Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications,such as mixed cryoglobulinemia or renal failure.

Early renal failure as a cardiovascular disease:Focus on lipoprotein(a) and prothrombotic state

Patients with renal failure are at increased risk of cardiovascular events even at the earliest stages of disease.In addition to many classic cardiovascular risk factors,many conditions that are commonly identified as emerging risk factors might contribute to occurrence of cardiovascular disease.Changes in circulating levels of many of these emerging risk factors have been demonstrated in patients with early stages of renal failure caused by different types of renal disease and have been associated with detection of cardiovascular complications.However,for most of these factors evidence of benefits of correction on cardiovascular outcome is missing.In this article,we comment on the role of lipoprotein(a) and prothrombotic factors as potential contributors to cardiovascular events in patients with early renal failure.

Kidney in primary aldosteronism: A key determinant of treatment outcome

Recently, it has been suggested that primary aldosteronism(PA) is associated with a variety of cardiac,vascular, metabolic, and renal sequelae that reflect the capability of elevated aldosterone to induce organ damage beyond that induced by hypertension itself. The evidence supporting of these views has been obtained from experiments conducted in rodents and clinica studies conducted in patients with this endocrine disorder. It has been suggested that untoward effects of high-salt intake are dependent on activation of mineralocorticoid receptors that might result from increased oxidative stress and changes in the intracellular redox potential. Unilateral adrenalectomy or treatment with mineralocorticoid receptor antagonists are the current options for treating an aldosterone-producing adrena adenoma or idiopathic adrenal hyperplasia. Treatments are largely effective in correcting hypertension and hypokalemia, and currently available information on their capability to prevent deterioration of renal function indicates that surgery and medical treatment are equallybeneficial in the long term. This editorial review will focus on the renal aspects of PA and highlights the role of the kidney as a key determinant of both adaptation to aldosterone-induced volume retention and response of blood pressure to treatment.

Diabetes, diabetic complications, and blood pressure targets

Association of diabetes with hypertension is frequent and it well known that high blood pressure potentiates the probability of diabetic patients to develop macrovascularand microvascular complications. Strong evidence obtained in a number of large scale prospective studies indicates that adequate blood pressure control in diabetic patients is highly beneficial for prevention of cardiovascular events. Nonetheless, only a limited proportion of hypertensive-diabetic individuals included in studies on anti-hypertensive treatment has met the predefined blood pressure goal. The optimal blood pressure goal to be pursued in diabetic patients with hypertension to guarantee effective protection from cardiovascular outcomes is still under intense debate and recommendations of current guidelines on hypertension treatment are still inconsistent. We comment here on the most important studies and conclude that current evidence does not conclusively support the need to reach a blood pressure target in hypertensive patients with diabetes different from nondiabetic hypertensive individuals.