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EXMD4743 > WK3 - Ex and Liver Disease > Flashcards

WK3 - Ex and Liver Disease Flashcards

1
Q

What is the pathophysiology of non-alcoholic fatty liver disease (NAFLD)?

A

> 5.5% liver fat (relative to water)
- inflammation and hepatocyte ballooning
- fibrosis

  1. health liver
  2. NAFLD 15-30%
  3. NASH 12-40%
  4. Cirrhosis (liver transplant/death) 15-25%
  5. hepatocellular cacrcinoma ~7%
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2
Q

List 5 names to replace NAFLD.

A
  1. liver steatosis
  2. lipid-induced liver disease
  3. Liver Steatopathy
  4. primary lipogenic liver disease
  5. metabolic associated fatty liver disease (MAFLD)
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3
Q

What is the adult cardiometabolic criteria?

A

at least 1 out of 5
* BMI >25 or WC >94cm (M) >80cm (F) or ethnicity adjusted
* fasting serum glucose >5.6 or 2hr post-load glucose >7.8 or HbA1c >5.7% or T2DM or Tx for T2DM
* BP >130/85 or on antihypertensive Tx
* plasma triglycerides >1.7 or lipid lowering Tx
* plasma HDL cholesterol <1 (M) and <1.3 (F) or lipid lowering Tx

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4
Q

What is the paediatric cardiometabolic criteria?

A

at least 1 out of 5
* BMI >85 percentile or WC >95 percentile or ethnicity adjusted
* fasting serum glucose >5.6 or serum glucose >11.1 or 2h post-load glucose >7.8 or HbA1c >5.7% or T2DM/Tx for T2DM
* BP (<13y) >95 percentile or >130/85 or on antihypertensive Tx
* plasma triglycerides (<10y) 1.15mmol/L (>10y) 1.7mmol/L
* plasma HDL <1 or lipid lowering Tx

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5
Q

What does a change in medical condition terminology mean?

A
  • Dx criteria is changing
  • transition of nomenclature: med charts, referrals, conferences, scientific journals etc
  • terminology transition in patient education resources
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6
Q

Provide the aetiology of NAFLD.

A
  • development of hepatic steatosis: delivery exceeds removal
  • increased circulating FFA, exceeding oxidative capacity
  • increased de novo lipogenesis
  • insufficient elimination of triglycerides (insufficient mitochondrial oxidation)
  • inhibition/dysregulation of VLDL assembly and secretion
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7
Q

What is the prevalence of NAFLD?

A
  • 37% patients with T2DM have NASH
  • 81% with NASH have comorbid obesity
  • Aus - expected 25% increase between 2019-2020 >7million cases
  • in community 25%
  • in obese 80%
  • in T2DM 85%
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8
Q

What are the risk factors for MAFLD?

A
  • central adiposity
  • overweight/obesity
  • IR and T2DM
  • atherogenic dyslipidaemia
  • arterial hypertension
  • metabolic syndrome
  • dietary factors (high calorie/HDL/ saturated fats/sugars/processed)
  • sedentary lifestyle/occupation/low PA
  • sarcopenia
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9
Q

What is MFALD associated with?

A
  • CVD
  • cerebrovascular disease
  • CKD
  • osteoporosis
  • Cancer
  • cognitive changes
  • hyperuricemia
  • hypothyroidism
  • PCOS
    *hypopituitarism
  • sleep apnoea syndrome
  • polycythaemia
  • gut dysbiosis
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10
Q

Provide the clinical presentation and diagnosis of NAFLD.

A

Asymptomatic/non-specific Sx…
* fatigue
* pain in upper R quadrant (some)
* hepatomegaly (common)

Dx
* ultrasound
* biopsy
* MRI
* serum biomarkers

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11
Q

What are the intra- and extra-hepatic consequences?

A

‘Hepatic manifestation of metabolic syndrome’

Liver fat = IR, dyslipidemia, impaired vascular function

  • independently predicts CVD and T2DM
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12
Q

What do physicians do?

