Predictors of 24-month onset of macular fibrosis in type 3 macular neovascularisation.

AIMS: To explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV). METHODS: This retrospective, exploratory, single-centre, cohort study comprised 65 eyes of 43 Caucasian patients with treatment naive T3 MNV, all with a 24-month follow-up post anti-VEGF therapy using a strict pro-re-nata (PRN) regimen. Data on demographic features, clinical findings, frequency of intravitreal treatments and optical coherence tomography biomarkers were collected at baseline and after 12 and 24 months of follow-up. Logistic regression models (LRM) and receiver-operating curve (C-index) analyses were performed to evaluate the prognostic ability of the studied biomarkers in discriminating between MF affected and unaffected patients. RESULTS: At final follow-up, MF was present in 46.2% of eyes. Subretinal hyper-reflective material (SHRM) and subretinal pigment epithelium multilaminar hyper-reflectivity (multilaminae) emerged as significant predictors for MF, with adjusted odds ratios (OR) of 18.0 (95% CL 13.4 to 24.1) and 11.8 (95% CL 8.66 to 16.0), respectively. Additionally, the presence of multifocal lesions (OR 0.04, 95% CL 0.01 to 0.30) appeared to decrease the likelihood of MF. C-indexes for the selected LRMs ranged between 0.92 and 0.88, indicating a comparably high discriminant ability. Despite consistent treatment schedules between the two groups (MF: median intravitreal treatment (IVT) number=10.5, IQR=7; non-MF: median IVT=10, IQR=6), a decline in best-corrected visual acuity was noted in the group with MF onset over the 24-month follow-up (-13.0 ETDRS letters; 95% CL -22.1 to -3.9; p=0.006). CONCLUSION: Our study identifies SHRM and multilaminae as relevant predictors of 24-month onset of MF in patients with T3 MNV. These findings enrich our understanding of the development of MF in T3 MNV and can guide improved risk prognostication. Future research should consider larger samples and prospective designs to validate these predictors.

Adherence to Mediterranean diet in liver transplant recipients: a cross-sectional multicenter study.

BACKGROUND: Seeing the importance of healthy diet after liver transplant (LT), our study aimed to evaluate the adherence to Mediterranean diet (MD) in a large population of LT recipients. METHODS: The present multicenter study was developed in clinically stable, liver transplanted patients, from June to September 2021. Patients completed a survey about adherence to MD, Quality of Life (QoL), sport, and employment. To analyze the correlations, we computed Pearson's coefficients; while to compare subgroups, independent samples t-tests and ANOVAs. We used a multivariable logistic regression analysis to find the predictors of impaired adherence to MD. RESULTS: The questionnaire was administered to 511 patients. They were males in 71% of cases with a mean age of 63.1 years (SD±10.8). LT recipients coming from central Italy displayed higher adherence to the MD (M=11.10±1.91) than patients from northern (M=9.94±2.28, P<0.001) or southern Italy (M=10.04±2.16, P<0.001). Patients from central Italy showed a significantly higher consumption of fruit, vegetables, legumes, cereals, olive oil, fish and a significantly lower intake of dairy products than patients resident in the other Italian areas. At multivariate analysis, recipients from central Italy were 3.8 times more likely to report adherence to the MD. Patients with a high physical health score were more adherent to MD, as well as patients transplanted at an earlier time. CONCLUSIONS: We demonstrated that place of stay, time from transplant and physical dimension of QoL significantly influences the adherence to MD. Continuous information campaigns about a correct diet and lifestyle would be necessary.

Prechoroidal Cleft Regression After Switch to Intravitreal Brolucizumab.

INTRODUCTION: Prechoroidal cleft has been described as a negative prognostic biomarker in patients affected with neovascular age related macular degeneration (nAMD). This peculiar finding consists of a lenticular hyporeflective space located between an outward bowing of Bruch's membrane and the base of a fibrovascular retinal pigment epithelium detachment (PED). Previous studies have reported the partial or complete regression of prechoroidal clefts after treatment with anti-vascular endothelial growth factor (VEGF) injections. CASE REPORT: To report a case of complete anatomical regression of an unresponsive prechoroidal cleft after switching to intravitreal Brolucizumab. The patient maintained cleft regression over time and no adverse events (i.e., RPE tears, intraocular inflammation) were observed during follow-up. CONCLUSIONS AND IMPORTANCE: To our knowledge, this case report is the first to analyze the clinical efficacy of brolucizumab targeting prechoroidal clefts. Clinical implication and pathogenesis of prechoroidal clefts are yet to be fully elucidated.

