Prevalence and features of SARS-CoV-2 infection in prisons in Tuscany.

BACKGROUND: Prisons can be a reservoir for infectious diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), due to the very intimate nature of the living spaces and the large number of people forced to share them. AIM: To investigate the SARS-CoV-2 epidemiology in prisons, this study evaluated the infection incidence rate in prisoners who underwent nasopharyngeal swabs. METHODS: This is an observational cohort study. Data collection included information on prisoners who underwent nasopharyngeal swab testing for SARS-CoV-2 and the results. Nasopharyngeal swab tests for SARS-CoV-2 were performed between 15 February 2021 and 31 May 2021 for prisoners with symptoms and all new arrivals to the facility. Another section included information on the diagnosis of the disease according to the International Classification of Diseases, Ninth Revision, and Clinical Modification. RESULTS: Up until the 31 May 2021, 79.2% of the prisoner cohort (n = 1744) agreed to a nasopharyngeal swab test (n = 1381). Of these, 1288 were negative (93.3%) and 85 were positive (6.2%). A significant association [relative risk (RR)] was found only for the risk of SARS-CoV-2 infection among foreigners compared to Italians [RR = 2.4, 95% confidence interval (CI): 1.2-4.8]. A positive association with SARS-CoV-2 infection was also found for inmates with at least one nervous system disorder (RR = 4, 95%CI: 1.8-9.1). The SARS-CoV-2 incidence rate among prisoners is significantly lower than in the general population in Tuscany (standardized incidence ratio 0.7, 95%CI: 0.6-0.9). CONCLUSION: In the prisoner cohort, screening and rapid access to health care for the immigrant population were critical to limiting virus transmission and subsequent morbidity and mortality in this vulnerable population.

Liver Stiffness Values to Predict Occurrence and Recurrence of Hepatocellular Carcinoma.

Globally, liver cancer is the third most frequent etiology of cancer death, with the rates of occurrence of both new cases and mortality estimated to increase. Given the availability of multiple treatments, interdisciplinary management of the patient is crucial. Moreover, the diagnostic assessment of patients with severe liver fibrosis is essential for the staging of HCC and liver cirrhosis and early diagnosis of HCC. In this context, non-invasive evaluation plays a critical role in identifying prognostic factors of clinical application for the surveillance of the occurrence or recurrence of HCC. The new frontiers of transient elastography have become a useful tool to assess the risk of HCC occurrence and recurrence. There has been a major increase in studies investigating the cutoff liver stiffness value that best predicts the need for monitoring for the onset of HCC. Therefore, this review discusses the new advances that have occurred in the last four years on HCC, highlighting the new frontiers of non-invasive evaluation of HCC subjects, with particular attention regarding the clinical application of liver stiffness assessment for de novo HCC and predicting recurrence in patients with chronic HCV achieving sustained virological response after treatment with direct antiviral agents.

Access to SARS-CoV-2 vaccination in immigrants in Italy, by geographical area of origin.

OBJECTIVE: Immigrants are commonly considered disadvantaged and at high risk of not receiving appropriate care, including vaccination. This study aimed to evaluate the access to SARS-CoV-2 vaccination in immigrants, by geographical area of origin, compared with Italian citizens. We also evaluated sex differences in vaccine's coverage by geographical area of origin. METHODS: We performed a retrospective observational study in four Italian regions, including all resident subjects aged 5-69 years, and undergoing first dose SARS-CoV-2 vaccination in the period 28th December 2020- 3rd April 2022. We estimated cumulative coverage percentages, by age class and geographical area. To compare first-dose vaccine coverage by geographical area of origin, we estimated, through a Poisson analysis, Vaccine Coverage Ratios (VCR) with 95 % confidence intervals (95 %CI), adjusting for age and sex. RESULTS: We included 16,294,785 Italian citizens and 2,534,351 immigrants aged 5-69 years and resident in the four regions considered. Regarding the geographical area of origin, 40.7 % of immigrants came from Eastern Europe, 13.5 % from North Africa and 13.1 % from Western Asia. A great variability in the first dose vaccine coverage emerged. We documented substantial heterogeneity in the first-dose vaccine coverage within immigrant's population, expressed with Italy as a reference, ranging from 0,768 (95 %CI: 0,766-0,769) in Eastern Europe countries to 1,013 (95 %CI: 1,009 - 1,018) in Eastern Asia. The chance of being vaccinated was found higher in males compared with females for African countries (VCR 1.07, 95 %CI 1.06-1.08) and Western Asian countries (VCR 1.08, 95 %CI 1.07-1.09). CONCLUSION: We observed substantial heterogeneity in first-dose SARS-CoV-2 vaccination coverage in immigrants, suggesting a different propensity to vaccines according to the geographical area of origin. These data can help define appropriate and tailored strategies in order to improve vaccine coverage in some specific immigrant groups at the local health district level.

