Doycheva, Iliana

Abstract Growth hormone and its mediator insulin‐like growth factor‐1 exert their effect on different organs and control various physiologic metabolic processes. Adult growth hormone deficiency (AGHD) presents with one or more components of metabolic syndrome and can be associated with nonalcoholic fatty liver disease (NAFLD). AGHD is present in spectrum of hypothalamic/pituitary disorders as well as cranial radiation of brain tumors and often remains underdiagnosed or untreated due to its nonspecific symptoms, relatively difficult diagnosis in some clinical scenarios, and various barriers to treatment. NAFLD usually develops soon after diagnosis of AGHD and might progress rapidly to nonalcoholic steatohepatitis (NASH) with advanced fibrosis, eventually requiring liver transplantation. A timely initiation of growth hormone replacement therapy might be important, although studies so far have demonstrated controversial results on NAFLD, primarily due to small sample size and different diagnostic methods of NAFLD. Increased awareness of the association between AGHD and NAFLD would facilitate early diagnosis of NAFLD and NASH if present. Therefore, a multidisciplinary approach involving hepatology and endocrinology should become a standard of care for these patients.

AbstractAutoimmune hepatitis (AIH) is a rare immune‐mediated liver disease with few major advances in treatment options over the last several decades. Available options are effective in most patients albeit are imprecise in their mechanisms. Novel and more tolerable induction regimens and alternative options for management of patients intolerant or with suboptimal response to traditional therapies including in the post‐transplant setting remain an important unmet need. This review aims to summarize recent data on pharmacological options and investigational drugs in development for patients with AIH. Standard therapy using prednisone with or without azathioprine remains the mainstay of therapy and is effective in most patients. Budesonide may be considered for induction in early disease and in those with mild fibrosis, but has not been approved for maintenance therapy. Mycophenolate mofetil (MMF) in combination with steroids might be an alternative first‐line therapy, but results from a randomized trial are awaited. MMF as a second‐line maintenance agent has moderate efficacy though more frequent adverse events in patients with cirrhosis may be seen. Tacrolimus may be an equally effective second‐line option particularly in non‐responders, but data remain limited. Management of recurrent AIH post‐liver transplantation remains controversial with insufficient data to support long‐term steroid use. Moving forward, expanding the scope of therapeutic options to include biologics including B‐cell depleting agents may be a promising step. Recent insights in understanding the pathogenesis of AIH could serve as a basis for future therapies, including the elucidation of different immunoregulatory pathways and the potential role of the intestinal microbiome.

Goals: To analyze the frequency and trend of liver transplantation (LT) for nonalcoholic steatohepatitis (NASH) cirrhosis in young adults aged 18 to 40 years and to assess post-LT outcomes in this age group. Background: NASH is currently the fastest-growing indication for LT in US adults. It is believed that NASH is a rare indication for LT among young adults. Study: Using the United Network for Organ Sharing database, we performed a retrospective cohort analysis of all LTs in young adults between 2002 and 2012. Incidence rate ratio was calculated for each indication. Results: A total of 5157 young adults underwent LT over the study period—54% were male, 23% obese. Mean (±SD) age and body mass index were 31.6±6.7 years and 26.3±6.1 kg/m2, respectively. The incidence of LTs performed for NASH cirrhosis increased from 0.53% in 2002 to 4.46% in 2012. NASH was the most rapidly growing indication for LT among all other etiologies with a 14% increment per year (incidence rate ratio, 1.14; 95% confidence interval, 1.09-1.20, P<0.001). The 5-year post-LT outcomes were comparable between NASH and non-NASH recipients, but graft survival was lower and retransplantation cumulative rates were higher in NASH recipients compared with those with other metabolic liver diseases (63.5% vs. 81.4%, P=0.003 and 12.7% vs. 4.2%, P=0.046, respectively). Conclusions: NASH is the fastest-growing indication for LT among young US adults aged 18 to 40 years and now accounts for almost 5% of all LTs in this age group.

Nonalcoholic fatty liver disease (NAFLD) is a significant health burden in adolescents and young adults (AYAs) which has substantially risen in prevalence over the last decades. The occurrence of NAFLD parallels high rates of obesity and metabolic syndrome in this age group, with unhealthy lifestyle also playing an independent role. Genetic factors, sex, and ethnicity should be considered in a risk stratification model. NAFLD and nonalcoholic steatohepatitis (NASH) in AYAs often go unrecognized and, if untreated, can progress eventually to cirrhosis requiring liver transplantation (LT) before the age of 40. Recently, NASH has increased as an indication for LT in this age group. Important knowledge gaps include the feasibility of noninvasive diagnostic tests and imaging modalities as well as uncertainty about unique histological features and their predictive value. Future clinical trials focused on AYAs are needed to determine effectiveness of therapies. Tools for increasing awareness and prevention of NAFLD in AYAs are greatly needed. (H epatology 2017;65:2100‐2109).