Access to Subspecialty Care And Survival Among Patients With Liver Disease.

OBJECTIVES: Access to subspecialty care may be difficult for patients with liver disease, but it is unknown whether access influences outcomes among this population. Our objectives were to determine rates and predictors of access to ambulatory gastrointestinal (GI) subspecialty care for patients with liver disease and to determine whether access to subspecialty GI care is associated with better survival. METHODS: We studied 28,861 patients within the Veterans Administration VISN 11 Liver Disease cohort who had an ICD-9-CM diagnosis code for liver disease from 1 January 2000 through 30 May 2011. Access was defined as a completed outpatient clinic visit with a gastroenterologist or hepatologist at any time after diagnosis. Multivariable logistic regression was used to determine predictors of access to a GI subspecialist. Survival curves were compared between those who did and those who did not see a specialist, with propensity score adjustment to account for other covariates that may affect access. RESULTS: Overall, 10,710 patients (37%) had a completed GI visit. On multivariable regression, older patients (odds ratio (OR) 0.98, P<0.001), those with more comorbidities (OR 0.98, P=0.01), and those living farther from a tertiary-care center (OR 0.998/mi, P<0.001) were less likely to be seen in clinic. Patients who were more likely to be seen included those who had hepatitis C (OR 1.5, P<0.001) or cirrhosis (OR 3.5, P<0.001) diagnoses prior to their initial visit. Patients with an ambulatory GI visit at any time after diagnosis were less likely to die at 5 years when compared with propensity-score-matched controls (hazard ratio 0.81, P<0.001). CONCLUSIONS: Access to ambulatory GI care was associated with improved 5-year survival for patients with liver disease. Innovative care coordination techniques may prove beneficial in extending access to care to liver disease patients.

Predictors of mortality in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BACKGROUND/AIM: Transarterial chemoembolization (TACE) is the recommended treatment for patients with Barcelona stage B hepatocellular carcinoma; however, community practice varies from these American Association for the Study of Liver Diseases guidelines. In this study, we sought to assess factors determining outcome after TACE and examine adherence to guidelines. METHODS: From January 2006 to December 2012, 308 patients with newly diagnosed HCC were treated at the Veterans Affairs (VA) Ann Arbor Healthcare System. Of these, 109 patients underwent TACE. The primary outcome measured mortality. Kaplan-Meier analysis was used to determine the cumulative probability of death. Cox regression was used to assess the predictors of mortality. RESULTS: The median age of the 109 patients was 60 years (48-90), 97 % were males and 82 % had chronic HCV infection. The median size of the largest lesion was 4 cm, 51 % were multifocal, and portal vein thrombosis was present in 3.6 %. Sixty-two patients died after median 333 days from the index TACE treatment. Median overall survival from index TACE was 11.2 months. Unadjusted 1-, 2-, and 3-year survival was 64, 35, and 24 %, respectively. CTP score (B vs. A: HR 2.51, p = 0.002; C vs. A: HR 7.96, p < 0.0001) and presence of complete response to TACE (HR 0.51, p = 0.004) were independent predictors of mortality. Barcelona stage (p = 0.88) and performance status as measured by ECOG (p = 0.98) were not associated with mortality after TACE. CONCLUSIONS: In this community based, single VA center study, we found a significant number of patients beyond Barcelona stage B were treated with TACE. Advanced TNM stage, poor liver synthetic function and achieving CR with TACE were better predictors of mortality than guideline-directed decisions based on Barcelona stage. These factors may be useful to guide future patient selection for TACE.

The educational impact of the Specialty Care Access Network-Extension of Community Healthcare Outcomes program.

