I Gede Palgunadi
FK UNRAM/RSUP NTB
Objectives
Order appropriate
screening tests
Initiate appropriate
referrals
Terminology
ALD:
NAFLD:
NASH:
Fatty liver
liver
Normal
Statistics
Alcoholic
liver disease
liver disease
Up to 20-40% adults
6 million children
By 2020
Mortality risk:
Cirrhotics with NAFLD vs hepatitis
C
Sanyal,et
al Hepatology 2006:
et al Gastroenterology and
Hepatology 2009:
No difference
Both
Middle age
Female gender
Over-weight or obese
Viral hepatitis
Iron overload
Medications
Rapid weight loss
Starvation/refeeding
syndrome
Reyes syndrome
Auto-immune disease
Malnutrition
Abetalipoproteinemia
Overgrowth of bacteria in
small intestines
TPN
Acute fatty liver of
pregnancy
HELLP syndrome
Hispanic ethnicity
Hereditary
ovary syndrome
Hypothyroidism
Obstructive sleep apnea
Hypopituitarism
Hypogonadism
Pancreatic-duodenal resection
acid
Highly active antiretroviral therapy
Screening Considerations
AASLD recs
Albumin
AST
ALT
http://nafldscore.com
>
Accidental discovery
AST or
Symptomatic liver disease
AST
elevated
normal
yes
Abstain
no
Imaging study
Echogenic US or fat on CT
May need biopsy
Liver biopsy
AASLD recs
Incidental
Assessment
Symptoms
Physical exam
Labs
Management:
Lifestyle Interventions
Lifestyle Interventions
Weight loss by lower caloric intake and
Management
Medications
Thiazolidinediones
Rosiglitazone**: improved enzymes and steatosis,
but not inflammation
Pioglitazone:***+weight gain, but improvement in
hepatocellular injury
2004
PIVENS Study
with NASH
without DM, cirrhosis, Hep C, heart failure
limited alcohol intake over previous 5 years
Randomized trial
Pio group: 80
Vit E group: 84
Placebo: 83
Sanyal et al, New England J of Medicine 2010
Primary outcome
Vitamin E vs
placebo
43% improvement
vs 19%: significant
(Steatosis, lobular
inflammation,
hepatocellular
ballooning and
fibrosis)
Pio vs placebo
34% improvement vs
19%: not significant
Secondary outcome
Vitamin E vs
placebo
Also reduction in
SGOT/SGPT
Pio vs placebo
Reduction in
SGOT/SGPT
Reduction in steatosis,
lobular inflammation
Improvement in IR
Increase in weight that
did not resolve after
discontinuance of Pio
Sanyal et al, New EngJ of Med 2010
PIVEN Conclusions
Vitamin
AASLD recommendations:
Pio
including 136,000
participants found taking Vitamin E
supplements > 400 IU/day had a
higher risk of all cause mortality
Vitamin E** > 400 IU/day increases
risk of prostate cancer in relatively
healthy men
*Miller et al Annals of Internal Medicine 2005
** Klein, et al, JAMA 2011
acid*
no histologic benefit
Omega-3
fatty acids**
Statins
CVD
GREACE study*
Concluded statins significantly
improve liver biochemistries and
CV outcomes in pts with elevated
enzymes likely due to NASH
AASLD Recommendation on
Statins
Given lack of evidence that patients
with NAFLD and NASH are at
increased risk for serious druginduced liver injury from statins, they
can be used to treat dyslipidemia in
patients with NAFLD and NASH.
Bariatric surgery
No RCTs
Cochrane review 2010: lack of RCTs prevents
definitive assessment of risks/benefits
Prospective study*
AASLD Recommendation on
Bariatric Surgery
Premature
Transplant Considerations
MS & Immunosuppression
Steroids
BP
lipid metabolism
gluconeogenesis
utilization
induce IR
weight gain
peripheral glucose
Nephrotoxicity
TAC - glucose intolerance and de novo DM
CSA - HTN and hyperlipdemia
mTOR inhibitors
hyperlipidemia
Metabolic Syndrome
in Kidney Transplant*
Metabolic
Metabolic Syndrome
in Kidney Transplant
Prevalence
of MS post KTx
22.6% at 1 year*
37.7% at 18 months*
63% at a median of 6 years**
* Porrini et al, Amer J of Kid Dis 2006
** de Vries et al, Amer J of Trans 2004
Metabolic Syndrome
in Kidney Transplant
MS
Metabolic Syndrome
in Kidney Transplant: Blood
Pressure
Choice of antihypertensive post KTx:
Cochrane Group Review
http://summaries.cochrane.org/CD00359
8/
blood-pressure-medication-for-kidneytransplant-recipients
Metabolic Syndrome
in Kidney Transplant:
Hyperlipdemia
ALERT trial*
Randomized, double blind, placebo control (N=1100)
Fluvastatin was superior to placebo in significantly
lowering total and LDL cholesterol in renal transplant
pts and in lowering rates of cardiac death and MI
transplant obesity
TAC based regimen
DM
Hyperglycemia
HTN
ETOH as primary cause for transplant
Pre-transplant allograft biopsy
showing steatosis
*Dumortier, et al Am J of Gastro March 2010
Obesity
Between 1990 and 2002 the % of obese OLT
recipients increased from 15% to 25% and average
increase of 1kg/year*
Orlistat (tetrahydrolipstatin)** Limited efficacy
May interfere with drug absorption
post OLT
High Triglycerides:
fish oils
Fenofibric acids derivatives: reduction in TAC/CsA dose???
ezetimide
* Watt & Charlton J Hepatology 2010
Differences observed
in MS group
No difference MS vs
nonMS
Gender
Underlying etiology
Smoking
DM history pre-tx
Immunosuppression
Special Considerations
0.02% at year 4
0.19% at year 8
0.51% at year 12
at 35-36 weeks
Mitochondrial dysfunction preventing
oxidation of FFA which accumulate in liver
Presents with malaise, N/V in 3 rd trimester,
RUQ pain, UGI bleed, ARF, FHF, confusion,
HTN, jaundice, hypoglycemia
Mortality: maternal 12.5-18%, infant 7-66%
Postpartum: may resolve or proceed to
needing a transplant
Pediatric Issues
Hispanic ethnicity
HTN
IR
Pediatric Issues
Alcohol
Inborn errors of metabolism
Storage disorders
Wilsons disease
Auto-immune hepatitis
Cystic fibrosis
Viral hepatitis
panel recommendations:
Biannual AST/ALT starting at age 10
in obese children and those whose
BMI >85% percentile with other risk
factors*
AASLD has no recommendations
* Barlow et al. Pediatrics 2007
AASLD Pediatric
Recommendations
Intensive lifestyle behavior
modification, including dietitian
consultation, is first line treatment
Metformin 500mg BID offers no benefit
Vitamin E 800 IU/d offers histological
benefit but confirmatory studies are
needed before it can be recommended
in clinical use.