title: Administration of anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody for the treatment of osteoporosis was associated with amelioration of hepatitis in a female patient with growth hormone deficiency: a case report.
abstract: BACKGROUND
  Growth hormone deficiency (GHD) is associated with non-alcoholic fatty liver disease (NAFLD). A recent animal study showed that hepatocyte-specific receptor activator of nuclear factor-kappa B (RANK) knockout mice had significantly lower liver fat content compared with control mice concomitant with a decrease in production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) from hepatocytes and kupffer cells. The role of anti-RANK ligand (RANKL) antibody for osteoporosis on hepatitis in patients with aGHD is still unknown.
  
  
  METHODS
  A forty-seven-year-old female patient was referred to our hospital to investigate chronic hepatitis caused by unknown etiology. She had past history of craniopharyngioma treated with craniotomy and post-surgical radiotherapy. She was for the first time diagnosed as panhypopituitarism including growth hormone deficiency and osteoporosis by endocrine examinations and bone mineral densitometry, respectively. In addition, non-alcoholic steatohepatitis (NASH) was histologically confirmed by liver biopsy in this time. Sixty mg anti-RANKL antibody, which was subcutaneously injected to treat the osteoporosis every six months after replacement of 5 mg hydrocortisone and 30 μg oral desmopressin, rapidly decreased the levels of her liver enzymes (ALT and γGTP were 133 to 72 U/L and 284 to 99 U/L at 16 months after the beginning of the treatment, respectively). Additional amelioration of liver dysfunction was not observed after growth hormone replacement.
  
  
  CONCLUSIONS
  The clinical course of the present case suggested that RANKL-RANK signaling may be a key pathological mechanism in establishment or development of NAFLD or NASH in patients with panhypopituitarism including GHD.
authors.affiliation: Internal Medicine 1, Shimane University Faculty of Medicine, 89-1, Enya-cho, Izumo, Shimane, 693-8501, Japan. atakeno@med.shimane-u.ac.jp.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Takeno
authors.affiliation: Internal Medicine 1, Shimane University Faculty of Medicine, 89-1, Enya-cho, Izumo, Shimane, 693-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Internal Medicine 1, Shimane University Faculty of Medicine, 89-1, Enya-cho, Izumo, Shimane, 693-8501, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Notsu
authors.affiliation: Internal Medicine 1, Shimane University Faculty of Medicine, 89-1, Enya-cho, Izumo, Shimane, 693-8501, Japan.
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
mesh_terms: D005260:Female; D006505:Hepatitis / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D007018:Hypopituitarism / Q000150:complications* / Q000175:diagnosis; D008099:Liver / Q000473:pathology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications; D010024:Osteoporosis / Q000150:complications / Q000188:drug therapy*; D053245:RANK Ligand / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D053245:RANK Ligand; C505688:TNFSF11 protein, human
keywords: Denosumab; Growth hormone deficiency (GHD); Non-alcoholic fatty liver disease (NAFLD); Non-alcoholic steatohepatitis (NASH); Receptor activator of nuclear factor-kappa B ligand (RANKL)