Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study.

BACKGROUND: Data on HCV-related hepatocellular carcinoma (HCC) early recurrence in patients whose HCC was previously cured, and subsequently treated by direct-acting antivirals (DAAs), are equivocal. AIM: To assess the risk of HCC early recurrence after DAAs exposure in a large prospective cohort of HCV-cirrhotic patients with previous successfully treated HCC, also looking for risk factors for cancer early recurrence. METHODS: We enrolled 143 consecutive patients with complete response after curative treatment of HCC, subsequently treated with DAAs and monitored by the web-based RESIST-HCV database. Clinical, biological, and virological data were collected. The primary endpoint was the probability of HCC early recurrence from DAA starting by Kaplan-Meier method. RESULTS: Eighty-six per cent of patients were in Child-Pugh class A and 76% of patients were BCLC A. Almost all patients (96%) achieved sustained virological response. Twenty-four HCC recurrences were observed, with nodular or infiltrative pattern in 83% and 17% of patients, respectively. The 6-, 12- and 18-month HCC recurrence rates were 12%, 26.6% and 29.1%, respectively. Main tumour size and history of prior HCC recurrence were independent risk factors for HCC recurrence by Cox multivariate model. CONCLUSIONS: Probability of HCC early recurrence in patients who had HCC previously cured remains high, despite HCV eradication by DAAs. Risk was comparable but not higher to that reported in literature in DAA-untreated patients. Previous HCC recurrence and tumour size can be used to stratify the risk of HCC early recurrence. Further studies are needed to assess impact of DAAs on late recurrence and mortality.

Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatitis C.

OBJECTIVES: Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients. METHODS: One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI. RESULTS: TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating characteristic curve (AUROC), the best cutoff values for TE and ARFI for significant fibrosis (≥F2) were ≥6.5 kPa (AUROC: 0.78) and ≥1.3 m/s (AUROC: 0.86), respectively. For severe fibrosis (F3-F4), these cutoff values were 8.8 kPa (AUROC: 0.83) for TE and 1.7 m/s (AUROC: 0.94) for ARFI. For cirrhosis, TE had its best cutoff at ≥11 kPa (AUROC: 0.80) and ARFI at ≥2.0 m/s (AUROC: 0.89). By pairwise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis (P=0.024 and P=0.002, respectively), while this difference was only marginal for cirrhosis (P=0.09). By partial AUROC analysis, ARFI performance results significantly higher for all three stages of fibrosis. The average concordance rates of TE and ARFI vs. liver biopsy were 45.4 and 54.7%, respectively. By multivariate analysis, ARFI was not associated with alanine aminotransferase (ALT), body mass index, Metavir grade, and liver steatosis, while TE was significantly correlated with the ALT value (P=0.027). CONCLUSIONS: In a cohort of patients with CHC, ARFI imaging was more accurate than TE for the non-invasive staging of both significant and severe classes of liver fibrosis.

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems.

BACKGROUND: A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately. AIM: To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC. METHODS: We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model. RESULTS: One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among treated patients, albumin, bilirubin and performance status were the only independent variables significantly associated with survival. Mortality was independently predicted by bilirubin, alpha-fetoprotein and portal vein thrombosis in untreated patients. CLIP achieved the best discriminative capacity in the entire HCC cohort and in the advanced untreatable cases, while BCLC was the ablest in predicting survival in treated patients. CONCLUSIONS: Overall predictive ability of BCLC, CLIP and GRETCH staging systems was not satisfactory, and was not uniform for treated patients and untreated patients. None of the scoring systems provided confident prediction of survival in individual patients.

Liver eosinophilic infiltrate is a significant finding in patients with chronic hepatitis C.

