Gastro Flashcards
(327 cards)
1
Q
What is the characteristic endoscopy finding in Gastric Antral Vascular Ectasia?
A
Watermelon stomach - longitudinal rows of flat, reddish stripes radiating from the pylorus into the antrum that resemble the stripes on a watermelon
2
Q
Are there any conditions associated with GAVE?
A
It is usually an isolated condition but may be associated with cirrhosis or systemic sclerosis
3
Q
What patient demographic is GAVE most commonly found in?
A
Older (>70yo) women (80%)
4
Q
How do you diagnose Gastric Antral Vascular Ectasia?
A
Based on classical endoscopic appearance.
Diagnosis may be confirmed by endoscopic biopsy, endoscopic ultrasound, tagged red blood cell scan, or computed tomography (CT) scan
5
Q
What are the histopathological characteristics of GAVE?
A
vascular ectasia, spindle cell proliferation, and fibrohyalinosis
6
Q
How might GAVE present?
A
Usually as chronic GI bleed causing iron deficiency anaemia.
However it may present with an acute upper GI bleed
7
Q
How do you treat GAVE?
A
Periodic blood transfusions
+
Endoscopic coagulation with a heater probe, bipolar probe, argon plasma coagulator, laser therapy, or radiofrequency ablation - these can obliterate the vascular ectasia and decrease the degree of bleeding
8
Q
Does portal decompression with TIPS reduce bleeding in GAVE?
A
No, underscoring the uncertain relationship between GAVE and portal hypertension
9
Q
Other than endoscopic therapies, what other treatments can be tried for refractory GAVE?
A
Combination oestrogen-progesterone therapy
Or
Antrectomy
10
Q
What is Zollinger-Ellison syndrome?
A
ZE refers to the syndrome of gastric acid hypersecretion by a duodenal or pancreatic neuroendocrine tumour (which secretes gastrin - ie a gastrinoma) that results in severe acid-related peptic disease and diarrhoea
11
Q
Is Zollinger-Ellison syndrome more common in males or females?
A
Males
Commonly diagnosed between age 20-50
12
Q
What autosomal dominant predisposition to tumors is associated with Zollinger-Ellison syndrome?
A
Multiple endocrine neoplasia type 1 (MEN1)
It is classically associated with the “3 Ps”
- parathyroid glands
- pituitary gland (anterior)
- pancreatic endocrine cells
But many other types of cancers recognised to be increased in this condition
13
Q
What are the 3 Ps of Multiple Endocrine Neoplasia type 1 (MEN1)?
A
Refers to classical tumour location that patients with MEN1 are predisposed to:
- Parathyroid gland
- Pituitary gland (anterior)
- Pancreatic endocrine cells
14
Q
What percentage of Zollinger-Ellison syndrome is linked to MEN1?
A
20-30%
The rest are sporadic
15
Q
What percentage of gastrinomas arise in the pancreas?
A
20-25%
The rest are in the duodenum - mostly D1
16
Q
What are some of the differences between duodenal and pancreatic gastrinomas?
A
Duodenal gastrinomas tend to be:
- small (<1cm)
- multiple
- less likely to have metastasised to liver at diagnosis
17
Q
In what percentage of patients with gastrinomas do the gastrinomas arise from sites other than the pancreas or duodenum? Where may they arise?
A
5-15%
Can arise from stomach, peripancreatic lymph nodes, liver, bile duct, ovary, heart, small cell lung ca
18
Q
How are neuroendocrine tumours arising from the digestive system classified by the WHO?
A
Based on the extent to which they resemble their normal non-neoplastic counterparts
19
Q
If a neuroendocrine tumour stains for gastrin and secretes gastrin but does not produce symptoms of Zollinger-Ellison syndrome, is it a gastrinoma?
A
No - the designation of the tumor as a gastrinoma is based upon the presence of a clinical syndrome that results from tumor production and secretion of gastrin, and not by its morphologic appearance or the presence of gastrin in the secretory granules
In many cases, whilst the tumour may secrete gastrin, the hormone is not processed to biologically active gastrin
20
Q
What is the pathophysiology of Zollinger-Ellison syndrome?
A
In ZE syndrome, gastrinomas secrete excessive gastrin which results in high gastric acid output due to the trophic actions of gastrin on parietal cells and histamine-secreting enterochromaffin-like cells
21
Q
Why do patients with Zollinger-Ellison syndrome experience chronic diarrhoea?
A
The high volume of gastric acid secreted cannot be fully reabsorbed in small and large intestines
It also exceeds the neutralising capacity of pancreatic bicarbonate secretion resulting in exceptionally low intestinal pH which inactivates digestive enzymes and the emulsification of fat as well as damaging intestinal epithelial cells and villi resulting in malabsorption
The high serum gastrin concentration also inhibits sodium and water reabsorption by the small intestine leading to a component of secretory diarrhoea
22
Q
What are the main clinical manifestations of Zollinger-Ellison syndrome?
A
Peptic ulcer disease
Heartburn
Diarrhoea
Weight loss
Complications of acid hypersecretion including bleeding, stricture fistulisation
In <10% - especially those with metastatic disease or MEN1 - may have symptoms due to second hormonal syndrome eg VIPoma
23
Q
What percentage of gastrinomas are malignant?
A
60-90%
24
Q
Are there any features on endoscopy that may raise suspicion for Zollinger-Ellison syndrome?
A
Ulcers are more likely to be refractory to PPI therapy and more likely to recur than in patients with sporadic ulcer disease
Ulcers often occur in unusual locations e.g. beyond the first or second fold of the duodenum
90% of patients with Zollinger-Ellison syndrome have prominent gastric folds
25
When should you suspect Zollinger-Ellison syndrome?
In patients with:
1) Multiple or refractory peptic ulcers
2) Ulcers distal to duodenum
3) Peptic ulcer disease and diarrhoea
4) Enlarged gastric folds
5) MEN1 or FHx of MEN1
6) Diarrhoea responsive to PPI
26
How do you confirm the diagnosis of Zollinger-Ellison syndrome?
By demonstrating an elevated serum gastrin concentration (typically fasting level) and low gastric pH
If not diagnostic then consider secretin stimulation test
Finally, if still suspicious but negative consider calcium gluconate IV infusion test
27
What other tests are considered helpful in establishing a diagnosis of Zollinger-Ellison syndrome and why?
- Gastric antral/body biopsy demonstrating a lack of atrophic gastritis
- The absence of parietal cell and intrinsic factor antibodies
As there are several causes of "appropriate" hypergastrinemic conditions that are more common (eg atrophic gastritis, PPI use, renal failure, vagotomy, pangastritis-associated H pylori infection)
28
How does the Secretin stimulation test work in Zollinger-Ellison syndrome?
Secretin is administered by rapid IV infusion over one minute with baseline fasting serum gastrin measured twice then at 2, 5 and 10 minutes.
Secretin stimulates the release of gastrin by gastrinoma cells, and patients with ZES tumors have a dramatic rise in serum gastrin. In contrast, normal gastric G cells are inhibited by secretin. Therefore a significant increase in gastrin levels = positive test.
Achlorhydria can lead to false positives and PPI use can lead to false negatives
29
After Zollinger-Ellison syndrome has been diagnosed, how can you localise the tumour?
UGIE
Triple phase contrast CT or MRI
Somatostatin receptor based PET imaging (DOTATATE)
Laparotomy
30
What other testing should you consider in a patient diagnosed with Zollinger-Ellison syndrome?
Biochemical screen for MEN1 eg parathyroid hormone, ionised calcium, prolactin levels
31
What is the first test you should order in a patient with suspected Acute Intermittent Porphyria?
A spot urine test for рοrрhοbilinοgеn (with paired urine creatinine)
32
What percentage of newly diagnosed colorectal cancer cancers are due to Lynch syndrome?
2-3%
33
What is Lynch syndrome?
The most common inherited colorectal cancer susceptibility syndrome
- autosomal dominant disorder
- results from germline mutations in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) or EPCAM gene
34
What is the most prevalent mutation in Lynch syndrome?
PMS2 (note these mutations tend to have lower penetrance than the others and confer comparatively smaller CRC and endometrial ca risk than others + are not associated with increased risk of other cancers
35
Which mutations confer the highest risks of colorectal cancer in Lynch syndrome?
