Metabolic Disorders in Liver Transplant Recipients: The State of the Art.

Liver transplantation represents a chief therapeutic approach for acute liver failure, end-stage liver disease and hepatocellular carcinoma. Despite witnessing advancements in short- and medium-term survival over recent decades, attributed to refinements in surgical techniques and immunosuppressive protocols, long-term mortality remains impervious to modification. Notably, cardiovascular disease emerges as a predominant cause of mortality among liver transplant recipients. This trend is accentuated by the increasing prominence of non-alcoholic steatohepatitis-related cirrhosis as an indication for liver transplantation. Moreover, the administration of immunosuppressive agents is intricately linked to the degradation of the metabolic profile in liver transplant recipients, thereby contributing to the initiation or exacerbation of cardiovascular risk factors, such as hypertension, diabetes, and dyslipidaemia. In addition, the post-liver transplantation period is marked by a decline in lifestyle quality and a failure to acknowledge the psychological distress experienced by patients throughout the transplant process. These factors can precipitate a deterioration in the patient's metabolic profile, exacerbated by suboptimal therapeutic compliance. This narrative review aims to comprehensively address the principal metabolic disorders intricately associated with liver transplantation.

Frailty after Liver Transplantation: A Complex Unexplored Issue.

Frailty is a multidimensional syndrome predominantly studied in the elderly, characterized by reduced resistance to stressors due to diminished physiological reserve and resilience. Advances in surgical techniques and immunosuppressive drugs have improved long-term survival rates in solid organ transplant recipients, yet the 10-year survival is satisfying. However, liver transplant recipients have a noteworthy risk of developing frailty status. After liver transplant, frailty can be favored by socioeconomic, cultural, and health-related factors, leading to increased risks of hospitalization, morbidity, and mortality. Various tools for frailty assessment exist, but none are universally validated for post-transplant patients. The integration of socioeconomic and psychological factors into frailty evaluation could improve quality of life and long-term outcomes for transplant recipients. Multidisciplinary approaches, including psychosocial support, are essential for managing frailty and enhancing the overall care of transplanted patients. This narrative review aims to comprehensively address the principal frailty risk factors associated with liver transplantation.

Itching for Answers: A Comprehensive Review of Cholestatic Pruritus Treatments.

Cholestasis is a clinical and laboratory syndrome indicating impaired bile production or excretion. One of the hallmark symptoms of cholestasis is pruritus. Itch can be severe and debilitating for patients, impacting their quality of life similarly to pain, and, in some cases, it can be refractory. Current therapies like anion exchange resins and rifampicin, offer partial relief but with side effects. Effective, well-tolerated treatments are urgently needed. This literature review examines existing options (bile acid sequestrants, antihistamines, opioid antagonists, sertraline, and rifampicin) and explores novel therapies (monoclonal antibodies, PPAR agonists, and bile-acid-based therapies). We analyze mechanisms, limitations, and adverse effects to aid clinicians and researchers. Novel approaches include monoclonal antibodies to inhibit bile recirculation and PPAR agonists targeting pruritus signaling. Despite the limited current options, ongoing research promises better treatments for cholestatic pruritus, addressing its distressing impact. In summary, cholestasis-associated pruritus poses a significant challenge with limited treatments. Advancements in understanding its pathophysiology offer hope for more effective therapies in the future.

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.

Treatment Options for Hepatitis A and E: A Non-Systematic Review.

Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal-oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results.

Investigating Acute Hepatitis after SARS-CoV-2 Vaccination or Infection: A Genetic Case Series.

