Gastroenterology Flashcards
1
Q
3 major determinants of acid production from the gastric parietal cells
A
- ACh from parasympathetic pathway
- Gastrin from the antral G cells
- Histamine from the ECL
2
Q
What responds rapidly to thiamine replacement in wernicke’s encephalopathy?
A
Ocular palsies are relieved within hours.
Improvement in ataxias, apathy and confusion takes longer.
3
Q
What medications are absolutely contraindicated with DAA therapy in hepatitis C?
A
Carbamazepine and amiodarone and rosuvastatin.
Rosuvastatin - increased risk of rhabdomyolysis
Amiodarone and DAA - sudden death
4
Q
FODMAP diet in IBS
A
FODMAPs is an acronym (abbreviation) referring to Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols.
Generally food to avoid in IBS are:
- Onions
- Garlic
- High fructose containing food eg beer, juice, most fruits
- Cereals and grains such as wheat
5
Q
Risk of perinatal HCV transmission?
Breast feeding with HCV positive mother?
How do you check for HCV infection in infant?
A
2-8%, much lower than HIV/HBV, risk is higher if coinfection with HIV.
Breastfeeding is OK - HCV RNA is detected in breast milk but no increased risk with breast feeding
Test baby by HCV antibody at >15-18 months or use HCV RNA PCR.
6
Q
HLA associations with coeliacs disease
A
HLA DQ2
HLA B8
7
Q
When is liver biopsy indicated in NAFLD?
A
- Abnormal ALT/GGT <2-3x ULN
- > 3 features of metabolic syndrome (++ waist circumference, increased TGL and decreased HDL, insulin resistance)
Biopsy is especially indicated if feature of metabolic syndrome includes type 2 DM as they have 75% chance of NAFLD.
8
Q
Mediterranean diet
A
High in monosaturated fats (olive oil, nuts, avocado), fish and green leafy vegetables.
Low in saturated fats and red meat.
9
Q
Side effects of PPI
A
- Pneumonia
- Gastroenteritis - campylobacter, salmonella, C diff
- Osteoporosis
10
Q
Name 5 contraindications for liver transplant
A
- Prior or current malignancy except for HCC
- Active infection (exceptions are HBV, HCV, HIV)
- Severe cerebrovascular/cardiovascular disease limiting with poor prognosis
- Alcoholic liver disease with repeated alcohol cessation and poor social circumstances
- Severe metabolic syndrome - OSA, diabetes, HTN, hyperlipidaemia, morbid obesity.
11
Q
What is the antiviral of choice in HBV/HIV coinfection?
A
Tenofovir - has both antiviral activity against HIV and HBV.
12
Q
Surveillance endoscopy for Barrett’s oesophagus depending on degree of dysplasia
A
No dysplasia - every 3-5 years
Low dysplasia - every 6 months
High grade dysplasia - every 3 months
If high grade dysplasia is found on first endoscopy, likely cancer and needs definitive management
If prevalent, close surveillance or definitive management.
Once high grade dysplasia is identified, can be managed with intensive 3 month screening, RFA, or surgery.
13
Q
Extrahepatic manifestations of hep C - name 6
A
- Cryoglobulinaemia
- Lymphoproliferative disorder - NHL, MALT
- Porphyria cutanea tarda
- Sjogrens syndrome
- Diabetes
- Thyroid dysfunction
Affects 40-70% of patients
14
Q
4 top causes of HCC
A
- HCV
- Alcohol
- HBV
- NAFLD
15
Q
Histological findings of eosinophilic oesophagitis
Management
A
Esophageal eosinophilia as characterized by >25 intraepithelial eos/HPF, basal zone hyperplasia, dilated intercellular spaces.
Management:
- Trial PPI
- SFED 6 weeks
16
Q
SAAG
A
SAAG = serum albumin – ascites albumin.
A high gradient (SAAG >1.1 g/dL) indicates portal hypertension and suggests a nonperitoneal cause of ascites:
- Cirrhosis
- CHF
- Nephrotic syndrome
- Protein losing enteropathy
- Portal hypertension
A low gradient (SAAG < 1.1 g/dL) indicates nonportal hypertension and suggests a peritoneal cause of ascites:
- Peritoneal mesothelioma/carcinomatosis
- TB peritonitis
- Sarcoidosis
- SLE
- HSP
- Fungal/parasitic infections
17
Q
Role of NS5A and NS5B in HCV life cycle.
Name some inhibitors for each.
A
NS5A - involved in transport from ER to golgi apparatus, therefore involved in viral replication and assembly.
Ledipasvir, Daclatasvir, Ombitasvir.
NS5B - has RNA dependent RNA polymerase involved in viral DNA synthesis.
2 kinds of drug classes exist -
- nucleoside inhibitor which causes chain termination (Sofosbuvir)
- non-nucleoside inhibitor which causes allosteric inhibition (Dasabuvir)
18
Q
What is the treatment of choice in HBV patient with previous exposure to lamivudine?
A
Tenofovir.
Increased entecavir resistance upto 30% in patients previously treated lamivudine.
19
Q
What is the relationship between 6-TGN level and 6-MMP level with TPMT activity?
When are measuring thiopurine metabolites helpful?
A
6-TGN levels are INVERSELY correlated with TPMT activity.
6-MMP levels are directly correlated with TPMT activity.
