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Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death. [ABSTRACT FROM AUTHOR]

Direct acting antivirals(DAAs) are effective in reducing inflammatory ant fibrotic markers in patients with chronic hepatitis C virus(HCV) infection and to prevent liver-related complications. Two-dimensional shear wave elastography(2D-SWE) is an effective technique for the assessment of liver fibrosis. To evaluate changes in liver stiffness(LS) in HCV cirrhotic patients undergoing DAA therapy and to identify non-invasive parameters that predict the occurrence of liver-related events. We enrolled 229 patients who received DAAs between January 2015 and October 2018. Ultrasound parameters and laboratory data were assessed before treatment and 24(T1) and 48(T2) weeks after end of treatment. Patients were followed up every 6 months to evaluate the development of HCC and other liver related complications. Multiple Cox regression analysis was used to determine parameters associated with the development of complications. Model for End-stage Liver Disease(MELD) score(HR 1.16; CI 95% 1.01–1.33; p = 0.026) and a change in LS at T2(1-year Delta LS) < 20%(HR 2.98; CI 95% 1.01–8.1; p = 0.03) were independently associated with HCC risk. One-year Delta-LS <20% was independently associated with the development of ascites(HR 5.08; CI 95% 1.03 - 25.14; p = 0.04). Dynamic changes of 2D-SWE-measured LS after DAA therapy may be a useful tool to identify patients who are at higher risk of liver related complications. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are first-line treatments for advanced melanoma and non-melanoma skin cancers. Liver injury (ChILI) affects ∼10% of patients. It remains unclear whether to permanently discontinue ICIs after ChILI or safely resume therapy or cross to a different class of ICI. Here we report the experience of ChILI on patients attending a third-level center for the treatment of skin neoplasms. This retrospective study included patients treated with ICIs for advanced skin cancers at Fondazione Policlinico Universitario "A. Gemelli" IRCCS (Rome) from June 2016 to April 2024. ChILI was diagnosed using CTCAE v5.0 criteria. Liver function tests (LFTs) at baseline, after 3 cycles of therapy and at ChILI suspicion of appearance have been retrieved, alongside ChILI management and outcome. Among 111 patients (32.4% female, median age 75), 70 (63.1%) had advanced melanoma, and 41 (36.9%) had advanced squamous cell carcinoma. ICIs included anti-PD1 (95.5%), anti-CTLA4 (2.7%) or their combination (1.8%). Over a median therapy duration of 10 months (IQR 5-21), 9 patients (8.1%) developed ChILI. CTCAE severity: grade 2 (n=2), grade 3 (n=5), grade 4 (n=2). Pattern of liver damage: 5 hepatocellular, 3 cholestatic, 1 mixed. 3 patients showed ANA positivity, 1 showed ENA positivity and 2 had previously diagnosed autoimmune disorder. All patients discontinued ICIs; 5 recovered spontaneously while 4 required steroids. No drug rechallenges occurred, but 2 switched to other ICIs without early or late ChILI recurrence. ChILI patients had higher rates of diarrhea (33%) and rash (44%) compared to non-ChILI patients (4.8% and 13.5%, p<0.05). Baseline and 3rd-infusion LFTs showed no significant differences among ChILI and non-ChILI patients (p>0.05). ChILI incidence aligns with literature, occurring after multiple cycles, suggesting an indirect damage mechanism. Dermatological or gastrointestinal AEs often preceded ChILI, highlighting potential early warning signs for clinicians to enable timely intervention. [ABSTRACT FROM AUTHOR]