BACKGROUND: With the aging hepatitis C cohort and increasing prevalence of fatty liver disease, the burden on primary care providers (PCPs) to care for patients with liver disease is growing. In response, the Veterans Administration implemented initiatives for primary care-specialty referral to increase PCP competency in complex disease management. The Specialty Care Access Network-Extension of Community Healthcare Outcomes (SCAN-ECHO) program initiative was designed to transfer subspecialty knowledge to PCPs through case-based distance learning combined with real-time consultation. There is limited information regarding the initiative's ability to engage PCPs to learn and influence their practice. MATERIALS AND METHODS: We surveyed PCPs to determine the factors that led to their participation in this program and the educational impact of participation. RESULTS: Of 51 potential participants, 24 responded to an anonymous survey. More than 75% of respondents participated more than one time in a SCAN-ECHO clinic. Providers were motivated to participate by a desire to learn more about liver disease, to apply the knowledge gained to future patients, and to save their patients time traveling to another center for specialty consultation. Seventy-one percent responded that the didactic component and case-based discussion were equally important. It is important that participation changed clinical practice: 75% of providers indicated they had personally discussed the information they learned from the case presentations with their colleague(s), and 42% indicated they helped a colleague care for their patient with the knowledge learned during discussions of other participants' cases. CONCLUSIONS: This study shows that the SCAN-ECHO videoconferencing program between PCPs and specialists can educate providers in the delivery of specialty care from a distance and potentially improve healthcare delivery.

Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet.

Diets high in trans fats are associated with an increased risk of cardiovascular disease and components of the metabolic syndrome. The influence of these toxic fatty acids on the development of nonalcoholic fatty liver disease has not been significantly examined. Therefore, we sought to compare the effect of a murine diet high in trans fat to a standard high-fat diet that is devoid of trans fats but high in saturated fats. Male AKR/J mice were fed a calorically identical trans fat diet or standard high-fat diet for 10 days, 4 wk, and 8 wk. Serum alanine aminotransferase (ALT), lipid, insulin, and leptin levels were determined and the quantitative insulin-sensitivity check index (QUICKI) was calculated as a measure of insulin resistance. Additionally, hepatic triglyceride content and gene expression of several proinflammatory genes were assessed. By 8 wk, trans fat-fed mice exhibited higher ALT values than standard high-fat-fed mice (126 +/- 16 vs. 71 +/- 7 U/l, P < 0.02) despite similar hepatic triglyceride content at each time point. Trans fat-fed mice also had increased insulin resistance compared with high-fat-fed mice at 4 and 8 wk with significantly higher insulin levels and lower QUICKI values. Additionally, hepatic interleukin-1beta (IL-1beta) gene expression was 3.6-fold higher at 4 wk (P < 0.05) and 5-fold higher at 8 wk (P < 0.05) in trans fat-fed mice compared with standard high-fat-fed mice. Trans fat feeding results in higher ALT values, increased insulin resistance, and elevated IL-1beta levels compared with standard high-fat feeding.

Hepatic uptake of gamma-butyrobetaine, a precursor of carnitine biosynthesis, in rats.

Gamma-butyrobetaine (GBB) is a precursor in the biosynthesis of carnitine, which plays an important role in the beta-oxidation of fatty acids, and is converted to carnitine by gamma-butyrobetaine dioxygenase (BBD) predominantly in liver. We investigated the molecular mechanism of hepatic uptake of GBB in rat hepatocytes. Cellular localization of rat Octn2 (rOctn2:Slc22A5) was studied by Western blot analysis. Uptake of deuterated GBB (d(3)-GBB) was examined in HEK293 cells expressing rOctn2 (HEK293/rOctn2) and freshly isolated rat hepatocytes. d(3)-GBB was quantified by use of liquid chromatography-tandem mass spectrometry. Western blot analysis demonstrated an expression of OCTN2 protein in hepatic basolateral membrane but not in bile canalicular membrane fraction. Furthermore, we found that d(3)-GBB was taken up by rOctn2 in an Na(+)-dependent manner with K(m) value of 13 microM. The apparent K(m) value for d(3)-GBB transport in freshly isolated rat hepatocytes was 9 microM. d(3)-GBB uptake by the rat hepatocytes was inhibited by gamma-aminobutyric acid (GABA) to 30% of the control, whereas it was inhibited by carnitine to 62% of the control, even at 500 microM. Furthermore, d(3)-GBB uptake by rat hepatocytes was decreased by 45% with rat Gat2 (Slc6A13, a major liver GABA transporter) silenced by the microRNA method. Accordingly, the present study clearly demonstrates that GBB is taken up by hepatocytes for carnitine biosynthesis not only via Octn2 but also via the GABA transporter, possibly Gat2.