Tx protease inhibitor CI
Child Pugh B or C OR portal HTN
Ribavirin precautions
PRegnant women
Men whose partners are pregnant
Haemoglobinopathies
Preexisting cardiac disease
NAFL Histo
Steatosis with lobular or portal inflammation, with or without hepatocyte ballooning
NASH Histo
presence of hepatic steatosis in association with hepatocyte ballooning degeneration and hepatic lobular inflammation
Pioglitazone in NAFLD
shown to improve fibrosis, inflammation, and steatosis
NAC MOA
replenishing body stores of the antioxidant glutathione.
Glutathione reacts with the toxic NAPQI metabolite so that it does not damage cells and can be safely excreted.
Alcoholic Hepatitis Histo
Neutrophil infiltration
MAllory Dank bodies (eosinophilic accumulations of intracellular protein aggregates within the cytoplasm of hepatocytes)
• Fibrosis with a perivenular, perisinusoidal, and pericellular distribution
Liver histo piecemeal necrosis
chronic viral hepatits/AI hepatitis
SIBO features
macrocytic anaemia
B12 deficiency
fecal fat
Histopathological findings associated with SIBO include villous blunting, cryptitis, intraepithelial lymphocytosis, and eosinophilia.
Diagnosing SIBO
positive carbohydrate breath test or jejunal aspirate culture
lactulose/glucose results in an early peak (w/i 90 mins) in breath hydrogen/methane levels due to metabolism by small bowel bacteria.
Colonic pseudo-obstruction
appearance of mechanical obstruction without demonstrable evidence of such an obstruction in the intestine
in the elderly with serious concurrent medical and surgical/post-operative conditions
Risk of perforation if not decompressed
UC Histo
Mucosal/submucosal Lymphocytic infiltrateGoblet cell depletion Cryptitis Crypt abscesses NO GRANULOMAS
Crohns histo
• Transmural inflammation • Infiltrate of lymphocytes and macrophages • Granulomas in ~ 50% of cases
NOD1/Card15 in Crohns
Younger onset of disease
Small bowel involvement
Stricturing phenotype
Early initial surgery and surgical recurrence
ASCA
Anti saccaromyces cervisiae antibodies
Associated with crohns
pANCA and IBD
Associatted with UC
Extraintestinal IBD manifestations associated with active GI disease
• Oral ulcers • Erythema nodosum • Large-joint arthritis • Episcleritis
IBD Mx: Sulfaslazine and 5 aminosalicylates MOA and SE
Mechanism of action unclear
SE
Diarrhea (3%), headache (2%), nausea (2%), rash (1%)
Main role in UC.
- Reduces risk of CRC
- Induce and maintain remission in mild-mod UC
IBD Mx: Thiopurines MOA
Inhibit purine synthesis
Inhibit T and B cell proliferation
Induce T-cell apoptosis
Low/Absent 6-TGN/
Low/Absent 6-MMP
Non adherence
Low 6-TGN/
Low 6-MMP
Underdosing
High 6-TGN/
High 6-MMP
Thiopurine refractory
Trial another drug
Low 6-TGN/
High 6-MMP
Thiopurine resistance
Add allopurinol and reduce thiopurine dose
IBD Mx: Cyclisporine MOA and SE
Calcineurin antagonist
•
Potent inhibitor of cell-mediated immunity
•
Rescue therapy for severe steroid refractory UC
SE:
Nephrotoxicity, hypertension, neurotoxicity, infections
IBD Mx: Vedolizumab MOA
Selectively binds α4β7 integrin on surface of T lymphocytes
•
Blocks interaction with MAdCAM-1 on intestinal endothelium
•
Inhibits trafficking of leukocytes to sites of inflammation
•
Approved for treatment UC and Crohn’s
•
Excellent safety profile
IBD Mx Ustekinumab MOA and indication
Monoclonal antibody to p40 subunit of IL-12 / IL-23
Indications: Crohns
Risk for hepatosplenic T cell lymphoma in IBD
Highest risk in men <35 on Infliximab and thiopurine
Definition of acute severe colitis in IBD`
Bloody stool frequency >6/day plus >1 of: • Pulse >90bpm • Temp >37.8oC • Hb<10.5g/dL • ESR >30mm/hr
Autoimmune hepatitis histo
predominantly periportal hepatitis
Interface hepatitis with lymphoplasmacytic infiltrate
Hepatic rosettes
Type 1 AIH
Any age
Antibodies:
ANA, SMA, Anti F-actin
Type 2 AIH
Childhood/young adult
Antibodies:
LKM-1, Anti LC1
USually severe and treatment failure common
PRedictor of relapse in AIH at end of therapy and rescue options
End of therapy histo
-TAc, Cyc, MMF, Ritux
PBC Histo
Non‐suppurative
lymphocytic destructive
cholangitis on biopsy
• Periportal fibrosis
Biochemistry findings in PBC
Serum ALP almost always elevated (typically 3‐4x ULN)
AST, ALT < 200 U/L (unless an overlap syndrome)
Bilirubin ‐ usually rises late
Cholesterol elevated in 85%
IgM ‐ commonly elevated
AMA Positive!
Mx of PBC
UDCA
• Improves liver biochemistries and overall survival
Second line: Obeticholic acid (OCA) is a semi‐synthetic analogue of cheno‐deoxycholic acid • Selectively activates the nuclear hormone receptor farnesoid X receptor (FXRagonist)
Non specific auto antibody that may be present in PSC
pANCA