Liver fibrosis is the primary prognostic factor in MASLD. Liver biopsy is the gold standard for staging fibrosis, although it is invasive and expensive procedure. Currently, non-invasive methods are available to stratify the degree of fibrosis.The aim of this study is to validate liver stiffness as a prognostic factor both at baseline and in its variation over time during follow-up. This is a retrospective single-center cohort study including 389 patients who underwent at least two Fibroscan liver stiffness measurements, with a minimum 6-month interval between scans, from January 2011 to December 2023. They were stratified into 3 risk groups according to Baseline liver stiffness measurements (LSM) (<10, 10-20, >20 kPa). Primary outcome was a composite of Liver Related Events (LRE), death or liver transplantation. Kaplan-Meier curves were generated for time to primary outcome stratified by Baseline LSM and Δ% Fibroscan categories (worsening: LSM increase >20%, stable, improved: LSM decrease >20%). Multivariable Cox regression analysis, adjusted for age, gender, BMI and type 2 diabetes, was used to assess the association of baseline LSM and Δ% fibroscan with primary outcome event. Cumulative incidence curves and incidence rates have been assessed and compared for each risk subgroup. During a median follow-up of 28 months (IQR 14.4 – 43.4), 29 (7.5%) patients experienced the composite primary endpoint. These patients were older and had a higher LSM at baseline (median 23.3 vs 6.2 kPa, p <0.01) and higher Δ% fibroscan (median 16.9% vs -3.5%, p <0.01) than patients who did not experienced a LRE. Baseline LSM show a good predictive performance for the composite endpoint events with an AUC of 0.897 (95% CI 0.845 – 0.948). Compared to patients with an LSM <10, patients with LSM between 10 and 20 kPa had a 9.7 fold higher risk for the primary outcome (HR 9.7 [2.05 – 45.79], p ≤0.01) and those with LSM>20 had a 55.6-fold higher risk (HR 55.63 [12.15 – 254.74], p ≤0.01). Multivariate Cox regression analysis also revealed significantly lower risk of developing LRE for high-risk patients (>20 kPa) who showed longitudinal improvements (Δ%LSM > -20%) on fibroscan results (HR 0.16, 95%CI 0.04 – 0.68, p=0.01), and a significantly higher risk of developing LRE in intermediate patients (10-20 kPa) who showed worsening longitudinal changes (Δ%LSM > 20%) on fibroscan results (HR 6.66, 95%CI 1.69 – 26.23, p<0.01). Incidence rate of composite outcome per 1000 person-year was 15.5, 19.7, 81.4 for LSM improved, stable or worsened groups respectively. Our study strengthens the use of LSM both at baseline and during follow up as reliable prognostic factors in MASLD able to identify the subgroups of patients with MASLD at risk of LREs. In patients with intermediate or high risk of events at baseline, elastography surveillance should be encouraged. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated with insulin resistance, and its association with metabolically associated fatty liver disease (MAFLD) has never been explored in prospective studies. The aim of this study was to assess the clinical features of MAFLD in DM1 patients. We investigated the prevalence and the diagnostic features of MAFLD in a cohort of 29 outpatient fully characterized DM1 patients; afterward, we compared the selected cohort of DM1-MAFLD individuals with a propensity-matched cohort of non-DM1-MAFLD 13/29 (44.83%) DM1 patients received a clinical diagnosis of MAFLD. Compared to DM1 patients with normal liver, DM1-MAFLD individuals showed a higher male prevalence (p = 0.008), BMI (p = 0.014), HOMA score (p = 0.012), and GGT levels (p = 0.050). The statistical comparison showed that the DM1-MAFLD group had a more severe MAFLD according to the FIB4 score than non-DM1-MAFLD patients. This association of a more severe form of liver disease with DM1 remained significant after logistic regression analysis (OR: 6.12, 95% CI 1.44- 26.55). [ABSTRACT FROM AUTHOR]