Eosinophilic infiltrate of liver tissue is described in primary cholestatic diseases, hepatic allograft rejection and drug-induced liver injury, but its significance and its implications in chronic hepatitis C are unknown. The aim of this study was to investigate the clinical significance of eosinophilic liver infiltrate in patients with chronic hepatitis C. We retrospectively evaluated 147 patients with chronic hepatitis C. The presence of eosinophilic infiltrate was investigated in liver biopsies, and a numeric count of eosinophilic leucocytes in every portal tract was assessed. An eosinophilic infiltrate of liver tissue (> or =3 cells evaluated in the portal / periportal spaces) was observed in 46 patients (31%), and patients who consumed drugs had an odds ratio (OR) of 4.02 (95% CI: 1.62-9.96) to have an eosinophilic infiltrate in liver biopsy. By logistic regression analysis, the presence of steatosis was independently associated with eosinophilic infiltrate (OR 5.86; 95% CI: 2.46-13.96) and homeostasis model assessment-score (OR 1.18; 95% CI: 1.00-1.39). Logistic regression analysis also showed that fibrosis staging > or = 2 by Scheuer score was associated with grading >1 by Scheuer score (OR 6.82; 95% CI 2.46-18.80) and eosinophilic infiltrate (OR 4.00; 95% CI 1.23-12.91). In conclusion, we observed that the eosinophilic infiltrate of liver tissue was significantly more frequent in patients who assumed drugs, and found a significant association between eosinophilic infiltrate, liver steatosis and liver fibrosis. These preliminary data could lead to a constant assumption of drugs as a co-factor of eosinophils-mediated liver injury in chronic hepatitis C.

Is there a future for depression digital motion constructs in psychiatry?

Psychomotor retardation has been recognized as a principal component of depression for centuries. Amongst symptoms and signs associated with depression, it is seen as having high predictive validity, correlating with severity of illness and the outcome of numerous therapeutic interventions. Of the two components-"psycho" and "motor"-the psychological component has received the most thorough investigation and has been given the greatest consideration. The "motor" (or motion) component has been given little consideration. A review of the literature suggests few studies have attempted to quantitatively characterize this phenomenon or use it as anything more than one indice among other signs and symptoms of depression. Unlike other phenomena associated with depression, the use of motion alterations has lagged in significance due to limited technology that would allow its study; depression has been seen predominantly as a " mood" disorder, with principal interest being in the "feelings" associated with the disorder. Recent advances in motion capture technologies allow motion alterations to be used for many purposes, both quantitative and qualitative. These sources of information appear to have direct and indirect impact. There is a fertile future for motion capture constructs in the study of depression,and recent technological advances will allow progress to occur in this area.

Digital motion phenomenology of depression.

The long-term objective of our project is to use motion capture technology to identify and characterize body alterations in motion associated with depression that have not been previously recognized or characterizable. These motion phenomena will be studied to determine their utility in the nosology and subtyping of depression. Quantitatively, they may have a significant impact in the areas of research, education and the clinical management of depression; and allow the creation of "virtual humans" which manifest depressive digital motion phenomena that can be used to train researchers, trainees and clinicians.

Ten year follow-up of patients with chronic hepatitis C treated with interferon.

BACKGROUND/AIMS: The impact of the treatment with interferon (IFN) on the natural history of chronic hepatitis C is not defined. The aim of this study was to evaluate the long term effect of the treatment in patients with chronic hepatitis C. METHODOLOGY: In 31 patients with chronic hepatitis C (9 with cirrhosis) consecutively treated with recombinant alpha 2a interferon (r alpha 2a IFN), the evolution of the disease at 10 years from the therapy was evaluated by means of upper endoscopy, liver ultrasonography (US), liver function tests and hepatitis C virus (HCV) viremia. RESULTS: Among 10/31 patients previously classified as responders, only 1 has signs of evolution to cirrhosis; HCV-RNA is still present in 2. Among 21 non-responder patients, 5 developed hepatocarcinoma (HCC) and 4 died during the follow-up; HCV-RNA is present in all the patients still alive. The 6 patients already cirrhotic when treated have clinical signs of progression to Child class B and C. The biochemical, ultrasonographical and endoscopical evaluation shows onset of cirrhosis in 7 of the others. CONCLUSIONS: Patients with chronic hepatitis C who respond to treatment with interferon have good outcome and rare evolution to cirrhosis. The treatment does not seem to influence the natural history of the disease in non-responders.

Presence as an emotional experience.

Presence or the sense of "being there" has been discussed in the literature as an essential, defining aspect of Virtual Reality (VR). The VR literature includes definitions rooted in behavioral response, signal detection theory, and philosophy, but has generally ignored the emotional aspects of experience. The purpose of this paper is to reexamine the concept of presence in terms of people's emotional engagement with reality and their environment. Emotions are an essential part of how people experience the world. Any theory of presence must take emotional factors into account. This thesis has implications about how research should be conducted to further our understanding of presence. Validated psychological techniques for assessing emotions by subjective report, behavioral observations, and facial analysis can all be applied to increase our understanding of virtual presence. Further understanding of the interaction between presence and emotional state will improve our understanding of the construct of presence as well as better inform us about how virtual environments can be applied in creating emotional effects or treating emotional disorders.

