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Background The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. Methods Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. Results We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8–47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0–44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00–6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18–3.36), platelet count p = 0.83). Conclusions Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.

OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.\ud \ud RESULTS:\ud The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively.\ud \ud CONCLUSIONS:\ud This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Background In patients treated for HCV infection, potential drug–drug interactions (DDIs) can occur among direct-acting antiviral drugs (DAAs) and comedications used. The real-life effectiveness and safety of elbasvir/grazoprevir (ELB/GZR) among co-medicated HCV patients was evaluated. Methods We prospectively evaluated consecutive patients from 15 clinical centres participating in PITER who were treated with ELB/GZR and had been followed for at least 12 weeks after treatment. Data were prospectively collected on the use of comedications (including discontinuation, dose modification and addition of drugs) and potential DDIs with DAAs. Results Of the 356 patients with at least 12-week post-treatment follow-up (median age 67, range 50–88 years), 338 (95%) achieved sustained virological response. Of these, 219 (60%) had at least one comorbidity (median 2, range 1–6); information on comedication was available for 212 of them. Of 190 comedications used, 15 (8%) drugs were modified during ELB/GZR therapy, specifically in 9 (4%) patients they were interrupted, in 2 (1%) of whom, the comedication was interrupted before the DAA therapy because of potential DDI (that is, patients treated with carbamazepine); in 12 (6%) patients the comedications were modified in terms of dosage. In 29 (14%) patients, the comedications required monitoring when used with ELB/GZR, as well as with all available DAAs. Of the 190 drugs, 27 (14%) used in 67% of patients were free of DDIs when used with ELB/GZR, whereas they required monitoring if used with other DAA regimens. Conclusions The results of this prospective study support findings that ELB/GZR is effective and safe in most treated patients.

Background and Aims Cost‐effective screening strategies are needed to make hepatitis C virus (HCV) elimination a reality. We determined if birth cohort screening is cost‐effective in Italy. Methods A model was developed to quantify screening and healthcare costs associated with HCV. The model‐estimated prevalence of undiagnosed HCV was used to calculate the antibody screens needed annually, with a €25 000 cost‐effectiveness threshold. Outcomes were assessed under the status quo and a scenario that met the World Health Organization's targets for elimination of HCV. The elimination scenario was assessed under five screening strategies. Results A graduated birth cohort screening strategy (graduated screening 1: 1968‐1987 birth cohorts, then expanding to 1948‐1967 cohorts) was the least costly. This strategy would gain approximately 144 000 quality‐adjusted life years (QALYs) by 2031 and result in an 89.3% reduction in HCV cases, compared to an 89.6%, 89.0%, 89.7% and 88.7% reduction for inversed graduated screening, 1948‐77 birth cohort, 1958‐77 birth cohort and universal screening, respectively. Graduated screening 1 yielded the lowest incremental cost‐effectiveness ratio (ICER) of €3552 per QALY gained. Conclusions In Italy, a graduated screening scenario is the most cost‐effective strategy. Other countries could consider a similar birth cohort approach when developing HCV screening strategies., See Editorial on Page 1538

Background Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. Aims To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. Methods Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. Results Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02–1.43] and 1.27 [1.05–1.53]), diabetes mellitus (odds ratio, 2.35 [1.68–3.29] and 2.12 [1.47–3.05]), chronic constipation (odds ratio, 1.60 [1.30–1.97] and 1.55 [1.23–1.94]), incomplete purge intake (odds ratio, 2.36 [1.90–2.94] and 2.11 [1.68–2.65]) and a runway time >12 h (odds ratio, 3.36 [2.40–4.72] and 2.53 [1.74–3.67]). Conclusions We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.

a b s t r a c t Background: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in “real world” chronic hepatitis C patients in Italy. Methods: Independent observational multicentre study including consecutive patients receiving Peginterferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. Results: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and -glutamil-transpeptidase >2 times the normal limit were associated with poorer response. Conclusions: The response to Peg-interferon/ribavirin therapy in “real world” clinical practice is distinctly lower than in registration trials. The difference in response rates was more pronounced among easy-totreat than among difficult-to-treat hepatitis C virus genotypes.