Fibroscan is a well-established NIT for the diagnosis of advanced fibrosis (F>2) in patients with NAFLD, recently defined as compensated advanced chronic liver disease (cACLD). EASL Guidelines proposed 8 and 12 kPa, respectively, as rule-out and rule-in cut-offs for cACLD. Patients with Fibroscan measurement between 8 and 12 fall in a grey zone where further investigations are recommended. We recently proposed the cACLD Risk Score to further stratify this population. The main aim of this study was to test the diagnostic performance of the main NITs in a two European cohorts of patients with histological diagnosis of NAFLD. Secondly, we assessed the performance of the cACLD risk score to further stratify patients in the Fibroscan's grey zone. This is a retrospective observational study. We enrolled consecutive patients with histological diagnosis of NAFLD/NASH from January 2014 to December 2021 at two tertiary liver units in UK (the Royal Free Hospital, London - RFH) and Italy (Fondazione Universitaria Policlinico A. Gemelli IRCCS, Rome – FPG). We excluded patients who did not perform at least one of these NITs at time of biopsy (± 6 months): FIB4, NAFLD Fibrosis score (NFS), Fibroscan, APRI, AGILE3+, cACLD Risk Score. We performed a ROC analysis to explore the diagnostic performance of NITs for cACLD (F>2). Secondly, in patients with intermediate Fibroscan results (between 8-12 kPa), we tested the diagnostic performance of cACLD Risk Score. We included 536 patients;201 were female, median age was 53 years, and 44% had diabetes. Fibroscan and AGILE3+ score had the best diagnostic performances for cACLD with an AUROC of 0.81 and 0.83 respectively. (Fig. 1) EASL criteria showed a high sensitivity and high specificity for 8 kPa and 12 kPa cutoffs, respectively (Sens 84.3%; Spec 86.6%), wrong classification of 14.2% and 129 patients (24.1%) in the grey zone (between 8 and 12 kPa). Diagnostic performance of cACLD Risk Score in Fibroscan's grey zone was suboptimal (AUROC: 0.682). The use of Fibroscan+cACLD Risk Score vs Fibroscan alone showed a better overall accuracy (77.8% vs 61.7%) and a slight worsening of overall wrong classification rate (22.7% vs 14.2%) mainly due to a higher number of false negative than false positive. Among patients with intermediate Fibroscan (8-12 kPa), cACLD risk score correctly classify 64.4% of patients with a PPV of 72.0% and NPV of 62.5%. Our results suggest that cACLD Risk Score should be used in patients with indeterminate Fibroscan results in order to further stratify their risk of cACLD. The use of cACLD Risk Score improve the performance in identifying patients with cACLD (high PPV) although its false negative rate could lead to missed diagnosis (suboptimal NPV). Patients with intermediate fibroscan and low cACLD risk score should be still considered for further investigation (liver biopsy). [ABSTRACT FROM AUTHOR]

Accurate pre-Liver Transplant(LT) cardiac risk estimation is paramount to guide graft allocation and to improve post-LT outcome. CAR-OLT-score predicts major 1-year post-LT cardiovascular complications(CVD-Com), but external validation is lacking. We aimed to test the performance of the score in identifying cardiac contraindication(Ca-Con) to LT-listing and to validate CAR-OLT-score to predict major 1-year CVD-Com post-LT. We consecutive enrolled all adult cirrhotics who underwent first pre-LT evaluation in Rome-Gemelli-Center(RO-cohort, N=342, from 2015 to 2019) and Turin-Center(TU-cohort, N=302, from 2015 to 2017). The main outcome measures were Ca-Con to listing(after center-specific cardiology work-up) and major 1-year CVD-Com post-transplant(death/hospitalization for CVD event). Discriminative performance of CAR-OLT-score was evaluated by area-under-the-ROC-curve(AUROC) method. Among 644 pre-LT cirrhotics, 23(3.6%) received a Ca-Con to listing (52.2% because of coronary artery disease, CAD). CAD, heart failure and atrial fibrillation were independent predictors of Ca-Con to listing. Among 431 first-LT recipients, 38(8.8%) patients experienced 1-year major CVD-Com (39.5% atrial-fibrillation, 23.7% heart-failure, 21% myocardial infarction). Diabetes, pulmonary hypertension, non-active workers were independent predictors of 1-year major CVD-Com. RO-cohort had higher prevalence of hypertensive, obese, diabetic, alcoholic patients and higher burden of CAD, atrial-fibrillation, heart-failure, peripheral vasculopathy compared with TU-cohort. CAR-OLT-score predicts Ca-Con to listing in RO-cohort (AUROC 0.806) and TU-cohort (AUROC 0.978) and 1-year major CVD-Com in RO-cohort (AUROC 0.746) and TU-cohort (AUROC 0.640). 193(29.9%) candidates had CAR-OLT-score ≤23. This cut-off had 99% NPV for Ca-Con to listing and 95% NPV for 1-year major CVD-Com post-LT. Candidates with CAR-OLT-score ≤23 underwent 18 cardiac-exercise-stress-test, 89 myocardial-perfusion-imaging, 24 dobutamine-stress-echocardiography, 10 coronary-computed-tomography, 17 coronary-angiography pre-listing, with estimated costs of 68.090€. CAR-OLT-score ≤23 identified candidates who can be safely listed without provocative cardiac tests, allowing time and cost savings and we validated CAR-OLT-score as predictor of major 1-year CVD-Com in an Italian cohort of LT recipients. [ABSTRACT FROM AUTHOR]