The use of an information system architecture modeling tool in the development of disease management systems.

UNLABELLED: A Disease Management System (DMS) refers to an integrated healthcare delivery system that provides patient centered care throughout the course of the disease independent of delivery site. A fundamental barrier for the development, implementation and monitoring of a DMS is lack of an appreciation by care providers of the complexity of these systems, and what is required for their maintenance. Foremost in the development of these systems is the presence of information systems that attempt to deal with the temporal, spatial and information needs of the DMS. PURPOSE: The Zachman Framework for Information Systems Architecture is used in many industries in the development of information systems. Its choice is based on the recognition of a need for a methodology in the conceptualization and modeling of complex information systems. This paper provides a brief overview of the Zachman Framework and its potential application in DMS development. In particular it will be the focus on the need for "perspective" clarification as the first step in the development of such complex systems. RESULTS: This paper reviews DMS and their potential information needs. The clarification of "perspectives" provides a method toward team building and unification of purpose by decreasing conflict and recognizing the unique contributions that each perspective holder makes.

Interferon retreatment of patients with chronic hepatitis C. A long-term follow-up.

BACKGROUND/AIMS: We retrospectively evaluated the long-term efficacy of interferon retreatment in patients with chronic hepatitis C, who did not have a sustained response to a 1st cycle of treatment. METHODOLOGY: Sixty-six patients, 43 non-responder and 23 relapser to alpha interferon treatment, were retreated with alpha interferon, 6 MU thrice weekly for 12 months. Response was defined as negative HCV viremia. Responders underwent long-term follow-up (27-43 months). RESULTS: The response rates were 14% and 35% at the end of retreatment, 7% and 22% at 6 months, and 2% and 13% at long-term follow-up in non-responders and relapsers respectively. The outcome of retreatment was not statistically influenced by age, cirrhosis, viral genotype, dose and duration of previous treatment. CONCLUSIONS: Interferon retreatment, for sustained viral eradication, is not effective in non-responders and useful in few relapsers. Whereas, retreatment could prove effective in slowing down the activity of the disease and reducing the incidence of hepatocarcinoma, since some relapses occur late during the follow-up. Therefore, retreatment should be confined to relapsers with contraindications to new more efficient therapeutic strategies.

Mental health implications for presence.

"Presence," as discussed in the virtual reality (VR) literature, is the sense of truly being in a virtual place. This literature explores many aspects of presence including interactive and environmental factors. This exploration has generally ignored the impact of the individual's mental status on the experience of presence. Mental disorders such as depression, anxiety, and psychosis may each define a population with specific tendencies to respond to VR in particular ways. To fully understand the experience of presence in virtual environments, we must understand more about the impact of different mental states on presence. Such an understanding will improve our insight into the construct of presence, assist in improved design of virtual environments, and better inform us about how virtual environments can be applied in the treatment of emotional disorders.

The potential relevance of attachment theory in assessing relatedness with virtual humans.

Primary efforts to create virtual humans have been in the production of computer generated ergonomically correct objects that look like humans. Although there has been concern with essential human factors, absent are the metrics of human relatedness, or the ability to assess the degree to which a virtual human elicits human emotions. We discuss the potential application of attachment theory as a context for the development of such an assessment paradigm, and specifically the application of the Ainsworth Strange Situation in the evaluation of a "Virtual Mom". Virtual relatedness fidelity is discussed as a macrometric to define relatedness that would occur with virtual humans. Potential lessons learned are discussed as they apply to the selection of those to develop the model, and its impact on the introduction of virtual humans into clinical psychiatry and psychology.

Current limitations into the application of virtual reality to mental health research.

Virtual Reality (VR) environments have significant potential as a tool in mental health research, but are limited by technical factors and by mental health research factors. Technical difficulties include cost and complexity of virtual environment creation. Mental health research difficulties include current inadequacy of standards to specify needed details for virtual environment design. Technical difficulties are disappearing with technological advances, but the mental health research difficulties will take a concerted effort to overcome. Some of this effort will need to be directed at the formation of collaborative projects and standards for how such collaborations should proceed.