MAFLD, ETOH, autoimmune RPA Flashcards
MAFLD comprises of
NAFLD (simple steatosis)
NAFL (ballooning degeneration +/- fibrosis)
NASH (inflammation)
Cirrhosis
Cryptogenic cirrhosis
MAFLD is associated with
Obesity
T2DM
Dyslipidaemia
Metabolic syndrome
70-90% in obese or T2DM have MAFLD
20-30% general population
Alternative causes
ETOH
Genetic causes - PNPLA3
Nutritional causes
What is Lean NAFLD?
NAFLD in the absence of obesity 20% Europeans, Americans Associated with increased visceral obesity, high fructose and fat intake and genetic risk factors Sedentary Insulin resistant High plasma TG levels Increased CV risk
Investigations of suspected MAFLD
Suspect in those with…
Obesity/metabolic syndrome
Abnormal LFTs (most will be normal) or changes in USS findings
Do... LFTs Fasting lipids Albumin FBC - platelet Hep serology ANA HbA1c Liver USS BP measurement BMI, waist circumference
Consider…
Abdo CT, USS
Liver USS
Exclude other diseases (not everyone needs a full liver screen)
Risk factor for fibrosis progression in MAFLD
Old age >50 High BMI >28 Rapid weight gain >5kg Necroinflammaatory activity (biopsy) ALT >2x ULN (and rising) AST/ALT >1 Elevated TG Insulin resistance DM
Tools to assess fibrosis in MAFLD
MAFLD fibrosis score
- Age, BMI, hyperglycaemia, platelet, albumin, AST/ALT ratio
- Good for ruling in and out but grey zone
Enhanced liver fibrosis panel
Fibroscan
- Good for excluding fibrosis or correlating with fibrosis if high score
- High failure rate if high BMI
What do most MAFLD die from?
More likely to die from CV disease than liver disease
Hence even if they have zero fibrosis, still important to manage metabolic risk factors
Also increases risk of malignancy including breast ca, HCC, colorectal ca
Management MAFLD
Diet
- Mediterranean diet has positive benefits
- Composition of diet is important not just weight loss
- Coffee is beneficial
Exercise
Target insulin resistance
Weight loss aim for 7-10%
Bariatric surgery
- best evidence due to biggest weight loss
- CI: portal HTN, cirrhosis
Vitamin E in non-diabetic, non-cirrhotic NASH (not used much)
Metformin and statin may be beneficial
No therapeutic drugs are approved at the moment (lots in trial, published)
Hyperferritinaemia in MAFLD
High ferritin very common in NASH
Associated with fibrosis severity and increased all cause mortality
Increased ferritin stores in liver is uncommon
PHELOBOTOMY IS NOT RECOMMENDED
ETOH in MAFLD
Don’t consume heavy amounts
But no recommendation re complete abstinence or light ETOH
Liver transplant in MAFLD - how common is it?
Currently number 2 indication in Aust/USA
Liver transplant in MAFLD - what other procedure should we consider at the same time?
Concomitant sleeve gastrectomy during transplant or after
If not, NAFLD can recur in the graft
What’s a tool used in excess ETOH screening?
AUDIT tools
Do all heavy drinkers develop alcoholic liver disease?
No
Genetic factors involved
Risk factors for development and disease progression in alcoholic liver disease?
Amount and duration of ETOH
Women
Genetic factors
Diagnostic tests for alcoholic liver disease
Indirect markers GGT ALT AST MCV
Direct markers EtG EtS PEth - new favourite, marker on red cells of ETOH exposure (similar to HbA1c) FAEEs
Evaluation of severity in alcoholic hepatitis
Maddrey DF score
- >=32 severe
Rx alcoholic hepatitis
Prednisolone +/- NAC
improvement, just stop the steroids.
Criteria for liver transplant in alcoholic liver disease
> 6/12 alcoholic abstiencne
Adequate social support
Review by psychiatrist and drug and EOH team
Concern in patients with active smoking, personality disorder, psychosis, history of ETOH dependence
Some Australian centres are offering liver transplant in 1st alcoholic hepatitis
Clinical features autoimmune hepatitis
Elevated AST, ALT Often jaundice, anorexia, fatigue Female, bimodal age (young and old) Hypergammaglobulinaemia Ciruclating autoantibdies HLADR3 or DR4 Negative viral markers 1/3 adults have cirrhosis at presentation
Need liver biopsy - ‘typical’ findings
Rx autoimmune hepatitis
Prednisolone +/- azathioprine
Induction therapy (40-60mg pred +/- azathioprine) followed by maintenance therapy once clinical and biochemical remission is achieved
Very high chance of relapse after stopping treatment
May require life-long low dose therapy
Aim normal AST, ALT and IgG levels
Treatment failure. Consider adding Cyclosporin Tacrolimus 6-MP Mycophenolate mofetil (most experience, particularly those that don't tolerate AZA)
Prognosis of autoimmune hepatitis
90% mortality at 10 years without treatment
If treated, good prognosis at 10 years even if there is cirrhosis
Needs ongoing monitoring lifelong
PBC clinical features
95% women
Cholestatic disorder
Positive AMA or ANA
Most diagnosed are asymptomatic now
Typical histology findings but biopsy not done that often
Clinical diagnosis of PBC
Elevated ALP + AMA at a titre >1:40 is diagnostic
Titre does not correlate with severity, stage or progression
AMA positive with normal LFTs
What does it mean?
Predicts the eventual development of PBC
Wait until abnormal LFTs before treatment
Rx PBC
Ursodeoxycholic acid (UDCA)
- Improves biochemical parameters, reduces death or LTx, delays progression in early stage PBC
- Put them on this ASAP
- The earlier you treat the better, especially when there is a biochemical response
Pruritis is a big problem
- Cholestyramine, rifampicin
- Fibrates is getting more data now
AIH/PBC overlap syndrome
Rx
Determine which is the dominant issue
May need biopsy
Need immunosuppression
PSC clinical features
Chronic, slowly progressive
Rare
Males
Age 30-40
PSC is associated with …
IBD
Cholangiocarcinoma, HCC and colorectal cancer
Prognosis PSC
Poor
Cirrhosis is common 1-2 decades post Dx
PSC and IBD (especially UC)
What screening do we need to do?
Increased risk of colorectal ca
Need annual colonoscopy screening even after liver transplant
How to diagnose PSC?
MRCP for diagnosis - see typical biliary strictures in the extra and intrahepatic bile ducts
ANCA positive
Biopsy is not usually indicated. Unless diagnosis is uncertain.
PSC Worsening cholestasis Weight loss Raised serum Ca19-9 New or progressive dominant stricture
What are we worried about?
Cholangiocarcinoma
Management of PSC
No medical therapy available
Currently just symptomatic treatment available
- Treat itch, recurrent bacterial cholangitis
- Treat dominant strictures (dilatation > strictures)
- Treat portal HTN
Urseodeoxycholic acid low dose may have some disease modifying effect, but high dose may make things worse
Majority will require transplant(s) but up to 20% will have recurrent PSC
IgG4 related systemic disease
Who does it affect?
What conditions is it associated with?
Increased serum IgG4
Biopsy evidence of IgG4 producing plasma cells
Elderly men mostly
Associated with autoimmune pancreatitis (most common), Sjogrens syndrome, tubulointerstitial nephritis, retroperitoneal fibrosis, autoimmune hepatitis, autoimmune cholangitis resembling PSC
IgG4 related systemic disease Rx
Highly responsive to Steroids