Foreigners living in Tuscany at the time of coronavirus outbreak.

Background: During the coronavirus outbreak, a worldwide state of emergency and lockdown significantly affected the volunteer services for foreigners. The SARS-CoV-2 surveillance program was strengthened among migrants arriving in Italy. However, few screening measures for SARS-CoV2 infection have been conducted on the foreign population already present in Italy. In Tuscany, a great effort was made to know the epidemiological features of coronavirus outbreaks in the foreigners. Based on these premises, this study describes the prevalence and characteristics of SARS-CoV-2 infection in foreigners present in the Tuscan territory during the months of the highest incidence of this pandemic. Methods: Ministry of Health established the COVID-19 surveillance and predisposed the methods for reporting cases of SARS-CoV-2 infection in agreement with the Department of Infectious Diseases of the Istituto Superiore di Sanità. Data on SARS-CoV-2, updated daily, were collected based on the platform of the Istituto Superiore di Sanità.For each patient were available data on diagnosis, gender, age, nationality, exposure place, hospitalization and symptoms severity. Symptoms severity was classified using a 6-level scale (asymptomatic, paucisymptomatic, mild symptoms, severe symptoms, critic, and died). Results: By July 14, 2020, 10,090 SARS-CoV-2 cases were recorded. Out of 10,090 cases, 8,947 were Italians (88.7%), 608 foreigners (6%); in 535 patients (5.3%) citizenship was missing. The average age of foreigners was 44.1 years (range: 42.9-45.4), compared to 61.1 years (range: 60.7-61.5) of Italians. Chronic pathologies affected 16.8% of foreigners (14.0% -20.0%) and 36.4% of Italians (35.4% -37.4%). Foreigners with asymptomatic or mild symptoms of COVID-19 were 81.7% (78.4% -84.6%), while the Italians were 67% (66.6% -68.5%). Foreigners with severe COVID-19 were 15.2% (12.6% -18.4%) and Italians were 17.6% (16.8% -18.4%). Foreigners in critical conditions were 1.0% (0.5% -2.2%) and Italians were 2.6% (2.3% -3.0%). 38.6% (33.7% -43.7%) of foreigners were infected at the workplace as a health or social-health worker, compared to 24.2% (23.1% -25.4%) of Italians. Conclusion: The time between the onset of symptoms and the execution of the laboratory tests was similar between foreigners and Italians. The foreigners infected by SARS-COV-2 were younger compared to the Italians. Foreigners showed few comorbidities, and asymptomatic or mild symptomatic COVID-19, and consequently, a low lethality index. National and Tuscany policy decisions are needed to create equity in the access to the health care system for immigrants and their families, regardless of their immigration status.

Italian guidelines for the management of irritable bowel syndrome: Joint Consensus from the Italian Societies of: Gastroenterology and Endoscopy (SIGE), Neurogastroenterology and Motility (SINGEM), Hospital Gastroenterologists and Endoscopists (AIGO), Digestive Endoscopy (SIED), General Medicine (SIMG), Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP) and Pediatrics (SIP).

The irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction. IBS is still associated with areas of uncertainties, especially regarding the optimal diagnostic work-up and the more appropriate management. Experts from 7 Italian Societies conducted a Delphi consensus with literature summary and voting process on 27 statements. Recommendations and quality of evidence were evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was defined as >80% agreement and reached for all statements. In terms of diagnosis, the consensus supports a positive diagnostic strategy with a symptom-based approach, including the psychological comorbidities assessment and the exclusion of alarm symptoms, together with the digital rectal examination, full blood count, C-reactive protein, serology for coeliac disease, and fecal calprotectin assessment. Colonoscopy should be recommended in patients with alarm features. Regarding treatment, the consensus strongly supports a dietary approach for patients with IBS, the use of soluble fiber, secretagogues, tricyclic antidepressants, psychologically directed therapies and, only in specific IBS subtypes, rifaximin. A conditional recommendation was achieved for probiotics, polyethylene glycol, antispasmodics, selective serotonin reuptake inhibitors and, only in specific IBS subtypes, 5-HT3 antagonists, 5-HT4 agonists, bile acid sequestrants.

[The impact of the COVID-19 pandemic on the Italian and foreign population in the various phases: the results of an interregional multicentre project]. / L'impatto della pandemia di COVID-19 nella popolazione italiana e straniera residente nelle diverse fasi: i risultati di un progetto multicentrico inter-regionale.

OBJECTIVES: to analyze the difference of the SARS-CoV-2 infection impact between Italian and foreigner subjects, evaluating the trend of infections and access to diagnostic tests (molecular or antigenic swabs for the detection of SARS- CoV-2) in the two different populations, inducing the detection of new positive cases in the population. DESIGN: retrospective population study for the period February 2020-June 2021. SETTING AND PARTICIPANTS: Italian and foreign resident population on 1st January of the years 2020 and 2021 in the Regions participating to the project: Piedmont, Lombardy, Veneto, Emilia-Romagna (Northern Italy), Tuscany, Lazio (Central Italy), and Sicily (Southern Italy). MAIN OUTCOME MEASURES: in the two populations, for every week and aggregated by macropandemic period were calculated: • the test rate (people tested on the population); • the swab positivity rate (positive subjects on those who are tested); • the new positives (positive subjects on study population); • the percentage of foreigners among the new positive cases. The ratio of the value of the indicators in the foreign and Italian populations (with 95% confidence interval) was calculated to evaluate the association between nationality (Italian vs not Italian) and outcome. The analyses were conducted at the regional level and at pool level. RESULTS: the trend of new positives by nationality (Italian vs not Italian) has a similar tendency in the different pandemic waves. However, the incidence of new positives during pandemic waves among foreigners is lower than in Italians, while it tends to increase during intermediate periods. Except for the summer periods, foreigners are less tested than Italians, but the percentage of new positives out of the total of new ones tested is higher among foreigners compared to Italians. The relative weight of new positives among foreigners tends to increase in periods with the greatest risk of inflow of SARS-CoV-2 for foreigners. CONCLUSIONS: the epidemic trends in the two populations are similar, although foreigners tend to show lower incidence values, probably in part because they are tested less frequently. Furthermore, in foreigners compared to Italians, there is a greater risk of contracting SARS-CoV-2 infection, especially in periods of relaxation of containment Coronavirus measures, reopening of national borders, production and commercial activities.

SARS-CoV-2 Vaccination and the Bridge between First and Fourth Dose: Where Are We?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has induced the explosion of vaccine research. Currently, according to the data of the World Health Organization, there are several vaccines in clinical (145) and preclinical (195) stages, while at least 10 are already in clinical phase 4 (post-marketing). Vaccines have proven to be safe, effective, and able to reduce the spread of SARS-CoV-2 infection and its variants, as well as the clinical consequences of the development of coronavirus disease-19 (COVID-19). In the two-dose primary vaccination, different time intervals between the two doses have been used. Recently, special attention has been paid to assessing the immunogenicity following booster administration. The third dose of the vaccine against COVID-19 may be administered at least 8 weeks after the second dose. In Israel, a fourth dose has already been approved in immunocompromised groups. The main objective of this review is to describe the principal results of studies on the effectiveness of first-to-fourth dose vaccination to reduce reinfection by variants and the incidence of severe disease/death caused by COVID-19. Vaccines have shown a high level of protection from symptomatic infection and reinfection by variants after a third dose. Accelerating mass third-dose vaccination could potentially induce immunogenicity against variants.