Primary Sclerosing Cholangitis (PSC) is a rare condition with low incidence in countries of the Mediterranean Basin, such as Italy; the timing for listing and the indication for liver transplantation (LT) are not entirely stated. To investigate the Italian trend in indication, timing, and outcome for PSC LT. In April 2022, we conducted a nationwide survey of LT in PSC over the last 15 years. 85% of Italian LT Centers took part in the project. Clinical features, indications and outcomes were evaluated. From January 2007 to December 2021, 445 PSC patients have been included in the Italian LT waiting-lists, and 411 underwent LT. The median age at LT was 46 years (18-73), with a high prevalence of males (n=287, 70%). Over 15 years, the number of transplants for PSC increased from 20 to 42 per year, reaching 3.0% of all indications in 2021. Recurring cholangitis and hepatic decompensation were the main indications for listing. The dropout rate from the waiting-list was 6% (26/445), cholangiocarcinoma (CCA) not eligible for LT and being too sick were the leading causes. 71% of the LT Centers utilized induction therapy with Basiliximab. Tacrolimus+MMF was the combined therapy of choice. Overall post-LT mortality was 15% (66/441): 24 patients died in the first year (50% due to surgical complications and 25% infections); 33 patients died between 1 to 5 years (36% PSC recurrence, 21% occult CCA-recurrence) and 9 patients after 5 years (56% cancer, 44% PSC recurrence). Likewise other Countries, PSC has been an increasing indication for LT in Italy. The dropout rate from LT waiting-list was relatively low, and CCA not eligible for transplantation or being too sick for surgery were the leading causes. 5-year post-LT survival was 87%, being PSC-recurrence or neoplastic disease the main causes of death. [ABSTRACT FROM AUTHOR]

An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups. We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords “nonalcoholic fatty liver disease” and “diabetes”, “obesity”, “hyperlipidaemia”, “familial heterozygous hypobetalipoproteinaemia”, “hypertension”, “metabolic syndrome”, “ethnicity”, “family history” or “genetic polymorphisms”. We found that age, sex and ethnicity are major physiological modifiers of the risk of non-alcoholic fatty liver disease, along with belonging to “non-alcoholic fatty liver disease families” and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolaemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of non-alcoholic fatty liver disease risk. Compared with these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of non-alcoholic fatty liver disease. A better understanding of the epidemiology of non-alcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups. [ABSTRACT FROM AUTHOR]

