NASH is currently the second leading cause for LT waitlist registration/liver transplantation overall, and in females, the leading cause. Given the rate of increase, NASH will likely rise to become the leading indication for LT in males as well.

BACKGROUND: Racial, ethnic, and socioeconomic disparities in the survival of patients with hepatocellular carcinoma (HCC) continue to exist. The authors of this report hypothesized that these differences result from inequities in access to care and in response to therapy. METHODS: Patients with HCC (n ¼ 20,920) were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and patients who underwent liver transplantation for HCC (n ¼ 4735) were identified from the United Network for Organ Sharing (UNOS) database. Clinical and pathologic factors were compared after patients were stratified by race and ethnicity. RESULTS: The survival of patients with HCC improved over time for all racial, ethnic, and income groups (P < .001). Black and low income individuals had the poorest long-term survival (P < .001). On multivariate analysis, black race was predictive of the poorest survival (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.09-1.22; P < .001), whereas Asian race was associated with the best survival (HR, 0.87; 95% CI, 0.83-0.91; P < .001). After liver transplantation, black patients had the worst graft survival and overall survival (median survival [MS], 30.5 months and 39.7 months, respectively; P < .001), whereas Hispanics had the best survival (MS, 83.4 months and 86.6 months, respectively; P < .001). In a multivariate analysis of transplantation patients, race and ethnicity were associated significantly with outcome. CONCLUSIONS: Significant racial and ethnic disparities in the outcome of patients with HCC persist despite the receipt of comparable treatment. The authors concluded that further investigations are warranted to identify the reasons for the stark disparity in outcomes between black patients and Hispanic patients after liver transplantation for HCC.

Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions.

Objective The goal of the study was to investigate the genetic and molecular basis of a novel syndrome of marked hyperglucagonemia and pancreatic α cell hyperplasia without glucagonoma syndrome. Methods The glucagon receptor gene (GCGR) and glucagon gene were sequenced in a patient with hyperglucagonemia and pancreatic α cell hyperplasia without glucagonoma syndrome. Enhanced green fluorescent protein (EGFP)-conjugated WT and mutant GCGR were used to characterize the functions of the mutant GCGR. Results The glucagon gene sequence was normal but GCGR sequencing uncovered a homozygous missense mutation, c.256C>T, p.P86S in the extracellular domain of GCGR. When expressed in HEK293 cells, GCGR P86S localized to the plasma membrane but bound 96% less radiolabeled glucagon than WT GCGR. The EC50 of glucagon-induced cAMP production was 24 nM for GCGR P86S but 2.4 nM for WT GCGR. The patient's α cells also express glucagon-like peptide 1 and pancreatic polypeptide. Conclusion We hereby report the first homozygous missense mutation in the human GCGR which is associated with α cell hyperplasia and hyperglucagonemia. This mutation lowers the receptor’s affinity to glucagon and decreases cAMP production with physiological concentrations of glucagon. Thus, the P86S mutation in GCGR likely causes α cells hyperplasia and hyperglucagonemia.

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