MLH1 and MSH2
36
What is the characteristic feature of loss of mismatch repair in tumours?
DNA mismatches commonly occur in regions of repetitive nucleoside sequences called microsatellites
Therefore, in Lynch-associated cancers, you typically see expansion or contraction of microsatellite regions in the tumour (compared to normal tissue) - which is termed microsatellite instability (MSI)
MSI may affect genes that control cell growth, regulate apoptosis and some of the DNA MMR genes themselves - the accumulation of mutations in these cancer-related genes is through to drive the process of carcinogenesis in Lynch syndrome
37
In patients with Lynch syndrome, which mismatch repair mutation confers the highest risk of urothelial cancer?
MSH2
38
What is the lifetime risk of CRC in patients with Lynch syndrome?
8.5-56% depending on sex, mismatch repair gene mutation and penetrance of the mutation in the patient and family
- highest in males with MLH1 and MSH2
Note age of onset of CRC tends to vary by genotype but usually occurs at a younger age than patients with sporadic CRC
39
How are colorectal cancers in patients with Lynch syndrome different from those with sporadic CRC?
In Lynch syndrome tend to have:
- high rates of synchronous and metasynchronous CRC
- more right sided CRC than sporadic disease
- may progress rapidly from adenomas (tend to be flatter, larger, high-grade dysplasia, villous histology)
- may bypass adenoma development and develop directly from microscopic colonic mucosal crypts
- demonstrate high MSI and loss of mismatch repair protein expression on immunohistochemistry
40
Other than colorectal cancer, what other cancers are patients with Lynch syndrome more prone to?
Endometrial ca
Ovarian ca
Stomach ca
Small bowel ca
Pancreatobiliary ca
Genitourinary ca incl TCC + prostate ca
Gliomas (brain ca)
Sebaceous neoplasms
Keratoacanthomas
41
What is the most common extracolonic tumour in Lynch syndrome?
Endometrial ca
42
What type of brain tumours are most commonly associated with Lynch syndrome (compared to Familial adenomatous polyposis)?
Gliomas
FAP = medulloblastomas
Old name for association between familial CRC and brain tumours = Turcot syndrome
43
What is the Amsterdam (family-history-based) criteria for identifying individuals with Lynch syndrome?
Can be remembered by the "3-2-1" rule
3 affected members (on same side of family)
2 generations
1 under age 50
44
When should you suspect Lynch syndrome in patients with CRC?
If synchronous or metachronous CRC or endometrial ca before the age of 50
OR
multiple Lynch associated cancers
OR
familial clustering of Lynch-assoc ca
OR
patients with tumours found to have deficient MMR on micosatellite instability or immunohistochemistry testing
45
What are some clues someone may have cirrhosis?
Thrombocytopenia
Nodularity on USS
Low albumin/high bilirubin/high INR
High ARFI/fibroscan/SWE
Stigmata of CLD
46
What other causes may result in high liver stiffness measurements?
High ALT
Congestion
Steatosis
47
What features make up Child-Pugh score?
Encephalopathy
Ascites
INR
Albumin
Bilirubin
48
What are the features of Model for End Stage Liver Disease (MELD +Na) score?
Creatinine
Bilirubin
INR
Na
Haemodialysis
49
How is HCC different to other cancers?
Mostly diagnosed radiologically - rarely need tissue biopsy - (arterial enhancement, portal vein washout on quad-phase CT)
Limited symptoms
Traditional chemotherapy has shown no benefit
Underlying liver function most important factor
90% of cases assoc with CLD (cirrhosis, HBV, aflatoxin)
50
What strain of Aflatoxin is considered most toxic?
Aflatoxin-B1 (AFB1)
- produced by aspergillus
51
What other conditions may be associated with AFP elevation besides HCC?
HCV
Untreated HBV
Testicular cancer
Pregnancy
52
What groups of patients are recommended to undergo HCC surveillance?
Cirrhotic patients with Child-Pugh A, B or C
Non-cirrhotic HBV carriers with active hepatitis or family hx of HCC
Non-cirrhotic HCV and advanced liver fibrosis F3
High risk start in men >40yo, women >50yo; african px >20yo
53
Should patients with seroconverted HBV undergo HCC surveillance?
Yes
54
What treatment is best for patients with stage 0 or A HCC (on Barcelona grading)
Ablation or resection with curative intent
55
What treatment is indicated for HCC (BCLC stage B)?
If ECOG <1, CP-A, nil portal HTN:
-> TACE (palliative intent)
56
What treatment is indicated for HCC BCLC stage C? (ie tumour vascular invasion, met disease, multifocal disease)
Lenvatinib (slightly more effective, better tolerated eg less hand and feet syndrome than Sorafenib)
Atezolizumab + Bevacizumab
57
What is the most sensitive and specific laboratory finding for the diagnosis of cirrhosis?
Thrombocytopenia
58
In what patients with chronic liver disease may you give vitamin K to (in the setting of asymptomatic lab changes eg prolonged INR)?
In those with suspected Vit K deficiency ie suspected poor nutrition and сirrhοsis, as well as those with cholestatic disease, diarrheal illness, or antibiotic use
59
How might you differentiate DIC from the haemostatic abnormalities of liver disease?
Factor VIII activity - reduced in DIC vs normal/increased in liver disease
60
Is it worth administering FFP or cryoprecipitate to correct the PT/INR value prior to a procedure in a patient with chronic liver disease?
No - studies have shown no clear benefit + additional risks/disadvantages incl transfusion reactions, volume overload (which increases portal pressure) and infection
61
WHat are the risk factors for portal vein thrombosis in individuals with cirrhosis?
Greater disease severity ie CP-C
HCC
Inherited thrombophilia e.g. factor V Leiden
62
What is the treatment of portal vein thrombosis?
In non-cirrhotics
- treat underlying condition + anticoagulate
In cirrhotics
- treat underlying condition + individual decision re anticoagulation (must balance benefits vs risks; may consider in those awaiting liver transplant; but usually not in those who are asymptomatic, Plt count <50, hepatic encephalopathy + evaluate for varices
63
What anticoagulant would you use for portal vein thrombosis?
LMWH initially then transition to VKA (eg warfarin) for at least 6 months
If chronic thrombotic condition OR thrombosis involving mesenteric veins - may continue anticoagulation indefinitely
Alternatively can use DOAC
64
What ART is best for px with HBV co-infection?
Biktarvy or Genvoya
(Should contain emtrictabine and tenofovir)
65
What are the two main phenotypes of GORD?
Non-erosive disease (70%) - reflux sx due to acid without mucosal breaks found at endoscopy
Erosive oesophagitis (30%) - mucosal breaks
Of px with GORD
Barrett's oesophagus occurs in 5-12%
Limited evidence of progression between phenotypes
66
Why do people get GORD?
Transient relaxation of the lower oesophageal sphincter
67
Why is scleroderma assoc with GORD?
Poor lower oesophageal sphincter tone
68
Is there any evidence for screening for Barrett's?
Not at present
69
When do you use ambulatory 24-hr pH monitoring?
When someone has persistent symptoms on optimal GORD treatment and you are querying functional component (as it allows you to correlate symptoms with oesophageal pH)
70
How do you treat GORD?
Non-pharm
- wt loss
- behavioural measures incl nocturnal head elevation
- avoidance of food 3hrs prior to sleep
- smoking cessation
- avoid precipitants such as alcohol, chocolate, spicy food
Pharm
- PPI (better for healing and symptom control than H2RA)
71
What are the long-term issues associated (not proven to be causally related) to PPI use?
Fractures
Pneumonia
Enteric infections eg salmonella, campylobacter, C diff
Vitamin B 12, iron and magnesium def
Acute interstitial nephritis
72
Which medications are most commonly associated with oesophageal ulceration?
Antibiotics are most common cause of pill-oesophagitis (esp doxycycline, tetracycline)
Bisphosphonates
NSAIDs
73
What is Eosinophilic Oesophagitis?
A chronic, immune-mediated inflammatory disease of the oesophagus characterised by:
- oesophageal dysfunction, esp dysphagia
- concentric rings (corrugated iron), white plaques and longitudinal furrows on endoscopy
- >15 eosinophils/HPF on histology
Classically occurs in young male px with hx of food bolus obstruction and hx of atopy
74
How do you treat eosinophilic oesophagitis?