The association of Budd-Chiari Syndrome (BCS) and Antiphospholipid Antibody Syndrome (APS) has been previously described in literature. We report the case of a 46-year-old woman who was admitted to our Unit of Hepatology for upper abdominal quadrant pain, asthenia and edema of the left upper arm. Her familiar history told about predisposition to Systemic Lupus Erythematosus (SLE) whereas her personal story showed a continuous use of oral contraceptives during the six years preceding diagnosis and the absence of episodes of obstetric complications. At the admission, a Doppler Ultrasound examination showed complete thrombosis of venous axis of the left upper arm and thrombosis of subclavian artery (with the aspect of “subclavian steal syndrome”). Abdominal ultrasonography revealed hepatic lesions (characterized by an abdominal Computed Tomography as ischemic injuries) at seventh and eighth segments and the presence of significant amount of ascites. Abdominal and thoracic Computed Tomography confirmed pleural effusion and pointed out a radiologic pattern of Budd-Chiari Syndrome. To verify the presence of concomitant pericardial effusion, an echocardiogram was performed. It allowed reaching the diagnosis of polyserositis. In order to investigate all potential causes of thrombotic diathesis, specific laboratory tests were performed. Normal level of protein C, S and antithrombin II, absence of JAK-2 mutation and negativity of Ham’s test were observed. Positivity was found for anti-SSA (60 kDa) and for antibodies routinely tested for Antiphospholipid Antibody Syndrome (APS), i.e. Lupus-Anticoagulant, Anticardiolipin and Beta2- Glycoprotein I. After the introduction of oral anticoagulant and diuretics a significant improvement of clinical condition of the patient was reached. To conclude, the exact role of oral contraceptives as triggering factor of an undetected APS need to be emphasize, as well as the potentiality of this disease to evolve in a “ to happen” SLE in patients with positive familiarity for autoimmune diseases.

Background & aims: The role of oral supplementation with branched-chain amino acids (BCAA) in advanced cirrhosis is far from settled. A nutritional approach might prevent progressive liver failure and improve nutritional parameters and quality of life. Methods: A multicenter, randomized study comparing 1-year nutritional supplementation with BCAA against lactoalbumin or maltodextrins was performed in 174 patients with advanced cirrhosis. Primary outcomes were the prevention of a combined end point (death and deterioration to exclusion criteria), the need for hospital admission, and the duration of hospital stay. Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh score, anorexia, health-related quality of life, and need for therapy. Results: Treatment with BCAA significantly reduced the combined event rates compared with lactoalbumin (odds ratio, 0.43; 95% confidence interval, 0.19–0.96; P = 0.039) and nonsignificantly compared with maltodextrins (odds ratio, 0.51; 95% confidence interval, 0.23–1.17; P = 0.108). The average hospital admission rate was lower in the BCAA arm compared with control treatments ( P = 0.006 and P = 0.003, respectively). In patients who remained in the study, nutritional parameters and liver function tests were, on average, stable or improved during treatment with BCAA and the Child-Pugh score decreased ( P = 0.013). Also, anorexia and health-related quality of life (SF-36 questionnaire) improved. Long-term compliance with BCAA was poor. Conclusions: In advanced cirrhosis, long-term nutritional supplementation with oral BCAA is useful to prevent progressive hepatic failure and to improve surrogate markers and perceived health status. New formulas are needed to increase compliance.

Background & Aims: Increasing interest is being given to health-related quality of life in chronic diseases. In cirrhosis, both physical functioning and mental well-being may be altered, but no study has investigated factors associated with a poor perceived health status. Methods: We measured quality of life by Short Form-36 and Nottingham Health Profile questionnaires in 544 patients with cirrhosis. Data were compared with age- and gender-adjusted values of 2 random samples of the Italian population (more than 2000 subjects). Factors associated with poor perceived health status were identified by logistic regression. Results: All domains of health-related quality of life, except pain, were altered in cirrhosis (by 9%-42%), mainly in younger patients. There were minor differences in relation to gender, whereas etiology had no effects. Severity of disease (Child-Pugh score) and, above all, muscle cramps were the factors most closely associated with poor health status perception. Self-rating of disease progression was associated with ascites and pruritus, whereas previous variceal sclerotherapy and the use of disaccharides had a protective effect. Most areas of daily life were affected by perceived health problems; this was mainly true for paid employment and sex life in men and home life and social life in women. Conclusions: Quality of life is variably impaired in cirrhosis, also in uncomplicated patients. Non-life-threatening symptoms, such as muscle cramps, are of major concern. These data are the basis for longitudinal studies measuring the effects of therapy and procedures on patient-derived health outcomes. GASTROENTEROLOGY 2001;120:170-178