(1) Background: Despite the advantages of COVID-19 vaccination, rare cases of acute hepatitis developing after the administration of the COVID-19 vaccine or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. The aim of the study is to describe a case series of patients who experienced the onset of acute hepatitis, with or without autoimmune features, following SARS-CoV-2 vaccination or infection and to hypothesize a genetic susceptibility in the pathogenesis. (2) Methods: A group of patients with acute onset hepatitis following SARS-CoV-2 vaccination or infection were evaluated in our hepatology outpatient clinic, where they underwent biochemical and autoimmune tests. Hepatitis A (HAV), B (HBV), and C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV) infections were excluded. Patients with a diagnosis of autoimmune hepatitis (AIH) or drug-induced liver injury (DILI) underwent HLA typing and histological testing. (3) Results: Five patients experienced new-onset AIH after COVID-19 vaccination, one of which developed mild symptoms after vaccination that strongly worsened during subsequent SARS-CoV-2 infection. One patient had AIH relapse after COVID-19 vaccination while on maintenance immunosuppressive treatment. All of them had HLA DRB1 alleles known to confer susceptibility to AIH (HLA DRB1*03,*07,*13,*14), and in three of them, HLA DRB1*11 was also detected. Two patients developed acute hepatitis without autoimmune hallmarks which resolved spontaneously, both positive for HLA DRB1*11. (4) Conclusions: An association between AIH and COVID-19 vaccine or infection can be hypothesized in individuals with a genetic predisposition. In patients without autoimmune features and spontaneous improvement of hypertransaminasemia, the diagnosis of drug-induced liver injury (DILI) is probable. Further studies are needed to determine the presence of an actual association and identify a possible role of HLA DRB1*11 in the pathogenesis of acute liver injury after SARS-CoV2 vaccination or infection.

The short cognitive evaluation battery in cognitive disorders of the elderly--Italian version.

AIMS: To validate the Italian version of the Short Cognitive Evaluation Battery (SCEB), consisting of 4 tests (temporal orientation, five words, clock drawing and verbal fluency) in healthy controls (CONT), patients with mild Alzheimer's disease (AD), mild cognitive impairment (MCI), and major depressive disorder (DEP). METHODS: Twenty-nine AD patients (mean Mini-Mental State Examination, MMSE, score: 22.1 ± 3.1), 27 MCI patients (mean MMSE score: 26.5 ± 2.0), 27 depressed patients (mean MMSE score: 26.9 ± 2.8), and 48 controls (mean MMSE score: 29.7 ± 0.5) were enrolled. RESULTS: MANCOVA showed highly significant (p < 0.0001) difference among groups. As for total SCEB score, AD were separated from CONT with high accuracy (93%; with sensitivity 93%, specificity 92%, area under ROC curve, AUC, 0.96) and from DEP with satisfying accuracy (84%; with sensitivity 76%, specificity 93%, AUC 0.84). Results in MCI versus CONT comparison yielded more moderate accuracy (80%; with sensitivity 70%, specificity 87%, AUC 0.80), which increased in the subgroup of MCI patients who later converted to AD (85%; with sensitivity 75%, specificity 83%, AUC 0.86). The direct comparison between MCI converters and nonconverters did not yield accurate results. CONCLUSION: The Italian version of the SCEB is a short (between 6 min in CONT and 12 min in DEP) screening tool in cognitive disorders of the elderly, and is potentially useful in clinical practice.

Virological Treatment Monitoring for Chronic Hepatitis B.

More than 250 million people worldwide are currently infected with hepatitis B, despite the effectiveness of vaccination and other preventive measures. In terms of treatment, new therapeutic approaches are rapidly developing, promising to achieve the elimination of infected cells and the complete cure of infection. The on-treatment monitoring of these innovative antiviral treatments will require the implementation of new virological tools. Therefore, new biomarkers are being evaluated besides the traditional virological and serological assays in order to obtain information on different steps of the viral replication cycle and to monitor response to therapy more accurately. The purpose of this work is to describe both standard and innovative tools for chronic hepatitis B treatment monitoring, and to analyse their potential and feasibility.

COVID-19 treatment options: a difficult journey between failed attempts and experimental drugs.