PPI (30% respond) OR topical budesonide (oral dispersible tablet)
PBS criteria = histological diagnosis + repeat endoscopy showing histological improvement after 8 weeks
Other options:
Food elimination diet or allergen-test based elimination diet
75
What biologic may be used for eosinophilic oesophagitis?
Dupilumab - IL-4/IL-13 blocker
- not yet PBS listed/in guidelines
76
What is achalasia?
Motility disorder
Main issue is: Failure of relaxation of the lower oesophageal sphincter (ie high tone)
Presents with reflux, regurgitation, weight loss and aspiration
77
What is the appearance of achalasia on various investigations?
Endoscopy - retained food/fluid
Barium swallow - bird's beak
Manometry - failure of relaxation of LOS
78
What are some of the key features of achalasia on manometry?
Failure of LOS to relax (pressure to drop) when initiate swallow
Impaired peristalsis
79
How do we manage achalasia?
Pharmacology (not that useful)
- nitrates
- CCB
Botox injections into LOS
- 60-70% response
- recurs (requires repeat) 6mthly
POEM
- per oral endoscopic myotomy
- 80-90% response
- low mortality but lengthy procedure
Pneumatic dilatation of LOS
- 80-90% response
- low recurrence rate
- 3% perf rate
- low mortality, quick procedure
Surgery
- Lap Hellers myotomy
- 85-95% response
- can recur
- GORD may be problematic
- 2% mortality rate
80
Which of the following is not a risk factor for PUD?
Alcohol
81
What are the most important risk factors for PUD?
H pylori
NSAIDs
82
Does PPI prophylaxis reduce risk of stress ulcers?
No - controversial and may still consider for high-risk patients
83
What is the most common reason for 1st line treatment failure of H pylori?
Clarithromycin resistance
(also need to exclude non-compliance)
84
What is H py
Gram neg bacilli bacteria
Has high urease activity which produces ammonia allowing it survive in acidic environment as well as artificially increasing gastric pH leading to decreased somatostatin secretion [ie reduces negative feedback] causing increased acid production
Flagella - motile so can move to gastric mucosa
Has lipopolysaccharides which help it adhere gastric cells
Then causes colonisation and chronic infection
Releases virulence factors: VacA and CagA which damage cells, inflammation and ulceration
85
What are the preferred tests for H pylori detection?
Urea breath test
- works on principle that presence of H pylori urease causes CO2 and NH3 production which can be measured
- high sens/spec
Stool antigen test
- similar sens/spec
UGIE+biopsy
86
What are the issues with H pylori serology?
Not very specific
Takes a long time to become negative after eradication therapy
87
What is the first line treatment of H pylori?
CEA for 7-14 days
Clarithromycin
Esomeprazole/PPI
Amoxicillin
88
What is current clarithromycin resistance rates in Aus?
10%
89
What is second-line therapy for H pylori?
LEA
Levofloxacin
Eso/PPI
Amox
OR
REA
Rifabutin
Eso/PPI
Amox
90
What is the treatment of H pylori if known clarithromycin resistance?
MEA
Metronidazole
Eso/PPI
Amox
91
What is the treatment of H pylori if penicillin allergy?
CEM - substitute metro for amox
Clarithromycin
Esomeprazole/PPI
Metronidazole
92
If NSAID-induced PUD, what should you do?
If can, cease NSAID
If not, use COX-2i + PPI
If primary prevention aspirin - cease
If secondary prevention - aspirin + PPI
93
How do you manage PUD?
1) Eradicate underlying cause
- eg cease NSAIDs, triple therapy fo H pylori
2) Acid suppression
- 8 weeks BD PPI
3) repeat gastroscopy after tx to exclude malignancy
- if gastric ulcer (not duodenal ulcer)
94
How much blood is required to produce melaena?
150ml
95
What are the two causes of bright red PR bleeding from an upper GI source?
Varices
Duodenal ulcers
96
In a patient with a bleeding gastric ulcer, which endoscopic finding confers the highest risk of re-bleeding?
Active arterial bleeding
97
What are some high-risk stigmata for bleeding ulcer?
Active arterial bleeding
Non-bleeding visible vessel
Non-bleeding adherent clot
Ulcer oozing
These px need endoscopic tx and IV PPI for 72hrs
98
What is dermatitis herptiformis?
Skin rash assoc with coeliac disease
99
What serology should you perform in a patient suspected of having coeliac disease who is IgA deficient?
tTG IgG +/- anti-gliadin antibody
100
What is the role of genetic testing in coeliac disease?
DQ2 and DQ8
Good neg predictive value - if neg, almost impossible to have coeliac disease
101
How do you diagnose coeliac disease?
Small bowel biopsy
- demonstrating villous atrophy/blunting + increased intraepithelial lymphocytes
Can repeat Bx 6-12 mth after diagnosis and Gluten free diet (previously required, now no longer always performed)
102
What is refractory coeliac disease and how do you treat it?
Persistent symptoms + villous atrophy despite strict adherence to gluten free diet for 6-12 mths
Occurs in <1% of coeliac px
Will have normal tTG
Treat with systemic immunosuppression / steroids
103
In a patient with long-standing coeliac disease compliant with gluten free diet who presents with weight loss and diarrhoea, what is the next best step?
UGIE + colonoscopy
104
What are the two malignancy complications of coeliac disease?
Small bowel adenocarcinoma
Enteropathy-associated lymphoma
- typically occurs with refractory coeliac disease, presents in 6th decade
105
What is the next best test in someone with occult GI bleeding if UGIE+colonoscopy is NAD?
Capsule endoscopy
106
What is occult vs obscure GI bleeding?
Occult = no overt bleeding seen (ie IDA)
Obscure = bleeding seen (usually melaena) but no source on scopes
Most commonly due to small bowel angioectasia
107
What is the PBS criteria for capsule endoscopy?
IDA with neg UGIE + colonoscopy
108
What are some of the features of microbiota dysbiosis in IBD?
Decreased biodiversity (alpha)
Decreased stability
Decreased Firmicutes and SCFA producing bacteria
Increased gammaproteobacteria eg AIEC
109
What are some of the key genetic abnormalities in IBD?
Complex polygenetic disease
Frameshift in NOD2 = assoc with fibrostenosing crohn's disease
Mutations in IL-10/IL-10R pathway = assoc with early infancy/childhood IBD
110
What environmental factors increase risk of ulcerative colitis?
Former smokers
Antibiotics
HRT/OCP
NSAIDs
Added sugar
Animal protein
111
What environmental factors decrease ulcerative colitis risk?
Active smoking
Breastfeeding
Appendicectomy
112
What environmental factors increased crohn's disease risk?
Tobacco exposure
Antibiotics
Low sunlight exposure
Animal fat
Highly processed food
113
What environmental factors decrease crohn's disease risk?
Breastfeeding
Fruit and fibre diet
114
What conditions fall under the Inflammatory Bowel Disease banner?
Idiopathic
- CD
- UC
- eosinophilic colitis
- microscopic colitis (eg collagenous colitis, lymphocytic colitis)
115
What is the differential diagnosis of IBD?
Infective colitis
Checkpoint inhibitor colitis
NSAID colitis
Ischaemic colitis
Autoimmune enteritis
Diverticular colitis
116
How does IBD present?
Diarrhoea - bloody, mucous, nocturnal
Urgency, tenesmus, incontinence
Abdo pain
Weight loss/poor appetite
Perianal symptoms
Extra-intestinal manifestations (eyes, joint, skin)
117
How do you evaluate/diagnose IBD?
Exclude alternative causes eg infective stool
Blood
- inflammatory markers, FBC, chem20, coeliac serology
Faecal testing
- PCR/culture/calprotectin
Endoscopy
Histology
Imaging
118
What is the role of faecal calprotectin in IBD?
Faecal calpro = noninvasive marker of intestinal inflammation
(it is a calcium binding protein found in cytosol of neutrophils and epithelial cells that is released by damage to GI wall)
Has a role in:
1) distinguishing IBS from IBD
2) treat-to-target IBD mx
- calpro <100 = quiescent disease
- calpro >250 = inflammation likely
in between = inflammation possible, ix further
119
What are some features on colonoscopy which may distinguish UC from CD?