Background: Bismuth quadruple (BQT) and non-bismuth quadruple (N-BQT) therapies are the recommended first-line treatments for Helicobacter (H.) pylori infection. Objective: To compare the efficacy of BQT and N-BQT in clinical practice in an area with high clarithromycin resistance, choosing the regimen on the basis of previous exposure to clarithromycin. Methods: A total of 404 consecutive Hpylori-positive, naïve patients were enrolled. A total of 203 patients without previous exposure to clarithromycin received N-BQT, 100 patients for 10days and 103 for 14days, whereas 201 with previous exposure to clarithromycin received 10-day BQT. Efficacy and treatment-related adverse events were assessed. Results and Conclusions: Eradication rates by intention-to-treat analysis were 88.2% for N-BQT and 91.5% for BQT (P=.26); per-protocol analysis eradication rates were 91.2% and 95.8% for N-BQT and BQT, respectively (P=.07). Eradication rates were significantly higher with 14-day than 10-day CT (P&nbsp

Background & Aims: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. Methods: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. Results: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5–4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. Conclusion: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin – 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. Lay summary: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.

Background Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794. Findings From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events. Interpretation In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Funding Italian Medicine Agency. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hepatic encephalopathy (HE) is a common, worrisome and sometimes difficult to manage complication of end-stage liver disease. HE is often recurrent, requiring multiple hospital admissions. It can have serious implications in terms of a patient's ability to perform complex tasks (for example driving), their earning capacity, their social and family roles. This guideline reviews current knowledge on HE definition, pathophysiology, diagnosis and treatment, both by general principles and by way of a summary of available drugs and treatment strategies. The quality of the published, pertinent evidence is graded, and practical recommendations are made. Where possible, these are placed within the Italian health service context, with reference to local diagnosis and management experience.

Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-4, transient elastography and controlled attenuation parameter, thiobarbituric acid reactive substances, tumor necrosis factor α, transforming growth factor β, interleukin-18 and interleukin-22, matrix metalloproteinase 2, epidermal growth factor receptor, insulin growth factor-II, cluster of differentiation-44, high mobility group box-1, and Endocan. Compared to the healthy controls, the nonalcoholic fatty liver disease patients had statistically significant differences for almost all parameters evaluated at baseline (p<0.05). Six months after the baseline, the proportion of nonalcoholic fatty liver disease patients treated that underwent a statistically significant improvement in metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease was greater than not treated nonalcoholic fatty liver disease patients (p<0.05). Even more relevant results were obtained for the same parameters by analyzing patients with a concomitant diagnosis of metabolic syndrome (p<0.001). The benefit that derives from the use of RealSIL 100D could derive from the action on more systems able to advance the pathology above all in that subset of patients suffering from concomitant metabolic syndrome.

Metabolic- (dysfunction) associated fatty liver disease (MAFLD) represents the predominant hepatopathy and one of the most important systemic, metabolic-related disorders all over the world associated with severe medical and socio-economic repercussions due to its growing prevalence, clinical course (steatohepatitis and/or hepatocellular-carcinoma), and related extra-hepatic comorbidities. To date, no specific medications for the treatment of this condition exist, and the most valid recommendation for patients remains lifestyle change. MAFLD has been associated with metabolic syndrome; its development and progression are widely influenced by the interplay between genetic, environmental, and nutritional factors. Nutrigenetics and nutrigenomics findings suggest nutrition’s capability, by acting on the individual genetic background and modifying the specific epigenetic expression as well, to influence patients’ clinical outcome. Besides, immunity response is emerging as pivotal in this multifactorial scenario, suggesting the interaction between diet, genetics, and immunity as another tangled network that needs to be explored. The present review describes the genetic background contribution to MAFLD onset and worsening, its possibility to be influenced by nutritional habits, and the interplay between nutrients and immunity as one of the most promising research fields of the future in this context.

