Real-world effectiveness for 12 weeks of ledipasvir-sofosbuvir for genotype 1 hepatitis C: the Trio Health study.

Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.

Disparate access to treatment regimens in chronic hepatitis C patients: data from the TRIO network.

Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid-covered group, must be resolved.

Predictive value of dobutamine stress echocardiography for coronary artery disease detection in liver transplant candidates.

Patients with obstructive coronary artery disease (CAD) undergoing orthotopic liver transplantation (OLT) are at increased risk of poor outcomes. The accuracy of dobutamine stress echocardiography (DSE) to detect obstructive CAD is not well established in this population. We retrospectively identified patients with end-stage liver disease who underwent both DSE and coronary angiography as part of risk stratification prior to OLT. One hundred and five patients had both DSE and angiography, of whom 14 had known CAD and 27 failed to reach target heart rate during DSE. Among the remaining 64 patients (45 men; average age 61 +/- 8 years) DSE had a low sensitivity (13%), high specificity (85%), low positive predictive value (PPV) (22%) and intermediate negative predictive value (NPV) (75%) for obstructive CAD. DSE as a screening test for obstructive CAD in OLT candidates has a poor sensitivity. The frequent chronotropic incompetence and low sensitivity in patients who achieve target heart rate, even in those with multiple cardiovascular disease risk factors, suggest that alternative or additional methods of risk stratification are necessary.

Real-world use of elbasvir-grazoprevir in patients with chronic hepatitis C: retrospective analyses from the TRIO network.

BACKGROUND: Elbasvir-grazoprevir is indicated for chronic hepatitis C virus (HCV) genotypes 1 and 4. AIM: To evaluate the utilization and outcomes of chronic HCV patients treated with elbasvir-grazoprevir in the United States. METHODS: We conducted a retrospective cohort study of adults treated with elbasvir-grazoprevir with or without ribavirin for chronic HCV genotypes 1 or 4 infection. Data were collected from healthcare providers and specialty pharmacies through Innervation Platform, a proprietary, cloud-based disease management program from Trio Health. The primary endpoint was per protocol sustained virological response 12 weeks post-treatment (SVR12). RESULTS: Among 470 patients treated in 2016, 95% had HCV genotype 1 infection, 80% (373/468) were HCV treatment naïve and 70% (327/468) had non-cirrhotic disease. Almost 3 quarters (73%) of patients received care in community practices. The majority (89%) of patients received elbasvir-grazoprevir for 12 weeks. Per protocol SVR12 rates were 99% (396/402) for HCV genotype 1 and 95% (21/22) for HCV genotype 4. Among patients with Stage 4 or 5 chronic kidney diseases, 99% (113/114) achieved SVR12. In univariate analyses, variables significantly associated with per protocol SVR12 for the entire sample were therapy duration (P = 0.001), treatment experience (P = 0.016), and cirrhosis status (P = 0.001). However, among HCV genotype 1 patients, no variables were significant. Intent-to-treat SVR12 rates were 89% (396/447) for HCV genotype 1 and 91% (21/23) for HCV genotype 4. CONCLUSION: Elbasvir-grazoprevir is highly effective, and in this 2016 cohort, its use was predominantly in patients with HCV genotype 1 and as a 12-week therapy without ribavirin.

Effectiveness of 8- or 12-weeks of ledipasvir and sofosbuvir in real-world treatment-naïve, genotype 1 hepatitis C infected patients.

BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. METHODS: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. RESULTS: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. CONCLUSIONS: In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.

Desiccant recovered, Crohn's disease discovered.

Foreign bodies occasionally lodge in strictures due to Crohn's disease. Most cases involve patients known to have Crohn's disease. However, some patients deny or cannot recall ingestion of foreign bodies. Gastrointestinal obstruction caused by a foreign body is a rare presentation of Crohn's disease. We report the first case of Crohn's disease presenting as gastrointestinal obstruction resulting from accidental ingestion of a pharmaceutical desiccant.

Risk factors associated with chronic hepatitis C virus infection: limited frequency of an unidentified source of transmission.

OBJECTIVES: Risk factors have been studied in patients with acute non-A, non-B hepatitis, and approximately 40-50% have no known risk factor for viral acquisition. A significant undefined source of viral transmission has been suggested. We sought to clearly delineate the risk factors in a population of patients with documented chronic hepatitis C virus (HCV) infection to assess the magnitude of HCV transmission without known risk factors. METHODS: Risk factor profiles were carefully assessed in 301 consecutive patients with chronic HCV infection. Patients were classified by gender and age. Overall risk factor distributions were calculated and comparisons were made between groups to detect differences in mode of HCV acquisition. RESULTS: One hundred ninety-six men and 105 women were studied; 223 were age < or = 45 yr and 78 were > 45 yr. Overall, 25% of patients had a history of transfusion and 49% had a history of intravenous drug use (i.v.DU). Only 12% had no history of risk factor exposure. Men were more likely to have a history of i.v.DU and less likely to have a history of blood transfusion or sexual exposure/household contact. Younger patients were more likely to have a history of i.v.DU and older patients were more likely to have a history of blood transfusion and to deny all risk factor exposure. CONCLUSIONS: A careful history delineated a potential risk factor for HCV acquisition in 88% of patients with chronic HCV infection. Men and younger patients had different risk factor profiles than women and older patients, respectively. It is likely that an important unknown mode of HCV transmission occurs in a significant minority of patients.

AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection.

OBJECTIVE: A liver biopsy is necessary to grade and stage chronic hepatitis C virus (HCV) infection. In a previous study of patients with nonalcoholic liver disease, an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio >1 suggested cirrhosis. We sought to examine the value of the AST/ALT ratio in distinguishing cirrhotic patients with chronic HCV infection from noncirrhotic patients and to correlate the ratio with the grade and stage of hepatitis and other biochemical indices. METHODS: We retrospectively studied 139 patients with chronic HCV infection. Routine biochemical indices were determined, and the histological grade of necroinflammatory activity and the stage of fibrosis of the liver biopsy specimens were scored. RESULTS: The mean AST/ALT ratio in the cirrhotic patients (n = 47) was higher than in the noncirrhotic patients (n = 92) (1.06 +/- 0.06 vs 0.60 +/- 0.09; p < 0.001). A ratio > or =1 had 100% specificity and positive predictive value in distinguishing cirrhotic from noncirrhotic patients, with a 53.2% sensitivity and 80.7% negative predictive value. The ratio correlated positively with the stage of fibrosis but not with the grade of activity or other biochemical indices. Of the cirrhotic patients, 17% had no clinical or biochemical features suggestive of chronic liver disease except for an AST/ALT ratio > or =1. CONCLUSION: The AST/ALT ratio is a dependable marker of fibrosis stage and cirrhosis in patients with chronic HCV infection.

Body mass index as a predictor of hepatic steatosis in living liver donors.

Evaluation of the living donor for liver transplantation is a complex process involving such invasive studies as liver biopsy and angiography. It is important to establish the likelihood and extent of hepatic steatosis in living donors by clinical, imaging, and biochemical parameters to avoid performing a liver biopsy, if possible. In this study, the predictive value of body mass index (BMI), liver chemistry tests, and imaging studies was compared with liver histological examination in 33 potential living donors. Patients were grouped and compared based on their BMI (<25, 25 to 28, >28). No patient with a BMI less than 25 had hepatic steatosis. Of patients with a BMI of 25 to 28, steatosis was found on biopsy in 3 of 9 patients. Thirteen of 17 patients (76%) with a BMI greater than 28 had hepatic steatosis on liver biopsy. There was a significant correlation between BMI and overall grade of steatosis (R = 0.49). All subjects with steatosis detected on magnetic resonance imaging (MRI) or computed tomography (CT) had steatosis on biopsy, and all but 2 such patients had greater than 10% steatosis on biopsy. Conversely, 30% of patients in the MRI group and 24% of patients in the CT group failed to show hepatic steatosis when it was present on biopsy. Thus, it appears that liver biopsy could be avoided in subjects with a normal BMI and absence of risk factors. Individuals with a high BMI should undergo liver biopsy because biochemical and imaging data are currently inadequate to determine the extent of steatosis. Future studies should aim at improving the sensitivity of imaging techniques in the diagnosis of steatosis.

Autocrine growth stimulation by secreted Kaposi fibroblast growth factor but not by endogenous basic fibroblast growth factor.

We studied the different potentials of a secreted and a nonsecreted member of the fibroblast growth factor (FGF) family to induce autocrine growth stimulation in human adrenal cortex carcinoma cells (SW-13). These epithelial cells express basic FGF (bFGF) cell surface receptors, and picomolar concentrations of bFGF suffice to induce anchorage-independent growth. The requirement for exogenously added bFGF contrasts with the intracellular storage of biologically active bFGF in SW-13 cells greater than 10,000-fold in excess of the concentration needed to stimulate anchorage independent growth. To study whether the expression of a secreted FGF would alter the growth phenotype of these cells, we transfected them with an expression vector coding for the Kaposi-fgf (K-fgf) oncogene. In contrast to controls, K-fgf-transfected cells secrete significant amounts of biologically active K-fgf protein into the growth media, show up to 50-fold increased colony formation in soft agar, and grow into rapidly progressing, highly vascularized tumors in athymic nude mice. A reversible inhibition of the autocrine growth stimulation in vitro is brought about by the polyanionic compound suramin. We conclude that FGF has to be released from SW-13 cells to function fully as a growth stimulator in vitro and in vivo.