UC begins at rectum and extends proximally
(CD = discontinuous lesions)
Diffuse superficial colonic inflammation (as opposed to cobblestoning)
Shallow erosions and ulcers (as opposed to deep ulcers and fissures)
120
What are some features on histology that may differentiate UC from CD?
Epithelial/superficial and continuous involvement (cf transmural, patchy involvement)
Goblet cell depletion (cf goblet cell preservation)
Crypt abscesses (cf less common in CD)
Distorted glandular architecture (cf preserved in CD)
Crypt branching = sign of chronicity but can occur in CD
CD = parietal metaplasia and granulomas (both not seen in UC)
121
What are the risk factors at diagnosis of UC for colectomy?
Age <40
Raised inflammatory markers
Extensive colitis
Systemic steroids
122
What portion of the GIT does CD affect?
Any and all
Terminal ileum 49%
Ileocolonic 27%
Colon only 20%
Upper GIT 4%
123
What are the key features of crohn's related granulomas?
Collection of mononuclear histiocytes
Multinucleated giant cells
Peripheral lymphocytes
124
What might MRE, CTE or intestinal USS show in Crohn's?
Bowel wall thickening, phlegmon, abscesses or fistulae
125
How do you phenotype Crohn's disease?
Montreal classification
Age
- A1 - <16
- A2 - 17-40
- A3 - >40
Location
- L1 - ileal
- L2 - colonic
- L3 - ileocolonic
- L4 - isolated UGIT
Behaviour
- B1 - non-stricturing, non-penetrating
- B2 - stricturing
- B3 - penetrating
126
What are the poor prognostic factors in crohn's disease?
Smoking
Age <40
>5kg weight loss at presentation
Extensive small bowel disease
Perianal/rectal disease
Stricturing disease
Deep and extensive colonic ulceration
Steroids at diagnosis
Steroid dependency
>2 Small bowel resections
Colonic resection
Stoma within 5yrs
127
What is the treatment principle for Crohn's disease?
Treat to target
Short term = symptomatic response
Intermediate term = symptomatic remission, normalisation of CRP, decreased calprotectin
Long-term = endoscopic healing, normal QOL, nil disability
128
What is the target in UC management?
Mucosal healing
- assoc with symptomatic remission, endoscopic remission, steroid-free remission, surgery and relapse-free survival
Poor correlation between symptoms and endoscopic disease activity
129
How do you treat mild-mod UC?
Induction
- ASA (topical or oral)
- steroids (topical or oral)
Maintenance
- ASA
130
How do you treat mod-severe UC?
Induction:
Oral or IV steroids
+
Anti-TNF OR Vedolizumab OR Tofacitinib
Maintenance:
Thiopurines (Aza)
If intolerant/ineffective
Anti-TNF OR Vedolizumab OR Tofacitinib
131
When do you require maintenance therapy beyond ASA in mild-mod UC?
If poor prognostic factors at baseline
If requirement for >2x steroid courses per year or steroid-dependent
132
How do you manage acute severe UC?
Admit to hospital
Exclude infective cause + AXR/CXR + flexisig + TB testing
DVT prophylaxis
IV steroids
- assess response at 3 days
If respond - switch to oral steroids + steroid-sparing agent (eg Aza, 5-ASA, 6-MP)
If non-responder - IV infliximab (or cyclosporine) OR subtotal colectomy with end ileostomy
133
How do you assess response to 3 days IV steroids in acute severe UC?
Travis index
Non-responder if >8 stools per day OR 3-5x stools per day and CRP >45
134
What is the definition of Acute Severe UC?
Bloody stool frequency ≥6 per day
PLUS at least one of the following characteristics (ie, evidence of systemic toxicity):
*Fever (>37.8)
*Tachycardia (heart rate ≥90 beats/minute)
*Anaemia (Hb <105)
*Elevated inflammatory marker (eg, C-reactive protein, erythrocyte sedimentation rate)
135
What is fulminant UC characterised by?
Bloody stool frequency ≥10 per day with fecal urgency, often accompanied by abdominal pain and abdominal distension, in addition to the criteria for acute severe UC
136
What are the contraindications to anti-TNF agents (eg infliximab)?
Active uncontrolled infection
Latent (untreated) tuberculosis
Demyelinating disease (eg, multiple sclerosis, optic neuritis)
Heart failure
Malignancy
137
How do you treat mild-mod Crohn's Disease?
Principle is to block disease progression and damage
For B1/inflammatory phenotype
Induction:
- ileocaecal = steroids
- colonic = steroids (esp if right sided) or 5-ASA (esp left sided; however evidence weak and only for sulfasalazine)
Maintenance:
Reassess after induction but often:
MTX or thiopurine
+/- biologic
No role for 5-ASA
138
How do you treat mod-severe Crohn's disease?
For B1/inflammatory phenotype?
Induction:
Steroids or exclusive enteral nutrition or biologics
OR primary surgical resection
Maintenance:
Often combo therapy biologic +/- MTX or thiopurine
139
How do you treat stricturing B2 crohn's disease?
Medical therapy
+
endoscopic balloon dilatation +/- needle knife sphincterotomy
Consider surgical options eg stricturoplasty or resection
140
How do you treat internal fistulas / penetrating crohn's disease?
Exclude infection
Optimise nutrition
Trial medical therapy
Consider surgery
141
How do you treat perianal crohn's disease?
Antibiotics
Anti-TNF +/- immunomodulators
Surgery
- EUA, abscess drainage, seton placement
142
What are the side effects of steroid therapy?
Swelling - face, ankles
Skin - easy bruising, acne
Eyes - increased intraocular pressure, cataracts
Infections
Mind - Memory problems, psychosis
Metabolic - hyperglycaemia, diabetes, osteoporosis, HTN
143
What are the side effects of 5-ASA?
Watery diarrhoea/occ bloody
Rash
Headache
Nausea
Fever
Rare - pneumonitis, hepatitis, pericarditis, thrombocytopenia, renal dysfunction/AIN/nephrotic syndrome
144
When prescribing thiopurines what bloods do you have to perform at baseline and during therapy?
Baseline - TMPT assay to assess if NUDT15 gene mutation/low metaboliser (if poor metaboliser/NUDT15 gene mutation present = high risk of myelosuppression)
- if <5 = poor = avoid
- >8 = high = can give
- if 5-8 = intermediate = trial half dose
Once commenced on therapy, monitor metabolites:
6TGN (active) - aim 235-450
6MMP
145
What do you do if you have low 6TGN and high 6MMP levels on Azathioprine therapy for IBD?
"Shunting"
Add allopurinol - will increase 6TGN + decrease 6MMP
146
What is the usual induction and maintenance doses for MTx in IBD?
Induction = 25mg subcut weekly
Maintenance = 15mg subcut weekly
147
Anti-TNF agents have broad benefits in IBD, what are some of the disadvantages?
Risk of infection esp TB reactivation
Unable to have live vax
Small increased risk of lymphoma
Often co-prescribe with immunomodulator
148
Is surgery safe on anti-TNF?
Yes
149
What do you do with anti-TNF if acute viral infection?
Withhold and talk to prescriber
150
When do hepatosplenic T-cell lymphomas typically occur in IBD?
In young males on thiopurine + anti-TNF (our best therapy)
- therefore still use for induction but then consider stopping thiopurine after 12mths or consider switching to MTx
151
How does Vedolizumab work?
Humanised monoclonal IgG1 antibody that blocks interaction between alpha-4-beta-7 and MadCAM-1 to stop leukocyte trafficking from blood to inflammed gastric mucosa
152
How does Ustekinumab work?
Human IgG1 MAB that binds to p40 subunit of Il-12/IL-23 which blocks those from binding/thus reducing IL-12/IL-23 signalling, activation and cytokine production (which play a role in pathogenesis of Crohn's)
153
What is the difference in action between Upadacitinib and Tofacitinib in Ulcerative colitis?
Upadacitinib is more JAK1 specific inhibitor whereas Tofacitinb is pan-JAK inhibitor
May potentially have greater efficacy with less adverse effects (particularly VTE and sudden cardiac death; still have risk of herpes infection)
154
How does Ozanimod work in ulcerative colitis?
Sphingosine-1-phosphate receptor modulator
- leads to internalisation of S1P1 receptor in lymphocytes thus preventing lymphocyte migration to inflammatory sites
155
What are the key adverse effects of Ozanimod?
