A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study.

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child-Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients.

Systematic review: interferon-free regimens for patients with HCV-related Child C cirrhosis.

BACKGROUND: It is unclear whether the efficacy and long-term outcome of treating patients with hepatitis C virus (HCV)-positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis. AIM: To assess the effectiveness of the interferon-free regimens in Child C cirrhotic patients with HCV infection. METHODS: A systematic Medline search was conducted to retrieve studies describing the treatment of Child C patients with direct-acting agents. Citations from identified studies were cross-referenced and abstracts from European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD) meetings were checked. Extracted data were evaluated using a meta-analysis to calculate a weighted response rate. RESULTS: Seven full-text records and two conference abstracts were retained for analysis from the 649 records identified. Data from an Italian real-life trial were also interrogated. Information on treatment outcome was available for 228 of the 240 Child C patients evaluated in the 10 trials. Overall, the weighted mean sustained virological response (SVR12) was 74.9% (95% CI: 65.6-82.4%). Neither duration of treatment (24 or 12 weeks), nor addition of ribavirin influenced these rates. The weighted SVR12 was 65.4% (95% CI: 46.8-80.2) after sofosbuvir/simeprevir, 76.0% (95% CI: 54.4-89.3%) after sofosbuvir/daclatasvir and 83.0% (95% CI: 73.4-89.6) after sofosbuvir/ledipasvir. Some studies did not provide information on the rate of post-treatment relapse or functional improvement. However, in those studies that did provide such data, a relapse was documented in 12.1% of patients and an improvement of ≥2 points on the model for end-stage liver disease (MELD) score in 61.1% of patients. CONCLUSION: The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents.

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome.

AIM: To evaluate similarities and differences in HCV-1 subtypes 1a and 1b in the presenting clinical features and the response to peg-interferon and ribavirin (Peg/RIBA). PATIENTS AND METHODS: A total of 1,233 naïve patients with HCV genotype-1 infection, 159 (13%) with subtype 1a and 1,074 (87%) with subtype 1b were treated with Peg-IFN/RIBA at 12 Italian centers. Covariates included in the logistic model were age, gender, BMI, serum alanine aminotransferase, serum gamma-glutamiltranspeptidase (γGT), platelets counts, liver fibrosis, the occurrence of type 2 diabetes, baseline viremia, and IL28B genotype. RESULTS: At multivariate analysis, baseline characteristics differentiating patients with HCV-1a versus HCV-1b were young age, male gender, no F4 fibrosis, and no diabetes. SVR was achieved by 37% of patients with subtype 1b and 45% of those with subtype 1a, a nonsignificant difference of 8% (p = 0.069). In patients with subtype 1a, predictors of SVR were IL28B CC (OR 5.78, CI 1.98-16.83), RVR (OR 4.18, CI 1.66-10.55), female gender (OR 2.83, CI 1.83-6.78), and HCVRNA (OR 0.55, CI 0.32-0.96). In patients with subtype 1b, the ranking of predictors was levels RVR (OR 6.49, CI 4.32-9.73), IL28B CC (OR 3.32, CI 2.15-4.58), γGT (OR 1.59, CI 0.14-2.22), HCVRNA (OR 0.61, CI 0.47-0.79), and age (OR 0.01, CI 0.02-0.42). CONCLUSION: In Italy HCV-1 subtype 1a prevails in young male patients with less advanced liver damage, findings that imply a more recent spreading of the infection with this viral strain. The two HCV-1 subtypes appear equally responsive to Peg-IFN/RIBA, with IL28B genotyping and monitoring of RVR mostly influencing the therapeutic response.

Evaluation of the effectiveness of a hyperoxidized oil-based medication in the treatment of skin lesions: observational study.

AIM: Aim of the study was to demonstrate the effectiveness, in the management of recalcitrant wounds, of a hyperoxidized oil-based gel with film-forming and protective functions. METHODS: The study involved 50 patients with recalcitrant not infected and/or necrotic chronic ulcers. All patients had 0.7 minimum ABPI value; terminal and/or cancer and/or under immunosuppressive therapy patients were excluded. The dressing consisted in a uniform gel layer applied on the lesion, after cleansing with a 0.05% sodium hypochlorite chloroxidating solution. The dressing was changed every 48 hours (or every 24 hours, in case of hyperexuding wound). The effectiveness was assessed by the evaluation of the WBP score changes and area reduction (via the Visitrak™ Digital System) after an observation period of 4 weeks. RESULTS: All patients achieved area improvement; WBP score improved in more than 90% of the B score patients; pain reduction was reported by all patients: more than 55% of the total number of patients limited the use of analgesic drugs and in 6 cases (12%) they discontinued the antalgic therapy. CONCLUSION: The dressing showed an actual effectiveness, promoting granulation and accelerating epithelialization; no patient suffered from allergy/intolerance and all of them reported a decrease in pain, until complete relief.

