Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study.

The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicentre prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centres; they underwent clinical, biochemical, ultrasound and transient elastography evaluations before treatment (T0), 12 weeks (SVR12) and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 vs 11.1 kPa, p = .002), with a progressive reduction until T24 (8.7 kPa, p < .001). However, only patients with steatosis and those who developed HCC did not experience a late improvement in LS. Multivariate analysis of baseline and follow-up variables identified steatosis as the only independent predictor of failure of LS improvement (OR 1.802, p = .013). ROC curve analysis of the association of LS with the risk of developing HCC showed that SVR12 ≥14.0 kPa had the highest accuracy (sensitivity 82%, specificity 99%; AUC: 0.774). Multivariate analysis revealed that LS was the only variable independently associated with an increased risk of developing HCC (OR 6.470, p = .035). Achieving an SVR was associated with a progressive, long-term decline of LS, suggesting a late improvement in liver fibrosis, besides the resolution of inflammation. Fatty liver and the development of HCC interfered with late reduction of LS. Patients with an LS ≥14 kPa at 12 weeks after the end of treatment were at higher risk for developing HCC.

Reduced incidence of type 2 diabetes in patients with chronic hepatitis C virus infection cleared by direct-acting antiviral therapy: A prospective study.

AIM: To assess the effect of hepatitis C virus (HCV) eradication on type 2 diabetes mellitus (T2DM). incidence. METHODS: A prospective multicentre case-control study was performed, which included 2426 patients with HCV, 42% of whom had liver fibrosis stage F0-F2 and 58% of whom had liver fibrosis stage F3-F4. The study population consisted of a control group including 1099 untreated patients and 1327 cases treated with direct-acting antivirals (DAAs). T2DM incidence was assessed during a median (interquartile range) follow-up period of 30 (28-42) months. Risk factors for T2DM were assessed using a Cox regression model (relative risk [RR], hazard ratio [HR], Kaplan-Meier analysis). Insulin sensitivity was evaluated by homeostatic model assessment (HOMA) and changes by repeated-measures ANOVA. Factors independently associated with T2DM were assessed by multivariate analysis. RESULTS: The absolute incidence of T2DM for controls and cases was 28 and 7/1000 person-years, respectively (P = 0.001). In cases compared to controls, HCV clearance reduced the RR and HR of T2DM by 81% and 75% to 93%, respectively (P = 0.001). It was calculated that, for every 15 patients who obtained HCV clearance, one case of T2DM was saved. HCV clearance was associated with significant reductions in HOMA-insulin resistance and HOMA-ß-cell function and an increase in HOMA-insulin sensitivity, as assessed in 384 patients before and after HCV clearance. At multivariate analysis, HCV clearance emerged as independently associated with a reduced T2DM risk. CONCLUSION: The results showed that HCV clearance by DAA treatment reduces T2DM incidence probably by restoring the HCV-induced alteration of glucose homeostasis mechanisms.

Efficacy of the "first wave" Direct Acting antivirals against HCV infection: results from the Italian LINA (Liver Network Activity) cohort.

Approximately 71 million people are chronically infected with HCV worldwide. Recently, interferonfree therapies effective against HCV became available and nowadays, therapeutic strategies include a combination of two or three drugs with different mechanisms of action. In the present study, we reported real-life SVR rates in a large cohort of four prescribing centers in a high-endemic area of Southern Italy. We conducted a prospective multicenter study among all the patients with chronic HCV infection, who received therapy with the first available interferon-free therapies between March 2015 and December 2017 and who referred to one of the 4 DAA-prescribing centers in Campania, Southern Italy. Patients with Child C cirrhosis, a diagnosis of active HCC at the baseline or who refused the consent form, were excluded. Nine-hundred fifty-three patients were enrolled. Most of the enrolled patients had HCV genotype 1b infection (66.4%), were older than 65 years (64.1%) and had advanced liver fibrosis (Metavir > F4) (73.5%). The overall SVR12 rate was 98.5%. Patients with clinical cirrhosis had a similar SVR12 rate compared with those without cirrhosis (97.8% vs 99.2%, p=0.09), while patients with decompensated cirrhosis had a significantly lower rate of SVR12 compared with those without decompensated disease (95.3% vs 99.0%, p<0.05). Patients aged more than 65 years had a similar rate of SVR12 compared with patients aged ≤ 65 years (98.6% vs 98.0%, p=0.57). Among patients >65 years, those with clinical cirrhosis, as well as those with advanced liver fibrosis, had a similar SVR12 rate compared with the patients with a Metavir score < F4 (98.3% vs 99.0%, p=0.70 and 98.6% vs 98.6%, p=1.00, respectively). In the present, real-life study, DAA regimens are effective and safe in patients with chronic HCV infection, regardless of age and stage of liver disease, providing very high rates of SVR12 (98.5%).