Herpes zoster
Lymphopenia
HTN
Bradycardia
Macular oedema
156
When is cyclosporine used in UC?
For acute severe UC as alternative to Infliximab for non-responders to IV steroid therapy
- comparable outcomes to infliximab in terms of colectomy-free survival
- used in thiopurine naive px
- can step down to oral ciclosporine until thiopurine maintenance therapy active
157
What is the rationale for choosing combination therapy over monotherapy in IBD?
Independent effects of 2 drugs
Synergistic effects
Lower rates of anti-drug antibody formation
Lower rates of infusion reactions
Lower rates of loss of response
Better outcomes
Monotherapy however is cheaper and avoids possible safety concerns with combination therapy
158
What markers predict anti-TNF antibody formation?
Low drug levels
HLA-DQA1*05
159
In moderate-to-severe UC, what drug is better out of Ustekinumab, adalimumab or vedolizumab?
Vedolizumab > Ada or uste (both equivalent)
160
What are the indications for surgical management in CD?
Stricturing disease with obstruction
Penetrating disease with phlegmon/abscess/perf
Internal fistula
Perianal disease
Severe colitis refractory to medical therapy
As an alternative to medical therapy (LIR!C trial)
161
When is surgery indicated in UC?
Fulminant colitis (eg toxic megacolon, perf, bleed)
Refractory disease
High-grade dysplasia/cancer
162
Which of these extraintestinal manifestations is more common in which type of IBD?
Erythema nodosum = CD
Pyoderma gangrenosum = UC
163
What are the risk factors for CRC in IBD?
Longer duration of disease
Greater extent or severity of disease
Fhx of sporadic CRC
Primary sclerosing cholangitis
164
What is the recommendation for screening colonoscopies in IBD?
If UC extends beyond sigmoid or CD >1/3 of colon then:
- start 8yrs post diagnosis
(immediately if PSC, start earlier if fhx)
- then depends on risk features
- high risk (eg inflammation, PSC) = yearly
- intermediate risk = 3yrly
- low risk = 5 yearly
165
When should you avoid live vaccines for someone on immunomodulatory/biologic therapy for IBD?
4-6 weeks before therapy, whilst on therapy and 3 months after therapy
166
When do you use JAKi in Crohn's?
In px who have not responded or not tolerated an anti-TNF agent
167
What extrahepatic conditions are assoc with Primary Biliary Cholangitis?
Coeliac disease
Scleroderma
Thyroid disease
Sicca syndrome
RA
168
What extrahepatic conditions are assoc with PSC?
IBD!
Coeliac
Thyroid disease
IDDM
169
What extrahepatic conditions are assoc with Autoimmune Hepatitis?
Most autoimmune conditions eg thyroid, RA, SLE, coeliac, IBD, scleroderma
170
What is the significance of having anti-centromere antibodies in PBC?
Confers 4-fold greater risk of developing progressive portal HTN
171
What are the risks of developing PSC in px with IBD?
Increased risk of cholangiocarcinoma, pancreatic ca, gallbladder ca, colorectal ca and colonic resection
172
In px with PSC, the absence of IBD or a crohn's disease phenotype (rather than UC) is assoc with what?
Reduced risk of transplantation, death, cholangiocarcinoma
independent of age, sex and timing of onset
173
What are the core clinical features of AIH?
Primarily affects women, 10-30yo or middle aged
Spectrum of presentation from insidious to fulminant
May involve jaundice, anorexia, fatigue, elevated transaminases
Hypergammaglobulinaemia
Circulating autoimmune markers
Negative viral hepatitis screen
174
What predisposing genes are there for AIH?
HLA DR3 and DR4
175
What % of px with AIH have cirrhosis at time of presentation?
1/3rd of adults
176
What autoantibodies are assoc with AIH?
Type 1:
ANA
Anti-smooth muscle
Anti-actin
Anti-soluble liver antigen
ANCA
Assoc with HLA DR3, DR4, DR13
Type 2:
Anti-LKM1 (rarely 3)
Anti-liver cytosol
Assoc HLA DR3 and DR7
177
What autoantibody is present in AIH/PBC crossover?
AMA
178
What autoantibody is present in AIH/PSC overlap?
Nil, require cholangiography to diagnose
179
What are the diagnostic criteria for AIH?
ANA or SMA >1:40 (1>80 = 2 pts)
Anti-LKM or SLA ab
Elevated IgG
Compatible liver histology
Absence of viral hepatitis
Score >7 = definite AIH
180
How do you treat AIH?
Induction then maintenance immunosuppression with steroids +/- azathioprine
(note px with AIH extremely sens to immunosuppression - major diagnostic criterion)
181
What factor 2 years post induction therapy in AIH is assoc with increased risk of relapse ?
Abnormal histology on liver biopsy - 80% risk
conversely normal histology at 2 yrs = 20% risk
182
What is the aim of treatment in AIH?
Complete normalisation of transaminases + IgG levels
(persistent levels assoc with relapse, active disease on histology, progression to cirrhosis, poor outcomes)
183
What is considered biochemical remission in AIH?
Normalisation of transaminases and IgG
Treatment should be continued at least 2yrs post biochemical remission
184
Is there a difference in 10yr survival in px with AIH if they have/do not have cirrhosis at presentation?
No - 90% for both if treated
However prognosis beyond 10yrs may be reduced in cirrhosis group
185
What is the annual incidence and risk factors for HCC in AIH?
If cirrhosis - 1-2%
RFs
- chronic cirrhosis >10y
- portal HTN
- persistent liver inflammation
- immunosuppressive tx >3yrs
Hence HCC surveillance indicated in all px with AIH+ cirrhosis
186
Who does PBC primarily affect?
Women (95%) between 30-60
Higher in px with affected sibling
187
How do px with PBC often present?
Asymptomatic 50%
Pruritis
Hyperpigmentation
Arthropathy
Sjogren's syndrome
Scleroderma
188
What is PBC?
A cholestatic disorder with serologic reactivity to ANA or AMA
Histologically characterised by non-suppurative granulomatous, lymphocytic small duct cholangitis
189
In adults with cholestasis and no likelihood of systemic disease, what is considered diagnostic of PBC?
An elevated ALP + AMA >1:40
190
What is the role of AMA in PBC?
Diagnostic in correct circumstances
Seen in 95% of cases
However titre does NOT correlate with stage, severity, risk of progression
If AMA+ but no cholestasis - may predict eventual development of PBC (however tx not indicated until LFT abnormalities)
191
What is the prognosis of untreated PBC?
Slowly progressive cholestasis, cirrhosis and liver failure
192
What therapy may modify the course of PBC?
UDCA
- improves liver biochem, delays histological progression and development of portal HTN/cirrhosis
193
What treatments may be required for symptom mx in PBC?
Cholestyramine
Rifampicin
Naltrexone
Sertraline
Gabapentin
Dialysis
Plasmapharesis
Liver transplant
194
Which px with PBC should be given UDCA?
All patients
195
If a patient with PBC doesn't respond to UDCA at 1 yr, what should you do?
Evaluate for PBC/AIH overlap
Add 2nd line therapy with obeticholic acid or enrol in clinical trials
196
What patients with PBC most benefit from UDCA?
Patients WITHOUT advanced disease (ie not very effective in those with advanced disease)
Patients who achieve a biochemical response ("biochemical responders" have excellent outcomes, nil need for additional therapy)
197
What is the goal of treatment of PBC?
Normalisation of ALP and bilirubin
198
What is PBC/AIH overlap?
A term used when features of AIH and PBC coexist
Occurs in 10-15% of px
Can be difficult to differentiate clinically, biochemically, serologically
Uncertain whether true overlap syndrome or part of PBC spectrum
Treat with immunosuppression (as in AIH) + UDCA (as in PBC); if no histological improvement after 6mths - withdraw immunosuppression
199
What features indicate px with PBC/AIH overlap are more or less likely to respond to tx?
Responders = higher ALT, IgG, bridging necrosis
Non-responders = higher ALP, IgM, AMA titres, nil bridging necrosis
200
When is Obeticholic acid used in PBC?
As monotherapy in those unable to tolerate UDCA OR added to UDCA in px with inadequate response to UDCA
201
When is Obeticholic acid contraindicated in PBC?