Ways to promote screening for hepatitis B virus and accelerated vaccination schedule in prison: Training, information, peer education.

The World Health Organization has suggested prioritizing preventive measures for communicable diseases, including the hepatitis B virus (HBV) infection. To reduce inequalities in health, we have conducted a study on the impact of HBV in prisons located in the region of Tuscany by recording the results of serum screening in clinical medical records, the objective being to increase anti-HBV vaccination in subjects susceptible to infection by means of an accelerated schedule. To further advance disease prevention, we conducted health promotion and education activities prior to a screening/vaccination program in Tuscany prisons; both staff working in the prisons and the prisoners themselves were actively involved. The study started on 11 April 2016 and ended on 10 October 2017. In this paper, we report on the interventions carried out beforehand, such as training, information, and peer education. In addition to information, in a previous study on the overall rate of inmate screening and vaccination, this article incorporates supplemental analysis to differentiate the rate of screening and vaccination among inmates previously present in this setting and those having recently arrived. For health staff, six courses were conducted on Continuing Education in Medicine. A total of 138 inmates of the main nationalities present were selected by justice, health and education staff as peer educators. Out of the 15 prisons participating in the screening and vaccination program, courses for prisoners were conducted in 10 prisons by a medical doctor and the International Organization for Migration cultural mediators, taking into account the multi-ethnic origins of the detainee population and applying a peer education approach. All prisoners received an HBV brochure in various languages. HBV screening was performed by the prisons' sanitary staffs. Out of the 1075 inmates who needed screening, 70.9% of those previously present and 93.6% of the recently arrived agreed to undergo screening for HBV. Out of the 601 prisoners who required vaccination, 85.2% of those previously present and 72% of the recently arrived received the first dose. In conclusion, training, information, and a peer education approach could explain a high rate of adherence to a screening and vaccination program.

Rapid improvement of psychiatric stigmata after IFN-free treatment in HCV patients with and without cryoglobulinemic vasculitis.

OBJECTIVE: Hepatitis C virus (HCV) causes neuropsychiatric disorders and quality of life impairment, especially in patients with cryoglobulinemic vasculitis (CV). Direct acting antivirals (DAAs) are effective in most extrahepatic HCV diseases, but limited information exists regarding the outcome of psychiatric disorders in patients with and without CV, after therapy. We aimed to evaluate psychiatric outcomes, in HCV-patients with and without CV, before and after successful DAA therapy. METHODS: We prospectively studied DAA-treated HCV-patients, stratified into presence (CV) or absence of CV (NON-CV). Four psychometric scales were administered to assess depression (HAM-D and MADRS), anxiety (HAM-A), and mania (MRS). Short-Form-36 questionnaires evaluated quality of life. RESULTS: Seventy-six patients were recruited, and 47 CV and 29 NON-CV were treated with antivirals. At baseline, depression and anxiety, from mild to severe, were frequently shown, with the most advanced cases in thee CV group; no patients achieved the scores for mania. A significant improvement emerged for all the psychometric scales in the entire population and in the subgroups, after viral eradication even in the short-term outcome. The Short-Form-36 summary components showed benefits. CONCLUSIONS: After HCV eradication, the depression and anxiety scores significantly improved and severity grade generally lowered. DAA-positive effects on mental disorders should be considered part of the therapy outcome, being beneficial especially in CV patients who usually have worse baseline mental scores. Key Points • HCV frequently causes psychiatric disorders and an often-invalidating autoimmune/lymphoproliferative disease called cryoglobulinemic vasculitis. • The new direct acting antivirals (DAAs) are very effective and well tolerated by HCV-patients. • This study shows DAA-induced benefits on depression and anxiety in HCV-patients that are especially evident in CV patients who usually have worse baseline mental scores. • DAA-induced benefits are observed in the short-term post-therapy follow-up, in contrast with data previously obtained in HCV patients treated with IFN-based anti-HCV therapy.

