Kimberly A. Forde

Successful Treatment of Hepatitis C in Renal Transplant Recipients With Direct-Acting Antiviral Agents.

The direct‐acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end‐stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon‐free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy‐proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon‐based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment‐related side effects.

Immunosuppressant Medications and Mortality in Inflammatory Bowel Disease

OBJECTIVE:This study examined whether treatment of Crohns disease (CD) and ulcerative colitis (UC) with immunosuppressant medications was associated with an increased risk of death in the era prior to antitumor necrosis factor (TNF) therapies.DESIGN: This retrospective cohort study used data from the General Practice Research Database from 1987 to 1997. CD and UC patients were matched to controls on age, sex, and primary care practice. CD and UC patients were stratified according to whether they used immunosuppressant medications during follow-up. Cox proportional hazards models adjusted for comorbidities were used to define the relative hazard of death. Additional models examined the relative hazard of death with current use of corticosteroids or thiopurines.RESULTS:The cohort included 5,539 patients with CD, 8,910 patients with UC, and 41,624 controls. Patients with CD had an increased mortality (not immunosuppressant-treated CD hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.07–1.51; immunosuppressant-treated CD HR 2.44, 95% CI 1.84–3.25). Increased mortality was only observed among UC patients treated with immunosuppressant medications (HR 1.67, 95% CI 1.34–2.09). In both CD and UC, current corticosteroid therapy was associated with increased mortality (CD HR 2.48, 95% CI 1.85–3.31; UC HR 2.81, 95% CI 2.26–3.50). Current use of thiopurines was not associated with increased mortality (CD HR 0.83, 95% CI 0.37–1.86; UC HR 0.70, 95% CI 0.29–1.70).CONCLUSIONS:Patients treated with corticosteroids, but not thiopurines, are at increased risk of death, although this study could not clarify whether this was as a result of the medication or the underlying disease severity.

Cancer incidence in The Health Improvement Network.

The utility of electronic medical record databases for clinical research relies on the validity and completeness of the recorded medical diagnoses. This study assessed whether the recorded incidence of cancer among patients in The Health Improvement Network (THIN) database is comparable to that expected in the UK based on national cancer registry data.

Validity of The Health Improvement Network (THIN) for epidemiologic studies of hepatitis C virus infection.

Before using computerized databases to study hepatitis C virus (HCV) epidemiology, the validity of the diagnosis must be assessed. We determined the accuracy of HCV diagnostic codes within The Health Improvement Network (THIN), an electronic database containing medical record data from general medical practices in the United Kingdom.

Association of Distance From a Transplant Center With Access to Waitlist Placement, Receipt of Liver Transplantation, and Survival Among US Veterans

IMPORTANCE Centralization of specialized health care services such as organ transplantation and bariatric surgery is advocated to improve quality, increase efficiency, and reduce cost. The effect of increased travel on access and outcomes from these services is not fully understood. OBJECTIVE To evaluate the association between distance from a Veterans Affairs (VA) transplant center (VATC) and access to being waitlisted for liver transplantation, actually having a liver transplant, and mortality. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of veterans meeting liver transplantation eligibility criteria from January 1, 2003, until December 31, 2010, using data from the Veterans Health Administrations integrated, national, electronic medical record linked to Organ Procurement and Transplantation Network data. MAIN OUTCOMES AND MEASURES The primary outcome was being waitlisted for transplantation at a VATC. Secondary outcomes included being waitlisted at any transplant center, undergoing a transplantation, and survival. RESULTS From 2003-2010, 50,637 veterans were classified as potentially eligible for transplant; 2895 (6%) were waitlisted and 1418 of those were waitlisted (49%) at 1 of the 5 VATCs. Of 3417 veterans receiving care at a VA hospital located within 100 miles from a VATC, 244 (7.1%) were waitlisted at a VATC and 372 (10.9%) at any transplant center (VATC and non-VATCs). Of 47,219 veterans receiving care at a VA hospital located more than 100 miles from a VATC, 1174 (2.5%) were waitlisted at a VATC and 2523 (5.3%) at any transplant center (VATC and non-VATCs). In multivariable models, increasing distance to closest VATC was associated with significantly lower odds of being waitlisted at a VATC (odds ratio [OR], 0.91 [95% CI, 0.89-0.93] for each doubling in distance) or any transplant center (OR, 0.94 [95% CI, 0.92-0.96] for each doubling in distance). For example, a veteran living 25 miles from a VATC would have a 7.4% (95% CI, 6.6%-8.1%) adjusted probability of being waitlisted, whereas a veteran 100 miles from a VATC would have a 6.2% (95% CI, 5.7%-6.6%) adjusted probability. In adjusted models, increasing distance from a VATC was associated with significantly lower transplantation rates (subhazard ratio, 0.97; 95% CI, 0.95-0.98 for each doubling in distance). There was significantly increased mortality among waitlisted veterans from the time of first hepatic decompensation event in multivariable survival models (hazard ratio, 1.03; 95% CI, 1.01-1.04 for each doubling in distance). For example, a waitlisted veteran living 25 miles from a VATC would have a 62.9% (95% CI, 59.1%-66.1%) 5-year adjusted probability of survival from first hepatic decompensation event compared with a 59.8% (95% CI, 56.3%-63.1%) 5-year adjusted probability of survival for a veteran living 100 miles from a VATC. CONCLUSIONS AND RELEVANCE Among VA patients meeting eligibility criteria for liver transplantation, greater distance from a VATC or any transplant center was associated with lower likelihood of being waitlisted, receiving a liver transplant, and greater likelihood of death. The relationship between these findings and centralizing specialized care deserves further investigation.