Cirrhosis (compensated or decompensated)
202
What is an alternative to Obeticholic acid in px with PBC unresponsive or intolerant of UDCA?
PPAR agonist elafibranor
203
What is the role of liver transplant in PBC?
Progressive end-stage disease despite medical therapy
Timing complex
PBC can recur post-transplant
Transplantation tends to resolve clinical symptoms (some like fatigue, bone disease can take time, splenomegaly generally not responsive but main symptoms eg pruritis should resolve)
204
What is Primary Sclerosing Cholangitis?
Rare condition more common in males (30-40yo) esp those with IBD (70%; UC rectal sparing, R) colonic disease with backwash ileitis, crohn's colitis)
Characterised by chronic, slowly progressive inflammation, fibrosis and destruction of intra- and extra-hepatic bile ducts
205
What is the prognosis of PSC?
Poor
- cirrhosis common (10-20yrs post diagnosis)
- cholangiocarcinoma (20% by 30yrs)
- CRC (10x inc risk in PSC-UC cf UC alone)
206
What is the preferred diagnostic test in PSC?
MRCP
207
How do you diagnose PSC?
Compatible clinical and biochemical findings
Characteristic imaging findings (MRCP, ERCP)
Exclusion of causes of secondary sclerosing cholangitis (eg AIDS cholangiopathy, congenital, trauma, surgery, bile duct neoplasm, choledocholithiasis etc)
208
What is the role of biopsy in PSC?
Not usually required for diagnosis (except small duct PSC)
May exclude alternative diagnoses
May be used to define stage of PSC for prognosis and clinical trials
209
When should cholangiocarinoma be suspected in px with PSC?
Any px with worsening cholestasis, weight loss, rising Ca19-9 or new/progressive dominant stricture
210
How do you diagnose cholangiocarcinoma in PSC?
Bile duct brushings - specific but only mod sens
Can improve by adding FISH analysis or taking ductal biopsies
211
What are the poor prognostic factors in PSC?
Extensive intra-and extra-hepatic bile duct involvement
Liver dysfunction
Portal HTN
Fibrosis/cirrhosis
Jaundice
212
What is the medical therapy of PSC?
There is none - no evidence anything works; can try UDCA +/- symptom-based measures
Most px will eventually require liver transplant
213
What is the incidence of PSC recurrence post-liver transplant?
8-20%
214
What medication may reduce cumulative incidence of HCC and liver-related mortality?
Aspirin
215
How do we do HCC surveillance?
6 monthly liver USS + AFP
(combined sens = 63% cf 45% with USS alone)
216
What do you do if you detect a <1cm mass/nodule on liver USS in cirrhotic px?
Repeat USS in 4mths to see if stable/changing
217
What do you do if you detect a >1cm mass/nodule on USS in cirrhotic px?
Multiphase CT (or MRI)
- may be diagnostic of HCC
- if not, consider additional imaging modality OR biopsy
218
How do HCC's appear on multiphase CT liver imaging?
Mass with arterial phase hyperenhancement, washout in portal and delayed phase
LiRADS 5 = HCC
LIRADS 4 = prob HCC
219
How do you treat early stage / single HCC <3cm?
Usually percutaneous (thermal or alcohol) ablation
alternatively surgical resection
220
What is the role of Transarterial chemoembolisation (TACE) in HCC mx?
Used for larger tumours and as palliative (not curative) tx whilst waiting for liver transplant
221
When should px with HCC be treated with systemic therapy?
After discussion in MDT
CP A
ECOG0-1
Unresectable HCC not amenable to transplant (ie BCLC B) or advanced disease (BCLC C)
222
What are the first line systemic therapies for HCC in Aus?
Atezolizumab+Bevacizumab = standard of care
(Anti-PDL1 + anti-VEGF)
Alternatives:
Lenvatinib or sorafenib (both anti-VEGF TKI)
223
What is acute liver failure?
A potentially reversible condition characterised by severe liver injury in the absence of pre-existing liver disease
Characterised by:
- absence of pre-existing liver disease
- severe liver injury (AST/ALT >2-3x ULN)
- impaired liver function (jaundice/coagulopathy)
PLUS
Hepatic encephalopathy
224
What are the timelines for acute liver failure?
Hyperacute <7d
Acute 7-21d
Subacute >21d
225
What are the main causes of ALF?
Drugs
- paracetamol
- anti-TB drugs
- statins
- carbamazepine
- NSAIDs
- phenytoin
- ectasy
- flucloxacillin
Viral hepatitis
- A, B, E, CMV, HSV, dengue
Toxins
- amanita phalloides
Vascular
- Budd-chiari
- hypoxic hepatitis
Pregnancy
- PET, HELLP
- AFLP
Other
- Wilson's
- AIH
- lymphoma
- HLH
- malignancy
226
What is amanita phalloides ?
Death cap mushrooms
- alpha-amanitin is the predominant toxin responsible for most toxic effects seen in human exposures
- heat stable so parboiling does not make safe
- concentrate in the liver
- bind to DNA-dependent RNA polymerase type II and halt intracellular protein synthesis, ultimately resulting in apoptosis
- leads to hepatic failure, necrosis and death
Clinical manifestations:
6-12hr delay in symptoms
Abdo pain, vomiting, severe cholera-like diarrhoea
Then get apparent recovery but worsening of LFTs
Then fulminant hepatitic and multi-organ failure over 48-72hrs
Treatment:
Supportive care
GI decontamination with multiple dose activated charcoal
Amatoxin uptake inhibitors
- preferred silibinin dihemisuccinate OR penicillin G (both inhibit amatoxin by organic anion transport protein (OATP)
NAC + cimetidine + Vit C
Consider liver transplant
227
What is the clinical course in ALF?
Depends on the aetiology and rate of progression of jaundice, HE, cardiovascular injury, cerebral oedema, renal failure
228
How do you manage px with ALF?
Early transfer to liver transplant unit
multiple supportive measure
229
What is the role of liver transplant in ALF?
1 year survival following liver transplant for ALF is 80%
Selection depends on anticipated survival without transplant, anticipated survival post-transplant, whether they are too sick to undergo transplant
230
What factors are assessed when making decisions about possible transplant in ALF?
King's college, Japanese and Clichy
generally assess:
- Age
- aetiology
- encephalopathy
- bilirubin
- coagulopathy
231
What are the King's college criteria for liver transplant in Paracetamol overdose ALF?
Arterial pH <7.25 after 24hrs of effective fluid resus + NAC
OR
INR >6.5 + SCr >300/anuric AKI + 3/4 Hepatic encephalopathy
232
What are the King's college criteria for liver transplant in non-Paracetamol overdose ALF?
INR >6.5
OR
3 of 5
- INR >3.5
- bili >300
- jaundice to encephalopathy >7d
- age <10 or >40
- unfavourable aetiology
233
What factors make up CP score?
Presence/severity of ascites
Presence/severity of encephalopathy
Bilirubin
Serum albumin
INR
CP A = 5-6 = compensated
CP B = 7-9
CP C = 10-15
1 point = no ascites, no HE, bili <35, cholestatic <70, albumin >35, INR <1.7
3 points = mod/severe ascites, 3-4 HE, bili >50, cholestatic >170, Alb <28, INR >2.3
2 points = in between
234
What is acute -on-chronic liver failure?
Acute decompensation (eg ascites, variceal bleeding, HE)
PLUS
Organ failure (eg renal, brain, circulation, coagulation, respiratory)
Severity of ACLF increases with increasing organ involvement - assoc with increased short-term mortality
235
How do you differentiate the 3 most common causes of ascites?
SAAG +/- hepatic venous pressures
Cirrhosis = high SAAG, low ascites protein
Cardiac ascites = high SAAG, high ascites protein, high free hepatic venous pressure
Peritoneal malignancy/TB = low SAAG, high ascites protein
236
What is the benefit of TIPS (with covered stents) in px with cirrhosis and recurrent ascites?
Increases transplant-free survival
237
What are the indications for TIPS?
Refractory ascites
Pre-emptive
Prevent rebleeding
238
How do you manage SBP?