Hepatitis C Virus Micro-Elimination Plan in Southern Italy: The "HCV ICEberg" Project.

This study evaluates the feasibility of a local action program for HCV micro-elimination in highly endemic areas. Retrospective analysis: administrative and laboratory data (Local Health Unit, southern Italy) were integrated to quantize the anti-HCV-positive subjects not RNA tested and untreated HCV-infected subjects (2018-2022). Prospective analysis: all subjects admitted to a division of the LHU largest hospital (2021-2022) were tested for HCV, with linkage of active-infected patients to care. Overall, 49287 subjects were HCV-Ab tested: 1071 (2.2%) resulted positive without information for an HCV RNA test and 230 (0.5%) had an active infection not yet cured. Among 856 admitted subjects, 54 (6.3%) were HCV-Ab+ and 27 (3.0%) HCV RNA+. Of HCV-infected patients, 22.2% had advanced liver disease, highlighting the need for earlier diagnosis; 27.7% were unaware of HCV infection; and 20.4% were previously aware but never referred to a clinical center. Of these, 26% died and 74% received treatment. Our study emphasizes the value of an active HCV hospital case-finding program to enhance diagnosis in patients with several comorbidities and to easily link them to care. Our data strongly suggest extending this program to all hospital wards/access as a standard of care, particularly in highly endemic areas, to help HCV disease control and take steps in achieving the elimination goals.

Changing epidemiology of patients treated with direct acting antivirals for HCV and persistently high SVR12 in an endemic area for HCV infection in Italy: real-life 'LIver Network Activity' (LINA) cohort update results.

BACKGROUND: Second generation direct acting antivirals (DAAs) drastically changed the landscape of chronic HCV (CHCV). Aim of this paper was to assess the effectiveness of DAAs, also looking at the demographic characteristics of subjects enrolled. RESEARCH DESIGN AND METHODS: Ambispective multi-center real-life study conducted among patients with CHCV treated with DAAs in Campania Region (Southern Italy). Patient were enrolled in two cohorts according to time of enrolment. RESULTS: 1,479 patients were enrolled. Patients aged ≥60 years were 74.7% in the historic cohort (953 patients) and 70.2% in the prospective cohort (526 patients. Patients aged ≥ 60 years showed a higher prevalence of genotype 1b (p<0.001) and 2 (p<0.001), while patients aged < 60 years showed a higher prevalence of genotype 1a (p<0.001), 3 (p<0.001) and 4 (p<0.05). SVR12 was 98.5% in both cohorts. SVR12 was similar among patients of the prospective cohort aged < and ≥ 60 years (99.4% vs 98.1%). SVR12 among patients with and without cirrhosis was 96.0% and 98.9%, respectively. CONCLUSIONS: DAAs provide high efficacy also in harder to treat patients. The effectiveness of DAAs is leading to a shift in patients characteristics with a greater prevalence of younger subjects and persons with mild liver disease.

Screening, Linkage to Care and Treatment of Hepatitis C Infection in Primary Care Setting in the South of Italy.

Hepatitis C virus (HCV) infection remains a pressing public health issue. Our aim is to assess the linkage to care of patients with HCV diagnosis and to support the proactive case-finding of new HCV-infected patients in an Italian primary care setting. This was a retrospective cohort study of 44 general practitioners (GPs) who managed 63,955 inhabitants in the Campania region. Adults with already known HCV diagnosis or those with HCV high-risk profile at June 2019 were identified and reviewed by GPs to identify newly diagnosed of HCV and to assess the linkage to care and treatment for the HCV patients. Overall, 698 HCV patients were identified, 596 with already known HCV diagnosis and 102 identified by testing the high-risk group (2614 subjects). The 38.8% were already treated with direct-acting antivirals, 18.9% were referred to the specialist center and 42.3% were not sent to specialist care for treatment. Similar proportions were found for patients with an already known HCV diagnosis and those newly diagnosed. Given that the HCV infection is often silent, case-finding needs to be proactive and based on risk information. Our findings suggested that there needs to be greater outreach, awareness and education among GPs in order to enhance HCV testing, linkage to care and treatment.

Direct acting antivirals treatment for hepatitis C virus infection does not increase the incidence of de novo hepatocellular carcinoma occurrence: Results from an Italian real-life cohort (LINA cohort).