Introduction: PNPLA3, TM6SF2, and MBOAT7 genes play a crucial role in non-alcoholic fatty liver disease (NAFLD) development and worsening. However, few data are available on their treatment response influence. The aim of this trial is to explore the effect derived from silybin-phospholipids complex (303 mg of silybin-phospholipids complex, 10 μg of vitamin D, and 15 mg of vitamin E twice a day for 6 months) oral administration in NAFLD patients carrying PNPLA3-rs738409, TM6SF2-rs58542926, or MBOAT7-rs641738 genetic variants.Materials and Methods: In all, 92 biopsy-proven NAFLD patients were grouped in 30 NAFLD wild type controls, 30 wild type treated patients, and 32 mutated treated ones. We assessed glycemia (FPG), insulinemia, HOMA-IR, aspartate and alanine aminotransferases (AST, ALT), C-reactive protein (CRP), thiobarbituric acid reactive substance (TBARS), stiffness, controlled attenuation parameter (CAP), dietary daily intake, and physical activity at baseline and end of treatment.Results: The wild-type treated group showed a significant improvement of FPG, insulinemia, HOMA-IR, ALT, CRP, and TBARS (p < 0.05), whereas no improvements were recorded in the other two study groups. NAFLD wild type treated patients showed higher possibilities of useful therapeutic outcome (p < 0.01), obtained from the prescribed therapeutic regimen, independently from age, sex, comorbidities, medications, CAP, and stiffness in comparison to the mutated group.Discussion: The assessed mutations are independently associated with no response to a silybin-based therapeutic regimen and could be considered as useful predictive markers in this context.Clinical Trial Registry Number:www.ClinicalTrials.gov, identifier: NCT04640324.

Introduction: Irritable bowel syndrome represents one of the most difficult gastroenterological diseases to treat, that usually induces the patients to follow different drug therapies, often not useful in symptom control. In this scenario low FODMAP diet could have positive effects in patients with irritable bowel syndrome, even because this type of diet regimen is characterized by a low gluten amount due to the exclusion of cereals. Methods: We enrolled 120 patients with irritable bowel syndrome, according to the Rome IV criteria, who were referred to Hepatogastroenterology Division of the University of Campania L. Vanvitelli from June to December 2018. They underwent a low FODMAP diet for six weeks, followed by a gradual weekly reintroduction of every category of food for three months. The patients had a follow-up evaluation for six months after the end of food reintroduction period. We measured abdominal pain with subjective numerical scale from 0 to 10. We evaluated other gastrointestinal symptoms with a questionnaire about symptoms of lower digestive tract, evaluating their frequency and intensity. We also evaluated the impact of irritable bowel syndrome on daily life with neurological bowel dysfunction score. Results: We obtained a good patient-adherence to diet and a statistically significant decrease of abdominal pain, bloating, flatulence, diarrhea, constipation, and neurological bowel dysfunction score (p &lt, 0.001) at the end of the diet. These results remained constant in the follow-up period. Conclusions: We recommend the use of a low FODMAP diet regimen in patients with irritable bowel syndrome in order to control the symptoms and improve the quality of life.

Background Percutaneous Endoscopic Gastrostomy (PEG) can involve some complications, despite the good safety of its track record. The Buried Bumper Syndrome (BBS) is a rare, late and dangerous complication that consists in the erosion of the internal bumper through the gastric wall. Case presentation We report the development of BBS in a man with chronic obstructive pulmonary disease (COPD) who had a persistent chronic cough which was prevalently but not solely in the morning and required placement of a PEG tube for continuous infusion of Levodopa/carbidopa intestinal gel for advanced Parkinson's disease. Conclusion We believe that COPD with chronic cough while not representing an absolute contraindication to PEG placement, may potentially cause BBS and therefore an appropriate regimen of tube care by expert personnel is mandatory in this setting.

The frailty represents a key determinant of elderly clinical assessment, especially because it allows the identification of risk factors potentially modifiable by clinical and therapeutic interventions. The frailty assessment in elderly patients usually is made by using of Fried criteria. However, to assess the frailty in cirrhotic patients, multiple but different tools are used by researchers. Thus, we aimed to compare frailty prevalence in elderly patients with well-compensated liver cirrhosis and without cirrhosis, according to Fried criteria.Among 205 elderly patients screened, a total of 148 patients were enrolled. The patients were divided into 2 groups according to the presence/absence of well-compensated liver cirrhosis.After clinical examination with conventional scores of cirrhosis, all patients underwent anthropometric measurements, nutritional, biochemical, comorbidity, and cognitive performances. Frailty assessment was evaluated according to Fried frailty criteria.Unexpectedly, according to the Fried criteria, non-cirrhotic patients were frailer (14.2%) than well-compensated liver cirrhotic patients (7.5%). The most represented Fried criterion was the unintentional weight loss in non-cirrhotic patients (10.1%) compared to well-compensated liver cirrhotic patients (1.4%). Moreover, cumulative illness rating scale -G severity score was significantly and positively associated with frailty status (r = 0.234, P < .004). In a multivariate linear regression model, only female gender, body mass index and mini nutritional assessment resulted associated with frailty status, independently of other confounding variables.Despite the fact that elderly cirrhotic patients are considered to be frailer than the non-cirrhotic elderly patient, relying solely on "mere visual appearance," our data show that paradoxically non-cirrhotic elderly patients are frailer than elderly well-compensated liver cirrhotic patients. Thus, clinical implication of this finding is that frailty assessment performed in the well-compensated liver cirrhotic patient can identify those cirrhotic patients who may benefit from tailored interventions similarly to non-cirrhotic elderly patients.

Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 g of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. Methods: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. Results: A direct proportionality between TBARS levels and BPA exposure was shown (p &lt, 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p &lt, 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p &lt, 0.0001, p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). Conclusions: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways.

Alcohol use disorder which includes alcohol abuse and dependence represents one of the leading risk factors for premature mortality in Europe and it is responsible of over 200 conditions, including neuropsychiatric disorders, chronic diseases, cancers and accidents leading to permanent disability. Alcohol use disorder represents the most common cause of liver damage in the Western world, with a wide spectrum of diseases ranging from steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. The present clinical practice guidelines by the Italian Association for the Study of the Liver (AISF) are focused on the current knowledge about epidemiology, pathophysiology, clinical features, diagnosis and treatment of alcohol associated liver disease, aiming to provide practical recommendations on the management of this complex pathological condition.

Non-alcoholic fatty liver disease (NAFLD) is considered a predominant chronic liver disease worldwide and a component of metabolic syndrome. Due to its relationship with multiple organs, it is extremely complex to precisely define its pathogenesis as well as to set appropriate therapeutic and preventive strategies. Endocrine disruptors (EDCs) in general, and bisphenol A (BPA) in particular, are a heterogeneous group of substances, largely distributed in daily use items, able to interfere with the normal signaling of several hormones that seem to be related to type 2 diabetes mellitus (T2DM), obesity, and other metabolic disorders. It is reasonable to hypothesize a BPA involvement in the pathogenesis and evolution of NAFLD. However, its mechanisms of action as well as its burden in the vicious circle that connects obesity, T2DM, metabolic syndrome, and NAFLD still remain to be completely defined. In this review we analyzed the scientific evidence on this promising research area, in order to provide an overview of the harmful effects linked to the exposure to EDCs as well as to frame the role that BPA would have in all phases of NAFLD evolution. ispartof: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH vol:16 issue:17 ispartof: location:Switzerland status: published

Background: Hepatitis C virus (HCV) infection represents one of the most important causes of chronic liver damage. The development of new therapeutic approaches based on the use of direct-acting antivirals allowed reaching the high rates of sustained virological response and on the other hand, the low rates of drug side effects. Objectives: The study aimed to evaluate the efficacy and safety of multiple direct-acting antiviral (DAA) therapies against the major HCV genotypes in Campania. Methods: We enrolled, in this monocentric observational study, 518 adult patients (> 18-years-old) affected by HCV who received a DAA anti-HCV-based therapy in the routine clinical practice. We collected direct data registered by the Hepatogastroenterology Division of the University of Campania “L. Vanvitelli”, which covers a catchment area from the entire Campania region. Results: A great number (98.2 %) of the 518 enrolled patients was naive to the antiviral treatment and genotype distribution was 1a = 32 (6.2%), 1b = 252 (48.7%), 2 = 146 (28.2%), 3 = 52 (10.1%), and 4 = 36 (6.9%). 300 patients were cirrhotic (57.9%) and most of them had a Child-Pugh A5 score. 79.56 % of the patients belonging to the population of our study were classified as fibrosis Metavir F3 or F4 by Fibroscan. All the enrolled patients completed the treatment with the exception of five (n = 5; 0.96%) who interrupted it due to adverse events. We observed a relapse of infection in three patients treated with Sofosbuvir and Simeprevir for 12 weeks (0.57%). Intention to treat analysis showed an overall rate of 98.46% (n = 510/518) sustained virological response. Six of the eight failure patients had a second line anti-HCV treatment and four of them obtained SVR (two patients are waiting for resistance test results). Conclusions: New antiviral regimens of DAA-based for HCV represent one of the greatest innovations in the scientific context in the last few years. Our prospective observational study confirms the elevated efficacy in terms of SVR12, independently from HCV genotype and disease stage, when these treatments are used as the methods of a good clinical practice.

