Hepatocellular Carcinoma in Patients Without Cirrhosis: The Fibrosis Stage Distribution, Characteristics and Survival.

BACKGROUND: The data on hepatocellular carcinoma (HCC) patients without liver cirrhosis is scarce. AIMS: To study the epidemiology, underlying etiology and fibrosis distribution in noncirrhotic HCC and compare the survival outcomes to cirrhotic HCC. METHODS: We conducted a retrospective study including all adult patients diagnosed with HCC at two US tertiary academic centers from 2000 to 2015. Univariable and multivariable Cox regression analyses were performed to evaluate the variables associated with patient survival. RESULTS: Two thousand two hundred and thirty-seven HCC patients were included in the final analysis, of which, 13% had no liver cirrhosis. The most common underlying liver disease in non-cirrhotic patients was cryptogenic cause (40%), followed by nonalcoholic fatty liver disease (NAFLD) (25.2%) and hepatitis C (19%). The percentage of F0-F1, F2, and F3 was 72%, 17%, and 11% (cryptogenic cause); 69%, 12%, and 19% (NAFLD); 50%, 17%, and 33% (alcohol); 33%, 39%, and 28% (hepatitis B); 20%, 40%, and 40% (hemochromatosis); and 12%, 40%, and 48% (hepatitis C), respectively. In non-cirrhotic compared to cirrhotic patients, the tumor was more likely to be larger and fell outside Milan criteria (all p < 0.001). Cirrhotic patients had significant shorter survival than non-cirrhotic patients (p < 0.001). On the multivariable analysis, having liver cirrhosis (HR 1.48; 1.21-1.82, p < 0.001), combined viral hepatitis and alcohol use (HR 1.51; 1.23-1.88, p < 0.001), morbid obesity (HR 1.31; 1.01-1.69, p = 0.040) and underweight (HR 2.06; 1.27-3.34, p = 0.004) were associated with worse patient survival. CONCLUSIONS: The fibrosis distribution in non-cirrhotic HCC differed among each etiology of liver diseases. Despite more advanced HCC, patients without cirrhosis had significantly longer survival than those with cirrhosis.

Chemopreventive Effect of Statin on Hepatocellular Carcinoma in Patients With Nonalcoholic Steatohepatitis Cirrhosis.

INTRODUCTION: To estimate the annual incidence of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis, to determine the risk factors for the development of HCC, and to evaluate the chemoprotective effect of statin use stratified by fibrosis stage. METHODS: We conducted a retrospective study at 2 US tertiary academic centers, including patients with NASH-related advanced liver fibrosis (bridging fibrosis [F3] and cirrhosis [F4]) followed between July 2002 and June 2016. Patients were followed from the date of diagnosis to the time of last abdominal imaging, liver transplantation, or HCC diagnosis. Multivariable Cox regression analysis was performed to evaluate the risk factors associated with HCC development, stratified by fibrosis stage. RESULTS: A total of 1,072 patients were included: 122 patients with F3 fibrosis and 950 patients with cirrhosis. No HCC was observed during 602 person-year follow-up among F3 patients. Among patients with cirrhosis, HCC developed in 82 patients with the annual incidence rate of 1.90 per 100 person-years (95% confidence interval [CI], 1.53-2.35). Multivariable analysis in patients with cirrhosis demonstrated that HCC development was associated with male sex (hazard ratio [HR] 4.06, 95% CI, 2.54-6.51, P < 0.001), older age (HR, 1.05, 95% CI, 1.03-1.08, P < 0.001), and CTP score (HR, 1.38, 95% CI, 1.18-1.60, P < 0.001). Statin use was associated with a lower risk of developing HCC (HR, 0.40, 95% CI, 0.24-0.67, P = 0.001). Each 365 increment in cumulative defined daily dose of statin use reduced HCC risk by 23.6%. DISCUSSION: Our findings suggest that patients with NASH and bridging fibrosis have a low risk of HCC. Dose-dependent statin use reduced HCC risk significantly in patients with NASH cirrhosis.

Utility of Endoscopy in Hospitalized Patients with Gastrointestinal Hemorrhage and Pulmonary Hypertension.

