Prashant K. Pandya

Statin Therapy Improves Sustained Virologic Response Among Diabetic Patients With Chronic Hepatitis C

BACKGROUND & AIMS Patients with chronic hepatitis C infection are 2- to 3-fold more likely to develop type 2 diabetes, which reduces their chances of achieving a sustained virologic response (SVR). To identify differences in predictors of SVR in patients with and without diabetes who received combination antiviral therapy, we conducted a retrospective analysis of a national Veterans Affairs administrative database. METHODS We analyzed data from the Veterans Affairs Medical SAS Datasets and Decision Support System for entire cohort and separately for diabetic patients (n = 1704) and nondiabetic patients (n = 6589). Significant predictors of SVR were identified by logistic regression analysis. RESULTS Diabetic patients had a lower SVR compared with nondiabetic patients (21% vs 27%, respectively, P < .001). Diabetic patients had higher clustering of previously established negative predictors of SVR. On multivariate analysis of diabetic patients for SVR, the positive predictors were higher low-density lipoprotein (odds ratio [OR], 1.45; P = .0129), use of statin (OR, 1.52; P = .0124), and lower baseline viral load (OR, 2.31; P < .001), whereas insulin therapy (OR, 0.7; P = .0278) was a negative predictor. Diabetic patients on statins had higher pretreatment viral loads (log 6.2 vs 6.4, respectively, P = .006) but better early virologic response. There was a graded inverse relationship between Hemoglobin A1c and SVR rate (P = .0482). This relationship was significant among insulin users (P = .0154) and non-significant among metformin users (P = .5853). CONCLUSIONS Statin use was associated with an improved SVR among both diabetic patients and nondiabetic patients receiving combination antiviral therapy. Diabetic patients who received insulin achieved lower SVR compared with those not receiving insulin. Poor diabetes control was associated with lower SVR rates.

Chronic hepatitis C genotype 1 patients with insulin resistance treated with pioglitazone and peginterferon alpha‐2a plus ribavirin

Patients with chronic hepatitis C and insulin resistance are less likely to respond to anti‐hepatitis C virus (HCV) therapy and are at risk for more rapid fibrosis progression. Coadministration of pioglitazone with peginterferon/ribavirin improves insulin sensitivity and increases virologic response rates in insulin‐resistant HCV genotype 4 patients, but it is unclear whether this finding applies to genotype 1 patients. For this reason we randomized treatment‐naive HCV genotype 1 patients with insulin resistance to receive either standard care (peginterferon alpha‐2a plus ribavirin for 48 weeks, n = 73) or pioglitazone 30‐45 mg/day plus standard care (n = 77) in an open‐label multicenter trial. Patients randomized to pioglitazone received the drug during a 16‐week run‐in phase, the 48‐week standard‐care phase, and the 24‐week untreated follow‐up phase. Pioglitazone treatment improved hemoglobin A1c (HbA1c), plasma glucose, insulin levels, and homeostasis model assessment of insulin resistance score and increased serum adiponectin levels during the 16‐week run‐in phase and maintained these improvements during the standard‐care phase. However, we observed no statistically significant difference between the two groups in the primary efficacy endpoint, the decrease from baseline to Week 12 of peginterferon alpha‐2a/ribavirin treatment in mean log10 HCV RNA titer (−3.5 ± 1.71 and −3.7 ± 1.62 IU/mL in the pioglitazone and standard‐care groups, respectively, Δ = 0.21 IU/mL, P = 0.4394). Conclusion: Treatment with pioglitazone before and during treatment with peginterferon alpha‐2a plus ribavirin improved several indices of glycemic control in patients with chronic hepatitis C and insulin resistance, but did not improve virologic response rates compared with peginterferon alpha‐2a plus ribavirin alone. (HEPATOLOGY 2012)

Predictors of hematological abnormalities in patients with chronic hepatitis C treated with interferon and ribavirin