The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection is ascertained. However, some authors raised the issue of an increased incidence of de novo hepatocellular carcinoma (HCC) in patients treated with DAAs. Aim of the study was to evaluate the rate of HCC occurrence in a real-life cohort of patients who received anti-HCV treatment with DAAs.A prospective multicentre study was conducted. All adult patients with HCV infection who received treatment between March 2015 and December 2017 in 4 hospital of Campania region (South Italy) with at least 6 months of follow-up were enrolled.A total of 323 patients were included in the study. Most patients had HCV genotype 1b (61.8%). The overall SVR12 rate was 95.5%. Median time of observation was 10 months. The incidence rate of HCC was 0.2 per 100 person-months (crude incidence rate 3.4%, 95 confidence interval: 1.5%-5.3%). The median time for HCC occurrence was 11 months. HCC occurrence rate was significantly higher among patients who did not achieve SVR12 compared with patients who did (28.6% vs 2.8%, P < 0.05). No patient with F0-F3 fibrosis developed HCC. Among patients with cirrhosis, at the multivariate time-to-event analysis, no covariates were independently associated with the risk of HCC occurrence.Treatment with DAAs did not increase the risk of HCC occurrence. Patients who achieved SVR12 had a lower rate of HCC occurrence. Further studies are needed to estimate the incidence and the risk for HCC in the long-term follow-up among patients undergoing treatment with DAAs.

Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: A prospective multicentre study.

BACKGROUND AND AIMS: HCV is associated with an increased risk of cardiovascular events (CV). Whether HCV clearance by direct-acting antivirals (DAA) reduces incident CV disease is poorly understood. We investigate whether HCV eradication reduces CV events. METHODS: In a prospective multicentre study, 2204 HCV patients (F0-F2:29.5%, F3-F4: 70.5%) were enrolled. Males were 48%, median age was 68 (59-74) years and BMI 25.9 (23.1-28); 24.7% were smokers, 18% had diabetes, 13.2% had cholesterol levels >200 mg/dl and 9.1% took statins, 44% had hypertension. During an overall median follow-up of 28 (24-39) months, incident CV events, such as ischemic heart disease (IHD) and ischemic cerebral stroke (ICS), were recorded. An overall of 2204 patients were evaluated as control group and 1668 patients after HCV elimination were followed as a case group. Factors associated with CV events were evaluated by uni- and multi-variate analyses. RESULTS: Incident CV rates per 100 patient years in pre-treatment and untreated controls and treated cases were 1.12, 1.14 and 0.44 (p = 0.0001 vs. controls), respectively, and a decreased of relative risk (RR = 0.379; p = 0.0002) was observed. CV risk was 2.0-3.5 times lower then in controls (HR 3.671; 95%C.I.:1.871-7.201; p < 0.001). The calculated number of patients to be treated to get a benefit in a patient was 55.26. The annual incidence reduction of CV events was 0.68%. HCV clearance was independently associated with CV events reduction (OR, 4.716; 95% C.I.:1.832-12.138; p = 0.001). CONCLUSIONS: HCV clearance by DAA reduces CV events (IHD and ICS) with both clinical and socio-economic benefits.

Interferon-free regimens improve kidney function in patients with chronic hepatitis C infection.

BACKGROUND AND AIM: The impact of directly acting antiviral agent (DAA) regimens on renal function is not well defined and quite controversial. We evaluated the effect of DAAs on kidney function and the factors associated with an improvement or worsening. PATIENTS AND METHODS: The changes in estimated glomerular filtration rate (eGFR) in a cohort of 403 patients treated with a DAA regimen were evaluated. RESULTS: The overall sustained virological response (SVR12) rate was 98%. The median eGFR progressively increased throughout treatment from 84.54 ml/min/1.73 m2 (IQR 70.8-97.3) to 88.12 ml/min/1.73 m2. Conversely, rates of patients with a eGFR more than 60 ml/min/1.73 m2 progressively increased from 83.1% at baseline to 87.8% at 12 weeks post-treatment (p < 0.05). Considering the change in eGFR according to the different factors, a significant improvement in eGFR was observed in the patients without diabetes (p < 0.001), in those with cirrhosis (p < 0.05), in those receiving a Sof-based regimen (p < 0.01) or not receiving RBV (p < 0.05), in those with a baseline eGFR less than 60 ml/min/1.73 m2 (p < 0.001) and in those with SVR (p < 0.05). An improvement in eGFR (defined as an increase in baseline eGFR of at least 10 ml/min/1.73 m2) was observed in 148 patients (36.7%). At multivariate analysis, age (aHR 0.96; 95 CI 0.93-0.99, p < 0.01) and a diagnosis of diabetes (aHR 0.02; 95 CI 0.20-0.87, p < 0.05) were inversely and independently associated with improvement in renal function, while the presence of Child-Pugh B cirrhosis at baseline was associated with an improvement in renal function (aHR 3.07; 95 CI 1.49-6.30, p < 0.01). CONCLUSIONS: DAAs correlate with an improvement in renal function, underlining the importance of hepatitis C virus eradication to achieve also an improvement in extra-hepatic disorders.