A
  • suspect from patient Hx
  • detect via investigation: abdominal imaging/abnormal liver enzymes

i) Ax severity of liver disease
ii) identify co-morbid cause of liver disease
iii) meds and OTC preparations
iv) screen for cardiometabolic risk/common comorbidities

Management
1. prevent cardiometabolic-related death
2. presentation of lifestyle-related cancer death
3. resolution of MAFLD/progression of liver disease

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13
Q

What is the recommended lifestyle therapy for physicla activity?

A
  • mental wellbeing management
  • aerobic Ex >3x/wk (>150mins/wk MIPA)
  • RT >2x/wk
  • reduce sedentary behaviour
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14
Q

What is the Ex prescription for hepatic steatosis (liver fat)?

A
  1. Aerobic Ex - at least MIPA for moderate reductions in hepatic steatosis (~2-4%) - strong evidence
  2. efficacy of RT on reducing steatosis uncertain - low certainty of evidence
  3. early evidence for HIIT promising but insufficient evidence for firm recommendation
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15
Q

What is the Ex prescription for liver histology (fibrosis, inflammation, hepatocyte ballooning, NAFLD activity score)?

A
  • very limited evidence - benefits of Ex not established
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16
Q

What is the Ex prescription for other variables?

A

Moderate evidence for aerobic Ex to improve:
* BMI
* WC
* total cholesterol
* Alanine aminotransferase
* CRF

17
Q

Does Ex intensity matter for NAFLD patients?

A
  • liver fat decreased by 4.2% in MIPA and 5% in VIPA at 6/12 compared to control group
18
Q

What is the recommended aerobic frequency for MAFLD?

A

3-7days/wk

19
Q

What is the recommended aerobic intensity for MAFLD?

A

MIPA 55-69% HRmax
RPE3-4/10

OR VIPA 70-89% HRmax
RPE5-6

OR combination of mod+vig

20
Q

What is the recommended aerobic duration for MAFLD?

A

150-300mins
- Start at 5-10mins and gradually increase to 30-60mins sessions

OR 75-150mins
- start at 5-10mins and gradually increase to 20-30min sessions

OR aim for 150-300mins week total

21
Q

What are the hepatic benefits from aerobic Ex? Include other health benefits

A
  • reduce liver fat
  • improve aminotransferases
  • decrease hepatic lipase activity
  • reduced VAT
  • improve inflammation

Other improved:
* CRF
* glycaemic control
* hypertension
* blood lipid profile
* mental health
* QoL

22
Q

What is the recommended RT in terms of frequency, intensity and duration?

A

2-3 nonconsecutive days/wk + aerobic Ex

Mod-vig
70-84% 1RM
8-12Ex
8-10reps
2-4sets
1-2mins rest inbetween

30-60min session duration

23
Q

What are the hepatic benefits? Include other benefits.

A
  • may reduce liver fat
  • improve liver aminotransferases

Other improved:
* glycaemic control
* muscle mass
* muscle function

24
Q

What evidence is available in MAFLD Ex prescription?

A

Yes:
* hepatic steatosis
* adiposity
* total cholesterol
* CRF

No:
* body weight

Maybe
* liver histology

25
Q

What are the Ex prescription recommendations for the goal of reducing hepatic steatosis?

A

mod-vig at least 135mins/wk across 3-5days/wk
- ideally progressing to 150-240mins/wk (strong evidence)

OR HIIT involving 1-5 intervals of 2-4mins with 2-3 mins lower intensity Rx over 3-5days/wk (mod evidence)

RT - insufficent evidence

Practical considerations
* prescription be prioritised for hepatic steatosis management
* benefits of RT unclear - should still perform - there are some available resources

26
Q

What are the Ex recommended prescription in reduce central adiposity (WC)?

A
  • mod-vig aerobic Ex for 150-240mins/wk across 3-5days/wk
  • RT - insufficient evidence

Practical consideration:
* even 60min of VIPA per wk may have equivalent benefits
* considerations similar to hepatic steatosis

27
Q

What are the Ex recommendations for MAFLD with goal of improving CRF?

