Liver

Question 1

Rx: Varices (primary & secondary)

Answer 1

No varices - just Rx liver dis

Varices - haven’t bled (primary prevention)
- NSBB (Carvedilol, NSBB w/ alpha) reduces portal Pb

Bleeding varices (secondary prevention)
Dual Rx (banding/ligation + NSBB)
Decreases bleeding risk but not mortality
Consider banding alone only is C/I to NSBB

Question 2

Resus in variceal bleeding - correcting haem abN

Answer 2

Aim Hb >70 (give blood/albumin over other fluids), Plt >50

Fibrinogen

• If high can resemble DIC (? tranexamic acid + epsilon aminocaproic acid)
• If low - Cryoprecipitate

Avoid PCC & FFP

Question 3

Resus in variceal bleeding - Pharm Rx (non haem related)

Answer 3

Octreotide & Terlipressin

• lowers portal Pb to control inflow
• aim Hepatic gradien Pb 70-80
• continue for 5 days

ABx prophylaxis (Ceftriaxone + 1wk Norfloxacin)

(PPI no efficacy but give as may reduce post banding bleeding)

Endoscopy <12hrs

Question 4

AI hepatitis - histo

Answer 4

• Lobular/portal inflammation w/ many plasma cells
• Lymphoplasmacytic infiltrate (extends from portal tract into lobule)
• Hepatic necrosis w/ rosetting liver cells (hepatic rosette formation)

Question 5

AI hepatitis - drugs that can cause

Answer 5

• Minocycline
• Nitrofurantoin
• Isoniazid
• PTU
• Methyldopa

Question 6

AI hepatitis - cut offs for “severe” & mortality

Answer 6

Severe = AST>10x (or 5x w/ GGT doubled)

40% mortality at 6months if unRx

Question 7

AI hepatitis - Dx parameters (including serological markers)

Answer 7

Serological markers: ANA/SMA (T1), LKM+ (T2) - not specific for AIH as elevated in other conditions

IgG/Cryoglobulins >ULN

Liver histo: hepatitis, lymphoplasmacytic infiltrates from portal tract to lobule, hepatic rosette formation

No viral hepatitis

Question 8

AI hepatitis - Rx

Answer 8

1. Pred +/- Aza
2. Budesonide (to spare S/E if mild) + Aza

Swap outs: Aza for MMF but C/I in pregnancy
Consider CNI in refractory, & go high dose Pred

Question 9

Pathophysiology in iron absorption (overload)

Answer 9

HepcidINHIBITS iron

1. Iron absorbed in duodenum across basolateral enterocyte mmb as ferrous iron (Fe³⁺)
2. Reduced by ferrireductase (on apical surface) to Fe²⁺/heme
3. Fe²⁺ absorbed by DMT1 receptor, heme (meat) absorbed elsewhere
4. On apical surface, release via ferroportin into portal cicrulation
5. Ferrioxidase converts back to Fe
6. Bound to transferrin within circulation

Hepcidin is “iron brake” - binds ferroportin /blocks iron absorption “gate” (degrades so less iron absorbed)
Also induces macrophages to keep storing iron rather than release

Produced by hepatocytes in response to increased iron (Tsats) & IL-6 inflammation (hence anaemia of chronic dis)
Inhibited by (ie to allow increased iron): anaemia (erythroblasts) & hypoxia (smokers)

Question 10

Iron studies - what they mean

Expected patterns: IDA, Anaemia chronic dis/inflammation, HH, Iron loading anaemias

Answer 10

• Tsats (in circulation) <20 is low; >45 is high (ratio 1:2 iron)
• Serum ferritin (within storage protein) >1000 high (ratio 1:4500 iron)
• Transferrin (opposite of Tsats): can differentiate IDA/inflammation (inc in iron def, dec in OL, inflammed, infection)
• Serum iron (unbound serum iron) - diurnal variation & depends on recent intake
• TIBC: ability to bind more iron

IDA: Hepcidin (L)
Anaemia chronic dis/inflammation: ferritin (H), Tsats (N/L), Hepcidin (H) - IL6
HH: Tsats (>45), Hb (N), Hepcidin (L)
Iron loading anaemias (MDS, Thal - NTDBT): Ferritin (H), Tsats (H), Hb (L), Hepcidin (L)
- Hepcidin is inhibited by early erythroblasts so they keep absorbing iron

Question 11

Iron overload syndrome - Fx (inc labs)

Answer 11

• Tsats >45%
• Ferritin >200 main cut off (lower in pre menopausal) - target 50(-100) w/ weekly bleeds
• If >1000 w/ increased AST/ALT + dec plt <200 - cirrhosis likely (if <1000 then unlikely cirrhosis)

Cardiac: CM - HF, arrhythmia - MUGA, T2 MRI reversible
Liver: T2 MRI, USS (HCC), LFTs
Endocrine: DM - non reversible ; Hypogonadism reversible
Arthropathy: pseudogout, chondrocalcinosis (eg 2nd/3rd MCP) non reversible
Skin bronzing & Hepatomegaly reversible

Question 12

HH - genetics

Answer 12

HFE gene mutation - similar to MHC class 1 like protein (bind B2 microglobulin)
 - usu missense mutation

C282Y (85%) - worse prognosis
- only 20% have penetrance of iron overload however (most don’t)
H63D - better prognosis (can get compound heterozygotes of both mutations)

Question 13

Spectrum of NAFLD & classification/histo

Answer 13

NAFLD: #1 cause liver dis. Presence of >5% hepatic steatosis w/o hepatocellular injury
- ballooning hepatocytes, lobular inflammation, fibrosis, fat globules - hepatic steatosis
- NALFD score to assess cirrhosis (4th stage of fibrosis) but usu need bx as can’t tell NAFLD/NASH otherwise
MAFLD: Fatty liver + any of metabolic syndrome or lean w/ BP >130, Tg >1.7, IGT, CRP>2
Insulin resistance key fx (increase of substrates to liver)

NASH: inflammation (steatohepatitis), >5% hepatic steatosis WITH hepatocellular injury

Rx is usual stuff but not a lot proven exc LOW (statins CVD risk , Metformin improves LFTS but not histo)
Pioglitazome improves histo but has S/E inc wt gain, CCF, OP, bladder Ca
Vit E benefits non-DM but stroke & prostate Ca
Obeticholic acid (FXR blocker - Farnesoid X receptor - bile acid receptor) improves fibrosis if present, but S/E
Antifibrotics (CCR5 blockers), PPAR blocker