Substance Abuse Disorder and Viral Infections (Hepatitis, HIV): A Multicenter Study in Tuscan Prisons.

Aims of this study were to define the prevalence of people with a substance use disorder (SUD) in Tuscan prisons and the relationship of such disorders with chronic viral hepatitis C or B (HCV, HBV) and human immunodeficiency virus (HIV). Of 3,291 adult prisoners, 3,100 were enrolled. Of the 3,100 inmates, 912 (29.4%) had at least one psychiatric disorder, 17.8% had a SUD/alcohol use disorder, 6.1% had adaptation disorder, and 5.5% had personality disorder. Of the drug users, 28.9% had at least one infectious disease such as HCV, HBV, and HIV. The probability of contracting HBV was higher in women than in men and in people over 50 years. The probability of contracting HCV was higher in prisoners aged 40-49, particularly among those who used opioids. Accurate national and global data on SUD and its association with HBV, HCV, and HIV are needed to permit accurate estimation of its impact in these settings.

Treatment or Prophylaxis against Hepatitis B Virus Infection in Patients with Rheumatic Disease Undergoing Immunosuppressive Therapy: An Update.

Chronic hepatitis B virus (HBV) flares or reactivations are serious causes of morbidity or mortality in rheumatologic patients undergoing immunosuppressive therapy. The recent insights in the pathogenesis of rheumatic diseases led to the use of new immunosuppressive therapies indicated in case of failure, partial response, or intolerance of conventional synthetic disease-modifying anti-rheumatic drugs. Based on these premises, this review examines and discusses the main rheumatologic treatments that could require the initiation of prophylactic treatment or close monitoring of occult HBV infection in patients beginning antiviral therapy at the first signs of HBV reactivation, or antiviral treatment in chronic HBV-infected patients. We searched for relevant studies published in the last five years. Studies suggested that the presence of HBV infection is common in rheumatic patients and HBV reactivation during these immunosuppressant treatments is quite frequent in these kinds of patients. Therefore, before starting an immunosuppressive therapy, patients should be screened for HBsAg, anti-HBs, and anti-HBc and, on the basis of markers positivity, they should be carefully characterized for HBV infection phases. In conclusion, screening of HBV infection in patients undergoing immunosuppressive therapy with subsequent HBV monitoring, prophylaxis or treatment consistently reduces the risk of clinical consequences.

Hematological and Genetic Markers in the Rational Approach to Patients With HCV Sustained Virological Response With or Without Persisting Cryoglobulinemic Vasculitis.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) usually lead to improvement/remission of cryoglobulinemic vasculitis (CV), although symptoms may persist/recur after a sustained virological response (SVR). We evaluated hematological and genetic markers in patients with HCV-SVR vasculitis with and without persisting/recurring symptoms to early predict the CV outcome. APPROACH AND RESULTS: Ninety-eight patients with HCV-CV were prospectively enrolled after a DAA-induced SVR: Group A: 52 with complete clinical response; Group B: 46 with symptom maintenance/recurrence. Monoclonal B-cell lymphocytosis, t(14;18) translocation, and abnormal free light chains κ/λ ratios were detected by flow cytometry or nested-PCR or nephelometry in 4% Group A versus 17% Group B (P = 0.04) patients, 17% Group A versus 40% Group B patients (P = 0.02), and 17% Group A versus 47% Group B (P = 0.003) patients, respectively. At least 1 out of 3 clonality markers was altered/positive in 29% of Group A versus 70% of Group B patients (P < 0.0001). When available, pretherapy samples were also tested for t(14;18) translocation (detected in 12/37 [32%] Group A and 21/38 [55%] Group B) and κ/λ ratios (abnormal in 5/35 [14%] Group A and 20/38 [53%] Group B) (P = 0.0006), whereas at least one clonality marker was detected/altered in 16/37 (43%) Group A and 30/38 (79%) Group B (P = 0.002). CV-associated single-nucleotide polymorphisms were tested by real-time PCR. Among them, notch4 rs2071286 T minor allele and TT genotype showed a higher frequency in Group B versus Group A (46% vs. 29%, P = 0.01, and 17% vs. 2%, P = 0.006, respectively). CONCLUSIONS: Hematological or genetic analyses could be used to foresee the CV clinical response after DAA therapy and could be valuable to assess a rational flowchart to manage CV during follow-up.

