Six Applications of Plant Based Diets for Health Promotion.

The field of medicine, despite its prominent influence in society, has invested little to promote healthy lifestyle choices. The consequence of this is reflected in our ever-rising chronic disease statistics, most notably obesity and diabetes rates. This is especially regrettable considering overwhelming evidence confirms most non-communicable disease is preventable by modifying our diets. In light of this critical knowledge that optimizing our nutrition could save innumerable lives, one would naturally assume physicians would be readily practicing its promotion with their patients. Yet, that is far from true. By no fault of their own. Medical schools, entrusted with the responsibility of educating our future healthcare leaders, have managed to largely bypass the topic of nutrition, arguably the most powerful healthcare intervention known to mankind. In fact, on average, medical schools offer an anemic number of hours of nutrition education over 4 years.1 What little is offered is focused on biochemistry and nutrient deficiencies, none of which prepares a physician in training for meaningful application in clinical care. This lapse in nutrition education continues throughout post-graduate training; in a recent survey of more than 600 cardiologists, 90% reported they had not received needed nutrition education during training.2 Although we agree that not all physicians must be experts in nutrition, in the very least all should have knowledge of rudimentary and essential facts. We offer this commentary on six vital clinical topics, to increase awareness amongst physicians as to the importance of diet and its role in human health.

Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study.

BACKGROUND & AIMS: Safety and tolerability of peginterferon-based hepatitis C virus (HCV) infection therapy remains suboptimal, even when direct-acting antiviral agents are added. This study assessed the efficacy, safety and tolerability of mericitabine combined with ritonavir-boosted danoprevir (danoprevir/r) ± ribavirin for up to 24 weeks in treatment-naïve HCV genotype (G)1 infected patients. METHODS: Patients received twice daily mericitabine (1000 mg) and danoprevir/r (100 mg/100 mg) plus either ribavirin (1000/1200 mg/day; Arm A) or placebo (Arm B) for 12 or 24 weeks. Patients with HCV RNA <43 IU/ml between Weeks 2 and 8 and HCV RNA <15 IU/ml at Week 10 were rerandomized (1:1) at Week 12 to discontinue/continue assigned regimens until Week 24. Because of unacceptable relapse rates in both 12-week arms and in ribavirin-free Arm B, treatment was extended to 24 weeks and patients in Arm B received peginterferon alfa-2a/ribavirin. The primary outcome was sustained virological response 24 weeks after end of treatment (SVR24). RESULTS: In Arm A, the SVR24 rate in patients receiving 24 weeks of therapy was 37.9% (25/66); 63.6% (14/22) in G1b and 25.0% (11/44) in G1a patients. Virologic breakthrough and relapse were associated with danoprevir-resistant virus in most cases. The mericitabine-resistance mutation (NS5BS282T) was detected in two patients bearing dual resistant virus NS3 R155K/NS5B S282T and dual resistance mutation L159F/L320F in one patient. Treatment was safe and well tolerated. CONCLUSIONS: Mericitabine, danoprevir/r plus ribavirin for 24 weeks were safe and well tolerated. However, SVR rates were poor, achieving rates of only 25.0% in G1a and 63.6% in G1b patients.

Current challenges and controversies in drug-induced liver injury.

Current key challenges and controversies encountered in the identification of potentially hepatotoxic drugs and the assessment of drug-induced liver injury (DILI) are covered in this article. There is substantial debate over the classification of DILI itself, including the definition and validity of terms such as 'intrinsic' and 'idiosyncratic'. So-called idiosyncratic DILI is typically rare and requires one or more susceptibility factors in individuals. Consequently, it has been difficult to reproduce in animal models, which has limited the understanding of its underlying mechanisms despite numerous hypotheses. Advances in predictive models would also help to enable preclinical elimination of drug candidates and development of novel biomarkers. A small number of liver laboratory tests have been routinely used to help identify DILI, but their interpretation can be limited and confounded by multiple factors. Improved preclinical and clinical biomarkers are therefore needed to accurately detect early signals of liver injury, distinguish drug hepatotoxicity from other forms of liver injury, and differentiate mild from clinically important liver injury. A range of potentially useful biomarkers are emerging, although so far most have only been used preclinically, with only a few validated and used in the clinic for specific circumstances. Advances in the development of genomic biomarkers will improve the prediction and detection of hepatic injury in future. Establishing a definitive clinical diagnosis of DILI can be difficult, since it is based on circumstantial evidence by excluding other aetiologies and, when possible, identifying a drug-specific signature. DILI signals based on standard liver test abnormalities may be affected by underlying diseases such as hepatitis B and C, HIV and cancer, as well as the concomitant use of hepatotoxic drugs to treat some of these conditions. Therefore, a modified approach to DILI assessment is justified in these special populations and a suggested framework is presented that takes into account underlying disease when evaluating DILI signals in individuals. Detection of idiosyncratic DILI should, in some respects, be easier in the postmarketing setting compared with the clinical development programme, since there is a much larger and more varied patient population exposure over longer timeframes. However, postmarketing safety surveillance is currently limited by the quantity and quality of information available to make an accurate diagnosis, the lack of a control group and the rarity of cases. The pooling of multiple healthcare databases, which could potentially contain different types of patient data, is advised to address some of these deficiencies.

