NAFLD and NASH Part II Flashcards
Wha may excess fat and fructose within the diet lead to?
Intestinal dysbiosis
Describe intestinal dysbiosis and how it relates to NAFLD
Microbes slip through the intestinal epithelium, as there is increased intestinal permeability, and will contribute to fatty and apoptotic hepatocytes and fibrosis
The severity of nonalcoholic fatty-liver disease is associated with what? (2)
- Gut dysbiosis
- Shift in the metabolic function of the gut microbiota
What is diagnostic of NASH?
Inflammation and steatosis
What indicates that NASH has progressed?
Liver fibrosis, staging, cirrhosis
NAFLD can sometimes be ____
a slient disease
How is NAFLD usually discovered?
Incidental LFT, bright liver on imaging or hepatomegaly during routine check ups
NAFLD is _____ and frequently ___
frequent
aysmptomatic
79% with NAFLD have normal/abnormal ALT
NORMAL
What is the be considered about ALT and NAFLD?
That both high and normal ALT levels can be associated with the progression of the disease, and no cut-off designated for predicting NASH or advanced fibrosis
We know that ALT is inaccurate is assessing NAFLD, what are other ways to asses? (3)
- Biopsy
- Imaging
- Biomarkers
How does transient elastrography (fibroscan) work?
The stiffer the liver, the FASTER the shear wave propagate the underlying tissue, measuring CAP (Controlled Attenuation Paramete)
_____ is the single most important predictor of mortality
Fibrosis
Describe the increasing prognostic value
Ballooning –> NASH –> Portal inflammation –> Fibrosis –>Advanced fibrosis
What increases with fibrotic stage?
Liver-related and all-cause mortality
What is the essential test for diagnosing NASH?
Liver biopsy showing steatosis, hepatocyte ballooning and lobular inflammation
Why is it unadvised to use clinical, biochemical or imaging measures when diagnosing NASH?
Cannot distinguish NASH from steatosis
NAFLD can progress to ___
NASH
Clinical predictors of NASH in patients with NAFLD?
- Advanced Age
- Sex
- Race
- HTN, central obesity, dyslipidemia, insulin resistance/diabetes
- AST/ALT ration >1, low platelets
- Persistently elevated ALT
Advanced age?
Greater duration of disease
Sex?
Post-menopausal women experience accelerated disease
Race?
Incr. in hispanic, asian and decr. in blacks
HTN, central obesity, dyslipidemia, insulin resistance/diabetes?
Increase risk wih MetS
60% prevalence of fibrosis if older that 50 y/o AND obese or diabetic?
If pt initially presents with NAFLD
Persistently elevated ALT?
Greater risk of disease progression
Gold standard of NAFLD diagnosis?
Liver biopsy
Discuss the importance of lifestyle in NAFLD
Unhealthy lifestyle will play a role in the development and progression of NAFLD. Assessment of dietary and PA habits is part of comprehensive NAFLD screening.
____ is needed for NASH improvement
Weight-loss
Weight loss >/= 10?
Reduces fibrosis in 45% of cases
Weight-loss >/= 7% ?
NASH resolution in 64-90%
Weight loss >/= 5% ?
Reduces ballooning/inflammation in 41-100%
Weight loss >/= 3%?
Steatosis improves in 35-100%
______ can improve NASH and fibrosis
Bariatric surgery
Macronutrient recommendations?
- Low-to-mod fat and mod-to-high CHO intake
- Low-CHO keto diet or high-protein
- Med diet
Fructose recommendations?
Avoid, contributes to intestinal dysbiota
PA recommendations?
150200 min/week of mod intensity PA
-Resistance training
What should be considered about PA?
Patient may be experiencing fatigue, and reduce compliance with PA
Energy restriction recommendations?
500-1000 kcal res./week
- 7-10% weight loss
- Long-term maintenance
Bottom line on coffee
Protective in NAFLD in reducing histological severity and liver-related outcomes
Alcohol in NAFLD?
Recall that NAFLD is CV risk factor, and alcohol can red. CV risk –> recommended 1 drink/day
Bottom line on alcohol?
Moderate alcohol consumption (wine) below the risk threshold is associated with lower prevalence of NAFLD, NASH and lower fibrosis and histology.
What are recommendations below the risk threshold for alcohol consumption?
30 g men
20 g women
When is total abstinence of alcohol mandatory?
NAHS-cirrhosis, reduce the risk of HCC risk
Paradox with alcohol?