Effect of soy consumption on liver enzymes, lipid profile, anthropometry indices, and oxidative stress in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of clinical trials.

 The present systematic review and meta-analysis was conducted to investigate the effects of soy intake on liver enzymes, lipid profile, anthropometry indices, and oxidative stress in non-alcoholic fatty liver disease (NAFLD). A systematic search was undertaken in PubMed, Embase, Scopus, Web of Science, and Cochrane Library covering up to 10 January 2020. A fixed-effect or random-effects models were applied to pool mean difference (MD) and its 95 % confidence intervals (CI). Four clinical trials comprising 234 participants were included in the meta-analysis. Compared to the controls, alanine aminotransferase (ALT) levels (MD=-7.53, 95% CI=[-11.98, -3.08], P=0.001, I2=0.0 %), body weight (MD=-0.77, 95 % CI=[-1.38, -0.16], P=0.01, I2=36.9%), and the concentration of serum Malondialdehyde (MDA) (MD=-0.75, 95% CI=[-1.29, -0.21], P=0.007, I2=63.6%) were significantly changed following soy intake. Lipid profile was not significantly affected by soy intake. Moreover, no evidence of a significant publication bias was found. The present study suggests lowering effects for soy intake on ALT levels, body weight, and MDA in nonalcoholic liver patients. Therefore, further large-scale and well-designed clinical trials are needed to find conclusive findings.

Update on Hepatitis C Epidemiology: Unaware and Untreated Infected Population Could Be the Key to Elimination.

Globally, the World Health Organization (WHO) estimates that 71 million people have chronic hepatitis C virus (HCV) infection. A significant number of these will develop cirrhosis or liver cancer. Currently, during the COVID-19 outbreak, a high mortality rate has been found in patients with COVID-19 and cirrhosis. New direct-acting antiviral agents can cure more than 90% of HCV-infected patients. The new WHO strategy has introduced global goals against viral hepatitis, including a 30% reduction in new HCV cases and a 10% reduction in mortality by 2020. HCV transmission has changed considerably, reflecting both the evolution of medicine and health and social changes. The HCV is usually spread through blood-to-blood contact. After the discovery of HCV in 1989, antibody screening has drastically decreased the incidence of post-transfusion hepatitis. Nowadays, routine blood donor screening by nucleic acid amplification testing for the presence of HCV RNA has been introduced in many countries. It is conceivable that HCV screening could be offered to people born between 1946 and 1964 in the developed world and to people at high risk for HCV infection such as those who have received blood transfusions, blood products or organ donations before the 1990s, prisoners, health care workers, drug users and infants born to HCV-infected women. To achieve HCV elimination, health programmes should include improvement to access to health care services, increased screening and new projects to identify a submerged portion of patients with HCV infection. Submerged people with HCV infection are both people who are unaware of their condition and people diagnosed with HCV but not yet treated. Based on these premises, this review will examine and discuss the epidemiological changes in contracting HCV, highlighting the ways in which to identify a submerged portion of patients with HCV infection.

Treatment for COVID-19: An overview.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by coronavirus-2 (SARS-CoV-2) that causes a severe acute respiratory syndrome, a characteristic hyperinflammatory response, vascular damage, microangiopathy, angiogenesis and widespread thrombosis. Four stages of COVID-19 have been identified: the first stage is characterised by upper respiratory tract infection; the second by the onset of dyspnoea and pneumonia; the third by a worsening clinical scenario dominated by a cytokine storm and the consequent hyperinflammatory state; and the fourth by death or recovery. Currently, no treatment can act specifically against the SARS-CoV-2 infection. Based on the pathological features and different clinical phases of COVID-19, particularly in patients with moderate to severe COVID-19, the classes of drugs used are antiviral agents, inflammation inhibitors/antirheumatic drugs, low molecular weight heparins, plasma, and hyperimmune immunoglobulins. During this emergency period of the COVID-19 outbreak, clinical researchers are using and testing a variety of possible treatments. Based on these premises, this review aims to discuss the most updated pharmacological treatments to effectively act against the SARS-CoV-2 infection and support researchers and clinicians in relation to any current and future developments in curing COVID-19 patients.

