cirrhosis

Question 1

consequences of cirrhosis

Answer 1

1) block blood flow
2) impede hepatocyte perfusion
3) impair liver synthetic function (e.g. produce albumin)

Question 2

aetiology of cirrhosis

Answer 2

1) alcohol
2) chronic Hep B & C
3) metabolic liver syndrome
- hemochromatomasis: body cannot process iron properly, accumulate
4) drug induced: isoniazid, methyldopa, amiodarone, diclofenac, methotrexate

Question 3

progression of cirrhosis

Answer 3

1) compensated
- silent, asymptomatic, generally good QoL

2) decompensated
- 1st clinical symptoms: ascites, bleeding, encephalopathy, jaundice
- progression due to development of complications
- end stage: death or liver transplant

Question 4

complications of cirrhosis

Answer 4

1) variceal bleeding
2) hepatic encephalopathy
3) cirrhotic cardiomyopathy
4) hepatopulmonary syndrome, portopulmonary syndrome
5) hepatorenal syndrome, AKI
6) ascites

Question 5

general ascites

Answer 5

• accumulation of excess fluid in peritoneal cavity
• prone to complications: bacterial infection, nutrient & electrolyte imbalance, HRS

Question 6

pathogenesis of ascites

Answer 6

structural component
- cirrhosis -> development of nodules surrounded by fibrotic material -> impede blood flow to liver

functional component
- increase in vascular tone (constriction) -> portal HTN -> sphlanic vasodilation (body detect increase in portal pressure)

• portal HTN -> increase in hydrostatic pressure
• lower albumin synthesis -> lesser albumin to maintain oncotic pressure -> lower intravascular oncotic pressure
• portal HTN + vasodilation -> underfilling & lesser aldosterone in liver -> further activation of RAAS -> further Na & H2O retention
• sphlanic vasodilation: lymph formation > lymph return
• end of day: fluid from portal circulation into peritoneal cavity

Question 7

ascites related sypmtoms

Answer 7

1) dyspnoea: difficulty breathing cuz stomach distended
2) abdominal distention & pain

Question 8

goals of therapy of ascites

Answer 8

1) control ascites
2) prevent/relieve ascites related symptoms
3) prevent life threatening conditions: SBP, HRS

Question 9

treatment of ascites

Answer 9

1) abdominal paracentesis
- insert needle into abdominal cavity to aspirate ascitic fluid
- send ascitic fluid for analysis: cell count w differential, ascitic fluid total protein, signs for bacterial infection, serum ascitic albumin gradient (SAAG, SAAG >/= 11 means portal HTN)
2) dietary
- no alcohol
- Na retention (2000mg/day) to prevent further fluid retention
3) spironolactone (aldosterone agonist) 100mg + frusemide 40mg (loop) OM PO
- titrate every 3-5 days with 100:40 ratio until adequate natriuresis & weight loss
- frusemide lower risk of hyperkaliemia & prevent water retention
4) antibiotics for SBP: long term prophylaxis
5) tie rubber band/BP lowering meds to prevent bleeding

Question 10

caution for treatment of ascites

Answer 10

1) no NSAIDs cuz worsen
2) no ACEi/ARB cuz risk of AKI and HRS
3) no need for fluid retention
- patient already in state of hypovolemia
- fluid retention further activate RAAS -> further water retention

Question 11

general varices

Answer 11

• swelling of veins around stomach & oesophagus -> burst & bleed
• asymptomatic until burst
• diagnosis: endoscopy to find swollen veins around stomach & oesophagus

Question 12

hepatic venous pressure gradient (HVPG)

Answer 12

. pressure difference between portal and central venin
. HVPG > 5 mmHg = portal HTN
. HVPG > 10 mmHg = variceal bleeding

Question 13

coagulation defects

Answer 13

. decrease synthesis of procoagulation factors and naturally occurring anticoagulants, antithrombin, protein C & S
. increase in anticoagulant factor VII & von Willdebrand
- state of rebalanced hemostasis
- balance can be tipped anytime (risk of bleeding/thrombosis)
. thrombocytopenia common

Question 14

diagnosis for cirrhosis - history taking

Answer 14

1) identifying symptoms
- asymptomatic: compensated
- initial symptoms (non-specific): fatigue, loss of appetite, weight loss
- signs of decompensated cirrhosis

2) determine cause of cirrhosis
- alcohol/drug abuse
- obesity, diabetes, NAFLD
- risk factors for Hep B & C
- personal/family history of immune/hepatic disease
- drugs that can cause cirrhosis

Question 15

diagnosis for cirrhosis - history taking

Answer 15

1) identifying symptoms
- asymptomatic: compensated
- 1st clinical sypmtoms (non-specific): fatigue, weight loss, loss of appetitie
- signs of decompensated cirrhosis

2) determine cause of cirrhosis
- alcohol/drug abuse
- obesity, diabetes, NAFLD
- risk factor for Hep B & C
- personal/family history of immune/hepatic disease
- drug induced

Question 16

diagnosis for cirrhosis - physical examination

Answer 16

1) jaundice: yellowing of skin/eyes
2) pruritus
3) plamar erythema
4) spider angiomata
5) hyperpigmentation
6) metabolic problems: gynaecomastia, testicular atrophy, axillary hair loss (lower oestrogen produced by liver)