Major risk factor for the global disease burden and results in significant loss of health
Alcohol and cancer risk?
Risk of death from all causes, and cancers in particular, increase as consumption is increased.
What else may be recommended in liver disease?
Vit E supplements (Not an official recommendation)
Pioglitazone (T2DM medication)
Why is Vit E not an official recommendation?
- Not recommended without a liver biopsy
- Not recommended in mild NAFL with no evidence of NASH
- Not recommended in diabetes or cirrhosis
When should caution be exerted with Vit E supplementation?
Older men, uncontrolled HTN, Hx of prostate cancer, PMx of stroke/prostate cancer
When is pioglitazone recommended?
For biopsy-proven NASH with diabetes or pre-diabetes
What should be monitored when on pioglitazone?
- Body weight
- ALT and AST
- DEXA scan
When should pharmacological agents be used?
Reserved with patients with biopsy-proven NASH, and with significant fibrosis.
Who else are candidates for pharmacological agents?
Less severe disease but at risk fo progression (diabetes, metS, ALT, inflammation)
What is recommended for pts with steatosis alone?
Focus on CVD risk factor modification in primary care, no need for liver clinic
How is fibrosis screened?
Surveillance for HCC/varices
Treatments for fibrosis?
- Life style intervention/co-morbidities treatment
- Bariatric surgery
- Pharmacotherapy
Most likely cause of death in NAFL/NASH stage 0?
CVD event or extrahepatic cancer
Most likely cause of death in NASH stage 1-2?
- CVD event/extahepatic cancer
- Liver-related disease q
Most likely cause of death in NASH stage 3-4?
Liver-related diseases
Which drug is mostly administered in end-stage NASH?
Selonsertib
What is recommended for diabetics with NAFLD?
Glycemic control, pioglitazone
When may 800 UI of Vit E be recommended?
Non-diabetics
Surgical options for NAFLD?
Bariatric surgery, liver transplantation
When a patient has fibrosis/cirrhosis, what next?
treatment and screning for cirrhosis/esophageal varices
What is occult cirrhosis?
No sign indicating such diagnosis to clinical
What are clinical signs of cirrhosis?
- Thrombocytopenia
- Ultrasound signs of liver disease
- Splenomegaly
- Varices
- Ascites
When should Hepatocellular Carcinoma (HCC) be screened for pt with NASH cirrhosis?
Every 6 months, where HCC in NAFLD have worse survival
HCC in NAFLD are less likely to have ____
curative Tx
Should we screen “at-risk” patients for NAFLD/fibrosis?
In Europe, Yes
In the US, no
But we should
What may indicate a high-risk patient who may benefit from screening?
- Age >50 y/o
- T2DM
- Obesity, dyslipidemia
- HIV +
- NAFLD at 50-90%
What does the MUHC conclude about liver screening?
Diabetic patients have a high prevalence of NAFLD and advanced fibrosis, where those with obesity and dyslipidemia are at high risk –> SCREEN!
What other group may be at increased risk for NAFLD, liver fibrosis and cirrhosis?
Inflammatory bowel disease
Metabolic risk factors —> Ultrasound/fibroscan screening —> steatosis present —> Normal liver enzymes —> Serum fibrosis markers Low risk?
continue to follow-up with liver enzymes in 2 yrs.
Metabolic risk factors —> Ultrasound/fibroscan screening —> steatosis present —> Normal liver enzymes —> Serum fibrosis markers med/high risk?
Refer to specialist, and identify other chronic liver diseases, assess severity, may perform biopsy
Metabolic risk factors —> Ultrasound/fibroscan screening —> steatosis present —> Abnormal liver enzymes?
Refer to specialist, and identify other chronic liver diseases, assess severity, may perform biopsy
Metabolic risk factors —> Ultrasound/fibroscan screening —> steatosis ABSENT —> Normal liver enzymes ?
Follow-up 3/5 yrs with ultrasound/liver enzymes
Metabolic risk factors —> Ultrasound/fibroscan screening —> steatosis ABSENT —> Abnormal liver enzymes?
Refer to specialist, and identify other chronic liver diseases, assess severity, may perform biopsy
NAFLD is the most _____ in western countries
frequent
NADLT is ______ disease which requires a multi-disciplinary approach
multi-system
What is the strongest prognostic predictor?
Liver fibrosis stage, where 3-4 has the worst prognosis