Measuring metabolites are only helpful if patients are not responding to standard doses of thiopurine as they clarify the reason for non response (ie, non compliance, under-dosing, TPMT resistance, thiopurine refractory
20
Q
Diagnosis of coeliac disease
A
Histology is still gold standard.
Serological diagnosis:
- Anti-tTG IgA and endomysial antibody has highest sn/sp - 95/100, however they are both IgA
- If IgA deficiency, use IgG deaminated anti-gliadin antibody (90/100)
Anti-gliadin antibody is now out of fashion due to above tests having superior sn/sp.
21
Q
Paracetamol metabolism
A
90% - metabolised into inactive sulphate and glucuronide conjugates and excreted in the urine
10% - metabolised by CYP P450 (mainly 2E1 and 3A4) and results in formation of NAPQI. This is bound to glutathione and eliminated in the urine.
Toxicity occurs in paracetamol due to glutathione depletion.
22
Q
Risk factors for variceal bleeding
A
- Varix size (large - 30% annual risk of bleeding)
- Child Pugh class C>B>A
- Red sign, red wale mark on varix
- Continued ETOH use
- Previous bleed - 60% risk per annum
23
Q
Indications for qualitative and quantitative HCV RNA PCR.
A
Qualitative PCR - can detect very low levels of HCV RNA. Indicates presence or absence of RNA. Therefore useful in diagnosis of cure or diagnosis of infection.
Quantitative PCR - quantifies viral burden. Useful in predicting response to interferon and determine the length of treatment with DAA.
24
Q
Three types of autoimmune hepatitis?
A
- Type 1 - ANA/SMA positive. Affects both adults and children
- Type 2 - Anti LKM1 (anti-liver, kidney microsomal type 1). Affects children only
- Type 3 - soluble liver-kidney antigen. Affects adults in middle age.
25
What is the significance of first episode of SBP?
Has 40% overall 1 year survival...
Therefore should trigger a referral for liver transplant if patient is a candidate.
26
Mechanism of hepatopulmonary syndrome
Significant intrapulmonary capillary vasodilation which leads to:
1. Ventilation-perfusion mismatch due to increased blood flow through the pulmonary capillaries in setting of preserved alveolar ventilation, resulting in the passage of mixed venous blood into the pulmonary veins.
2. Diffusion-perfusion limitation due to more blood flow through the capillaries which leads to insufficient partial pressure (or driving pressure) of oxygen for oxygenation of blood moving near the center of the alveolar capillary because of the increased diameter of the intrapulmonary capillaries. Giving O2 improves this diffusion gradient and eliminates this physiological shunting.
27
Why are sodium phosphate enemas contraindicated in older adults?
Associated with complications including hypotension and volume depletion, hyperphosphatemia, hypo- or hyperkalemia, metabolic acidosis, severe hypocalcemia, renal failure, and EKG changes (prolonged QT interval)
28
4 causes of early (<3/12) liver transplant morbidity/mortality
1. Infection - bacterial, CMV, fungal
2. Biliary stricture
3. Renal/diabetes
4. Graft failure (now rare)
CMV/PJP risks are managed with PO valgancyclovir for 3 months and cotrimoxazole for 6 months. Gancyclovir is not used as it is myelosuppressive.
29
Barrett's oesophagus treatment
1. Life long PPI
2. Surveillance endoscopy as per degree of dysplasia
3. Endoscopic ablative therapy for dysplasia with RFA
4. Manage risk factors - eg obesity, smoking
No benefit from anti-reflux surgery
30
Primary sclerosing cholangitis
Associated with IBD (75%)
pANCA positive
MRCP shows beading of biliary tree.
If MRCP is normal - may be small duct PSC, and consider biopsy to confirm.
Ursodeoxycholic acid improves LFT.
Increased risk of cancer - check CA19-9 (pancreatic, bile duct cancer)
31
Factors associated with spontaneous clearance of HCV
1. Younger age
2. Female
3. MHC genes, IL28B
32
According to the Milan criteria in HCC and liver transplantation, in which situation is it acceptable to transplant?
1. Single tumour <5cm
| 2. No more than 3 tumours with largest less than 3cm in diameter
33
Name examples of following laxative classes
1. Bulk forming
2. Osmotic laxatives
3. Stimulant laxatives
4. Stool softeners
1. Bulk forming - psyllium, methylcellulose
2. Osmotic laxatives - lactulose, sorbitol, macrogol
3. Stimulant laxatives - Senna, bisacodyl
4. Stool softeners - bisacodyl, docusate.
34
What is the benefit of variceal band ligation
1. Significant reduction in bleeding at 1 year and 2 year
2. There is an actual mortality benefit - significant reduction at 2 years.
Therefore, compared to propranolol, variceal band ligation is much more effective in that it reduces incidence of variceal bleeding as well as reduce mortality.
35
Autoimmune associations with coeliac disease
1. Type 1 DM
2. Hypothyroidism
3. IgA deficiency
36
Name 6 contraindications for liver transplantation.
1. Pulmonary hypertension >40mmHg
2. AIDS responding poorly to HAART
3. Multiorgan failure
4. Active substance abuse
5. Extrahepatic malignant disease
6. Severe uncontrolled systemic infection
37
Primary biliary cirrhosis
ANA/AMA positivity
Presents with fatigue and pruritis
Treat with ursodeoxycholic acid,
Pruritis - cholestyramine, antihistamines, rifampin
Definitive treatment is liver transplant.
