PNPLA3 Gene Polymorphism and Liver- and Extrahepatic Cancer-Related Mortality in the United States.

The palatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 G allele is associated with nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma,1 and all-cause or cardiovascular mortality in the general population.2 One recent Italian study reported an association between PNPLA3 polymorphism and liver-related events and mortality in biopsy-confirmed NAFLD.3 Regarding extrahepatic cancer-related mortality, one study showed that only women carrying the G allele without hepatic steatosis had a 60% lower risk for cancer-related mortality.4 However, owing to insufficient follow-up and selected populations, the results from these studies cannot generalize about the association between PNPLA3 polymorphism and liver- and extrahepatic cancer-related mortality at a population level. Thus, we investigated the association between PNPLA3 polymorphism and liver- and extrahepatic cancer-related mortality based on the presence of NAFLD in the U.S. general population.

PNPLA3 gene polymorphism and overall and cardiovascular mortality in the United States.

BACKGROUND AND AIM: The association between palatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) polymorphism and mortality is not well understood. We investigated the impact of PNPLA3 I148M (rs738409) polymorphism on overall and cardiovascular mortality based on the presence of nonalcoholic fatty liver disease (NAFLD). METHODS: The third National Health and Nutrition Examination Survey (NHANES) from 1991 to 1994 and National Health and Nutrition Examination Survey III-linked mortality data through 31 December 2015 were utilized in this study. RESULTS: Of 4814 participants, 50.7% were homozygous for the C-allele and 12.6% were homozygous for the G-allele. During a follow up of 20 years, there were a total of 1255 deaths, 422 attributed to cardiovascular disease. There was a significant association with overall mortality among those with the PNPLA3 I148M (rs738409) GG genotype (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.02-1.77) or G-allele (HR 1.22, 95% CI 1.09-1.36) in the general population. NAFLD with homozygous PNPLA3 I148M (rs738409) GG genotype had higher overall mortality after adjusting for multiple metabolic risk factors (HR 1.45, 95% CI 1.01-2.08). The PNPLA3 I148M (rs738409) G-allele had a tendency of increased cardiovascular mortality in the total population. This association was not noted in those with NAFLD. CONCLUSIONS: The homozygous PNPLA3 I148M (rs738409) GG genotype showed an increase in overall mortality in the general population and NAFLD independent of multiple metabolic risk factors.

Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) may be associated with sarcopenia. This study aims to determine whether sarcopenia is independently associated with NAFLD and advanced fibrosis. PARTICIPANTS AND METHODS: Cross-sectional data from 11 325 participants in the third National Health and Nutrition Examination Survey were analyzed. NAFLD was defined as the presence of hepatic steatosis from the ultrasound. Sarcopenia was defined as the skeletal muscle index. RESULTS: NAFLD was more common in participants with sarcopenia than in those without (46.7 vs. 27.5%). Univariate analysis showed that sarcopenia was associated with NAFLD [odds ratio (OR): 2.31; 95% confidence interval (CI): 2.01-2.64], which remained significant after adjustment for age, sex, ethnicity, metabolic risk factors (OR: 1.24; 95% CI: 1.03-1.48). This finding persisted after adjustment for C-reactive protein as a marker of chronic inflammation. NAFLD-associated advanced fibrosis was more common in participants with sarcopenia than in those without (7.8 vs. 1.6%). Sarcopenia was associated with NAFLD-associated advanced fibrosis independent of metabolic risk factors (OR: 1.79; 95% CI: 1.18-2.72). CONCLUSION: Sarcopenia was independently associated with increased odds of NAFLD and NAFLD-associated advanced fibrosis independent of well-defined risk factors. Interventions to strengthen muscle mass may reduce the burden of NAFLD and advanced fibrosis.

Does Early Endoscopy Improve Mortality in Patients with Acute Non-variceal Gastrointestinal Bleeding? A Retrospective review.