Background Our aim was to evaluate the effectiveness of the single-step combined therapy with radiofrequency ablation and drug-eluting beads transarterial chemoembolization in single hepatocellular carcinoma (HCC) larger than 3 cm. Secondary aim was to compare the results with those obtained in a matched population treated with drug-eluting beads transarterial chemoembolization alone. Methods 40 consecutive cirrhotic patients with single HCC were prospectively enrolled and treated. Twenty-three patients had tumours between 3 and 5 cm (Group A), and 17 larger than 5 cm (Group B). Twenty cirrhotic patients with single HCC treated only with chemoembolization formed the control group. Results Complete response at 1 month was achieved in 32/40 tumours (80%). During follow-up, complete response was maintained in 25 patients (25/40, 62.5%), and this rate was higher in Group A (69.6% vs 53%, p = 0.008). The group treated with combined therapy showed a significantly lower 2-year recurrence (48.1% vs 78.2%, p < 0.001) and significantly higher survival (91.1% vs 60.6%, p = 0.004) than the group treated with chemoembolization alone. Conclusions Balloon-occluded-radiofrequency ablation plus drug-eluting beads transarterial chemoembolization is an effective treatment of HCC larger than 3 cm not amenable to surgical resection, providing better results than transarterial chemoembolization alone. The best results are achieved in tumours up to 5 cm. [ABSTRACT FROM AUTHOR]

Abstract: Background: Increased intestinal permeability seems to play a major role in non-alcoholic liver disease development and progression. Aim: To investigate the prevalence of altered intestinal permeability in children with non-alcoholic fatty liver disease, and to study its potential association with the stage of liver disease. Methods: We performed a case–control study examining intestinal permeability in children using the lactulose–mannitol bowel permeability test. Results: Overall, 39 consecutive patients (30 males, median age 12 years) and 21 controls (14 males, median age 11.8 years) were included. The lactulose/mannitol ratio resulted impaired in 12/39 patients (31%) and none of the controls. Intestinal permeability was higher in children with non-alcoholic fatty liver disease (lactulose/mannitol ratios: 0.038±0.037 vs. 0.008±0.007, p <0.05). Within the non-alcoholic fatty liver disease group, intestinal permeability was increased in children with steatohepatitis compared to those with steatosis only (0.05±0.04 vs. 0.03 vs. 0.03, p <0.05). Pathological lactulose/mannitol ratio correlated with portal inflammation (p =0.02), fibrosis (p =0.0002), and ballooning of hepatocytes (p =0.003). Blood lipopolysaccharides levels were higher in children with steatohepatitis (2.27±0.68 vs. 2.80±0.35, p <0.05). Conclusions: Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with the severity of the disease. [Copyright &y& Elsevier]

Abstract: Background: In 2007, sorafenib was the first drug able to improve overall survival in patients with advanced hepatocellular carcinoma. Aim: In 2005 we designed a phase II study to assess safety and efficacy of sunitinib. Methods: This is a single arm, open-label, single-centre phase II trial. Eligibility criteria were advanced hepatocellular carcinoma; no prior chemotherapy, performance status 0–1; and Child≤B8. The treatment schedule was 50mg each day orally, 4 weeks on, 2 weeks off. Results: Between 10/2007 and 10/2010, 34 patients were enrolled. A significant worsening of liver functional reserve after sunitinib was observed. Grade 3/4 adverse effects occurred in 80% of patients and included fatigue (47%), nausea (15%), liver failure (15%), encephalopathy (12%) and upper gastrointestinal bleeding (12%). Six patients (18%) died within 60 days of enrolment. A partial response was observed in 4 patients (12%). Median time to tumour progression was 2.8 months and median overall survival was 5.8 months. Conclusion: A dose of 50mg/d induces a high rate of severe adverse events. Toxicity remains a key concern also at the dose of 37.5mg/d. However, sunitinib is able to induce a prolonged response in some patients. Positron Emission Tomography/Computed Tomography scans may select good responders. [Copyright &y& Elsevier]

Abstract: Background: Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease. Methods: Cross-sectional, case–control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication. Results: The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16–4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24–5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12–3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76–6.36). Conclusion: Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms. [Copyright &y& Elsevier]