A
  • mod-vig aerobic PA at leat 135mins/wk across 3-5days/wk
  • RT - insufficient evidence

Considerations:
* emerging evidence suggests HIIT may equally improve CRF with MAFLD

28
Q

What are the Ex recommendations for MAFLD wanting to lose weight?

A
  • mod-vig aerobic Ex 150-240mins/wk across 3-5days/wk
  • RT - insufficient evidence

Considerations
* appropriately communicate modest magnitude of weight loss (~2-3kg or 1.5%) expected with Ex intervention of this volume alone

29
Q

What are putative mechanisms?

A
  • reduces VAT/enhances insulin sensitivity –> lower hepatic FFA uptake
  • increase VLDL clearance (reduce lipid storage)
  • peripheral insulin sensitisation –> enhanced substrate uptake in muscle
  • reduced gene expression for lipogenic proteins (e.g. fatty acid synthase)
30
Q

What were the results of the study between Ex in NASH?

A

Biopsy confirmed MAFLD - 12wk intervention

  • 58% regressed one fibrosis stage
  • 67% regressed one ballooning stage
  • despite not sig’ weight loss
  • patients who regressed NASH have ~26% improved CRF
31
Q

What did the NASHFit trial study find?

A

PAI-1 improve (-40 vs +70ng/mL)

MRI-PDFF response (40 vs 13%)

VO2 peak fitness gain (+3 vs -1.8mL/kg/min)

32
Q

What are the pros and cons of HIIT in MAFLD patients?

A

Pros:
* comparable reductions in hepatic steatosis
* improve diastolic function and hepatic stiffness

Cons:
* People with metabolic associated steatohepatitis: fatigue, pain, MSK issues and low mood
* would this be appropriate and a feasible option?

33
Q

What did the HIIT 4 NASH study find?

A
  • it was safe
  • feasible - HIIT session and intensity targets met
  • increase Ex capacity
  • increase peripheral insulin sensitivity
34
Q

Provide some clinical considerations.

A
  • generic barriers: time, work, study, travel time
  • multi-morbidty and multiple specialist appts
  • HIIT educations and logistic support
  • feeling safe
  • social connection
  • point of commitment and accountability
35
Q

What is metabolic steatohepatitis-related cirrhosis?

A
  • liver cirrhosis (late stage fibrosis/liver scarring)
  • “compensated” cirrhosis - liver coping with damage, maintaining important function, no overt Sx
  • “decompensated” cirrhosis - liver function compromised, Sx of complications present (ascites, gastroesophageal varices and hepatic encephalopathy)
  • increased sarcopenia risk - frailty, loss of functional ability
  • maintaining functional status and improving QoL goals

Data for Ex lacking - low intensity likely safe for decompensated cirrhosis - but consultation with MDT before starting

Considers for hypercatabolic condition (nutritional Ax and adequate protein and calories)

36
Q

What clinical Ax would we perform as AEPs?

A
  1. cardiometabolic disease risk factors (inc. meds)
  2. comorbidities and MSK conditions
  3. PA Hx, CRF, functional/Ex capacity
  4. patient-important outcomes - fatigue, energy, sleep, Ex-related self efficacy, QoL
  5. barriers/enablers
  6. ? need for referral - dietitian, psychologist, GP/specialist
37
Q

What are some special considerations for Ax and programming?

A
  • low work capacity - due to excess weight
  • MSK
  • multimorbidity
  • CVD risk e..g MI
  • polypharmacy and meds - oral hypoglycaemic agents, beta-blockers, anti-hypertensive agents and lipid lowering meds
38
Q

What are the current research and knowledge gaps in Exercise and Liver disease?

A
  1. effects of Ex on liver fibrosis, steatohepatitis, disease severity
  2. whether Ex can resolve MAFLD in isolation
  3. whether RT in isolation can improve liver fat and other liver and cardiometabolic variables
  4. long-term Ex sustainbility

EXMD4743 (9 decks)

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