The effects of metformin administration on liver enzymes and body composition in non-diabetic patients with non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis: An up-to date systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. One treatment is the use of metformin but its efficacy remains to be established. OBJECTIVE: The present systematic review and meta-analysis aimed to provide a more robust examination of the evidence for the effectiveness of metformin for treating non-diabetic NAFLD patients. METHODS: An extensive literature search was undertaken using online databases (PubMed, Embase, Scopus, Web of Science and Cochrane Library) to detect randomized controlled trials (RCTs) investigating the effect of metformin administration on liver enzymes and body composition in non-diabetic NAFLD patients up to 10 December 2019. A random-effects or fixed-effect models were performed to pool weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: Six RCTs involving 307 individuals were included to the present meta-analysis. Compared to controls, metformin significantly reduced body mass index (BMI) (WMD: -0.77 kg/m2, 95 % CI = [-1.46, -0.07], P = 0.03, I2 = 0.0 %) and serum aspartate aminotransferase (AST) (WMD: -5.94 U/L, 95 % CI = [-11.51, -0.38], P = 0.03, I2 = 67.6 %). Also, body weight (WMD: -2.70 kg, 95 % CI = [-5.49, 0.09], P = 0.05, I2 = 33.7%) was marginally significant and serum alanine transaminase (ALT) (WMD: -5.04 U/L, 95 % CI = [-13.92, 3.84], P = 0.26, I2 = 60.9 %) was not statistically significant affected by metformin administration. There was no evidence of publication bias. CONCLUSION: In summary, the present study emphasizes the clinical importance of metformin administration for improving liver function and body composition in non-diabetic NAFLD patients. Moreover, the further large-scale and well-designed RCTs are required to confirm these findings.

Hepatitis B vaccination and immunotherapies: an update.

World Health Organization (WHO) estimates that 257 million people were living with chronic hepatitis B virus (HBV) infection. Highest HBV prevalence was found in the WHO Western Pacific Region (6.2%) and in the WHO African Region (6.1%). The HBV vaccine is the best protection against chronic HBV infection and its complications. Globally, routine infant immunization against HBV has increased with an estimated coverage of 84% in 2017. Nevertheless, in many countries further efforts are needed to implement this coverage and ensure national immunization programs for people at major risk for HBV infection. Therapeutic vaccination in chronic HBV infected patients can cause anti-HBV immune responses able to remove and/or cure infected hepatocytes. It shows promising results in murine model and human trials, but these results need to be consolidated by further multicenter clinical studies. In particular, the efficacy of therapeutic vaccine seems to improve by combination therapies.

Longitudinal evaluation of liver stiffness and outcomes in patients with chronic hepatitis C before and after short- and long-term IFN-free antiviral treatment.

Background: New direct-acting antiviral drugs can eradicate hepatitis C virus (HCV) infection in over 90% of patients and can even reduce the risk of complications in advanced fibrosis/cirrhosis. The aims of this study were to evaluate (1) changes in fibrosis during and after antiviral treatment and (2) incidence of hepatocarcinoma and mortality in various fibrosis stages.Methods: This is a longitudinal monocentric prospective study. Blood and instrumental examinations were evaluated at baseline, at the end of therapy, and 1 and 2 years following treatment.Results: Two hundred and ninety-six patients with chronic HCV were evaluated, of whom 115 were experienced, 181 were treatment-naïve, and 2 had previous hepatocellular carcinoma (HCC) and were therefore excluded from the study. At baseline, stiffness values were 13.46 ± 9.97 kPa. Out of the 294 HCV patients enrolled, 100 had lymphoproliferative disorders and were evaluated separately. This group of patients showed stiffness values pertaining to the F0-F2 group (mean stiffness values were 6.07 ± 1.68 kPa). All other patients showed stiffness values pertaining to the F3-F4 group (mean stiffness values were 17.93 ± 10.23). No statistically significant difference was found between stiffness at baseline compared to the end of treatment (EOT), while significant differences were found between the baseline, 1 year (p = .05), and 2 year follow-ups (p < .01). Significant differences were found between baseline and EOT, as well as 1 and 2 years after the end of treatment (p < .001) in the F3-F4 group. Four out of 140 patients with baseline cirrhosis developed HCC during the post-treatment follow-up, 1 of whom died.Conclusions: Non-invasive methods provide important prognostic information, particularly concerning the observed regression of fibrosis and could be extremely useful for monitoring patients with long life expectancies after direct-acting antiviral treatment.