Histology will show granulomas with bile duct damage.
38
Definition of SVR (sustained virological response) in Hep C
Hep C PCR negative 12 weeks after finishing the course of therapy. ie, elimination of reservoir.
39
Management of alcoholic hepatitis
1. Establish disease severity using MELD or MDF scores
- MDF >32, presence of hepatic encephalopathy
- MELD score of >18
2. Consider transjugular liver biopsy to confirm diagnosis of alcoholic steatohepatitis
3. Treat with prednisolone if high risk, pentoxifylline if steroids are contraindicated or early renal failure
4. Reassess response at 7 days to see whether prednisone should continue for 3 more weeks or stop depending on Lillie score
40
Definition of portal hypertension
As defined by HVPG
HVPG = Wedged hepatic venous pressure - free hepatic venous pressure
>5 = portal hypertension
Clinically significant PTH is HPVG of >10 which increases the likelihood of clinical decompensation, HCC and variceal formation.
41
What is the benefit of propranolol in varices management?
Meta-analysis showed reduced bleeding rates vs placebo, however this benefit is seen mainly in medium to large varices, not small varices.
Also reduces risk of 1st variceal bleeding via 50%.
No clear mortality benefit compared to placebo.
Also poorly tolerated - 1/4 do not tolerate it
<40% achieve desired reduction of HPVG.
42
Causes of hypergastrinaemia
1. Prolonged acid inhibition - PPIs, H2RA
2. Atrophic gastritis
3. Vagotomy/SB resection
4. Gastrin secreting tumours
5. Renal failure
6. Hypercalcaemia
Best test for hypergastrinaemia is fasting gastrin level.
43
2 types of hepatorenal syndrome
Type 1 - acute deterioration with usually identifiable trigger (sepsis, bleeding etc), potentially reversible with IV albumin and terlipressin. Complicates 25% of SBP.
Type 2 - slow progression/indolent. Annual incidence of 8% in patients with cirrhosis and ascites. Poor outcome without transplant. Often associated with refractory ascites.
44
What is the significance of HCV genotypes as it relates to interferon and DAA treatment?
Reason for doing genotype testing?
Higher SVR achieved in interferon treatment - 2>3>1b>1a
Higher SVR achieved with DAA treatment 1>3 (as current DAAs are developed to target genotype 1)
Therefore genotype testing is important in that:
1. Predicts response to interferon
2. Determines duration of treatment with IFN
3. Determines which DAA combination to use.
45
4 risk factors for neonatal vaccination failure in HBV
1. eAg positivity
2. HBV DNA >10e7
3. Intrauterine transmission
4. Vaccine escape mutations
46
Management of HCC in the following:
1. Single lesion <3cm
2. Upto 3 nodules of less than 3cm in diameter
3. Single lesion less than 3cm, with evidence of portal hypertension or raised bilirubin
4. Multinodular HCC or portal invasion
1 - Resection
2 and 3 - Liver transplant, or RFA if comorbidities preclude transplantation. All curative intent.
4 - sorafenib. Not curative.
47
Advantage of IFN over antiviral therapy in HBV
Duration of treatment is shorter - 48 weeks
| Good for young patients who might consider pregnancy in the future.
48
Treatment of NAFLD
1. Weight loss!!! and Mediterranean diet
2. Treat insulin resistance with metformin
3. Reduce fibrosis - Vitamin E has some evidence especially in NON DIABETIC PATIENTS - significant overall histological improvement in NASH at 96 weeks when compared to placebo
4. Manage co-factors (Alcohol, HBV, HCV)
49
King's college criteria for liver transplant in paracetamol poisoning
What about non-paracetamol related acute liver failure?
Paracetamol related acute liver failure:
pH 7.3 or all of the following:
- INR >6.5
- Hepatic encephalopathy grade 3-4
- Creatinine 300mmol/L
Non-paracetamol related:
INR >6.5 or 3/5 criteria (which I won't try to remember...)
50
Cag A positivity in H pylori
More virulent.
| Clinically associated with more duodenal ulcers, worse gastritis, higher risk of relapse.
51
Indications for annual colonoscopy in UC (ie high risk)
If high risk as defined below:
1. Stricture in the past 5 years
2. Extensive colitis with mod/severe active endoscopic/histologic inflammation
3. Dysplasia in the last 5 years AND declining surgery
4. PSC
5. FmHx of CRC in 1st degree relatives <50
(if family history of IBD and CRC in first degree above age of 50, then screening is 3 yearly)
52
Pathophysiology of portal hypertension
Cirrhosis leads to intrahepatic resistance with resultant increased splanchnic and systemic vasodilation.
Vasodilation leads to activation of RAA due to relative renal hypoperfusion and intravascular volume depletion with increased , water and renal vasoconstriction.
Sodium retention leads to refractory ascites, water retention leads to hypervolaemic hyponatremia, and renal vasoconstriction leads to HRS.
53
SBP prophylaxis in cirrhosis
Used in patients at high risk for SBP which includes:
1. Patients with cirrhosis and gastrointestinal bleeding.
2. Patients who have had one or more episodes of SBP
3. Patients with cirrhosis and ascites if the ascitic fluid is 15 g/L along with either impaired renal function or liver failure.
4. Patients with cirrhosis who are hospitalized for other reasons and have an ascitic protein concentration of less than 1 g/dL (10 g/L).
