Porphyria cutanea tarda in an HCV-positive liver transplant patient: a case report

Introduction. Porphyria cutanea tarda (PCT) is the most common type of porphyria. The strong association between PCT and hepatitis C virus (HCV) infection is well established. Although antiviral treatment of chronic hepatitis C may improve PCT in some cases, de novo onset of PCT has been observed in patients undergoing peginterferon/ribavirin treatment. We present a rare case of a genotype 3 HCV-positive liver transplant recipient who developed PCT during antiviral treatment and discuss its probable etiopathogenesis. Case presentation. A genotype 3 HCV-positive liver transplant recipient, a 42-year-old man, was treated with peginterferon alfa-2a (180 µg/week) combined with ribavirin (1,200 mg/day) for recurrence of HCV infection after liver transplantation. He presented with hyperferritinemia but tested negative for genetic hemochromatosis (C282Y and H63D mutations). During antiviral therapy, he developed skin lesions on his hands characterized by vesicles and erosions consistent with PCT. PCT was confirmed by skin biopsy and elevated urinary uroporphyrin levels (1,469 mg/24 h). He was treated with chloroquine (200 mg) twice weekly, resulting in gradual regression of the skin lesions. Antiviral treatment was stopped after 48 weeks, and the patient achieved a sustained virological response. In conclusion, we report an extremely rare case of PCT in a genotype 3 HCV-positive liver transplant patient treated with antiviral therapy. We believe that the combination of HCV genotype 3 infection; hemolysis due to ribavirin treatment; and increased plasma levels of cytokines, such as IL-6 and TNFα, could have altered the patient's iron metabolism and thus caused PCT

Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment

Background: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and solid tumours. Objective: Analyse the influence of sarcopenia on survival and treatment duration in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods: We conducted a multicentre, retrospective study on 96 patients with advanced HCC treated with sorafenib, all with available abdominal computed tomography (CT) scan within 30 days from treatment start. Anthropometric, laboratory, treatment and follow-up data were collected. Sarcopenia was defined by reduced skeletal muscle index calculated from an L3 section CT image. Results: Sarcopenia was present in 49% of patients. Patients were divided into two groups according to sarcopenia: age was significantly higher in the sarcopenic group (SG) (66 years (31–87) versus 72 years (30–84), p = 0.04], with no difference in other baseline characteristics. The SG showed shorter overall survival (OS) (39 (95% confidence interval (CI) 26–50) versus 61 (95% CI 47–77) weeks (p = 0,01)) and shorter time on treatment (12.3 (95% CI 8–19) versus 25.9 (95% CI 15–33) weeks (p = 0.0044)). At multivariate analysis, sarcopenia was independently associated to reduced OS (p = 0.03) and reduced time on treatment (p = 0.001). Conclusion: Sarcopenia is present in almost half of patients with advanced HCC, and is associated with reduced survival and reduced duration of oral chemotherapy

Voltage control of magnetic single domains in Ni discs on ferroelectric BaTiO<inf>3</inf>

For 1 μm diameter Ni discs on a BaTiO3 substrate, the local magnetization direction is determined by ferroelectric domain orientation as a consequence of growth strain, such that single domain discs lie on single ferroelectric domains. On applying a voltage across the substrate, ferroelectric domain switching yields non volatile magnetization rotations of 90°, while piezoelectric effects that are small and continuous yield non volatile magnetization reversals that are non-deterministic. This demonstration of magnetization reversal without ferroelectric domain switching implies reduced fatigue, and therefore represents a step towards applications

From current status to optimization of HCV treatment: Recommendations from an expert panel

Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-related extra hepatic manifestations, eventually reducing both liver-related and overall mortality. Together with the rapidly accumulating data about the evolution of treatment landscape, different guidelines from national and international Liver Scientific Societies have been published until today. However, these recommendations may not be applied worldwide as, due to high treatment costs, most of them identify as priority groups only patients with advanced liver disease. Moreover some types of patients pose clinical management problems for which even the guidelines do not always provide useful answers. With the aim of treatment optimization by filling some of the gaps of the current guidelines and addressing the remaining unmet needs in practice, a group of Italian experts, experienced on treatment of HCV infection, met in Stresa in February 2016. The summary of all the considerations arising from this two-day meeting and the final statements are reported in this position paper

Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment

Background: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and solid tumours. Objective: Analyse the influence of sarcopenia on survival and treatment duration in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods: We conducted a multicentre, retrospective study on 96 patients with advanced HCC treated with sorafenib, all with available abdominal computed tomography (CT) scan within 30 days from treatment start. Anthropometric, laboratory, treatment and follow-up data were collected. Sarcopenia was defined by reduced skeletal muscle index calculated from an L3 section CT image. Results: Sarcopenia was present in 49% of patients. Patients were divided into two groups according to sarcopenia: age was significantly higher in the sarcopenic group (SG) (66 years (31\u201387) versus 72 years (30\u201384), p = 0.04], with no difference in other baseline characteristics. The SG showed shorter overall survival (OS) (39 (95% confidence interval (CI) 26\u201350) versus 61 (95% CI 47\u201377) weeks (p = 0,01)) and shorter time on treatment (12.3 (95% CI 8\u201319) versus 25.9 (95% CI 15\u201333) weeks (p = 0.0044)). At multivariate analysis, sarcopenia was independently associated to reduced OS (p = 0.03) and reduced time on treatment (p = 0.001). Conclusion: Sarcopenia is present in almost half of patients with advanced HCC, and is associated with reduced survival and reduced duration of oral chemotherapy

Decline of Prevalence of Resistance Associated Substitutions to NS3 and NS5A inhibitors at DAA-failure in Hepatitis C Virus in Italy over the years 2015 to 2018

Background: A minority of patients fail to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens. Material and methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018. NS3, NS5A and NS5B Sanger sequencing was performed using homemade protocols. The geno2pheno system was used to infer HCV-genotype/subtype and predict drug resistance. The changes in the prevalence of RASs over time were evaluated using the chi-square test for trend, predictors of RASs at failure were analysed by logistic regression. Results: We included 386 real-life HCV pts failed to recommended DAA regimens: 92% (271/294) Italians, 75% (286/384) males, median age was 56 years (IQR 52-61); 106 (28%) were treatment-experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAA-based regimens. Metavir fibrosis stage was F4 in 76% (245/322), 65% (240/369) had clinical cirrhosis. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype (G) was G1b in 122 pts (32%), G3a 103 (27%), G1a 97 (25%), G4d 30 (8%), G2c 19 (5%), G3h 5 (1.3%), G4a 4 (1%) and 1 (0.3%) each for G3g, G4n/o/v. DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%). Antiviral treatment was completed by 352 pts (91%), while 34 (9%) discontinued prematurely. The NS5A fasta-sequence was available for all pts, NS5B for 361 (94%), NS3 for 365 (95%). The prevalence of any RASs was 87%, namely 78/135 (58%) in NS3, 303/359 (85%) in NS5A, 114/286 (40%) in NS5B (Tab 1). The prevalence of any RASs significantly declined from 2015 to 2018 (100%, 13/13 vs 81%, 101/125, p=0.01): NS5A RASs from 100%, 13/13 to 76%, 76/100 (p&lt;0.001), NS3 RASs from 88%, 7/8 to 44%, 28/63 (p=0.02), while NS5B RASs remained stable. Independent predictors of any RASs included liver cirrhosis/advanced fibrosis (AOR 3.72, CI 95% 1.51-9.17, p=0.004) and genotype (G2 vs G1a AOR 0.01, CI 95% 0.0-0.3, p&lt;0.001; G3 vs G1a AOR 0.22, CI 95% 0.05-0.98, p&lt;0.047; G4 vs G1a AOR 0.13, CI 95% 0.03-0.63, p&lt;0.011), with a modest effect scored for past treatment (AOR 3.45, CI 95% 1.00-11.92, p=0.05), after adjusting for DAA regimen and year of genotype. Notably, full activity was predicted for GLE/PIB in 75.9% of cases and for at least two components of VEL/SOF/VOX in 59% of cases and no case with full-resistance to either regimen was found (Tab 2). Conclusions: Despite decreasing prevalence over the years, RASs remain a common signature at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. Their distribution may vary according to genotype, so the identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Usefulness and limitations of transthoracic echocardiography in heart transplantation recipients

Transthoracic echocardiography is a primary non-invasive modality for investigation of heart transplant recipients. It is a versatile tool which provides comprehensive information about cardiac structure and function. Echocardiographic examinations can be easily performed at the bedside and serially repeated without any patient's discomfort. This review highlights the usefulness of Doppler echocardiography in the assessment of left ventricular and right ventricular systolic and diastolic function, of left ventricular mass, valvular heart disease, pulmonary arterial hypertension and pericardial effusion in heart transplant recipients. The main experiences performed by either standard Doppler echocardiography and new high-tech ultrasound technologies are summarised, pointing out advantages and limitations of the described techniques in diagnosing acute allograft rejection and cardiac graft vasculopathy. Despite the sustained efforts of echocardiographic technique in predicting the biopsy state, endocardial myocardial biopsies are still regarded as the gold standard for detection of acute allograft rejection. Conversely, stress echocardiography is able to identify accurately cardiac graft vasculopathy and has a recognised prognostic in this clinical setting. A normal stress-echo justifies postponement of invasive studies. Another use of transthoracic echocardiography is the monitorisation and the visualisation of the catheter during the performance of endomyocardial biopsy. Bedside stress echocardiography is even useful to select appropriately heart donors with brain death. The ultrasound monitoring is simple and effective for monitoring a safe performance of biopsy procedures