Physical activity in liver transplant recipients: a large multicenter study.

AIM: Healthy lifestyle and appropriate diet are of critical importance after liver transplant (LT). We provided an analysis of the main patterns of physical activity and found factors associated with physical activity itself. METHODS: Clinically stable LT recipients were enrolled between June and September 2021. Patients completed a composite questionnaire about physical activity, adherence to Mediterranean Diet (MD), quality of life (QoL), and employment. Correlations were analysed using the Pearson coefficients while different subgroups were compared by t-test for independent samples or ANOVAs. Multivariable logistic regression analysis was conducted to find predictors of inactivity. RESULTS: We enrolled 511 subjects (71% males, mean age 63 ± 10.8 years). One hundred and ninety-three patients reported high level of physical activity, 197 a minimal activity and 121 declared insufficient activity. Among these latter, 29 subjects were totally inactive. Considering the 482 LT recipients performing some kind of physical activity, almost all reported a low-quality, non-structured activity. At multivariate analysis, time from LT (odds ratio 0.94, 95% CI 0.89-0.99, p = 0.017), sedentary lifestyle (odds ratio 0.99, 95% CI 0.19-0.81, p = 0.012), low adherence to MD (odds ratio 1.22, 95% CI 1.01-1.48, p = 0.049), and low level of QoL (physical dimension) (odds ratio 1.13, 95% CI 1.08-1.17, p < 0.001), were independently associated with total inactivity. CONCLUSION: A large portion of LT recipients report an insufficient level of physical activity or are wholly inactive. Inactivity increases with time from LT and was strongly associated with suboptimal diet and low QoL.

Multimodal imaging for the management of Lyme-associated uveitis: A case report from an Italian tertiary center.

INTRODUCTION: Lyme borreliosis may present with different systemic manifestations and also the ocular involvement may be difficult to diagnose because of its multifaceted presentation. Considering the growing incidence of Lyme disease in European countries, ophthalmologist should be trained to distinguish ocular borreliosis. CASE REPORT: Several clinical presentations have been previously described, including uveitis, unilateral or bilateral chorioretinitis, keratitis, episcleritis, papillitis and ischemic optic neuropathy, retinal vasculitis and acute posterior multifocal placoid pigment epitheliopathy (APMPPE); however our case report showed a rare presentation with the presence of unilateral uveitis with vitreitis and multiple, patchy, yellowish lesions, in association with retinal vasculitis. This clinical picture was to be considered in differential diagnosis with ocular Toxoplasmosis. CONCLUSIONS: The appropriate management of this patient was made possible by the combination of multimodal imaging and appropriate laboratory tests, representing the optimal process in the diagnostic and therapeutic pathway in high-risk patients for ocular Lyme disease.

Needs evaluation questionnaire for liver disease: a novel assessment of unmet needs in patients with chronic liver disease.

Patients with chronic liver disease face debilitating complications in their daily living and constantly report several types of unmet needs, but there is a paucity of validated questionnaires to assess these needs. In this study, we present the development of the Needs Evaluation Questionnaire for Liver Diseases (NEQ-LD) for the assessment of unmet needs in patients with chronic liver disease. Two hundred eighty-six outpatients with chronic liver diseases from a single tertiary referral center completed the NEQ-LD and related validity measures. Item response theory analyses were performed and demonstrated the strong psychometric properties of the questionnaire. Differential item functioning analyses showed that the scale functions equally across groups differing for age, sex, and presence of cirrhosis, suggesting the large applicability of the NEQ-LD for the assessment of unmet needs and between-group comparisons. Criterion validity measures provided evidence that unmet needs were positively associated with measures of depression and anxiety and negatively associated with measures of subjective well-being and physical and mental health. Unmet needs were expressed by a high percentage of patients, especially in the areas of information and dialogue with clinicians. One third of the sample reported material needs. Most of the items describing unmet needs were reported more frequently by patients with cirrhosis. Conclusion: We developed a reliable, valid, and largely employable instrument that can promote patient-centered care and facilitate support services in Hepatology.