Hematological abnormalities including neutropenia, anemia, and thrombocytopenia are commonly seen in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The aim of this study was to identify factors which would help to predict the development of hematological abnormalities in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. During a 4-year period, all patients with chronic hepatitis C started on treatment with pegylated interferon and ribavirin were identified. Patients were defined as having hematological abnormalities if they had the presence of either anemia, neutropenia, thrombocytopenia, or a combination of the above during treatment with pegylated interferon and ribavirin. A total of 136 patients with chronic hepatitis C were included in this study. Fifty-two (38.2%) of the patients developed significant hematological abnormalities during treatment with pegylated interferon and ribavirin with 28 (20.6%), 30 (22.1%), and 11 (8.1%) developed neutropenia, anemia, and thrombocytopenia, respectively. Genotype 1, history of hypertension, low baseline platelet count, low baseline hemoglobin, as well as a raised creatinine were significant factors associated with the development of hematological abnormalities. Significant hematological abnormalities are commonly present in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. This study identifies pretreatment parameters that may help identify high-risk patients who are more likely to develop hematological abnormalities during treatment for chronic hepatitis C.

Emergency department visits related to cirrhosis: a retrospective study of the nationwide emergency department sample 2006 to 2011.

AbstractThere is scant literature about cirrhosis and its associated complications in a non-hospitalized population.To study the epidemiology of cirrhosis-associated Emergency Department visits in the US.Estimates were calculated in patients’ ≥18 years using the Nationwide Emergency Department Sample.The number of visits associated with an International Classification of Diseases-9 diagnosis code of cirrhosis increased non-significantly from 23.81/10,000 population (2006) to 23.9/10,000 population (2011; P = 0.05). A majority of these patients (75.30%) underwent hospital admission, the greatest risk factor for this was the presence of ≥3 comorbidities (adjusted odds ratio 30.8; 95% Confidence Interval 30.4–31.2). Infection was the most frequent concurrent complicating diagnosis associated with cirrhosis (20.1%). There was a decreased incidence in most of the complicating conditions except for hepatorenal syndrome and spontaneous bacterial peritonitis.Our results indicate a stable trend for cirrhosis-associated Emergency Department visits from 2006 to 2011. Further studies are required to investigate the increased incidence of spontaneous bacterial peritonitis and hepatorenal renal syndrome in the cirrhotic population.

Impact of sustained viral response postcurative therapy of hepatitis C-related hepatocellular carcinoma: a systematic review and meta-analysis.

Antiviral therapy with interferon based therapies (IBT) has shown potential in improving survival in patients who have undergone resection or locoregional therapy for hepatitis C‐associated hepatocellular carcinoma (HCV‐HCC). However, this benefit has not been definitively ascribed to sustained viral response (SVR). Since IBT has been replaced with new directly acting agents (DAA), which are more efficacious in the treatment of HCV, we sought to better determine the prognostic impact of SVR in HCV‐HCC. A systematic search of MEDLINE and EMBASE from inception through October 2015 was performed to identify studies that described the impact of presence of SVR in patients who underwent curative treatment of HCV‐HCC. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated for recurrence‐free survival (RFS) and overall survival (OS) utilizing a random‐effects model. After reviewing 858 abstracts, ten studies which included a total of 1,794 patients were selected and data was extracted. Of these ten studies, the impact of SVR on RFS and OS was reported in eight and seven studies respectively. In a meta‐analysis which included 1,519 patients, SVR was associated with improved OS (HR 0.18; 95% CI 0.11–0.29, I2 = 2%). We also found that SVR was associated with better RFS in a meta‐analysis (1,241 patients; HR 0.50; 95% CI 0.40–0.63, I2 = 0). In conclusion, SVR is associated with improved OS and RFS in patients with HCV who have undergone resection or locoregional therapy for HCC. Newer DAA therapies which offer increased tolerability and viral eradication should be considered as adjunctive therapy.

Sustained virologic response and other potential genotype-specific roles of statins among patients with hepatitis C-related chronic liver diseases.