If inpatient variceal bleed - use IV ceftriaxone
Otherwise, daily norfloxacin 400mg, cotrimoxazole 960mg (regular dosing preferred as it reduces resistance)
54
Cardinal feature of achalasia
Management of achalasia
Incomplete LOS relaxation with oesophageal aperistalsis.
Management:
1. Surgery - Modified heller myotomy - surgical division of LOS with fundoplication. Good response with response upto 85% at 5 years, mortality 0.3%
2. Botulinum toxin - similar efficacy to dilatation but much safer. Median effect of duration 12 months.
3. Pneumatic dilatation - perforation 5%, mortality 0.2%, response 65% at 5 years.
55
In the setting of HBV viremia as detected on HBV DNA PCR, what dose absence of HBeAg mean?
Suggests presence of pre-core HBV mutant or basal core promotor mutant.
Pre-core mutant - eliminates HBeAg production
Basal core promotor mutant - down regulates HBeAg production.
These mutants are associated with increased development of advanced disease (such as cirrhosis, HCC). Makes up around 50% of chronic HBV infection.
56
What is the treatment for HBV/HDV coinfection?
HBV/HDV coinfection is associated with more severe acute hepatitis and higher mortality. Treat with peg-interferon alpha for at least 48 weeks.
57
Factors associated with more rapid HBV disease progression
1. Male
2. Alcohol and smoking
3. Older age (longer duration of infection)
4. Family history of HCC
5. Coinfection with HCV, HDV or HIV
6. HBV genotype C (C for cirrhosis)
58
3 major classifications of causes for vitamin B12 deficiency
1. Dietary - eg vegans
2. Gastric - pernicious anaemia, atrophic gastritis, gastrectomy
3. Small bowel
- Bacterial overgrowth
- Pancreatic insufficiency
- Crohns disease (due to removal of terminal ileum)
59
6 diseases associated with IgG4 disease
Treatment?
1. Riedel's thyroiditis
2. Autoimmune pancreatitis
3. Mediastinal/retroperitoneal fibrosis
4. Sjogrens syndrome
5. Salivary/lacrimal/submandibular gland tumours
6. IgG4 cholangiopathy - Stricturing of the intrapancreatic portion of the distal common bile duct is the most frequent bile duct finding. Appearances are similar to PSC which is the main differential diagnosis.
Treatment is corticosteroids
60
Contraindication for VIEKIRA PAK ie PrOD combination (Ombitasvir, pariteprevir-retonavir, Dasabuvir)
Child pugh B/C cirrhosis
Unlike HARVONI, PrOD is safe and effective in eGFR <30 but most patients require rivabarin.
61
What are the indications for liver transplantation in paracetamol poisoning?
1. pH <7.3 24 hours after ingestion
OR all of the following:
Grade 3-4 encephalopathy
Creatinine >300
Prothrombin time >100s
62
Amsterdam criteria for hereditary colon cancers?
3 family members with CRC
Case spans at least 2 generations
At least 1 case diagnosed before <50 age
63
Management of HRS
1. Avoid nephrotoxic meds
2. Treat underlying precipitant
3. Withhold diuretics
4. Vigorous IV Albumin at 1g/kg to treat low oncotic pressure with low intravascular volume
5. Terlipressin to create splanchnic vasoconstriction.
64
Management of HBV in chemotherapy
If HBsAg positive or HBV DNA positive, start prophylactic lamivudine. If long term therapy is required, TDF/ADV or ETV may be preferred.
HBsAg negative, anti-HBc positive - insufficient evidence to support prophylaxis. Treat if reactivation. Could consider vaccination.
If HBsAg and anti-HBc negative - no prophylaxis required.
Generally if they are receiving R-CHOP, then would consider prophylaxis with lamivudine, or tenofovir/entecavir if long term prophylaxis is required.
65
2 major patterns of gastric involvement with H pylori infection
1. Antrum predominant gastritis with increased acid output and increased risk of duodenal ulcer
2. Pan-gastritis pattern with reduced acid production, increased risk of gastric ulcer.
66
Classical clinical findings with Wilson's disease
Treatment?
AR disease
Due to copper overload.
Clinical features include neuropsychiatric manifestations, dystonia, choreoathetoid, parkinsonian features
Increased urine ceruloplasmin, decreased serum ceruloplasmin.
Treatment is with penicillamine, zinc
67
Contraindication to use HARVONI (Ledipasvir and sofosbuvir)
eGFR <30 mL/min
68
Post liver transplant complication occurring months to years after transplant with worsening cholestatic LFT derangement?
Likely reflecting chronic rejection manifested as vanishing bile duct syndrome. Treatment is with increased immunosuppression (tacrolimus).
69
Name 5 risk factors for HCV acquisition
1. IVDU
2. HIV + MSM
3. Transfusion/frequent exposure to blood products before 1990s
4. Children of HCV antibody positive mothers
5. Low SES, high risk sexual behaviour
70
6 Risk factors for gastric cancer
```
H. pylori infection
blood group A: gAstric cAncer
gastric adenomatous polyps
pernicious anaemia
smoking
diet: salty, spicy, nitrates
```
71
5 Adverse effects of IFN
1. Flu like illness
2. Neuropsychiatric disturbances eg: psychosis, depression
3. Leucopenia/thrombocytopenia
4. Weight/hairloss
5. Induction of autoimmune diseases eg: severe flare of RA
72
How do you manage necrotizing pancreatitis?