The Relationship Between the Serotonin Metabolism, Gut-Microbiota and the Gut-Brain Axis.

BACKGROUND: Serotonin (5-HT) has a pleiotropic function in gastrointestinal, neurological/psychiatric and liver diseases. The aim of this review was to elucidate whether the gut-microbiota played a critical role in regulating peripheral serotonin levels. METHODS: We searched for relevant studies published in English using the PubMed database from 1993 to the present. RESULTS: Several studies suggested that alterations in the gut-microbiota may contribute to a modulation of serotonin signalling. The first indication regarded the changes in the composition of the commensal bacteria and the intestinal transit time caused by antibiotic treatment. The second indication regarded the changes in serotonin levels correlated to specific bacteria. The third indication regarded the fact that decreased serotonin transporter expression was associated with a shift in gut-microbiota from homeostasis to inflammatory type microbiota. Serotonin plays a key role in the regulation of visceral pain, secretion, and initiation of the peristaltic reflex; however, its altered levels are also detected in many different psychiatric disorders. Symptoms of some gastrointestinal functional disorders may be due to deregulation in central nervous system activity, dysregulation at the peripheral level (intestine), or a combination of both (brain-gut axis) by means of neuro-endocrine-immune stimuli. Moreover, several studies have demonstrated the profibrogenic role of 5-HT in the liver, showing that it works synergistically with platelet-derived growth factor in stimulating hepatic stellate cell proliferation. CONCLUSION: Although the specific interaction mechanisms are still unclear, some studies have suggested that there is a correlation between the gut-microbiota, some gastrointestinal and liver diseases and the serotonin metabolism.

Screening for hepatitis B virus and accelerated vaccination schedule in prison: A pilot multicenter study.

BACKGROUND AND AIM: Vaccine against hepatitis B virus (HBV) is highly effective in preventing HBV infection. The aims of this study were to (1) increase the epidemiological knowledge on the impact of HBV in Tuscany region prisons by registering the results of serum screening on a clinical medical record and (2) increase the anti-HBV vaccination using an accelerated schedule. METHODS: Our study population was composed of all detainees present in prisons and all constrained from freedom or at institutions in the Tuscany region and not vaccinated at these facilities from 1 December 2016 to 31 May 2017. RESULTS: Of 17 detention facilities in the Tuscany region, 15 were enrolled in the study. On 28 February 2017, there were 3068 detainees present in these institutions. Considering the 1075 subjects screened for HBV serum markers, 730 (67.9%) were susceptible to infection and needed to be vaccinated. Five hundred and ninety-six agreed to be vaccinated (82%); 27 (2.5%) of our subjects had an isolated anti-HBc, 20 (1.9%) were HBV infected (HBsAg+), 127 (11.8%) had previous HBV infection (anti-HBs+, anti-HBc+ and HBsAg-), and 171 had been previously vaccinated. Five hundred and fifty-five inmates (95.1%) received the first vaccine dose, and 404 (83%) underwent the third dose at day 21. CONCLUSION: This study showed that of a high percentage of subjects who underwent screening, more than half needed to be vaccinated. Moreover, our study reached very high levels of vaccination coverage, considering both the entire enrolled population and the new inmates.