Syed-Mohammed Jafri

Effect of Inflammatory Bowel Disease–Related Characteristics and Treatment Interventions on Cardiovascular Disease Incidence

Background:An association between inflammatory bowel disease (IBD) and cardiovascular diseases has been shown in multiple studies. However, little is known about the effect of IBD-related characteristics on cardiovascular events. Methods:The authors conducted a retrospective, nested case-control study of IBD patients who presented to the institution from 2000 to 2004, allowing for a 10-year follow-up period. One hundred eleven patients who developed cardiovascular events (cases) and 222 patients who did not develop cardiovascular events (cases) were included in the study after matching for Framingham cardiovascular risk score (2008). Relationships between predictor variables and cardiovascular outcome were assessed by conditional logistic regression. Results:The cases and controls were similar in age, gender, smoking and cholesterol level. There was no difference in disease subtype (ulcerative colitis or Crohns disease). On conditional logistic regression, thiopurine treatment (odds ratio [OR]: 0.42, 95% confidence interval [CI]: 0.19–0.87; P = 0.02) was associated with decreased cardiovascular events and tumor necrosis factor alpha antagonist use (OR: 2.63, 95% CI: 1.49–4.63; P = 0.001) was associated with increased cardiovascular events. Although not statistically significant, disease-related surgery (OR: 0.57, 95% CI: 0.32–1.02; P = 0.06) was associated with decreased cardiovascular events and disease-related hospitalization (OR: 1.58, 95% CI: 0.96–2.57; P = 0.07) was associated with increased incidence of cardiovascular disorders. Conclusions:The authors observed decreased incidence of cardiovascular diseases in patients with IBD who were treated with thiopurines and increased incidence of cardiovascular outcomes among patients treated with tumor necrosis factor alpha antagonist.

The Consequences of Cirrhosis in America

In the evolution of liver disease, the phase between the development of cirrhosis and the development of complications, termed decompensated cirrhosis, is often prolonged, with a reported median survival of 12 years [1]. The development of cirrhotic complications (variceal bleeding, overt encephalopathy, infection, cancer, renal failure, ascites and hepatic hydrothorax) has immediate implications as it relates to the utilization of health care; moreover, such complications herald the larger risk of future clinical deterioration [2]. Development of any one of these complications denotes a turning point in the life of the cirrhotic patient. Hospitalization for a decompensation event markedly changes the median survival of the cirrhotic patient to \2 years [3]. Quality-of-life and mobility decline followed by a progressive rise of healthcare expenditures. Individuals with compensated and decompensated cirrhosis have significantly worse health status, have more comorbid conditions and have a greater use of healthcare services including hospital visits, nursing homestays and physician visits compared to an age-matched patients without cirrhosis [4]. Rakowski et al. [4] reported the profound functional disability in cirrhotics as it relates to activities of daily living. Cirrhotics receive double the informal caregiving hours compared with age-matched non-cirrhotics leading to monetary loss due to medications, medical fees, home health costs and missed wages by patients and relations. Bajaj et al. [5] observed that hepatic encephalopathy is associated with a significant decline in employment status and financial status and significant increase in caregiver burden which rose with Model EndStage Liver Disease score. The prevalence of cirrhosis in the USA is expected to increase, attributed largely to an aging hepatitis C birth cohort and the rising incidence of nonalcoholic steatohepatitis [6]. In the face of heightened Medicare utilization by the baby boomers, the direct cost of managing chronic liver disease—even excluding hepatitis C therapy—exceeds US

Acute Kidney Injury in Patients Undergoing Chronic Hepatitis C Virus Treatment With Ledipasvir/Sofosbuvir

1.4 billion annually [7]. The clinical hepatologist, in turn, strives toward minimizing the emergency room visits, prolonged hospitalizations and costly therapeutic interventions that characterize this complex patient population. In this issue of Digestive Diseases and Sciences, Otgonsuren et al. [8] focus on how to better understand the economic and medical outcomes of Medicare patients who suffer from decompensated cirrhosis. This timely study highlights the impact of complications of chronic liver disease in the growing Medicare population. The findings include a high rate of death over 1 year after evidence of decompensation, with a 70 % overall death rate within 1 year following a decompensation event. Despite an improvement in mortality over the study period, the study additionally reflects a significant overall cost increase from 2005 to 2010, coinciding with an increase in the rates of spontaneous bacterial peritonitis and bleeding esophageal varices. Additionally, there was an 11 % increase in ICU stays, which represented a major driver of costs. In an attempt to determine the highest relevant predictors of mortality, the authors identified older age, a higher comorbidity index and male gender as major influences. While these factors are not surprising, the authors interestingly identified hepatocellular carcinoma (HCC) as a major predictor of cost as well as mortality. This finding adds to a growing body of literature documenting that the incidence of HCC is growing at an alarming rate in the S. R. Jafri S. C. Gordon (&) Department of Gastroenterology and Hepatology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, MI 48302, USA e-mail: sgordon3@hfhs.org

Grazoprevir/elbasvir for the treatment of adults with chronic hepatitis C: a short review on the clinical evidence and place in therapy

Ledipasvir‐sofosbuvir, a once‐a‐day, oral combination pill, was approved in 2014 for the treatment of chronic hepatitis C infection. Initial trials did not comment on nephrotoxicity; however, recent data suggest a risk of acute kidney injury (AKI) with the use of the medication. We assessed the rates of AKI in patients undergoing ledipasvir‐sofosbuvir in a large, urban tertiary care center. This single‐center retrospective observation study included all patients undergoing therapy from October 1, 2014, to October 1, 2015. Rates of AKI, defined by more than a 0.3 mg/dL increase in serum creatinine level, were calculated. Patients were followed 12 weeks after therapy to assess for sustained viral response as well as to assess for improvement of AKI after completion of therapy, defined by less than 0.2 mg/dL above baseline serum creatinine. In total, 197 patients were included in the final analysis who had completed ledipasvir‐sofosbuvir therapy and completed laboratory values. Among the patients treated, 38 (19%) had AKI during therapy. An additional 4 (2%) had AKI at the end of therapy. Of the 38 patients who experienced AKI, 20 (53%) had improvement in serum creatinine to less than 0.2 mg/dL above their baseline. When comparing for chronic kidney disease (CKD) stage, those with CKD I or II experienced AKI 17% of the time compared with 47% of the time in CKD III or worse (P = 0.005). Conclusion: AKI was seen in nearly one‐fifth of our patients, and patients with CKD stage III or worse are at increased risk. Although ledipasvir‐sofosbuvir is generally safe in the general population, close monitoring of renal function is recommended.

35 – Hepatitis A

Chronic hepatitis C virus (HCV) infection impacts approximately 71 million people and approximately 400,000 deaths are attributed to HCV-related liver disease annually worldwide. Mainstay of treatment for over 25 years has been pegylated interferon until the advent of protease inhibitors, which has led to all-oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. Grazoprevir/elbasvir provides high rates of efficacy and tolerability and is an all-oral once daily treatment option for HCV infection. Efficacy of grazoprevir/elbasvir has been proven in patients with cirrhosis, patients who have previously failed treatment with peginterferon and ribavirin (RBV), patients with end-stage renal disease and patients with HIV co-infection. Data have shown a high barrier to resistance despite the presence of resistance-associated substitutions. Grazoprevir/elbasvir represents a very promising regimen for treatment of HCV infection. This review provides a summary of pharmacology, efficacy, and safety of grazoprevir/elbasvir for the treatment of HCV infection.