Conservative management is superior to early surgery (necrosectomy) in terms of incidence of major complications.
73
3 M rule for PBC
IgM
Middle aged female
anti-Mitochondrial antibodies
74
Clinical features of Wilsons disease
Cause?
Management?
liver: hepatitis, cirrhosis
neurological: basal ganglia degeneration, speech and behavioural problems are often the first manifestations. Also: asterixis, chorea, dementia
Kayser-Fleischer rings
renal tubular acidosis (esp. Fanconi syndrome)
haemolysis
blue nails
Cause: Mutation of ATP7B gene in Ch 13
Management - chelation with penicilliamine
75
ABCB4 disease
Recently recognized cause of several biliary tract diseases:
1. Intrahepatic cholestasis of pregnancy
2. Progressive familial intrahepatic cholestasis
3. Recurrent pancreatitis.
76
Cancers associated with PSC
CRC
| Cholangiocarcinoma
77
Causes of false negative HCV antibody testing
1. Immunosuppressed
2. Window period (initial 2-4 weeks after infection)
3. Organ transplant
Once a patient is positive for HCV antibody, it remains positive for life.
78
Describe SFED diet in eosinophilic oesophagitis
Involves elimination of six food for at least 6-8 weeks then reintroduce one at a time.
Eliminate nuts, wheat, soy, seafood, eggs, milk.
More effective in identifying triggers of EoE than skin prick test which are not very accurate.
79
How do you screen for hereditary haemochromatosis?
Fasting morning transferrin saturation >45%
It will detect almost all C282Y homozygotes.
Serum ferritin rises later in iron overload and is an acute phase reactant therefore can rise with alcohol abuse, inflammatory states, steatosis etc...
In absence of these conditions, ferritin >1000 can be used to indicate liver biopsy.
Normal ferritin and transferrin saturation is very high at 97% therefore no further testing is recommended.
80
How is peristalsis controlled?
By pacemaker cells of the gut - interstitial cells of Cajal.
| Affected in gastroparesis, Crohn's disease, Chaga's disease, achalasia of LES.
81
How do you manage HBV?
1. If you have compensated/decompensated cirrhosis, generally just treat and screen for HCC using USS/AFP every 6-12 months
2. If no evidence of cirrhosis, depends on ALT level and HBe Ag status and HBV DNA level.
If HBeAg positive with high HBV DNA and normal ALT, consider liver biopsy +/- treat if moderate/severe inflammation or fibrosis on biopsy.
If HBeAg positive with high HBV DNA level >20000 IU/mL with elevated ALT level (>2x ULN), observe for 3-6 months for spontaneous serocoversion prior to treatment.
If HBeAg negative with normal ALT and low viral load, observe only.
If HBeAg negative, mildly elevated ALT (1-2x ULN) and HBV DNA (>2000 IU/mL), consider biopsy +/- treat if moderate to severe inflammation/fibrosis.
82
What is the natural history of HCV?
25% - spontaneous clearance
75% - chronic hep C
Of those who develop chronic HCV infection:
10% develop cirrhosis at 20 years
HCC tends to develop 30 years after initial infection
Once you develop HCV cirrhosis, risk of decompensation is 4-5% per year, HCC and death risks are 3% per year.
83
What are the 4 key information required for hep C management?
1. Does this patient have Hep C? (check HCV-Ab and HCV PCR)
2. Genotype? (1 and 3 common in Australia)
3. Cirrhosis?
4. Previous treatment?
If previous treatment exposure and cirrhosis, treatment is lengthened out for 24 weeks of dual therapy or dual DAA therapy plus ribavirin.
If cirrhosis, needs ongoing HCC surveillance.
Sofosbuvir + ledipasvir - for genotype 1a/b
Sofosbuvir + daclatasvir - for genotype 3
84
Role of gastrin
secreted by G cells of the antrum of the stomach upon sensing peptides.
Gastrin stimulates ECL cells to secrete histamine, which then acts on parietal cells to produce H+.
Ie, gastrin INDIRECTLY stimulates parietal cells to produce acid.
85
Classical histological appearance of alcoholic liver injury
Mallory's hyaline, seen as globular red hyaline material within hepatocytes.
86
In paracetamol poisoning, how long should NAC be continued for?
NAC replenishes glutathione and also neutralizes NAPQI.
Should be continued until:
1. Paracetamol level is undetectable
2. INR and AST/ALT are normal or showing downward trend over at least 24 hour period
87
Risk factors for acute fatty liver of pregnancy
1. Male fetus
2. Multiple gestations
3. Primiparous women
88
Histological features of NASH
1. Steatosis - generally greatest in zone 3 (peri-central vein)
2. Lobular inflammation (zone 3)
3. Ballooning degeneration, apoptosis, and necrosis
89
When do HCV antibodies become detectable?
4-24 weeks after infection.
90
5 agents with highest risk of HBV reactivation
1. TNF alpha inhibitor
2. Leflunomide
3. Methotrexate
4. Cyclophosphamide
5. Medium-high prednisone (>7.5mg/day)
Generally poses a higher risk if combination therapy is used.
91
5 Contraindications to combination therapy of rivabarin and peg-IFN in HCV treatment
Mainly relates to the side effect profile of INF and rivabarin:
1. Significant psych disease
2. Decompensated cirrhosis
3. Pregnancy/lactation
4. Autoimmune disease
5. Unable to tolerate low Hb
92
Variceal screening in cirrhosis
Annual screening if small varix
2 yearly if no varix.