Diagnostic paracentesis
- if ascites PMN >250
= commence IVABx
- if bili >40, SCr >100 - IV albumin
- if not don't treat
Once start tx, repeat paracentesis in 48hrs
- if good response (ascites PMN <50%) = switch to POABx for 3-5 days then long-term prophylaxis
- if poor response = broaden abx spectrum and consider alternative causes of peritonitis
239
What are the antibiotics of choice for SBP?
IV Ceftriaxone 2g daily
240
What are the prophylactic agents of choice for px with previous episode of SBP to prevent recurrent SBP?
Bactrim
OR
norfloxacin
241
Who should you perform an ascitic tap on?
Unless there is an alternative explanation, any patient with CLD and ascites who has:
- fever (temperature higher than 38°C)
- hypothermia (temperature lower than 35°C)
- encephalopathy
- septic shock
- deteriorating kidney function.
242
What finding on paracentesis is diagnostic of SBP?
neutrophil count more than 0.25 x 109/L (ie PMN >250)
243
What do you give to patients with SBP who have a severe immediate hypersensitivity to penicillins?
Ceftriaxone
OR seek expert advice
244
What do you give to patients with SBP on SBP prophylaxis?
Piptaz - because of Cef-resistant gram neg disease + streptococcal or enterococcal infection more common
245
What are the two types of hepatorenal syndrome?
HRS-AKI (prev type 1)
- SCr >27mmol or >50% or oliguria within last 48hrs
HRS-NAKI (prev type 2)
- describes subacute-chronic or less severe reductions in eGFR in cirrhotic px (ie not meeting AKI criteria)
246
How do you treat px with HRS-AKI?
Hold nephrotoxics incl diuretics, beta-blockers, NSAIDs
Treat infections if present
Optimise fluid status
Terlipressin + Albumin - bridge to:
liver transplant
247
When should you avoid terlipressin?
Age >70yo
Heart disease
Stroke
Asthma/COPD
PAD
248
What are the adverse effects of terlipressin?
Abdo pain (ischaemia)
Diarrhoea
Circulatory overload/arrhythmia/CV death
Respiratory failure
249
How do you treat hyponatraemia in cirrhosis?
If hypovolaemic - stop diuretics + give normal saline
If hypervolaemic + severe:
- IV hypertonic saline
- if no response, dialysis
If hypervolaemic + moderate:
- stop diuretics, fluid restrict
- if nil response IV albumin
- if still no response then IV albumin, Frusemide + terlipressin
250
What are the non-oncotic properties of albumin in cirrhosis?
Immunomodulatory
Scavenging activity
Anti-inflammatory
Anti-thrombotic
Endothelial stabilisation
251
What is the preferred primary prophylaxis for variceal bleeding?
Carvedilol 12.5mg daily (as it also slows liver disease)
252
What are the options for secondary prevention of varices?
Variceal banding + carvedilol
TIPSS
Surgical shunt
Liver transplant
253
What is the role of Carvedilol in cirrhosis?
Indicated to prevent decompensation, prevent 1st variceal bleed, prevent variceal re-bleed, and treat portal hypertensive gastropathy
254
What are the indications for TIPS?
Refractory ascites
Portal hypertensive bleeding
Hepatic hydrothorax
Budd chiari syndrome
255
What are the contraindications to TIPS?
RHF or severe pulmonary HTN
Active infection
Biliary obstruction
CPC >13
HCC
256
What grade of HE is hepatic flap indicative of?
Grade 2-3
Not present in 4, rarely in 1
257
What preventative measures are indicated to prevent recurrent HE?
Lactulose + Rifamixin
258
Why should PPIs be avoided in px with cirrhosis?
Increased risk of SBP
Increased risk of HE
259
What are the features/key differences between hepatopulmonary syndrome and portopulmonary HTN?
HPS pw progressive dyspnoea, PoPHT may also have chest pain or syncope
HPS may have cyanosis, clubbing
cf PoPHT no cyanosis but RV heave + loud P2
HPS = no ECG findings cf PoPHT RBBB, RAD, RVH
HPS = mod-severe hypoxaemia on ABG, PoPHT = nil/mild hypoxaemia only
HPS = normal CXR; cf PoPHT = cardiomegaly and hilar enlargement
HPS = always positive contrast-enhanced echo cf PoPHT usually neg
99TC shunting = present in HPS, neg in PoPHT
Pulmonary haemodynamics = normal/low pulmonary venous resistance in HPS, high in PoPHT
Pulmonary angiography = normal or spongy appearance or discrete AV communications in HPS, large main pulmonary arteries and distal pruning in PoPHT
Liver transplant = indicated in severe HPS, only indicated in mild-mod PoPHT
260
In a px with cirrhosis undergoing invasive procedures, is correction of INR with FFP indicated ?
No - INR does not correlate with peri-procedural risk in cirrhotics and correction may increase risk of VTE
261
How do you treat portal vein thrombosis?
Initial = UFH/LMWH
Longer term = LMWH or warfarin (nil data yet for NOACs)
262
Who should be assessed for MALFD?
Adults with obesity
Adults with T2DM
Adults with 2 or more metabolic risk factors
263
What is the first line test to evaluate for MAFLD?
Liver USS
264
What are the risk factors for progression in fibrosis in MAFLD?
Age >50
BMI >28
Weight gain >5kg
Necroinflammatory activity
ALT >2x ULN and rising
AST/ALT ratio >1
Elevated TG
Insulin resistance / DM or poor glycaemic control
Systemic HTN
265
What is the most important risk factor for progression in MAFLD?
Diabetes
266
What are the non-invasive measures you can use to assess fibrosis in MALFD?
Fib-4 score
Transient elastography
Fib4 = age, platelet count, AST, ALT
267
When should px with MAFLD be referred to liver specialist?
If elevated Fib4 (>2.7) or intermediate risk Fib4 with elevated fibrosis on transient elastography
268
What are patients with non-cirrhotic MALFD most likely to die from?
Cardiovascular disease or cancer rather than liver disease
269
How do you treat MAFLD?
Weight loss - diet and exercise, SGLT2i, GLP-1Ra, bariatric surgery
Treat T2DM - SGLT2i, GLP-1Ra
Treat CV risk factors - antiHTN, statins, smoking cessation
Target NASH - vitamin E, pioglitazone, resimetron
Try to prevent end-stage complications - statins (reduce portal HTN), metformin (?lower HCC risk), reduce alcohol consumption
270
What is the potential role of statins in MALFD?
Beyond CVD risk reduction, assoc with lower overall mortality, liver-related clinical events and liver stiffness progression in MASLD px
271
What is the most effective treatment in NASH ?
Bariatric surgery (Roux-en-y or sleeve gastrectomy) superior to optimal medical therapy and lifestyle in NASH
272
What is the significance of hyperferritinaemia in MASLD?
Seen in 60%
Assoc with fibrosis severity and increased all-cause mortality
However, phlebotomy not effective
273
80% of heavy drinkers do not develop advanced liver disease, what are the risk factors for developing ARLD?
Amount and duration (>80g >5y), daily >intermittent
Genetic factors
Females
Race
Malnutrition
Diets high in pork
Viral hepatitis/ HIV
Iron overload
Smoking
Interestingly caffeine intake = protective
274
What is phosphatidylethanol (PETH)?
Blood test that detects heavy drinking in the last month
275
What score/model is used to predict Alcohol-related hepatitis mortality?
MDF - score >32 indicates severe alcoholic hepatitis - indication for steroid therapy
276
How do you treat severe alcoholic hepatitis (MDF >32)?
Pred 40mg/d +/- NAC
Assess response at D7 with Lille score
277
What are the criteria for liver transplant in px with alcohol-related liver disease?
Abstinent >6mths
Adequate social support
Rarely may offer someone with first episode of alcoholic hepatitis not responding to medical tx
278
What is hepatitis E?
A single stranded RNA virus of the herpevirus family
It is the most common cause of acute hepatitis globally
Most outbreaks assoc with faecally contaminated drinking water
279
There are 8 genotypes of HEV, which one is most commonly found in Aus?
Genotype 3
- endemic in pigs/wild boars
- primarily spreads through pork; also blood products
280
Do immunocompetent individuals develop chronic hepatitis E?
No
May progress to chronic hepatitis in immunosuppressed px who fail to clear acute HEV infection eg solid organ transplants, haem px, HIV, rheum px with heavy immunosuppression
Most of these are asymptomatic and present with mild/persistent LFT abnormalities
281
Who should you test for HEV?