Acute-on-chronic liver failure before liver transplantation: impact on posttransplant outcomes.

Background. Acute decompensation in patients with chronic liver disease, resulting from acute kidney injury and infections, leads to significant morbidity and mortality. It is unclear whether patients who develop acute-on-chronic liver failure (ACLF) have poor outcomes after liver transplantation. Methods. We performed a single-center retrospective cohort study of 332 patients to evaluate the effect of ACLF, defined as an acute rise in the Model for End-Stage Liver Disease score of more than 5 within 4 weeks before transplantation, on posttransplant outcomes including stage 4 chronic kidney disease, death, recurrent cirrhosis, or graft failure requiring retransplantation. Results and Conclusions. One hundred fifty-seven patients in the study had ACLF and 175 patients had no ACLF (non-ACLF) pretransplant. Thirty-four patients in the entire cohort received dual organs, 10 of them (29.4%) had ACLF. Seventy-six percent of the patients with ACLF had acute kidney injury as their reason for decompensation and 23.6% had an infection. Mean Model for End-Stage Liver Disease score at transplant was significantly different between the groups (ACLF 28.77 vs. non-ACLF 21.23, P<0.0001). A total of 16.6% of the patients achieved an estimated glomerular filtration rate (eGFR) less than 30 mL/min, 21% of patients died, 12.3% developed cirrhosis, and 7.5% received a second transplant. There was no difference in mean eGFR between the ACLF and non-ACLF cohorts at 3 years posttransplant (56.35 mL/min vs. 59.93 mL/min, respectively, P=0.27). On multivariate analysis, ACLF was not significantly associated with eGFR less than 30 mL/min, death, recurrent cirrhosis, or retransplantation when adjusted for potential confounders.

No Increased Risk of Myocardial Infarction Among Patients With Ulcerative Colitis or Crohn's Disease

BACKGROUND & AIMS Patients with chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis have an increased risk of myocardial infarction (MI). Studies of the risk of MI among patients with inflammatory bowel disease have provided inconsistent results. We aimed to determine the risk of first-time acute MI in patients with ulcerative colitis (UC) or Crohns disease (CD) compared with patients from general practice. METHODS We conducted 2 retrospective cohort studies using the General Practice Research Database. A total of 15,498 UC patients were matched to 144,605 general practice patients (for age, sex, year of enrollment in the General Practice Research Database, and general practice of attendance) and were followed up for a mean of 4.7 years; 9829 CD patients were matched to 92,987 patients from general practice and followed up for a mean of 4.5 years. Univariable and multivariable Cox regression analyses were adjusted for age, sex, history of hypertension, diabetes mellitus, hypercholesterolemia, smoking status, body mass index, and aspirin use for each cohort. RESULTS Patients with UC had a significantly increased risk of first-time acute MI compared with patients from general practice in unadjusted, but not adjusted, analysis (adjusted hazard ratio, 1.11; 95% confidence interval, 0.98-1.27). Patients with CD did not have an increased risk of MI in either unadjusted or adjusted analyses (adjusted hazard ratio, 1.09; 95% confidence interval, 0.89-1.34). CONCLUSIONS Unlike some other chronic inflammatory diseases, inflammatory bowel disease is not associated with an increased risk of MI.