Question 17

diagnosis for cirrhosis - lab test

Answer 17

1) assessment
- LFT: hepatocellular/cholestatic
- coagulation test (PT, aPTT, INR): synthetic function of liver
- complete blood count + platelet

2) other causes of cirrhosis
- Hep B/C: serologic test for viral load
- autoimmune disease: antinuclear antibody titer
- haemochromasis: serum Fe & transferrin saturation, genotype testing (maybe)
- alpha-1 antitrypsin deficiency: alpha-1 antitrypsin levels & genotyping

Question 18

diagnosis for cirrhosis - imaging test

Answer 18

1) ultrasound
- presence of varices, portal HTN, cirrhosis

2) elastography
- if ultrasound cmi

Question 19

diagnosis for cirrhosis - tissue biopsy

Answer 19

if non-invasive cmi

Question 20

general approach to treating cirrhosis

Answer 20

A) identify and eliminate (if possible) causes for cirrhosis
B) assess risk for variceal bleeding and benign pharmacological prophylaxis when indicated
. prophylactic endoscopic therapy
- for patients with high risk medium-large size varices
- for patients CI/intolerant of BB
- tie rubber band around varices
. variceal obliteration w endoscopic techniques
- for acute bleeding

C) monitor for patient for ascites + pharmacotherapy + paracentesis
- monitor for spontaneous bacterial peritonitis (SBP) & acute deterioration of clinical status

D) monitor for other causes of HE
- pharmacotherapy (diet, lactulose, ribavirin)

E) monitor for other liver complications
- HRS, pulmonary insufficiencies, endocrine dysfunction

Question 21

levels of treatment of cirrhosis

Answer 21

1) primary prophylaxis
- compensated, HVPG >/= 10 mmHg
- presence of varices
- goal: prevent decompensation

2) treat acute variceal bleeding
- first blood, presence of variceal haemorrhage
- goal: control bleeding, prevent early rebleeding and death

3) secondary prophylaxis
- goal: prevent rebleeding

Question 22

primary prophylaxis

Answer 22

. for high risk varices
- small + red wales + Child-Pugh score C
- medium/large irregardless of Child-Pugh

. BB
- MOA:
1) B1 blockade: lower cardiac output
2) B2 blockade: lower splanchnic blood flow
- carvedilol: alpha blockade as well to increase release of NO
- target HR: 55-60bpm
- caution
1) systolic BP needs to be > 90 mmHg
2) refractory/tense ascites
3) other complications (AKI, bleeding)
- SE: pulmonary bronchospasms, bradycardia

. endoscopy variceal ligation
- tie rubber band around varices
- goal: eradication (until no further ligation possible)
- dose: every 2-3 wks until eradication

Question 23

treatment for acute variceal bleeding

Answer 23

1) stabilise patient
- ABC
- volume replacement: crystalloids, transfusion (Hb < 7)

2) drug therapy
. vasoactive drug
- splanchnic dilation -> lower blood flow -> reduce bleeding
- doesnt stop bleeding, still require ligation
- osteopresin: hyperglycemia, HTN, bradycardia
- vasopressin, somatostatin
. antibiotics
- prevent risk of infection

3) endoscopic techniques
- within 12 hrs of bleed
- confirm site of bleed, ligation

4) continue drug therapy
- vasoactive: 3-5 days
- antibiotics: 5-7 days

5) after continuing drug therapy
. controlled: secondary prophylaxis
. bleeding
- transjugular intrahepatic portosystemic shunt (TIPS): insert stent between portal and hepatic vein to relieve pressure off varices, don’t need secondary prophylaxis but refer for transplant
- balloon tamponade: insert & inflate balloon tamponade, last 24 hrs

Question 24

secondary prophylaxis

Answer 24

. BB + EVL
. TIPS if above cmi

Question 25

what is hepatic encephalopathy + symptoms

Answer 25

. functional disturbance of brain
. wide spectrum of symptom severity
1) lowest: alteration in attention, memory, psychomotor skills
2) higher: behavioural changes (irritation, disinhibition)
3) worst: affect consciousness (coma)

Question 26

pathogenesis of hepatic encephalopathy

Answer 26

. resistance in liver -> blood shunted to other organs (varices around stomach, brain)
. decrease liver function & shunting of blood through portosystemic collaterals bypassing liver -> accumulation of N substances -> go straight to brain
. entry of N substances into brain -> alter neurotransmission -> affect consciousness & behaviour

Question 27

approach to treatment of hepatic encephalopathy

Answer 27

1) Care for patient with altered mental state
2) identify & treat other causes for altered mental state
3) identify & treat precipitating factors
4) begin empiric therapy
5) focus on lowering blood NH3 concentration (lab values)

Question 28

therapy for hepatic encephalopathy

Answer 28

1) dietary measures
- lower protein intake (1.2g/kg/day - 1.6g/kg/day)
- veg & diary sources preferred
- supplement with Zn

2) lactulose
- lower oncotic pH, promote conversion of ammonia to ammonium for excretion, increase bowel movement for excretion
- initiate high dose to achieve catharsis (increased bowel movement), titrate to achieve 2-3 soft stools/day

3) rifaximin
- target anaerobic bacteria in gut that produce urease (convert urea to ammonia)
- 550mg BD
- + lactulose for recurrent HE
- low systemic absorption = low AE profile, preferred antibiotics