Background: Bisphenol A is an endocrine disrupting chemical associated with type 2 diabetes mellitus (T2DM), cardiovascular disease and liver enzyme abnormalities. Aim: To evaluate bisphenol A plasma and urine levels in non-alcoholic fatty liver disease (NAFLD) patients compared to healthy subjects. Furthermore, we evaluated, in human HepG2 cells, the effects of exposure to different concentrations of bisphenol A on both oxidative stress induction and cell proliferation. Methods: We enrolled 60 patients with histological diagnosis of NAFLD with or without T2DM and sixty healthy subjects. In vitro, the proliferation of bisphenol A-exposed HepG2 cells at two different concentrations (0.025 and 0.05 μM) was evaluated, both at high (H-HepG2) and at low (L-HepG2) glucose concentrations for 48 h. Lipoperoxidation was assessed by thiobarbituric acid reactive substances (TBARS) assay. Results: Bisphenol A levels were significantly higher in 60 NAFLD subjects, both in urine and in plasma (P < 0.0001) when compared to controls and, in this group, it appeared to be higher in 30 non-alcoholic steatohepatitis patients compared to 30 simple steatosis subjects (P < 0.05), independently from the presence of T2DM. After a bisphenol A-free diet for 1 month, NAFLD patients showed a significant reduction in bisphenol A circulating levels (P < 0.05), without a significant reduction in urine levels. H-HepG2 cells treated with bisphenol A (0.05 μM) increased proliferation compared to controls at 48 h (P < 0.0001). Bisphenol A increased TBARS levels at 48 h versus controls. Conclusions: Our study reveals a possible role of bisphenol A as an environmental factor involved in the promotion of NAFLD, particularly in T2DM patients.

Lifestyle interventions remain the first-line treatment for non-alcoholic fatty liver disease (NAFLD), even if the optimal alimentary regimen is still controversial. The interest in antioxidants has increased over time, and literature reports an inverse association between nutrients rich in antioxidants and the risk of mortality due to non-communicable diseases, including NAFLD. Mediterranean diet (MD) is a model characterized by main consumption of plant-based foods and fish and reduced consumption of meat and dairy products. MD represents the gold standard in preventive medicine, probably due to the harmonic combination of many foods with antioxidant and anti-inflammatory properties. This regimen contributes substantially to the reduction of the onset of many chronic diseases as cardiovascular diseases, hypertension, type 2 diabetes mellitus, obesity, cancer, and NAFLD. The present review aims to clarify the intake of antioxidants typical of the MD and evaluate their effect on NAFLD.

The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disease occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and an assessment of the available treatment options. The report contains in three sections: (1) specific liver diseases of pregnancy; (2) liver disease occurring during pregnancy; and (3) pregnancy in patients with pre-existing chronic liver disease. Each topic is discussed considering the most relevant data available in literature; the final statements are formulated according to both scientific evidence and clinical expertise of the involved physicians, and the AISF expert panel recommendations are reported.

Background. It has been shown that health-related quality of life is reduced in patients with cirrhosis and with chronic hepatitis in relation to antiviral therapy. No data are available on patients with hepatocellular carcinoma. Aim. To assess health-related quality of life in cirrhotic patients with hepatocellular carcinoma. Patients and methods. Health-related quality of life was assessed in 101 hepatocellular carcinoma patients by means of Short Form-36 and Nottingham Health Profile questionnaires. Final scores of domains for individual patients were compared to age-adjusted normative Italian values, using Z-score and with values obtained in 202 matched patients with cirrhosis, without hepatocellular carcinoma. Results. All Short Form-36 domains and 4 out of 6 Nottingham Health Profile domains were altered. When hepatocellular carcinoma patients were compared with matched cirrhotics, differences were present for Bodily Pain, Role Limitation-Physical, and the Physical Component Summary of Short Form-36, as well as Pain of Nottingham Health Profile. Perceived health status had changed significantly in the year prior to assessment. Health-related quality of life was not primarily related to tumour mass or hepatocellular failure, whereas sleep disorders were selected by logistic regression as strongly associated with poor health-related quality of life. Conclusions. The present data stress the relevance of pain in poor perceived health status of hepatocellular carcinoma patients, and the importance of minor symptoms, such as sleep disorders. © 2002 Editrice Gastroenerologica Italiana S.r.l. Published by Elsevier Science Ireland Ltd. All rights reserved.