BACKGROUND While statins have shown antiviral effects in different studies, few data are available about their effect among different HCV genotypes. AIM To evaluate the effect of concomitant statin use on sustained virologic response (SVR) and other treatment outcomes among patients with HCV genotypes 1-3. METHOD Using US Department of Veterans Affairs database, multivariate (MV), propensity score matched (PSM) and repeated measures mixed model analyses were performed on patients who received combination therapy with Peg-IFN and Ribavirin for treatment of HCV genotypes 1-3 between October 2001-December 2011. Concomitant statin users were matched with non-users in each genotype and SVR rates were compared. Changes in serum ALT during treatment was assessed. RESULTS Of 37,611 treated patients, 236 genotype 1 (GT1), 78 genotype 2 (GT2) and 23 genotype 3 (GT3) statin users and non-users were used for PSM. SVR among GT1 patients was 22.8% (overall), significantly higher among statin users (26.3% vs. 19.5% P<0.01 from PSM; OR=1.49 CI 1.06-2.08 P=0.02 from MV). No significant impact of statin use was observed among GT2 (overall SVR - 55.8%, statin users vs. non-users - 53.9% vs. 57.7%, P=0.32), and GT3 (overall SVR - 58.7%, statin users vs. non-users - 60.9% vs. 56.2%, P=0.39) patients. Higher baseline LDL was positively associated with SVR while statin use reduced ALT during treatment in GT1 patients. CONCLUSION In view of additional benefits of statins, and the prohibitive cost of newer HCV therapies, statins could be a potential assist for hard-to-treat GT1 patients especially in resource-poor settings.

Emergency department visits related to Clostridium difficile infection: results from the nationwide emergency department sample, 2006 through 2010.

OBJECTIVES The objective was to estimate emergency department (ED) visits for Clostridium difficile infection in the United States for the years 2006 through 2010. METHODS Estimates of ED visits for C. difficile infection were calculated in patients 18 years and older using the Nationwide Emergency Department Sample. RESULTS During the calendar years 2006 through 2010, there were an estimated total of 491,406,018 ED visits. Of these, 462,160 ED visits were associated with a primary International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis of C. difficile. The C. difficile infection ED visit rate (visits/100,000 census population) increased from 34.1 in 2006 to 42.3 in 2010, an increase of 24% (p < 0.01). There was also a significant overall increased trend in the number of ED visits for C. difficile from 2006 through 2010 (p < 0.01). The highest ED visit rate for C. difficile was observed for patients 65 years and older (163.18 per 100,000), while the lowest visit rate was for patients aged 18 to 24 years (5.10 per 100,000). The greatest increase in C. difficile infection visits occurred in the age group 18 to 24 years. CONCLUSIONS These results indicate an increased trend of ED visits for C. difficile in the period 2006 through 2010 with an overall population-adjusted increase of 24%. This represents important complementary data to previous studies reporting an increase in the rate of C. difficile infections in the U.S. hospitalized population.

Hepatorenal syndrome in hospitalized patients with chronic liver disease: results from the Nationwide Inpatient Sample 2002-2012.

Hepatorenal syndrome (HRS) is one of the leading causes of hospitalizations in patients with chronic liver disease (CLD). We conducted a retrospective national database study to determine the epidemiology of HRS in hospitalized patients with CLD. Data from a Nationwide Inpatient Sample were extracted from 2002 to 2012 using ICD-9-CM codes related to CLD and HRS. The following outcomes were examined: in-hospital mortality, total charges, length of stay (LOS), patient demographics, procedures, complications, and comorbidities. Statistical analysis including regression was performed to examine factors associated with HRS. During 2002–2012, hospital discharges related to CLD increased from 407,246 to 836,475 with an increase of 37.9% for HRS as a complication in this population. Patients with CLD and HRS had worse outcomes compared with patients with CLD without HRS. This was manifested as a higher mortality rate (32.0% vs 10.3%), increased LOS (median 7 vs 5 days), and increased hospital costs (median

Adding to the evidence base: Effectiveness of hepatocellular carcinoma surveillance in clinical practice

16,000 vs

Tu1186 Trainee Participation Increases Adenoma Detection Rates During Screening Colonoscopies Performed With High-Definition Colonoscopes but Not With Standard-Definition Colonoscopes

11,000). Logistic regression demonstrated that HIV/AIDS (adjusted OR 2.9, 95% CI 2.2 to 3.9), pneumonia (aOR 2.8, 95% CI 2.3 to 3.2), and esophageal variceal bleeding (aOR 1.9, 95% CI 1.7 to 2.0) were associated with higher mortality in patients with HRS. Conversely, liver transplantation (aOR 0.1, 95% CI 0.1 to 0.1), transjugular intrahepatic portosystemic shunt (aOR 0.5, 95% CI 0.4 to 0.6), and hospitalization in the Midwest region of the USA (aOR 0.7, 95% CI 0.6 to 0.7) were associated with reduced mortality. The incidence of HRS in hospitalized patients with CLD increased during 2002–2012. HRS is associated with significant mortality and morbidity in these patients.