RT Book, Section
A1 Chang, Charissa Y.
A1 Friedman, Scott
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102702312
T1 Nonalcoholic Fatty Liver Disease
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessmedicine.mhmedical.com/content.aspx?aid=1102702312
RD 2024/04/19
AB Disease  summary:Nonalcoholic  fatty  liver  disease  (NAFLD)  refers  to  a  spectrum  of  conditions  involving  excess  fat  accumulation  in  the  liver.  The  term  encompasses  conditions  ranging  from  simple  steatosis  to  nonalcoholic  steatohepatitis  (NASH),  which  is  defined  by  histologic  findings  of  steatosis,  inflammation,  ballooned  hepatocytes,  Mallory-Denk  bodies,  and  varying  degrees  of  fibrosis.  Simple  steatosis  is  thought  to  have  a  benign  prognosis,  whereas  a  subset  of  individuals  with  NASH  progress  to  end-stage  complications  of  cirrhosis  and  hepatocellular  carcinoma.  The  pathogenesis  of  NAFLD  has  not  been  clearly  defined;  however,  there  is  a  strong  association  with  metabolic  syndrome  and  insulin  resistance.Differential  diagnosis:Alcoholic  liver  disease,  viral  hepatitis,  autoimmune  hepatitis,  hemochromatosis,  Wilson  disease,  medication-induced  fatty  liver  disease  (amiodarone,  tamoxifen,  valproic  acid,  TPN).Monogenic  forms:There  is  no  single  gene  known  to  cause  NAFLD.  However,  there  are  rare  monogenic  inherited  disorders  of  lipid  metabolism,  insulin  signaling,  and  mitochondrial  function  that  result  in  hepatic  steatosis.  These  disorders  usually  have  other  phenotypic  manifestations  which  dominate  over  hepatic  steatosis.Family  history:Small  studies  in  kindreds  demonstrate  a  higher  prevalence  of  NAFLD  among  first-degree  relatives  of  patients.  One  study  demonstrated  a  59%  prevalence  of  fatty  liver  in  siblings  and  a  78%  prevalence  of  fatty  liver  in  parents  of  children  with  NAFLD.  About  18%  of  patients  with  NASH  have  an  affected  first-degree  relative.Twin  studies:One  study  of  monozygotic  twins  discordant  for  obesity  demonstrated  intrapair  differences  in  liver  fat  that  correlated  with  acquired  obesity,  suggesting  the  presence  of  strong  nongenetic  determinants  of  hepatic  steatosis.Environmental  factors:Western  diets  containing  increased  amounts  of  high  fructose  corn  syrup,  saturated  fats,  and  trans  fats  have  been  implicated  in  rising  obesity  trends  and  increasing  incidence  of  NAFLD.Genome-wide  associations:The  strongest  association  has  been  with  a  single-nucleotide  polymorphism  (SNP)  variant  in  the  PNPLA3  gene  (also  called  “adiponutrin”).  Other  SNPs  have  been  described  in  patients  with  NAFLD  (Table  75-1).  Testing  for  gene  variants  is  not  yet  clinically  validated  for  diagnosis  or  management  of  NAFLD.Pharmacogenomics:There  are  no  known  genetic  predictors  of  response  to  pharmacotherapy.