Introduction: Dermatological adverse events are an existing concern during treatment of hepatitis C virus infection. Peginterferon/ ribavirin treatment is associated with well-characterized dermatological lesions tending towards a uniform entity of dermatitis. New telaprevir- or boceprevir-based triple-therapy has led to significant improvements in sustained virological response rates, although associated with an increase in cutaneous adverse events compared peginterferon/ribavirin alone. Case Presentation: We report a case of a patient who discontinued telaprevir because of severe skin eruptions and who, during ribavirin and interferon treatment, after a period free of skin lesions, developed new dermatological lesions different than those experienced during telaprevir treatment. Conclusions: Several adverse effects are associated to anti-HCV drugs, hence appropriate skin care management and follow-up are very important. A careful anamnesis before the initiation of triple therapy is necessary to identify previous dermatological diseases that could increase skin adverse effects incidence.

Background/Aims : Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. Methods : We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). Results : Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. Conclusions : Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.

Background & Aims Helicobacter pylori have become resistant to antimicrobial agents, reducing eradication rates. A 10-day sequential regimen that contains levofloxacin was efficient, safe, and cost saving in eradicating H pylori infection in an area with high prevalence of clarithromycin resistance. We performed a noninferiority randomized trial to determine whether a 5-day levofloxacin-containing quadruple concomitant regimen was as safe and effective as the 10-day sequential regimen in eradicating H pylori in previously untreated patients. Methods We randomly assigned patients with H pylori infection to groups that were given 5 days of concomitant therapy (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily; n=90) or 10 days of sequential therapy (esomeprazole 40 mg twice daily, amoxicillin 1g twice daily for 5 days followed by esomeprazole 40 mg twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily for 5 more days; n=90). Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events, and costs were determined. Results Intention-to-treat analysis showed similar eradication rates for concomitant (92.2%; 95% confidence interval [CI], 84.0%–95.8%) and sequential therapies (93.3%; 95% CI, 86.9%–97.3%). Per-protocol eradication results were 96.5% (95% CI, 91%–99%) for concomitant therapy and 95.5% for sequential therapy (95% CI, 89.6%–98.5%). The differences between sequential and concomitant treatments were 1.1% in the intention-to-treat study (95% CI; −7.6% to 9.8%) and −1.0% in the per-protocol analysis (95% CI; −8.0% to 5.9%). The prevalence of antimicrobial resistance and incidence of adverse events were comparable between groups. Concomitant therapy cost $9 less than sequential therapy. Conclusions Five days of levofloxacin-containing quadruple concomitant therapy is as effective and safe, and less expensive, in eradicating H pylori infection than 10 days of levofloxacin-containing sequential therapy.

Total parenteral nutrition is a life saving therapy for patients with chronic gastrointestinal failure, being an effective method for supplying energy and nutrients when oral or enteral feeding is impossible or contraindicated. Clinical epidemiological data indicate that total parenteral nutrition may be associated with a variety of problems. Herein we reviewed data on the gastroenterological tract regarding: (i) total parenteral nutrition-related hepatobiliary complications; and (ii) total parenteral nutrition-related intestinal complications. In the first group, complications may vary from mildly elevated liver enzyme values to steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis. In particular, total parenteral nutrition is considered to be an absolute risk factor for the development of biliary sludge and gallstones and is often associated with hepatic steatosis and intrahepatic cholestasis. In general, the incidence of total parenteral nutrition-related hepatobiliary complications has been reported to be very high, ranging from 20 to 75% in adults. All these hepatobiliary complications are more likely to occur after long-term total parenteral nutrition, but they seem to be less frequent, and/or less severe in patients who are also receiving oral feeding. In addition, end-stage liver disease has been described in approximately 15-20% of patients receiving prolonged total parenteral nutrition. Total parenteral nutrition-related intestinal complications have not yet been adequately defined and described. Epidemiological studies intended to define the incidence of these complications, are still ongoing. Recent papers confirm that in both animals and humans, total parenteral nutrition-related intestinal complications are induced by the lack of enteral stimulation and are characterised by changes in the structure and function of the gut. Preventive suggestions and therapies for both these gastroenterological complications are reviewed and reported in the present review.

