Recombinant human growth hormone increases albumin and prolongs survival in patients with chronic liver failure: A pilot open, randomized, and controlled clinical trial

Li, N.; Zhou, Lihong; Zhang, B.; Dong, Paul R; Lin, Wei; Wang, H.; Xu, Ruiping; Ding, Heyu

doi:10.1016/j.dld.2007.11.011

Cited by 14 publications

(10 citation statements)

References 14 publications

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“…Our study suggests that previous treatment of liver‐transplant patients with HLA‐G or with rhGH or both will be beneficial in suppressing inflammation, and this together with the other positive hepatic actions of GH may also account for the striking decrease in mortality reported in patients with liver failure following administration of rhGH. ( 50 )…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2‐Bl/HLA‐G

et al. 2020

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BaCKgRoUND aND aIMS: Growth hormone (GH) is important for liver regeneration after partial hepatectomy (PHx). We investigated this process in C57BL/6 mice that express different forms of the GH receptor (GHR) with deletions in key signaling domains. appRoaCH aND ReSUltS: PHx was performed on C57BL/6 mice lacking GHR (Ghr −/−), disabled for all GHdependent Janus kinase 2 signaling (Box1 −/−), or lacking only GH-dependent signal transducer and activator of transcription 5 (STAT5) signaling (Ghr391 −/−), and wild-type littermates. C57BL/6 Ghr −/− mice showed striking mortality within 48 hours after PHx, whereas Box1 −/− or Ghr391 −/− mice survived with normal liver regeneration. Ghr −/− mortality was associated with increased apoptosis and elevated natural killer/natural killer T cell and macrophage cell markers. We identified H2-Bl, a key immunotolerance protein, which is up-regulated by PHx through a GH-mediated, Janus kinase 2-independent, SRC family kinase-dependent pathway. GH treatment was confirmed to up-regulate expression of the human homolog of H2-Bl (human leukocyte antigen G [HLA-G]) in primary human hepatocytes and in the serum of GH-deficient patients. We find that injury-associated innate immune attack by natural killer/natural killer T cell and macrophage cells are instrumental in the failure of liver regeneration, and this can be overcome in Ghr −/− mice by adenoviral delivery of H2-Bl or by infusion of HLA-G protein. Further, H2-Bl knockdown in wild-type C57BL/6 mice showed elevated markers of inflammation after PHx, whereas Ghr −/− backcrossed on a strain with high endogenous H2-Bl expression showed a high rate of survival following PHx. CoNClUSIoNS: GH induction of H2-Bl expression is crucial for reducing innate immune-mediated apoptosis and promoting survival after PHx in C57BL/6 mice. Treatment with HLA-G may lead to improved clinical outcomes following liver surgery or transplantation. (Hepatology 2020;0:1-17). T he innate immune system has been shown to play a major role in liver regeneration, with key roles being attributed to hepatic natural killer (NK) and natural killer T cells (NKT), the major resident lymphoid cell populations that are located

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Section: Discussionmentioning

confidence: 99%

Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2‐Bl/HLA‐G

et al. 2020

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“…A relatively high dose of GH (0.25 IU/kg body weight) administration for 7 days significantly increased serum IGF-I levels and improved nitrogen balance in these patients. Interestingly, a prospective randomized study demonstrated that rhGH administration significantly improved the prognosis of the patients with chronic liver failure, suggesting a beneficial effect of GH on a life expectancy [ 90 ]. A pilot study showed that IGF-I administration in cirrhotic patients improved serum albumin and energy metabolism after 120 days [ 91 ].…”