Acute macular neuroretinopathy as the first stage of SARS-CoV-2 infection.

INTRODUCTION: To report two cases of Acute Macular Neuroretinopathy (AMN) presented as the first stage of SARS-CoV-2 infection in two European countries during the third wave of pandemic viral infection in the early months of 2021. OBSERVATIONS: A unilateral case of type 1 AMN in a man and a bilateral case of type 2 AMN in an otherwise heathy patients were reported. Sudden onset of paracentral scotoma characterized the cases with no systemic symptoms. Structural optical coherence tomography (OCT) shows multifocal middle and inner retinal hyperreflective infarctions. OCT-Angiography showed the presence of hypoperfusion of the deep capillary plexus (DCP) corresponding to the hyperreflective lesions visible on structural OCT, confirming the diagnosis. CONCLUSIONS AND IMPORTANCE: Type 1 and type 2 AMN may be the first stage of SARS-CoV-2 infection. We suggest testing all patients with AMN for SARS-CoV-2. In our cases, the natural history of AMN associated with SARS-CoV-2 infection was similar to already described cases of AMN.

Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives.

Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis (PBC), affecting over 50% of PBC patients. One in five patients with PBC suffer from severe fatigue, which significantly impairs quality of life. Fatigue is made up of a central and a peripheral component, whose pathophysiology is still greatly unresolved. Central fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities (lack of intention). Peripheral fatigue includes neuromuscular dysfunction and muscle weakness (lack of ability). Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery time. As opposed to itching, and with the exception of end-stage liver disease, fatigue is not related to disease progression. The objective of this review is to outline current understanding regarding the pathophysiology of fatigue, the role of comorbidities and contributing factors, the main tools for fatigue assessment, the failed therapeutic options, and future treatment perspectives for this disabling symptom. Since fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients, further research is warranted to understand its causative mechanisms and to find an effective treatment.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHARACTERIZATION OF EVOLVING LESIONS IN FELLOW EYES OF EXUDATIVE TYPE 3 MACULAR NEOVASCULARIZATION PATIENTS.

PURPOSE: To investigate fellow eyes of newly diagnosed unilateral exudative Type 3 (T3) macular neovascularization (MNV) patients by assessing the presence and progression of a preclinical neovascular component during a 3-year follow-up. METHODS: This is a longitudinal study involving three retinal referral centers. Patients affected by unilateral exudative treatment-naive T3 MNV were enrolled. RESULTS: Twenty-four eyes of 24 patients (79 ± 6 years old) were enrolled. Nine eyes (37%) displayed a nonexudative T3 MNV at baseline that developed exudation after a mean of 9 ± 9 months. Fifteen eyes that did not display a nonexudative Type 3 MNV at baseline. Five eyes (21%) did not display neovessels at baseline, but showed a nonexudative T3 after 13 ± 9 months, and exudation after 8 ± 3 months. Five eyes (21%) developed active exudative T3 MNV after 23 ± 9 months, with no detectable nonexudative stage at baseline. Five eyes (21%) did not show MNV, but progressed to geographic atrophy by 36 months of follow-up. Overall, T3 MNV in the fellow eye accounted for 79%, all developing exudation over 3 years of follow-up. CONCLUSION: The occurrence of a nonexudative T3 MNV is a frequent event in the fellow eye of patients newly diagnosed with unilateral exudative T3 MNV and it precedes the development of exudation over 3 years (prevalence of 37% and cumulative incidence of 79%). Optical coherence tomography angiography approach may be used to perform an early diagnosis and treatment of patients with T3 MNV.

Practical insights into chronic management of hepatic Wilson's disease.