This is because 10-20% patients with initially detected small varices become large in the year after first detection.
90% of cirrhotic patients will eventually develop varices therefore continued screening even if no varices is important. 7% of the cirrhotics will develop varices/year.
93
Management of HBV in pregnancy
1. All babies born to HBsAg positive women should receive HBV vaccine and HBIG <12 hours of birth.
2. Can breast feed after administration of HBIG. Do not breast feed if crackled nipple or bleeding
3. Consider tenofovir in third trimester if highly viraemic (HBV DNA 10e6-7), mostly in HbeAg positive mothers who will have >10% vertical transmission risk despite HBV vaccine and HBIG.
Mode of delivery does not matter.
94
When should you consider treating pregnant women with HBV infection?
Treat with tenofovir if initial assessment in first trimester suggest cirrhosis or active infection.
In 2nd trimester, depends on HBV DNA level:
HBV DNA level <10e6 - just give the newborn HBIG within 12 hours and HBV vaccine x3
HBV DNA level >10e6 - consider initiating treatment with tenofovir at 28-32 weeks. Infants to receive HBIG and vaccine at birth.
95
What is the effect of smoking cessation at diagnosis of chronic pancreatitis?
Reduces risk of calcification at 6 years.
| Alcohol cessation makes no difference to degree of calcification.
96
Describe the significance of HBV genotype as it relates to IFN response, severity of liver disease, seroconversion rate
10 HBV genotypes identified with distinct geographic distribution.
A and B have better response to peg-IFN than C and D,a nd higher rates of sAg seroconversion are seen with A and B compared to C and D.
Genotype C and D have more severe liver disease including cirrhosis and HCC.
Genotype C have lower rates of spontaneous eAg seroconversion than genotype B and have multiple disease flares which may accelerate disease progression.
Genotype B and C are most common in Asia.
97
When is it appropriate to stop HBV treatment?
Depends on HBeAg status and which guideline you look at...
In HBeAg, generally most guidelines suggest HBeAg seroconversion and undetectable DNA for 6-12 months on treatment. However despite this cumulative off therapy clinical relapse rate was 45.3% in 1 year.
In HBeAg negative HBV infection, EASL and AASLD guidelines suggest indefinite therapy until HBsAg clearance, which may never happen.
Therefore long term therapy is the rule at this stage.
98
Mechanism of action of lactulose in hepatic encephalopathy
Acidifies the gut by being converted to lactic acid which neutralizes ammonia
99
Mechanism of action of terlipressin
Long acting vasopressin analogue comprised of one molecule of lysine vasopressin and 3 additional glycine residues.
Mediates vasoconstriction by activation of vasopressin 1 receptor which is preferentially expressed on vascular smooth muscle cells within the splanchnic bed.
Reverses splanchnic vasodilation.
100
HBV treatment of choice in following situations:
1. Pregnancy
2. Decompensated cirrhosis
3. Renal failure
4. Women of child bearing age wishing to eradicate virus prior to pregnancy
5. HIV coinfection
1. Pregnancy - tenofovir
2. Decompensated cirrhosis - entecavir
3. Renal failure - entecavir with dose reduction
4. Women of child bearing age wishing to eradicate virus prior to pregnancy - peg IFN
5. HIV coinfection - tenofovir with emtricitabine or lamivudine
101
Inheritance pattern for HNPCC
Autosomal dominant
102
Which genotypes manifest phenotypic HH?
69-100% of C282Y homozygosity
4-7% Compound heterozygote C282Y/H63D
3-10% heterozygous C282Y or H63D
only 1% are homozygous H63D mutations
Compound heterozygotes/heterozygotes have lesser degree of iron overload than homozygotes.
Also, in order for compound heterozygotes to develop clinical disease/hepatic fibrosis, they need to have other comorbid features such as excessive alcohol consumption, steatosis, diabetes, viral hepatitis.
103
Mechanism of action of ribavirin
Name 3 important side effects
Synthetic guanosine analogue. Broad spectrum antiviral which is orally active. Ineffective as monotherapy.
SE:
1. Haemolysis
2. Teratogenicity - 2x forms of contraceptives required
3. Pruritis, nausea and vomiting
104
Mechanism of action of NSAID induced gastrointestinal toxicity
Due to systemic inhibition of COX enzyme inhibition.
Healthy gastric and duodenal mucosa expresses COX-1 which produces prostaglandins such as PGE2 which protects gastroduodenal mucosa from pepsin.
105
NOD2/CARD 15 variants
```
Seen in Crohn's disease. Susceptibility gene.
Associated with:
1. Younger age at onset
2. Small bowel involvement
3. Stricturing phenotype
4. Early initial surgery
5. Early surgical recurrences
```
106
What is the effect of smoking in UC/Crohns?
Protects against UC, increases the risk of Crohn's disease.
107
4 extraintestinal manifestations of UC/Crohns associated with active GI disease
1. Oral ulcers
2. Erythema nodosum
3. Large joint arthritis
4. Episcleritis
108
Budesonide in Crohn's disease
Steroids in general are effective in INDUCING remission but not good at maintaining remission.
Budenoside undergo significant first pass metabolism and are delivered specifically to terminal ileum and proximal colon. Therefore effective in ileocaecal Crohn's disease.