Introduction Initial management of acute upper gastrointestinal bleeding (UGIB) aims towards aggressive fluid resuscitation to maintain hemodynamic stability. Existing evidence regarding the benefit of early endoscopy is unclear with some studies suggesting mortality benefits and some suggesting otherwise. The purpose of this study is to evaluate if there is any mortality benefit of doing early endoscopy within 24 hours of presentation. Methods From July 2013 to July 2016, 179 patients admitted with a diagnosis of non-variceal UGIB were retrospectively reviewed. Clinical variables including 30-day mortality were then compared between the patients who had endoscopy within 24 hours with those who had endoscopy after greater than 24 hours. Results Out of 179 patients admitted for non-variceal UGIB, 146 underwent endoscopy within 24 hours of presentation and 33 underwent endoscopy after 24 hours. The overall mortality associated with UGIB was 6.7% (12/179). There was no statistically significant difference found in 30-day mortality between the two groups (6.8% within 24 hours vs 6.1% after 24 hours). There was also no difference in 30-day readmission or rates of rebleeding among the two groups. The length of stay was also similar in both groups (6.0 days vs 6.1 days). Conclusion This study did not find any advantage of endoscopy within 24 hours on length of stay, rate of complications, and 30-day mortality. As hemostasis is achieved in almost 90% of patients with supportive management without any endoscopic intervention, focus should be made on aggressive fluid resuscitation to achieve hemodynamic stability before endoscopy.

Effect of cold storage and freezing on the biomechanical properties of swine growth plate explants.

Ex vivo biomechanical testing of growth plate samples provides essential information about its structural and physiological characteristics. Experimental limitations include the preservation of the samples since working with fresh tissues involves significant time and transportation costs. Little information is available on the storage of growth plate explants. The aim of this study was to determine storage conditions that could preserve growth plate biomechanical properties. Porcine ulnar growth plate explants (n = 5 per condition) were stored at either 4 °C for periods of 1, 2, 3, and 6 days or frozen at -20 °C with slow or rapid sample thawing. Samples were tested using stress relaxation tests under unconfined compression to assess five biomechanical parameters. The maximum compressive stress (σmax) and the equilibrium stress (σeq) were directly extracted from the experimental curves, while the fibril-network reinforced biphasic model was used to obtain the matrix modulus (Em), the fibril modulus (Ef), and the permeability (k). No significant changes were observed in σeq and Em in any of the tested storage conditions. Significant decreases and increases, respectively, were observed in σmax and k in the growth plate samples refrigerated for more than 48 h and in the frozen samples, when compared with the fresh samples. The fibril modulus Ef of all stored samples was significantly reduced compared to the fresh samples. These results indicate that the storage of growth plates in a humid chamber at 4 °C for a maximum of 48 h is the condition that minimizes the effects on the measured biomechanical parameters, with only Ef significantly reduced. Refrigerating growth plate explants for less than 48 h maintains their maximal stress, equilibrium stress, matrix modulus, and permeability. However, cold storage at 4 °C for more than 48 h and freezing storage at -20 °C significantly alter the biomechanical response of growth plate samples. Appropriate growth plate sample storage will be beneficial to save time and reduce transportation costs to pick up fresh samples.

Isolated duodenal varices as the initial presentation of hepatocellular carcinoma.

Duodenal varices are an uncommon, life-threatening cause of acute gastrointestinal (GI) bleeding commonly caused by portal hypertension. Though generally regarded as a complication of advanced cirrhosis and portal hypertension, often overlooked is that in about 2.7% of cases, it can be the first presenting symptom of advanced hepatocellular carcinoma (HCC). We report a case of an isolated, duodenal variceal bleeding as the first clinical manifestation of HCC, complicated by portal venous thrombosis. Diagnosis of HCC was established by a markedly elevated α-fetoprotein, hepatitis B surface and core antibody positivity and consistent radiological findings. Although not the first choice, variceal bleeding was successfully arrested with endoclips. The patient thereafter declined further evaluation and unsurprisingly died within a few weeks from a massive GI bleed. An initial bleed from a duodenal varix often confers a poor prognosis. Patients with HCC who present with variceal bleeding reportedly have a median survival of 71 days.