Population-Representative Incidence of Drug-Induced Acute Liver Failure Based on an Analysis of an Integrated Health Care System

BACKGROUND & AIMS Medications are a major cause of acute liver failure (ALF) in the United States, but no population-based studies have evaluated the incidence of ALF from drug-induced liver injury. We aimed to determine the incidence and outcomes of drug-induced ALF in an integrated health care system that approximates a population-based cohort. METHODS We performed a retrospective cohort study using data from the Kaiser Permanente Northern California (KPNC) health care system between January 1, 2004, and December 31, 2010. We included all KPNC members age 18 years and older with 6 months or more of membership and hospitalization for potential ALF. The primary outcome was drug-induced ALF (defined as coagulopathy and hepatic encephalopathy without underlying chronic liver disease), determined by hepatologists who reviewed medical records of all KPNC members with inpatient diagnostic and laboratory criteria suggesting potential ALF. RESULTS Among 5,484,224 KPNC members between 2004 and 2010, 669 had inpatient diagnostic and laboratory criteria indicating potential ALF. After medical record review, 62 (9.3%) were categorized as having definite or possible ALF, and 32 (51.6%) had a drug-induced etiology (27 definite, 5 possible). Acetaminophen was implicated in 18 events (56.3%), dietary/herbal supplements in 6 events (18.8%), antimicrobials in 2 events (6.3%), and miscellaneous medications in 6 events (18.8%). One patient with acetaminophen-induced ALF died (5.6%; 0.06 events/1,000,000 person-years) compared with 3 patients with non-acetaminophen-induced ALF (21.4%; 0.18/1,000,000 person-years). Overall, 6 patients (18.8%) underwent liver transplantation, and 22 patients (68.8%) were discharged without transplantation. The incidence rates of any definite drug-induced ALF and acetaminophen-induced ALF were 1.61 events/1,000,000 person-years (95% confidence interval, 1.06-2.35) and 1.02 events/1,000,000 person-years (95% confidence interval, 0.59-1.63), respectively. CONCLUSIONS Drug-induced ALF is uncommon, but over-the-counter products and dietary/herbal supplements are its most common causes.

Radiofrequency Ablation Is Associated With Decreased Neoplastic Progression in Patients With Barrett's Esophagus and Confirmed Low-Grade Dysplasia

BACKGROUND & AIMS Barretts esophagus (BE) with low-grade dysplasia (LGD) can progress to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) has been shown to be an effective treatment for LGD in clinical trials, but its effectiveness in clinical practice is unclear. We compared the rate of progression of LGD after RFA with endoscopic surveillance alone in routine clinical practice. METHODS We performed a retrospective study of patients who either underwent RFA (n = 45) or surveillance endoscopy (n = 125) for LGD, confirmed by at least 1 expert pathologist, from October 1992 through December 2013 at 3 medical centers in the United States. Cox regression analysis was used to assess the association between progression and RFA. RESULTS Data were collected over median follow-up periods of 889 days (interquartile range, 264-1623 days) after RFA and 848 days (interquartile range, 322-2355 days) after surveillance endoscopy (P = .32). The annual rates of progression to HGD or EAC were 6.6% in the surveillance group and 0.77% in the RFA group. The risk of progression to HGD or EAC was significantly lower among patients who underwent RFA than those who underwent surveillance (adjusted hazard ratio = 0.06; 95% confidence interval: 0.008-0.48). CONCLUSIONS Among patients with BE and confirmed LGD, rates of progression to a combined end point of HGD and EAC were lower among those treated with RFA than among untreated patients. Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for LGD.

Risk of Myocardial Infarction Associated with Chronic Hepatitis C Virus Infection: A Population-Based Cohort Study

Summary.  Hepatitis C virus (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis. However, it remains unclear if HCV infection increases the risk of acute myocardial infarction (MI). To determine whether HCV infection is an independent risk factor for acute MI among adults followed in general practices in the United Kingdom (UK), a retrospective cohort study was conducted in The Health Improvement Network, from 1996 through 2008. Patients ≥18 years of age with at least 6 months of follow‐up and without a prior history of MI were eligible for study inclusion. HCV‐infected individuals, identified with previously validated HCV diagnostic codes (n = 4809), were matched on age, sex and practice with up to 15 randomly selected patients without HCV (n = 71 668). Rates of incident MI among patients with and without a diagnosis of HCV infection were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards regression, controlling for established cardiovascular risk factors. During a median follow‐up of 3.2 years, there was no difference in the incidence rates of MI between HCV‐infected and ‐uninfected patients (1.02 vs 0.92 events per 1000 person‐years; P = 0.7). HCV infection was not associated with an increased risk of incident MI (adjusted HR, 1.10; 95% confidence interval [CI], 0.67–1.83). Sensitivity analyses including the exploration of a composite outcome of acute MI and coronary interventions yielded similar results (adjusted HR, 1.16; 95% CI, 0.77–1.74). In conclusion, HCV infection was not associated with an increased risk of incident MI.