Peginterferon alfa-2a plus ribavirin for HIV-HCV genotype 1 coinfected patients: a randomized international trial.

BACKGROUND: The safety and efficacy of weight-based ribavirin (RBV) dosing regimens in patients with HIV-HCV coinfection has not been demonstrated in randomized clinical trials. OBJECTIVE: This randomized, double-blind, international, parallel-group study in specialist outpatient clinics in the United States, Spain, and Portugal compares the efficacy and safety of 2 RBV dose regimens (800 mg/day and 1000/1200 mg/day) combined with peginterferon alfa-2a (40KD) in patients with HIV-HCV (genotype 1) coinfection. METHODS: Patients with HIV-HCV coinfection, quantifiable HCV RNA in serum, HCV genotype-1 infection, compensated liver disease, and stable HIV disease (CD4+ count ≥100 cells/µL) with or without ongoing antiretroviral therapy were randomized to 48 weeks' treatment with RBV at standard dose (800 mg/day) or weight-based dose (1000 mg/day for patients weighing <75 kg; 1200 mg/day for patients weighing ≥75 kg) in combination with peginterferon alfa-2a (40KD) 180 µg once a week. Planned enrollment was 400 patients with ≥100 non-Latino African Americans. The primary endpoint was sustained virological response (SVR) (undetectable HCV RNA [<20 IU/mL] at the end of a 24-week untreated follow-up period [week 72]). RESULTS: SVR rates were 19% (26/135) and 22% (60/275) in patients randomized to RBV 800 mg/day and 1000/1200 mg/day, respectively (odds ratio, 1.15; 95% CI, 0.68-1.93; P = .6119). In the 1000/1200 mg/day RBV dose group, the incidence of hemoglobin reductions <100 g/L and anaemia reported as an adverse event were higher versus the standard 800 mg/day RBV dose group. CONCLUSIONS: Compared with the standard RBV dose (800 mg/day), weight-based RBV dosing (1000/1200 mg/day) did not significantly increase SVR rates, but did increase the incidence of anemia in HIV-HCV (genotype 1) coinfected patients.

Prevalence of hepatitis C and coinfection with HIV among United States veterans in the New York City metropolitan area.

OBJECTIVES: The aims of this study were to determine the prevalence of hepatitis C virus (HCV) infection and its risk factors, as well as the prevalence of coinfection with HIV and its risk factors, among patients with confirmed HCV infection. METHODS: In a 1-day cross-sectional HCV survey at six Veterans Affairs Medical Centers in the New York City metropolitan area, all 1943 patients undergoing phlebotomy for any reason were asked to be tested for HCV antibody by enzyme immumoassay (EIA). A total of 1098 patients (57%) agreed to HCV testing, 1016 of whom also completed a questionnaire on demographics and HCV risk factors. All HCV EIA(+) samples were confirmed by HCV RNA and HCV recombinant immunoblot assay (RIBA) antibody testing and were also tested for HCV viral load, HCV genotype, and antibodies to HIV in a blinded fashion. RESULTS: The prevalence of confirmed HCV infection was 10.6% (95% CI = 8.7-12.4%), and the prevalence of HCV viremia was 8.2% (95% CI = 6.6-9.8%). The rate of HCV viremia among anti-HCV(+) patients was 77.6%, and HCV genotype 1 was present in 87.5% of viremic patients. Independent risk factors for HCV infection were injection drug use (OR = 35.6, 95% CI = 16.9-75.2), blood exposure during combat (OR = 2.6, 95% CI = 1.2-5.7), alcohol abuse (OR = 2.4; 95% CI = 1.2-4.8), and service in the Vietnam era (OR = 2.1; 95% CI = 1.0-4.5). Coinfection with HIV was present in 24.8% of anti-HCV(+) patients. The only independent risk factor for coinfection was age <50 yr (OR = 3.7, 95% CI = 1.1-12.1). CONCLUSIONS: U.S. veterans who are receiving medical care at VA medical centers in the New York City metropolitan area have a much higher rate of chronic hepatitis C than the general population, with a high frequency of genotype 1. Coinfection with HIV is very common in patients with confirmed HCV infection, and these patients should routinely be offered HIV testing.