Wilson's disease (WD) is a rare inherited disorder of human copper metabolism, with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations. In healthy individuals, the bile is the main route of elimination of copper. In WD patients, copper accumulates in the liver, it is released into the bloodstream, and is excreted in urine. Copper can also be accumulated in the brain, kidneys, heart, and osseous matter and causes damage due to direct toxicity or oxidative stress. Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood. Adherent, non-cirrhotic WD patients seem to have a normal life expectancy. Nevertheless, chronic management of patients with Wilson's disease is challenging, as available biochemical tests have many limitations and do not allow a clear identification of non-compliance, overtreatment, or treatment goals. To provide optimal care, clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment. The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD. In particular, it summarises current knowledge on Wilson's disease clinical and biochemical monitoring and treatment. It also analyses available evidence on pregnancy and the role of low-copper diet in WD. Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.

OCT Predictors of 3-Year Visual Outcome for Type 3 Macular Neovascularization.

PURPOSE: To identify baseline OCT predictors of the 3-year visual outcome for type 3 (T3) macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) treated by anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Retrospective longitudinal study. PARTICIPANTS: Forty eyes of 30 patients affected by exudative treatment-naive T3 MNV were enrolled. METHODS: Baseline best-corrected visual acuity (BCVA) and several baseline OCT features were assessed and included in the analysis. Univariate and multivariate analyses served to identify risk factors associated with the 3-year BCVA. MAIN OUTCOME MEASURES: Baseline OCT features that are associated with bad or good visual outcomes of T3 MNV treated by anti-VEGF injections. RESULTS: Mean baseline BCVA was 0.34 ± 0.28 logarithm of the minimum angle of resolution (LogMAR), which significantly decreased to 0.52 ± 0.37 LogMAR at the end of the 3-year follow-up (P = 0.002). In the univariate analysis, the following baseline features were associated with the 3-year BCVA outcome: baseline BCVA (P = 0.004), foveal involvement of exudation (P = 0.004), and presence of subretinal fluid (SRF; P = 0.004). In the multivariate model, baseline BCVA (P = 0.032), central macular thickness (P = 0.036), number of active T3 lesions (P = 0.034), and presence of SRF (P = 0.008) were associated with the 3-year BCVA outcome. Interestingly, 3-year BCVA was significantly lower in 19 eyes with SRF at the baseline (0.69 ± 0.42 LogMAR) than 21 eyes without SRF (0.37 ± 0.24 LogMAR; P = 0.004). CONCLUSION: We identified structural OCT features associated with BCVA outcome after 3-year treatment with anti-VEGF injections. In contrast to previous studies on neovascular AMD, in our series, the presence of SRF at baseline was the most significant independent negative predictor of functional outcomes. Current findings may be employed to identify less favorable T3 patterns potentially deserving a more intensive treatment.

Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study.

INTRODUCTION AND OBJECTIVES: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. PATIENTS: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. RESULTS: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). CONCLUSIONS: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

Quality of life in liver transplant recipients during the Corona virus disease 19 pandemic: A multicentre study.

BACKGROUND: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic. METHODS: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t-tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis. RESULTS: We analysed data from 511 patients observing significant associations between quality of life's physical score and both age and adherence to Mediterranean diet (p < .01). A significant negative correlation was observed between mental score and the sedentary activity (p < .05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors. CONCLUSIONS: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it.

Retinal Vein Occlusion Following Two Doses of mRNA-1237 (Moderna) Immunization for SARS-Cov-2: A Case Report.

INTRODUCTION: Published data on possible ocular adverse events potentially associated with vaccination with the SARS-Cov-2 mRNA-1237 vaccine are scarce. In this report, we describe the case of a patient who had a hemispheric retinal vein occlusion potentially associated with being vaccinated with the second dose of the SARS-Cov-2 mRNA-1237 vaccine. METHODS: Case report including a discussion on multimodal imaging. RESULTS: A 74-year-old woman presented with painless vision loss in the right eye experienced 48 hours after receiving a second dose of the mRNA-1237 vaccine. The patient was receiving oral anticoagulant therapy for atrial fibrillation. Her best-corrected visual acuity (VA) was 20/32, and fundus examination showed venous congestion and widespread blot haemorrhages in the inferior quadrants. Based on multimodal imaging evaluation, the diagnosis of hemispheric retinal vein occlusion was made. Due to the development of cystoid macular oedema with intraretinal fluid and the decline in VA, the patient was treated with two injections of intravitreal ranibizumab, leading to functional improvement and regression of oedema. CONCLUSIONS: We report a case with retinal vein occlusion 48 hours after vaccination with the SARS-Cov-2 mRNA-1237 vaccine; however, the relationship between these two events remains unclear. Further research is warranted to better understand the potential link between retinal thrombotic events and vaccination.