All immunosuppressed individuals with unexplained abnormal LFTs
282
What are the extrahepatic manifestations of HEV?
Neurological eg GBS, meningoencephalitis
Renal incl membranoproliferative and membranous GN, IgA nephropathy
Haematological incl aplastic anaemia, haemolytic anaemia, thrombocytopenia
Other - acute pancreatitis, arthritis, myocarditis, autoimmune thyroiditis
283
How do you diagnose acute HEV infection?
anti-IgM + rising IgG +/- HEV RNA CR
284
What serological test indicates past infection with HEV?
anti-HEV IgG
285
How do you treat acute HEV infection?
Usually nil treatment required as most cases spontaneously cleared
If severe acute hepatitis or ACLF -> treat with ribavirin
If immunosuppressed - decrease immunosuppression (if possible) + ribavirin
286
Who is most at risk of hepatitis C?
PWID or ever injected drugs
287
What are the key extra-hepatic manifestations or associated conditions with HCV?
Mixed cryoglobulinaemia
CKD
Diabetes
Lymphoma
Lichen Planus
Sjogren's syndrome
Porphyria Cutanea Tarda
RA-like arthritis
Depression
288
Progression of fibrosis in HCV is unpredictable and is influenced by what patient factors?
DM
Obesity
MASLD
Alcohol
Genetic factors
Post-menopausal women
Age at infection
HCV 3 genotype
HIV co-infection
289
How does fibrosis stage influence HCV management?
It doesn't - ALL px should be treated independent of fibrosis stage, virtually no contraindications to DAA
290
How do you assess fibrosis in HCV?
Non-invasively:
- APRI score
- TE
291
What is the cut off for cirrhosis on transient elastography in HCV?
Has high NPV so liver stiffness <12.5kpa on TE = very unlikely cirrhosis
>12.5 = possible
292
When is the benefit of achieving SVR most felt in HCV?
Prior to development of cirrhosis
halts progression to cirrhosis or fibrosis, liver decompensation, HCC and need for transplant
Also reduces extra-hepatic disease incl lymphoma,
293
What is the efficacy of current DAA for HCV?
98-100% SVR
Use combination therapy to avoid resistance and optimise efficacy
294
What are the two main DAA used in Aus?
Epclusa - 12 wks of sofosbuvir + velpatasvir
Maviret - 8 weeks glecaprevir + pibrentsavir
Both pan-genotypic regimens
295
What do you do for salvage therapy for HCV?
Vosevi
- epclusa + voxilaprevir
296
When can you discharge a patient with HCV-induced cACLD from portal HTN surveillance?
In the absence of co-factors, if achieve SVR and LSM <12kpa + Plt >150
297
What are the Baveno criteria to rule out high-risk varices in px with HCV who achieve SVR?
LSM <20, Plt >150
298
Which px with treated HCV who achieve SVR are at risk of liver decompensation?
Patients with baseline LSM >20 who fail to achieve reduction in LSM following tx
299
Are there similar rule outs that allow you to discontinue HCC surveillance in treated HCV?
No - still recommended to undergo long-term HCC surveillance following SVR in HCV even if improving biomarkers/LSM
300
What medications may interact with DAA?
Statins, PPIs, amiodarone, OCP
301
Protease inhibitors are contraindicated in which group of patients?
Decompensated cirrhotics
(ie don't use Maviret in decompensated cirrhotics)
302
Which patient groups are DAAs not recommended in?
Pregnancy and breastfeeding
303
What are the main Resistance Associated Substitutions affecting DAA therapy?
NS3 and NS5A
NS5B = rare
- may be present before DAA therapy
- low rates in Aus so still use current DAAs
- if fail to achieve SVR -> test for resistance, may require salvage therapy
note reinfection common (relapse after SVR) rather than resistance/failure
304
In HBV-HCV co-infection, what is usually the driver of liver inflammation?
HCV
HBV viral load usually low/undetectable
305
What is the risk of commencing HCV DAA therapy in px with HCV-HBV coinfection?
Potential for HBV reactivation during or after HCV clearance with DAA
Therefore need to test for chronic HBV before starting
306
Which patients with chronic HBV should you consider concurrent HBV and HCV antiviral tx for?
Px with HBV who are HBsAg+
307
How do direct acting antivirals work in HCV?
Epclusa = Sofosbuvir is metabolised to active uridine analogue triphosphate and this inhibits HCV NS5B RNA polymerase; velpatasvir inhibits HCV NS5A protein (also prevents assembly of the virus)
Maviret = glecaprevir is an HCV NS3/4A protease inhibitor and pibrentasvir is an HCV NS5A inhibitor (also prevents assembly of the virus).
308
How do you treat decompensated cirrhotic px with HCV?
Epclusa + ribavirin
309
Patients who are HbsAg+ have what?
Either active infection or chronic infection
310
Patients who are HBsAg-, anti-HBs+ and anti-HBc+ are?
Immune through previous HBV infection
311
Someone who is HBsAg-, anti-HBs+ and anti-HBc- are?
Immune through vaccination
312
What are the two main antiviral drugs for treating HBV?
Entecavir and Tenofovir diproxil (TDF)
Both can be used in decompensated cirrhosis
313
When might you favour entecavir over TDF?
If renal disease/at risk
Alternatively could use TAF
314
Which antiviral (entecavir or TDF) would you use in pregnant women with HBV?
TDF
315
Which antiviral (entecavir or TDF) would you use in HBV tx if px had previously been exposed to nucleoside analogues?
TDF
316
What are the three indications for antiviral HBV treatment?
HbeAg+ chronic HBV if:
- HBV DNA viral load >20,000 +
ALT >ULN OR evidence of fibrosis
HbeAg- chronic HBV if:
- HBV viral load >2000 +
ALT >ULN OR evidence of fibrosis
All px with HBV + cirrhosis and any detectable HBV DNA (regardless of ALT)
note fibrosis usually determined non-invasively with Apri, Fib4 or TE
317
Outside of those 3 indications for antiviral tx in chronic HBV, when might you consider tx (although not PBS approved)?
HBeAg+ px at increased risk of HCC based on:
- fhx
- age <35
- coinfection with HDV or HCV
- concurrent liver disease eg MASLD
- extrahepatic manifestations of HBV
318
When can you consider stopping antiviral therapy in HBV?
12 months after HBsAg loss (ie seroconversion)
12 months after HBeAg loss (ie seroconversion)
HBeAg negative if >2yrs undetectable viral load
MUST continue in px with cirrhosis, concurrent HCV tx or px with HCC
319
What immunosuppressive agents are considered low risk for HBV reactivation?
Anti-TNF
Immune checkpoint inhibitors
TKIs
T-cell depleting agents
Antiproliferative agents
Alkylating agents
In these cases - monitor liver function and test for HBV viral load if elevate during tx
Rest = favour commencing antiviral prophylaxis (eg entecavir)
320
How long do you continue HBV prophylaxis for after stopping immunosuppressive therapy?
6-12 months
- 6months for most
- anti-CD20 therapy / B cell depleting therapy such as Rituximab is >12 mths
321
What immunosuppressive agent is assoc with the highest risk of Hep B reactivation?
Rituximab / B cell depleting therapy
322
Under what circumstances does HBV reactivation rarely occur in those at risk?
HBV reactivation occurs rarely in HBsAg-negative and anti-HBc-positive patients receiving the following: cytotoxic chemotherapy without glucocorticoids, anti-TNF therapy, methotrexate, or azathioprine.
323
Who should you give HBV antiviral prophylaxis to?
Px at moderate to very high risk of HBV reactivation
324
What do you use for HBV antiviral prophylaxis?
Entecavir or TDF
325
How do you manage a HBsAg + or HBeAg+ pregnant women with high viral load >200,000 in T3?
Antiviral therapy with tenofovir from week 28 onwards - reduces 10% risk of vertical transmission to almost 0%
326
What is Hepatitis D virus?
A defective virus that requires coinfection with HBV
327
How do you treat HDV?
HBV nucleos(t)ide antiviral therapy has no impact on HDV
Can trial peginteferon but limited benefit - 25% response
Buleviritide - which blocks HBsAg entry into hepatocytes - reduces HBV DNA load and normalises ALT levels - available via compassionate access