Compared to conventional corticosteroids, fewer SE but less effective (particularly in severe disease)
109
Role of methotrexate in IBD
Folic acid analogue which induces and maintains remission in CD, but less data in UC.
110
Role of cyclosporine in IBD
Calcineurin antagonist.
Used as a rescue therapy for severe steroid refractory UC, short term bridge to therapy with AZA/6MP.
Not used for Crohn's disease - only UC.
111
Mechanism of action of vedolizumab
Selectively binds to a4b7 integrin on surface of T lymphocytes and blocks interaction with MAdCAM-1 on intestinal endothelium. Inhibits trafficking of leukocytes to sites of inflammation.
Vedolizumab is gut specific and has great safety profile - used in UC and Crohns disease.
112
What is the risk/benefit of AZA and anti-TNF combination therapy in management of IBD?
Combination therapy is definitively superior to monotherapy in terms of achieving mucosal healing and steroid free remission.
However combination therapy has OR of 15 for opportunistic infection, and significantly increases risk of hepatosplenic T cell lymphoma (seen in almost all young males, and almost all universally fatal disease)
113
Management of fistulising crohn's disease
If superficial, use antibiotics + fistulotomy
If deep, use setons + antibiotics +/- 6MP/AZA
If failing above, use anti-TNF alpha therapy, tacrolimus or surgery.
114
Treatment of pouchitis?
Antibiotics - ciprofloxacin, metronidazole.
Prophylaxis with probiotics.
115
3 ways of reducing recurrence of Crohn's disease after surgical resection
1. Metronidazole for 3 months
2. Smoking cessation
3. Combination adalimumab and infliximab for 12 months
116
Risk factors for cancer in UC
1. Duration of disease
2. Extent of the disease
3. Concurrent PSC
4. Coexistent family history of CRC
117
When should you start colonoscopy in UC/Crohns?
How frequent should the screening be?
Start at 8 years of disease duration for ALL UC extending above rectum and Crohn's disease with more than 1/3 of colon involved
Generally 3 yearly if inactive UC, crohn's colitis, IBD and family history of cancer in first degree relative above 50 years old.
Move to 5 yearly screening if 2 previous normal colonoscopies
118
4 predictors of severity for Crohn's disease at diagnosi
1. Perianal disease
2. Fibrostenosing disease
3. Need for steroids
4. Loss of body weight >5kg
119
Treatment of UC
UC activity is generally reflected by symptoms (proctitis can be different)
1. 5-ASA - generous use both as oral and rectal form in most cases
2. Steroids - if inadequate control with 5ASA - but always taper
3. Introduce thiopurines if requiring steroids >1/year
4. Anti-TNF
5. Vedolizumab
120
Therapeutic aims in UC/Crohns
1. Normalization of CRP - high CRP is associated with increased risk of surgery
2. Fecal calprotectin level <50
3. Mucosal healing
121
Side effects of 5-ASA
| Side effects specific to sulfasalazine
1. Interstitial nephritis
2. Pancreatitis
3. Diarrhoea
Specific side effects to sulfasalazine
1. SJS
2. Reversible azospermia
3. Sulfur intolerance
122
How would you manage IBD patients who are known 'shunters' resulting in low 6-TGN level and high 6-MMP level?
Block xanthine oxidase to increase level of 6MP. (prevents conversion of 6MP to 6TU)
Add allopurinol 100mg PO OD, reduce azathioprine to 25-50% of original dose with close haematological monitoring and repeat metabolites after 4 weeks.
123
Malignancy risk with azathioprine use in UC
1. Increase in non-melanoma skin cancers
| 2. Increase in lymphoma
124
Management of Crohn's disease
1. Prednisone
2. Methotrexate
3. Infliximab/adalimumab if refractory to above or fistulising crohns disease
azathioprine and 5ASA not shown to be effective.
125
Mechanism of action of vedolizumab
Binds selectively to a4/b7 integrin on T lymphocyte surface and blocks interaction with MAdCAM-1 on the intestinal endothelium and prevents trafficking of leukocytes to sites of inflammation.
Excellent safety profile.
Efficacious and safe in UC/CD
126
Management of acute severe UC
Medical emergency.
First line medical therapy:
1. IV hydrocortisone 100mg QID
2. Clexane
3. IVF
4. Transfuse Hb >100
Reevaluate at day 3-5 - 20% of UC patients do not respond to steroids.
If no clinical response:
1. Infliximab or cyclosporine therapy
2. Surgery
127
5 routine vaccinations given to IBD patients
1. Pneumococcal 5 yearly
2. Influenza vaccine yearly
3. VZV (need to give before TNF alpha therapy as live attenuated vaccine)
4. HBV
5. HPV vaccine
128
3 key information for HCV management
1. Does the Pt actually have HCV?
2. Genotype?
3. Cirrhosis? (lengthens treatment duration to 24 weeks with HARVONI if previous treatment and concurrent cirrhosis, or need to add ribavarin)
129
How do you distinguish between inactive HBV carrier state and HBeAg negative chronic hepatitis?
In both cases, HBeAg is negative, Anti-HBe positive, Anti-HBc positive, HBsAg positive.
Differentiated by HBV DNA level.
Inactive carrier state DNA level <2000
Chronic hepatitis >2000
130
When would you consider treating HBeAg positive HBV infection?