Treatment with direct-acting antivirals improves the clinical outcome in patients with HCV-related decompensated cirrhosis: results from an Italian real-life cohort (Liver Network Activity-LINA cohort).

BACKGROUND: Direct-acting antivirals (DAAs) are safe and effective for the treatment of HCV infection. However, data regarding their efficacy in patients with Child-Pugh B cirrhosis are scarce and their capability in improving liver function is debated. The aim of our study was to assess the clinical benefits of treatment with DAA in subjects with Child-Pugh B cirrhosis. METHODS: We conducted a prospective multicentre study among patients with Child-Pugh B cirrhosis of an Italian real-life HCV cohort (LINA cohort) who received treatment with DAAs. RESULTS: Among 89 patients enrolled, the rate of sustained virologic response 12 was 95.5%. No discontinuation occurred, no patient died during treatment. Most patients had Genotype 1 (1b 61.8%, 1a 11.2%). Conversely, 22.5%, 1.1% and 3.4% of patients had Genotype 2, 3 and 4, respectively. At last observation, 61.8% of patients switched to a Class A cirrhosis, 33.7% remained in Class B and 4.5 worsened to Child C (p < 0.001). Liver parameters significantly improved from baseline to 12 weeks after the end of treatment. Previous anti-HCV treatments and the presence of decompensated cirrhosis at 1 month of treatment were significantly associated with a decompensated cirrhosis at the last observation. CONCLUSIONS: Treatment with DAA in patients with Child-Pugh B cirrhosis is safe and leads to a very high rate of viral clearance, a significant rate of re-compensation and an improvement in liver function. Further studies are needed to assess the impact of treatment on survival and quality of life in long-term follow-up.

Dietary pattern and blood pressure control in a hypertension outpatient clinic.

Although it is well known that some dietary measures are able to beneficially affect blood pressure (BP) levels, hypertensive patients find it very difficult to definitively change their nutritional habits. The aim of this study was to evaluate the effects on BP of a return to the habitual diet following a dietary intervention period. Three hundred and seven hypertensive patients (149 females, 158 males) with a mean age of 52+/-12 years were included in the study. All enrolled patients had reported having reverted to their habitual diet after a period of at least 6 months on a prescribed low-energy and/or low-sodium diet. Nutritional habits were investigated by a simple semiquantitative 24-item food-frequency questionnaire. Patients were divided into tertiles according to their systolic BP. The groups differed in regard to their body mass index (27.6+/-4, 28.7+/-4, and 30.4+/-6 kg/m(2), respectively, for the low- to high-systolic BP groups, but were similar in regard to the number of antihypertensive pills taken (2.1+/-0.9, 2.2+/-1.2, 2.2+/-1.3) and metabolic parameters. Patients in the lowest tertile consumed a diet significantly lower in the percentage of energy from saturated fats and sodium content and significantly higher in the percentage of energy from carbohydrate, and the fiber and potassium content in comparison to the highest tertile. The number of servings of legumes, fish and cooked vegetables was higher and that of salami and cheese lower in the 1st tertile. Definitively changing a habitual diet to a healthier one is a difficult task for hypertensive patients. However, those who return to a diet richer in vegetables, legumes and fish and poorer in saturated fat and salt achieve better control of their BP, without increasing the number of antihypertensive pills.

Lifestyle educational program strongly increases compliance to nonpharmacologic intervention in hypertensive patients: a 2-year follow-up study.

The authors investigated the efficacy of a lifestyle educational program, organized in small group meetings, in improving the outcome of a nonpharmacologic intervention. One hundred and eighty-eight hypertensive patients with stable blood pressure (BP) levels and drug therapy in the previous 6 months were randomly divided into educational care (EC) and usual care (UC) groups. They were followed at 3-month intervals up to 2 years. In addition to the visits in an outpatient clinic, patients in the EC program participated in small group meetings in order to improve their knowledge of the disease and reinforce their motivation for treatment. At baseline, EC and UC groups were similar for age, sex, body mass index (BMI), blood pressure (BP) levels, and pharmacologic treatment. Patients in the EC group had significantly reduced total energy, total and saturated fats, and sodium intake. Physical activity was significantly increased in the EC group as well. At the end of the 1-year follow-up, BMI (P<.001), visceral fat (P<.001), and BP (P<.001) were significantly lower in the EC group compared with the UC group. Pharmacologic treatment during the study was similar for all classes of drugs apart from diuretics whose dose was higher in the UC group at the end of the study.