Since its outbreak in China in December 2019 a novel Coronavirus, named SARS-CoV-2, has spread worldwide causing many cases of severe pneumonia, referred to as COVID-19 disease, leading the World Health Organization to declare a pandemic emergency in March 2020. Up to now, no specific therapy against COVID-19 disease exists. This paper aims to review COVID-19 treatment options currently under investigation. We divided the studied drugs into three categories (antiviral, immunomodulatory and other drugs). For each molecule, we discussed the putative mechanisms by which the drug may act against SARS-CoV-2 or may affect COVID-19 pathogenesis and the main clinical studies performed so far. The published clinical studies suffer from methodological limitations due to the emergency setting in which they have been conducted. Nevertheless, it seems that the timing of administration of the diverse categories of drugs is crucial in determining clinical efficacy. Antiviral drugs, in particular Remdesivir, should be administered soon after symptoms onset, in the viraemic phase of the disease; whereas, immunomodulatory agents, such as tocilizumab, anakinra and steroids, may have better results if administered in pneumonia/hyperinflammatory phases. Low-molecular-weight heparin may also have a role when facing COVID-19-related coagulopathy. Up to now, treatment choices have been inferred from the experience with other coronaviruses or viral infection outbreaks. Hopefully, in the near future, new treatment strategies will be available thanks to increased knowledge on SARS-CoV2 virus and COVID-19 pathogenesis. In the meanwhile, further well-designed clinical trials are urgently needed to establish a standard of care in COVID-19 disease.

Treatments for HBV: A Glimpse into the Future.

The hepatitis B virus is responsible for most of the chronic liver disease and liver cancer worldwide. As actual therapeutic strategies have had little success in eradicating the virus from hepatocytes, and as lifelong treatment is often required, new drugs targeting the various phases of the hepatitis B virus (HBV) lifecycle are currently under investigation. In this review, we provide an overview of potential future treatments for HBV.

Obsessive-compulsive disorder and related disorders: a comprehensive survey.

Our aim was to present a comprehensive, updated survey on obsessive-compulsive disorder (OCD) and obsessive-compulsive related disorders (OCRDs) and their clinical management via literature review, critical analysis and synthesis. Information on OCD and OCRD current nosography, clinical phenomenology and etiology, may lead to a better comprehension of their management. Clinicians should become familiar with the broad spectrum of OCD disorders, since it is a pivotal issue in current clinical psychiatry.

Proximal and isolated distal deep vein thrombosis and Wells score accuracy in hospitalized patients.

Deep vein thrombosis (DVT) is an important cause of morbidity and mortality in hospitalized patients. The Wells score for DVT pretest probability (PTP) was validated in outpatients, but its utility for inpatients is unclear. The aim of this study was to establish the prevalence of inpatient proximal and distal DVT and the Wells score performance in inpatients. A single-center cross-sectional study was conducted in a university hospital. During 183 days, all inpatients with suspected lower-extremity DVT were evaluated with the Wells score and whole-leg ultrasound. Among 634 inpatients (age 77.5 ± 13.8 years, males 39.3%), 507 (80.0%) were from medical wards and 127 (20.0%) from surgical wards. During the study period, there were 11,662 hospital admissions in the surgical/medical services. Whole-leg ultrasound detected 128 DVTs (20.2%); 51 (39.8%) were proximal and 77 (60.1%) were isolated distal DVTs. Estimated DVT prevalence in hospital setting was 1.09% (95% CI 0.93-1.31), and isolated distal DVT prevalence was 0.66% (95% CI 0.53-0.82). DVT frequency in low-, moderate-, and high-PTP groups was 9.8%, 24.3%, and 41.5%, respectively (p = 0.001). The area under the receiver operating characteristic curve for the Wells score was 0.67 ± 0.03 for all DVTs and 0.75 ± 0.04 for only proximal DVTs. A high PTP had a sensitivity of 24% (95% CI 14-37%) and a specificity of 93% (95% CI 91-95%) for proximal DVT diagnosis. In hospitalized patients, isolated distal DVT has a higher incidence than expected, and the Wells score accuracy for proximal DVT is similar to that found in outpatients.

Aripiprazole augmentation in poor insight obsessive-compulsive disorder: a case report.