BACKGROUND: Gastrointestinal hemorrhage (GIH) has been reported as one of the most common GI complications in patients with pulmonary hypertension (PH). There is paucity of data on the national burden of GIH in patients with PH. We aimed to assess the prevalence, trends and outcomes of endoscopic interventions in patients with PH who were admitted with GIH. METHOD: We queried National Inpatient Sample (NIS) database from 2005 to 2014 and identified the patients hospitalized with primary or secondary discharge diagnosis of PH (ICD 9 CM Code: 416.0, 416.8, and 416.9). Using Clinical Classification Software Coding system (153) patients with concurrent diagnosis of GIH were then identified. We studied the prevalence and trends of GIH in PH, factors associated with GIH, use of endoscopy, factors associated with utilization of endoscopic interventions, endoscopy outcomes including mortality, and overall healthcare burden. RESULTS: Out of 7,586,973 PH hospitalizations 3.2% (N = 246,358) had concurrent GIH, with a rising prevalence of GIH in PH patients during the last decade. Clinical predictors for GIH in PH included older age, congestive heart failure, anticoagulation therapy and concurrent alcohol abuse. Mean length of stay (LOS) in PH patients hospitalized with GIH was significantly higher than without GIH (8.6 vs. 6.4 days, p < 0.01) along with a significant increase in hospitalization cost ($20,189 vs. $14,807, p < 0.01). Similarly, odds of in-hospital mortality increase by ~ 1.5 times in PH patients with GIH than those without it (adjusted odds ratio [aOR: 1.45, 95%CI: 1.43-1.47]). Endoscopic interventions were performed in 48.6% of patients with PH and GIH during their hospitalization. Older patients were more likely to undergo endoscopy, as well as the patients who received blood transfusion, and those with hypovolemic shock. Patients with acute respiratory failure and acute renal failure were less likely to get endoscopy. Mean LOS in patients undergoing endoscopic intervention was significantly higher than those who did not receive any intervention (8.7 vs. 8.4 days, p < 0.01), without a substantial increase in hospitalization cost ($20,344 vs. $20,041, p < 0.01). Also, there was a significant decrease in in-hospital mortality in patients undergoing endoscopic interventions. CONCLUSION: Concurrent GIH in patients with PH increases length of stay; healthcare costs and increases in-hospital mortality. Use of endoscopic interventions in these patients is associated with reduced length of stay, in-hospital mortality without significantly increasing the overall health care burden and should be considered in hospitalized patients with PH who are admitted with GIH. Future studies comparing GIH patients with and without PH should be done to assess if PH is a risk factor for worse outcomes. CLINICAL TRIAL REGISTRATION NUMBER: No IRB required due to use of national de-identified data.

Short-Bowel Syndrome: Epidemiology, Hospitalization Trends, In-Hospital Mortality, and Healthcare Utilization.

INTRODUCTION: Short-bowel syndrome (SBS) is a common cause of chronic intestinal failure and is associated with increased morbidity, mortality, poor quality of life, and an increased burden on healthcare costs. METHODS: We used the US Nationwide Inpatient Sample database from 2005 to 2014. We identified adult SBS hospitalizations by using a combination of International Classification of Diseases, Ninth Revision, Clinical Modification codes. We studied the demographics of the patients with SBS and analyzed the trends in the number of hospitalizations, in-hospital mortality, and healthcare costs. We also identified the risk factors associated with in-hospital mortality. RESULTS: A total of 53,040 SBS hospitalizations were identified. We found that SBS-related hospitalizations increased by 55% between 2005 (N = 4037) and 2014 (N = 6265). During this period, the in-hospital mortality decreased from 40 per 1000 to 29 per 1000 hospitalizations, resulting in an overall reduction of 27%. Higher mortality was noted in SBS patients with sepsis (6.7%), liver dysfunction (6.2%), severe malnutrition (6.0%), and metastatic cancer (5.4%). The overall mean length of stay (LOS) for SBS-related hospitalizations was 14.7 days, with a mean hospital cost of $34,130. We noted a steady decrease in the LOS, whereas the cost of care remained relatively stable. CONCLUSIONS: The national burden of SBS-related hospitalizations continues to rise, and the mortality associated with SBS has substantially decreased. Older SBS patients with sepsis, liver dysfunction, severe malnutrition, and metastatic cancer had the highest risk of mortality. Healthcare utilization in SBS remains high. healthcare utilization; hospitalization trend; mortality; research and diseases; short-bowel syndrome.

Medications in type-2 diabetics and their association with liver fibrosis.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) is significantly rising worldwide. Type-2 diabetes (T2D) is a major risk factor for NAFLD progression. AIM: To assess the association of commonly used medications to advanced fibrosis (AF) in patients with biopsy-proven NAFLD and T2D. METHODS: We used the International Classification of Disease 9th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF. RESULTS: A total of 1183 patients were included in the final analysis, out of which 32% (n = 381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females (65%) and Caucasians (85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF. CONCLUSION: In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.