Section: The Clinical Applications Of Gh and Igf-i In Nash And Cirmentioning

confidence: 99%

The Role of Growth Hormone and Insulin-Like Growth Factor-I in the Liver

Takahashi

2017

IJMS

153

109

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Adult growth hormone deficiency (GHD) is characterized by metabolic abnormalities associated with visceral obesity, impaired quality of life, and increased mortality. Patients with adult GHD show increased prevalence of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), and growth hormone (GH) replacement therapy has been shown to improve these conditions. It has also been demonstrated that a decrease in the GH insulin-like growth factor-I (IGF-I) axis is closely associated with the progression of general NAFLD, suggesting a physiological role of these hormones for the maintenance of the liver. NASH histologically demonstrates inflammation, necrosis, and fibrosis, in addition to steatosis (and is a serious disease because it can progress to liver cirrhosis and hepatocellular carcinoma in a subset of cases). While fibrosis determines the prognosis of the patient, efficacious treatment for fibrosis is crucial; however, it has not yet been established. Recent studies have clarified the essential roles of GH and IGF-I in the liver. GH profoundly reduces visceral fat, which plays an important role in the development of NAFLD. Furthermore, GH directly reduces lipogenesis in the hepatocytes. IGF-I induces cellular senescence and inactivates hepatic stellate cells, therefore ameliorating fibrosis. IGF-I treatment has been shown to improve animal models of NASH and cirrhosis, suggesting potential clinical applications of IGF-I in these conditions. In this review, I will focus on the important roles of GH and IGF-I in the liver, their underlying mechanisms, and their potential therapeutic applications.

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“…Following rhGH treatments, altered amounts and plasma concentrations of albumin have been noted in humans [37,38] and rats [39]. It is possible that, in this study, the albumin was increased by the rhGH treatment.…”

Section: Pharmacokinetics Of Carbamazepinementioning

confidence: 78%

“…The plasma protein binding of CBZ is 60% to 80% in rats [36]. It is reported that rhGH can alter the amount and plasma concentrations of albumin in humans [37,38], depending on the dose and the duration of the growth hormone treatments. Also, growth hormone has been shown to increase albumin concentrations in rats [39].…”

Section: Pharmacokinetics Of Carbamazepinementioning

confidence: 99%

Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

Lin

Lee²,

Ravis³

2013

Clin Exp Pharmacol

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Objectives: To investigate the pharmacokinetics of Carbamazepine (CBZ) in rats during growth hormone treatment.Methods: Recombinant Human Growth Hormone (rhGH) was injected subcutaneously at a daily dose of 0.1 mg/ kg, 2 mg/kg, or phosphate buffered saline (control) for 5 days in male Sprague-Dawley rats. On day 6, a dose of 25 mg/kg of CBZ was injected intravenously via a jugular vein cannula into the rat. Growth rate were compared between treatment groups. The pharmacokinetics of CBZ was determined from its concentrations in rats' blood and urinary samples.Results: Over the 5-day treatment period, growth rate were greater than control for the 2 mg/kg rhGH dosed group. The volume of distribution (V ss ) was significantly (p<0.05) decreased in the high dosed rhGH rats compared to the control group. Total body clearance (CL) in the 2 mg/kg rhGH group was also significantly (p<0.05) decreased compared with the control group (0.497 ± 0.076 L/hr/kg vs 0.685 ± 0.109 L/hr/kg). Urinary data showed that renal and metabolic clearances were both significantly (p<0.05) decreased in the 2 mg/kg rhGH group. Conclusions:A dose dependent effect of rhGH was observed on growth rates and CBZ pharmacokinetics in rats. After 5 days rhGH treatment, the volume of distribution of CBZ was significantly changed in the 2 mg/kg/day rhGH treated groups. In the 2 mg rhGH/kg treated rats, both renal and metabolic clearance of CBZ were also significantly decreased compared with the control group. Similar decreases in volume of distribution and both clearances may suggest the interaction may involve increased CBZ plasma protein binding during rhGH treatment in rats.

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Recombinant human growth hormone increases albumin and prolongs survival in patients with chronic liver failure: A pilot open, randomized, and controlled clinical trial

Cited by 14 publications

References 14 publications

Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2‐Bl/HLA‐G

Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2‐Bl/HLA‐G

The Role of Growth Hormone and Insulin-Like Growth Factor-I in the Liver

Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

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