Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. \ua9 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved

Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: A pilot case-control study

Background:Limited therapies are available for large ( 6540 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule 6540 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively (p < 0.001). Subsequently we stratified the HCCs in 3 categories according to the nodule size: 40-50 mm, 51-60 mm, and > 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively (p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC

Mylonitic gabbro nodules of Stromboli (southern Italy): Microstructural evidence of high-temperature deformation of cumulates during the evolution of the magmatic crustal roots of an active volcano

We collected and investigated mylonitic gabbro nodules from Stromboli’s oldest pyroclastic rocks, and they are reported on here for the fi rst time. The petrography, bulk-rock geochemistry, and mineral chemistry of these ylonitic gabbros show that they are cognates with undeformed cumulate gabbros also found in the same host rocks. Both types of gabbro nodules are inferred to have crystallized within the lower crustal levels of this active volcano. The mylonitic gabbros are characterized by discontinuous layers of plagioclase aggregates, interspersed with amphibole, pyroxene, and olivine crystals, and they are enveloped by a mylonitic foliation consisting of <5- to <100-μm-sized, dynamically recrystallized plagioclase grains. The deformed rims of the plagioclase porphyroclasts disaggregate by fracturing into rectangular grains along the main cleavage systems {010} and {001}. In higher-strain zones, the grain size becomes smaller, and the shape is controlled by grain boundary migration driven by melt-assisted diffusion creep that accommodates grain boundary sliding. This is consistent with the dispersed crystallographic orientations of the mylonitic grains and their complex compositional zoning patterns. We invoke a switch from cataclastic fl ow to melt-assisted, grain boundary sliding as the main deformation mechanisms for these mylonitic gabbro nodules. The cataclastic fl ow was triggered by the hydrostatic pressure of a magma column acting atthe base of the lowermost Stromboli crustal magma chamber (7–11 km). These intrusive processes, which occur along the transtensional shear zones of the Stromboli NESW–striking fault systems, should have fi nally driven the mylonitic deformation in a brittle-ductile transition zone that is inferred to have been active during the evolution of the magmatic crustal roots of the volcano

Helicobacter pylori Bacteremia: An Unusual Finding

We report a case of Helicobacter pylori transient bacteremia in a woman with ulcerated antral gastric cancer. The patient was hospitalized for laparoscopy and subtotal gastrectomy. After surgery she developed fever (39°C) and was empirically treated with levofloxacin. Blood cultures, collected and sent immediately to Laboratory, were positive for a spiral Gramnegative bacterium. This isolate was identified as H. pylori and the specific susceptibility test was performed. One day after the fever was decreased but antibiotic treatment with levofloxacin was continued and it was maintained until discharge. In summary, H. pylori transient bacteremia may occur as a rare complication after stomach surgery. Further studies are necessary to elucidate the potential role of H. pylori presence in blood

Ischemic nephropathy: proteinuria and renal resistance index could suggest if revascularization is recommended

Background: The aim of endovascular therapy in renal artery stenosis (RAS) is to preserve renal function and have a better hypertension control. The purpose of our study was to determine which biochemical and instrumental parameters could predict a better renal outcome in patients with RAS treated with percutaneous transluminal angioplasty and stenting (RPTAS). Methods: We performed an observational study based on 40 patients with RAS who met the following criteria before revascularization: urinary protein excretion of over 250 mg/24 h, normal renal function, and/or mild-moderate renal insufficiency (I, II, and III levels of classification of chronic kidney disease, K-DOQI). Results: Assessment at 12 months after RPTAS showed in 20 patients (Group A) that proteinuria serum creatinine (Scr) and creatinine clearance (CrCl) significantly worsened from the baseline; whereas in 20 patients (Group B) proteinuria remained unchanged and the renal function improved after the procedure. Conclusions: In our study, the decline of renal function after RPTAS is associated with an elevated renal resistance index (RI) in both kidneys (0.83 +/- 0.2) and preexisting proteinuria

Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis

Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed. Actuarial survival estimates were computed using the Kaplan–Meier method and compared with the log-rank test. We performed an event-based counterfactual mediation analysis to estimate direct (chronic inflammation and immunosuppression), indirect (tobacco smoking, alcohol use, illicit drug abuse with injections), and the total effect of viral etiology on OS. Results were expressed as hazard ratio (HR) and 95% CI. Results: Median OS was 21 months (95% CI: 20–23) in the group with other etiologies and 15 months (14–16) in the group with viral etiology (p p < 0.0001). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Patients affected by HCC with nonviral etiology treated with lenvatinib exhibit longer survival than those with viral etiology. This finding may have relevance in the treatment decision-making process

Effect of direct-acting antivirals on future occurrence of hepatocellular carcinoma in compensated cirrhotic patients

Background: The achievement of high rates of sustained virological response (SVR) with direct-acting antivirals (DAAs) in hepatitis C virus (HCV) infected patients will reduce decompensating terminal events. Aims: To investigate whether hepatocellular carcinoma (HCC) occurrence could change due to the DAA-induced increase in life-expectancy. Methods: A Markov model was built on clinical data of 494 cirrhotic patients and available literature to estimate probabilities of \u201cdeath before HCC\u201d and of \u201cHCC occurrence\u201d without and with DAA. Results: In comparison to untreated patients, DAA therapy reduced the 20-year mortality before HCC by 21.9% in patients without varices and by 21.5% in those with varices, considering an SVR of 95% and no direct effect on hepatocarcinogenesis. Tumour occurrence increased by 5%\u20138.2% and the proportion of HCCs diagnosed in compensated stages increased to &gt;98%. If we consider DAA as having \u201canti-tumoral\u201d effects, the benefit becomes greater, achieving a 20-year survival of 81.5% in patients without varices, and 52.2% in patients with varices. Instead, if we consider DAA as having a \u201cpro-tumoral\u201d effect, then, the increased incidence of HCC nullifies the survival benefits. Conclusion: DAAs drastically reduce the mortality caused by the liver function worsening, increasing the proportion of HCCs diagnosed in compensated stages. Knowledge of the DAA effect on hepatocarcinogenesis remains pivotal