Long-term outcome of hepatitis B virus-related Chronic Hepatitis under protracted nucleos(t)ide analogues.

Long-term outcome of patients with chronic hepatitis B virus (HBV) infection under continuous nucleos(t)ide analogues (NUCs) has been poorly elucidated. We enrolled 121 anti-HBe-positive patients into a prospective surveillance programme while on (>36 months) NUCs therapy. HBV-DNA clearance, add-on therapy and safety were evaluated. Development of cirrhosis, events of liver decompensation and hepatocellular carcinoma (HCC) during the follow-up were the main endpoints, as the complication-free survival. At baseline, 74 patients (61%) had chronic hepatitis, the remainders a cirrhotic liver. HBV-DNA levels >38 000 IU/mL were discovered in 103 patients. At enrolment, 79 patients were naïve to NUCs treatment. Lamivudine monotherapy (n = 70) or a different NUC (n = 51) was administered. At month 6 of therapy, HBV-DNA clearance was documented in 88 patients (73%). Treatment schedule was modified in 52 patients due to breakthrough or suboptimal response. During a mean follow-up of 6 ± 3 years, viral clearance was achieved in the majority of patients. Ten of 74 patients (13.5%) with chronic hepatitis progressed to cirrhosis, 1 patient developed a HCC. In the 47 patients with cirrhosis at presentation, HCC occurred in 14 (30%) and liver decompensation in 5 (11%). The 5 and 10-year event-free survivals were, respectively, 89.3% (95% CI, 81.7 -96.9) and 75.6% (95% CI, 61.5 -89.7) for patients with chronic hepatitis, and 70.2% (95% CI, 56.3 -84.1) and 40.4% (95% CI, 16.9 -63.9) for those with cirrhosis. Protracted, effective treatment with oral NUCs affects the natural history of chronic HBV infection by reducing the incidence of cirrhosis and risk of complications, but does not guarantee against the development of HCC in cirrhosis at presentation.

A controlled, randomised study on the efficacy of two overlays in the treatment of decubitus ulcers.

AIM: The aims of this study were to evaluate the performance and effectiveness of an antibedsore overlay in 3D structure of new conception towards an overlay of common use. Evaluation parameters: wound area reduction, healing, safety and comfort. METHODS: Open randomized multicenter study comparing the two overlays for the treatment and prevention of pressure sores. Patients were recruited in long-term carewards. Recruitment and randomization systems were made using envelopes, with goal of 70 patients with pressure ulcers from I to IV degree. Observation period was extended for 12 weeks. Data collection was made using paper CRF. RESULTS: We enrolled 72 patients: 35 in the study group and 37 in the control. The two groups were similar. Mortality during the observation period was 13.8% (unrelated events). Approximately 50% of patients withdrew from the study before the end (trend in favor of the overlay three-dimensional). The resolution of the lesions occurred in 8 cases (11.1%), 3 cases in the overlay 3D and 5 in the gel group (P=NS). The reduction of the area was in favor of the three-dimensional overlay (P<0.005%), data with significance were obtained also in patient comfort (P=0.08) and ease of care (P<0.001). CONCLUSION: The first objective of this study was to evaluate the effectiveness of an innovative antibedsore overlay versus a commonly used one. The data obtained showed a better performance, both in terms of treatment of lesions and in terms of comfort for the patients and the operators.

Unawareness of HBV infection among inpatients in a Southern Italian hospital.

Hepatitis B virus (HBV) infection may run undetected. Unawareness of an ongoing infection delays the diagnosis of HBV-related liver disease and favours the spread of the virus. We have evaluated among hepatitis B surface antigen-positive (HBsAg) inpatients admitted to a Southern Italian hospital the proportion of those aware of their carrier status and correlated the status to signs of liver disease. All patients admitted to the San Giovanni Rotondo Hospital from March 2008 to July 2009 were tested for HBV and hepatitis C virus (HCV) markers, and those positive for HBsAg were interviewed and underwent examinations for liver function and abdominal ultrasound. Overall, of 25,000 patients admitted during the observation period 311 (1.2%) were positive for HBsAg, most of them (98%) being anti-HBe positive. HCV and HDV co-infections were ascertained in 2.9% and 0.6% of cases, respectively. Two hundred and fifty-three subjects (81%) agreed to undergo further investigation, 132 of them (52%) were HBV-DNA positive. One hundred and two patients (40.3%) were unaware of their infection; this was encountered among 29% of HBV-DNA-positive and 52% of HBV-DNA-negative subjects (P < 0.01). Subjects already aware of their infection were more likely to present with abnormal alanine aminotransferase (ALT) levels (27%vs 15%), serological presence of HBV-DNA (63.6% vs. 36%) and liver cirrhosis (30%vs. 13%). A high proportion of HBsAg-positive patients (40.3%) were unaware of their infection, which had evolved to the stage of liver cirrhosis in a consistent percentage of them.