Determine if HBV DNA >20,000 IU/mL
Then, determine whether HBV infection is in immune tolerance phase or immune clearance phase (depending on ALT level)
Immune tolerance phase (normal ALT) - consider liver biopsy if >40 age, and treat if moderate/severe inflammation or fibrosis on biopsy.
Immune clearance phase (ALT >2x ULN) - can observe 3-6 months to see if the patient will seroconvert spontaneously. If no seroconversion occurs, baseline liver biopsy then start treatment.
131
When would you start treatment for HBeAg negative HBV infection?
Determine the HBV DNA level
If HBV DNA level <2000 with normal ALT, then most likely in immune control phase. Tend to observe, but can consider therapy in patients with significant inflammation or fibrosis on biopsy even if DNA level or ALT is normal.
If HBV DNA level >2000, this represents immune escape.
1. If ALT 1-2x ULN, consider biopsy and treat if mod/severe inflammation on biopsy
2. If >2x ULN, treat.
132
How would you treat HBV infection in compensated cirrhosis?
What about decompensated cirrhosis?
Generally treat if HBV DNA level is >2000 IU/mL.
Would generally just treat even if HBV DNA level is <2000 as HBV flare will cause decompensation.
In decompensated cirrhosis, start treatment regardless of HBV DNA level with combination therapy of tenofovir/adefovir or lamivudine/entecavir
133
Describe the population group in which you could consider budesonide and azathioprine combination therapy in autoimmune hepatitis.
Mainstay of treatment usually is prednisone +/- azathioprine.. however in select group with following characteristics, budesonide can be considered instead:
1. Mild AIH
2. No cirrhosis
3. At risk of prednisone induced complications including obesity, diabetes, osteoporosis, poorly controlled hypertension
134
Features of PBC
| Treatment?
Thought to be autoimmune in aetiology
Presents with fatigue and pruritis
Usually IgM positive, AMA positive, ANA positive (30%)
AMA negative PBC will have positive anti-GP210 or anti-SP100.
Biopsy will show bile duct damage due to granulomas.
Treatment:
1. UDCA
2. Manage pruritis with Cholestyramine, antihistamine, rifampin
3. Liver transplantation
135
Investigation of liver nodule
If <1cm - repeat USS 3 monthly - if seen to grow, investigate further with CT triphasic liver
If >1cm, investigate using CT triphasic liver or contrast enhanced MRI. Arterial hypervascularity AND venous or delayed phase washout confirms HCC.
136
Test with highest negative predictive value in investigation of coeliacs disease in asymptomatic individual?
HLA DQ2/DQ8
137
Spur cell haemolysis
Spur cell haemolytic anaemia is a form of haemolytic anaemia that results secondary to severe impaired liver function or cirrhosis. Chronic liver disease impairs the liver's ability to esterify cholesterol, causing free cholesterol to bind to the red cell membrane, increasing its surface area. This condition also creates rough or thorny projections on the erythrocyte named acanthocytes
138
MoA of ursodeoxycholic acid
Ursodeoxycholic acid is thought to exert its effects in cholestatic conditions via protection of cholangiocytes against cytotoxic hydrophobic bile acids, stimulation of hepatobiliary secretion, protection of hepatocytes against bile-acid induced apoptosis, and induction of antioxidants
139
2 protective factors for UC
1. Smoking
| 2. Appendicectomy
140
4 Extra-intestinal manifestations of IBD which correlate with active GI disease
1. Oral ulcers
2. Erythema nodosum
3. Large joint arthritis
4. Episcleritis
141
Definition of acute severe colitis according to Truelove and Witt's criteria
Bloody stool >6/day plus one of:
1. Pulse >90
2. Temp >37.8
3. Hb <100
4. ESR >30mm
142
What investigations needs to be done before consideration of surgical management of reflux disease?
1. Oesophageal manometry to screen for severe oesophageal hypomotility or occasional achalasia
2. pH study to confirm excessive exposure (sometimes heartburn can be functional due to oesophageal hypersensitivity, and these people do poorly with fundoplication)
143
Diagnosis of distal oesophageal spasm
Treatment?
Synchronous incoordinated contraction of smooth muscle of oesophageal body, probably due to loss of inhibitor innervation.
Manometry will show synchronous pressure waves.
Barium swallow showing corkscrew oesophagus.
Treatment - eat soft food, eat slowly
Can trial PPIs - acid reflux can sensitize and cause DOS
Botox injection
144
Dumping syndrome - early and late
Dumping syndrome can occur in up to 50% of patients following gastric surgery. It commonly occurs following ingestion of high level sugar and/or fat, bypassing the stomach too rapidly and enter the small intestine largely undigested.
1. Early dumping syndrome - rapid onset usually within 15 minutes of a meal, as a result of rapid emptying of food into the small bowel. Due to the hyperosmolality of the food, rapid fluid shifts from the plasma into the bowel resulting in hypotension and sympathetic nervous system response. Patients are advised to avoid sweet/simple sugar food and instead to have high fiber, complex carbohydrate and protein rich foods. Also advised to have small frequent meals.
2. Late dumping syndrome - dumping of food triggers pancreas to release excess insulin leading to hypoglycaemia 2-3 hours after a meal. Treatment also same as early dumping syndrome.
145
Which type of hepatocellular injury is most commonly seen after paracetamol poisoning?
Centrilobular (zone 3) necrosis. Has the lowest O2 content therefore most sensitive to ischaemic injury.
Periportal (zone 1) - highest O2 content