DNA Damage Response Protein CHK2 Regulates Metabolism in Liver Cancer.

Defective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased CHK2 mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by CHK2 knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies. SIGNIFICANCE: This study uncovers a link between a central effector of DNA damage response, CHK2, and cellular metabolism, revealing potential therapeutic strategies for targeting hepatocellular carcinoma.

Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study.

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

Epidemiological, demographic and clinical data on chronic viral hepatitis C in Tuscany.

BACKGROUND: Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries' economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy. METHODS: We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress. RESULTS: Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44 ± 15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin's lymphoma in 10.5%). CONCLUSIONS: Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.

Clinical epidemiology of chronic viral hepatitis B: A Tuscany real-word large-scale cohort study.

AIM: To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus (HBV)-infected patients in the Tuscan public health care system. METHODS: This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS: Of 4015 chronic viral hepatitis patients, 1096 (27.3%) were HBV infected. The case report form was correctly completed for only 833 patients (64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years (only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures (23%), mother-to-child (17%) and sexual transmission (12%). The most represented HBV genotypes were D (72%) and A (14%). Of the patients, 24.7% of patients were HBeAg positive, and 75.3% were HBeAg negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic (35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION: Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

Prevalent use of combined prophylaxis of hepatitis B after liver transplantation in Italy: results of a national survey in a large cohort.

BACKGROUND: Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins efficiently protect the majority of recipients; however recent experiences suggest a decline of HBsAg-positive candidates and the use of hepatitis B Immunoglobulin-free schedules. METHODS: This national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 Italian centers. RESULTS: With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsAg-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. Similar rates (18% of HBsAg-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. Combined prophylaxis with Hepatitis B Immunoglobulins remained prevalent among centers and was effective in 96% of HBsAg-positive recipients and in 94% of HBsAg-negative recipients of anti-HBc-positive grafts. CONCLUSIONS: Data from this survey confirm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B Immunoglobulin-on and only rare -off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsAg-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years.

Prospective Evaluation of Liver Stiffness Using Transient Elastography in Alcoholic Patients Following Abstinence.

AIMS: Fibroscan® is a non-invasive method to evaluate liver stiffness (LS), however, its accuracy in alcohol-related liver diseases (ALD) especially with respect to active or stopped alcohol drinking is largely unknown. We prospectively evaluated the LS changes in patients with ALD following alcohol withdrawal. METHODS: Sixty-four patients were evaluated by FibroScan® and lab tests at baseline and after 4 weeks of abstinence. RESULTS: At baseline, 21 patients (33%) had an abnormal LS (> 7 kPa) and 32 patients (50%) had abnormal liver function tests. More specifically, 3 and 11 subjects had a LS higher than 9.6 kPa and 12.5 kPa, respectively. The LS significantly declined in abstinent from 9.2 ± 10.1 (M±SD) at the baseline to 6.9 ± 6.1 kPa at 4 weeks (P = 0.03), respectively, while did not change significantly in drinkers. In addition, 80% of abstainers had a significant LS reduction (-2.6 ± 5.5 kPa), compared to drinkers (2.2 ± 3.6 kPa) (P = 0.004). After 6 months, 27 patients accepted a further evaluation: 22 abstinent and 5 relapsed to drink. At the final evaluation, only 4 out of 22 abstainers had still a LS higher than 7 kPa. CONCLUSIONS: During active drinking LS is probably overestimated by Fibroscan® in ALD, since 1 month after abstinence it is dramatically reduced, especially in subjects with baseline values higher than 7 kPa. SHORT SUMMARY: We prospectively evaluated liver stiffness by Fibroscan® in patients with alcohol-related liver disease at baseline and following abstinence. After 1 month of abstinence, the LS is dramatically reduced, especially when values are greater than 7 kPa and transaminase elevated at baseline.