Cold thyroid nodule reduction with L-thyroxine can be predicted by initial nodule volume and cytological characteristics.

In a previous study we demonstrated that a 1-yr treatment with L-T4 induces substantial nodule volume reduction (> or = 50%) in approximately 40% of patients with a benign solitary cold thyroid nodule. The present prospective study investigated whether it is possible to identify, before starting L-T4 treatment, nodules with a high probability to shrink in response to L-T4. We recorded several clinical and cytological features in a continuous series of 42 patients with a cold nodule and related them to the nodule volume response to 1-yr treatment with L-T4. Fisher discriminant analysis showed that a combination of some cytological features (colloid, degenerative changes, cellular hyperplasia, and fibrosis) and initial nodule volume can be used for predicting nodule volume reduction. In fact, although only 33% of all nodules shrank, 62% of colloid nodules and 57% of small degenerative nodules shrank. None of the hyperplastic or fibrotic nodules shrank. These results were validated in a different retrospective series of 46 patients and allowed us to predict nodule reduction in over 80% of the cases.

Assessment of the value of treatment with granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a randomized clinical trial.

The present trial was designed to test the effects of G-CSF on the duration of the second phase of induction chemotherapy in children with newly diagnosed acute lymphoblastic leukemia (ALL). A total of 32 patients were assigned randomly to a group that received (14 patients; group A) or a group that did not receive (18 patients; group B) G-CSF (10 g/kg/day subcutaneously and daily) throughout of the second phase of induction therapy. One of 14 (7.1%) patients in group A and 2 of 18 (11.1%) patients in group B completed the course of chemotherapy within the planned time. The median length of this phase was 37 days (range, 29 to 65; mean, 40; SD, 8.6) for patients in group A and 36 days (range, from 29 to 55; mean, 38; SD, 7.4) for those in group B, and the difference was not statistically significant. The number of days during which patients had granulocyte counts of less than 2 x 10(9)/l, the number of febrile episodes of unknown origin, the number of bacterial and fungal infections and the number of days of hospitalization did not differ in a statistically significant manner between the two groups. Our data suggest that G-CSF supportive therapy may be unnecessary in children with neutropenia of short duration, for whom the risk of infection is low.

6-Mercaptopurine cumulative dose: a critical factor of maintenance therapy in average risk childhood acute lymphoblastic leukemia.

A multivariate survival analysis including gender, age, log white blood cell (WBC) count, liver and spleen size at diagnosis, mean log WBC count during maintenance therapy, and the prescribed cumulative doses of 6-mercaptopurine (6-MP), methotrexate (MTX), vincristine (VCR), and prednisone (PDN) during maintenance therapy was performed on 53 children with average-risk acute lymphoblastic leukemia (ALL). The 6-MP cumulative dose prescribed during maintenance therapy resulted in the most important statistically significant independent prognostic factor. Patients who received less than the median cumulative dose of 6-MP (86% of planned protocol dose) fared significantly worse than the other patients, regardless of WBC count at diagnosis, gender, age, and other factors studied. Therefore, 6-MP cumulative dose during maintenance therapy may be the critical factor for effective maintenance therapy in childhood ALL.

Incidence and morbidity of infection by hepatitis C virus in children with acute lymphoblastic leukaemia.

A group of 90 patients with acute lymphoblastic leukaemia (ALL) in first continuous complete remission (CCR), admitted in our hospital between January 1986 and September 1992, were tested for the presence of antibodies against hepatitis C virus (HCV), antibodies against hepatitis B virus and antibodies against HIV-1 during maintenance therapy or thereafter. They were compared with a group of 71 children with other malignancies in first CCR who had been diagnosed consecutively from January 1986 to September 1992. No patient with ALL or any other malignancy was found to be positive for hepatitis B surface antigen or HIV-1. HCV-specific antibodies were detected in 28 out of 87 children (32.1%) with ALL and in 4 out of 44 patients (9%) with malignancies other than ALL who had received at least one transfusion of blood or platelets (P < 0.01). HCV-specific antibodies were also detected in one out of three untransfused children with ALL but in none of the untransfused children with malignancies other than ALL. HCV-specific seropositivity influenced the management of children with ALL during maintenance therapy. In fact, as a result of abnormal liver function tests, maintenance therapy had to be suspended significantly more often in the case of HCV-seropositive patients with ALL than in HCV-seronegative ones. Despite the high morbidity during maintenance therapy, chronic liver disease (CLD) was uncommon in both groups: five children with ALL (17.2% of HCV-seropositive children) and one child with a malignancy other than ALL (25%) had CLD.(ABSTRACT TRUNCATED AT 250 WORDS)