Several experimental studies have suggested that specific nutrients might play a role on the risk of liver damage. Nevertheless, few epidemiological studies have evaluated the role of diet on the risk of symptomatic liver cirrhosis, giving contradictory results. To evaluate the role of the intake of nutritional factors and dietary patterns on the risk of symptomatic liver cirrhosis and to examine their combined action with alcohol consumption we used data from the Italian Study on Liver Cirrhosis Determinants project. From 1994 to 1998 all the consecutive cirrhotic inpatients admitted to 19 Italian collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (259 cases) and one or two gender, age and area of residence matched individuals (416 controls) were recruited. Data on lifetime alcohol intake, usual consumption of 191 food items and on markers of hepatitis B and C viral infection were collected. The analysis of principal components identified a nutritional pattern positively correlated with vegetable and fruit intakes and negatively with animal and no-fruit sugar products. With respect to abstainers, relative risks in consumers of use < or = 25 and > or = 51 g/day of alcohol increased from 0.4 [95% confidence interval 0.0, 5.9] to 9.3 [1.3, 69.0] and from 2.1 [1.1, 4.2] to 18.1 [2.8, 118.3] for the lowest and the highest value of this nutritional pattern, respectively. Diet might therefore modulate the damaging effect of alcohol on the liver.

Glomerular filtration rate (GFR) was measured in 19 patients with Child A liver cirrhosis by comparing the endogenous creatinine clearance with inulin clearance. Inulin clearance averaged 90 +/- 4.4 ml/min x 1.73 m2, while creatinine clearance averaged 122 +/- 7 ml/min x 1.73 m2 (p < 0.001). The overestimation of GFR by creatinine was present in 18 of 19 patients and was inversely correlated with inulin clearance (r = -0.452, p < 0.04). The data point to the unsuitability of creatinine as a marker of filtration in early posthepatitic cirrhosis (Child A).

Background. Nutritional status affects the course, ensuing complications and prognosis of virtually all diseases. Aims. To define the role of nutrition in Gastroenterology Units by means of two investigations that analyse: a) availability of devices for assessing nutritional status; b) nutritional treatment in clinical practice: incidence and frequency of indications for its use, together with type of treatment adopted. Patients and Methods. Two questionnaires were sent to Italian Academic and Hospital Gastroenterology Units, all with clinical wards. Results. Results refer to 27 Units, 22 of which took part in both parts of the analysis, enrolling 547 patients during the two-week study. The first analysis shows that scales and the altimeter are not available everywhere, while more specific tools, such as skinfold calipers are available in 54% of the Units, and caloric intake can be assessed in 22–41%. The second analysis reveals that nutritional treatment was necessary in 50% of patients in the series examined, and that this was taken into account and prescribed in almost all cases (91%). Of the patients treated, 69% received dietetic supplementation and 31% artificial nutrition (12% enteral, 88% parenteral), although supportive parenteral nutrition is often contraindicated in conditions where good bowel function provides the conditions for enteral nutrition. Conclusion. Data emerging from the investigation showed that i) artificial nutrition is commonly used in gastroenterology Units in Italy, although 23% of them never consider either enteral or parenteral nutrition as medical treatment of gastrointestinal disease; ii) malnutrition is a very frequent complication (mean 27%; range 4–55%) in Gastroenterology Unit patients albeit only 42% of malnourished patients received artificial nutrition; iii) indications for enteral and parenteral nutrition are not always respected, as there is an excessive use of parenteral nutrition and an unjustified resistance to the use of enteral nutrition; iv) nutritional treatment is often administered without adequate nutritional assessment and without a complete adherence to the standards recommended for preparation of parenteral bags, supported by suitable technology, v) only two Gastroenterology Units report admitting and following patients in a home parenteral nutrition programme; vi) this investigation probably reflects the response of those Gastroenterology Units most aware of the importance of nutritional problems. Better awareness of correct practices for nutritional support should be promoted, encouraging greater use of diagnostic and monitoring techniques and a more discerning choice of the most suitable type of artificial nutrition to be administered in gastroenterology.

Background. Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. Aim. To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. Patients and methods. This retrospective, cross-sectional study involved 1195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. Results. Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. Conclusions. This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.