BACKGROUND: Obsessive-compulsive disorder is associated with a relevant impairment in social and interpersonal functioning and severe disability. This seems to be particularly true for the poor insight subtype, characterised by a lack of consciousness of illness and, consequently, compliance with treatment. Poor responsiveness to serotonergic drugs in poor insight obsessive-compulsive patients may also require an augmentation therapy with atypical antipsychotics. METHODS: We reviewed a case in which a patient with a long history of poor insight obsessive-compulsive disorder was treated with a high dosage of serotonin reuptake inhibitors. RESULTS: The treatment resulted in a poor outcome. This patient was therefore augmentated with aripiprazole. CONCLUSION: Doctors should consider aripiprazole as a possible augmentation strategy for serotonergic poor responder obsessive-compulsive patients, but further research on these subjects is needed.

Cortical sources of awake scalp EEG in eating disorders.

OBJECTIVE: To investigate quantitative EEG (qEEG) in anorexia nervosa (AN) and bulimia nervosa (BN) in comparison with healthy controls. METHODS: Resting EEG was recorded in 30 healthy females (age: 27.1+/-5.5), 16-AN females (age: 26.4+/-9.5) and 12-BN females (age: 27.0+/-6.3). Cortical EEG sources (delta, theta, alpha 1, alpha 2, beta 1, beta 2) were modeled by LORETA solutions. The statistical analysis was performed considering the factors Group, power Band, and region of interest (central, frontal, parietal, occipital, temporal, limbic). RESULTS: Alpha 1 sources in central, parietal, occipital and limbic areas showed a greater amplitude in Controls versus AN and BN groups. Alpha 2 sources in parietal, occipital and limbic areas showed a greater amplitude in Controls than in both AN and BN groups. Alpha 1 sources in temporal area showed a greater amplitude in Controls compared to both the BN and AN groups as well as in the BN group compared to AN group. Central alpha 1 source correlated significantly with BMI in patients. CONCLUSIONS: These results support the hypothesis that eating disorders are related to altered mechanisms of cortical neural synchronization, especially in rolandic alpha rhythms. SIGNIFICANCE: To our knowledge this is the first study by LORETA able to detect modifications of cortical EEG activity in eating disorders.

Employment status, inflation and suicidal behaviour: an analysis of a stratified sample in Italy.

BACKGROUND: There is abundant empirical evidence of a surplus risk of suicide among the unemployed, although few studies have investigated the influence of economic downturns on suicidal behaviours in an employment status-stratified sample. AIMS: We investigated how economic inflation affected suicidal behaviours according to employment status in Italy from 2001 to 2008. METHODS: Data concerning economically active people were provided by the Italian Institute for Statistical Analysis and by the International Monetary Fund. The association between inflation and completed versus attempted suicide with respect to employment status was investigated in every year and quarter-year of the study time frame. We considered three occupational categories: employed, unemployed who were previously employed and unemployed who had never worked. RESULTS: The unemployed are at higher suicide risk than the employed. Among the PE, a significant association between inflation and suicide attempt was found, whereas no association was reported concerning completed suicides. No association was found between completed and attempted suicides among the employed, the NE and inflation. Completed suicide in females is significantly associated with unemployment in every quarter-year. CONCLUSION: The reported vulnerability to suicidal behaviours among the PE as inflation rises underlines the need of effective support strategies for both genders in times of economic downturns.

Combined venlafaxine and olanzapine prescription in women with psychotic major depression: a case series.

Patients with psychotic major depression suffer prolonged duration and greater severity of illness, including an increased likelihood of recurrent episodes and resistance to conventional pharmacotherapies. They do not respond to placebo and respond poorly to antidepressant or antipsychotic monotherapy. On the other hand, as has been demonstrated, they do respond well to antidepressant and antipsychotic combination therapies. Different combinations of drugs were studied, but little is known up to now with regard to the combination of venlafaxine and olanzapine. The following paper presents three separate case studies of female patients suffering from psychotic unipolar major depression, all of whom were admitted to a psychiatric ward and successfully treated with a combination of venlafaxine and olanzapine.