Abstract: Background: The prevalence of hepatitis C virus infection increases with advancing age, but elderly hepatitis C virus patients remain an understudied population. Aim: To define the virological, epidemiological and clinical profiles of Italian outpatients aged 65 years and over infected by hepatitis C virus. Methods: We evaluated 1544 anti-hepatitis C virus positive patients aged ≥65 years referred to 34 Italian outpatient specialty clinics over a two-year period. Results: The study population included 1134 (73%) early elderly (65–74 years) and 410 (27%) late elderly patients (≥75 years). Late elderly subjects were less likely to have their virus genotyped, their viral load assessed or a histological evaluation of liver disease. Overall, 30% of patients had advanced liver disease whose prevalence increased with increasing age. In both age groups, about 40% of patients had normal transaminase levels. Excluding patients with past infection, 51% had not received any antiviral treatment and only 25% were treated after the age of 65. Late elderly patients, women and patients with advanced liver diseases had been less frequently treated. The main reason for exclusion from treatment was age followed by the presence of comorbid conditions. Conclusions: Elderly hepatitis C virus patients referred to Italian specialty clinics have advanced and underestimated liver disease. Nevertheless, they are progressively understudied in parallel with increasing age. [Copyright &y& Elsevier]

Abstract: We report the evidence-based Italian Association for the Study of Liver guidelines for the appropriate diagnosis and management of patients with nonalcoholic fatty liver disease in clinical practice and its related research agenda. The prevalence of nonalcoholic fatty liver disease varies according to age, gender and ethnicity. In the general population, the prevalence of nonalcoholic fatty liver disease is about 25% and the incidence is of two new cases/100 people/year. 2–3% of individuals in the general population will suffer from nonalcoholic steatohepatitis. Uncomplicated steatosis will usually follow a benign course. Individuals with nonalcoholic steatohepatitis, however, have a reduced life expectancy, mainly owing to vascular diseases and liver-related causes. Moreover, steatosis has deleterious effects on the natural history of HCV infection. Nonalcoholic fatty liver disease is usually diagnosed in asymptomatic patients prompted by the occasional discovery of increased liver enzymes and/or of ultrasonographic steatosis. Medical history, complete physical examination, etiologic screening of liver injury, liver biochemistry tests, serum lipids and insulin sensitivity tests should be performed in every patient. Occult alcohol abuse should be ruled out. Ultrasonography is the first-line imaging technique. Liver biopsy, the gold standard in diagnosis and prognosis of nonalcoholic fatty liver disease, is an invasive procedure and its results will not influence treatment in most cases but will provide prognostic information. Assessment of fibrosis by composite scores, specific laboratory parameters and transient elastography might reduce the number of nonalcoholic fatty liver disease patients requiring liver biopsy. Dieting and physical training reinforced by behavioural therapy are associated with improved nonalcoholic fatty liver disease. Diabetes and the metabolic syndrome should be ruled out at timed intervals in nonalcoholic fatty liver disease. Nonalcoholic steatohepatitis patients should undergo periodic evaluation of cardiovascular risk and of advancement of their liver disease; those with nonalcoholic steatohepatitis-cirrhosis should be evaluated for early diagnosis of hepatocellular carcinoma. [Copyright &y& Elsevier]

Abstract: Background and aim: Aim of this study was to compare contrast-enhanced ultrasound and multi-detector row computed tomography in detecting arterial hypervascularity in small cirrhotic nodules. Patients and methods: Sixty-two nodules (41 measuring 1.0–2.0cm, 21 measuring 2.1–3.0cm) found in 55 cirrhotic patients were examined with both methods. Lesions displaying arterial hypervascularity with washout in the portal/venous phase on both studies were considered hepatocellular carcinomas and treated; all other nodules were subjected to ultrasound-guided fine-needle biopsy. Results: The larger nodules (2.1–3.0cm) included 19 hepatocellular carcinomas (90%), 1 macroregenerative nodule type I and 1 macroregenerative nodule type II; 35 (87%) of the smaller nodules were hepatocellular carcinomas, 2 were macroregenerative nodules type I, 2 macroregenerative nodules type II and 2 hemangiomas. The two studies yielded concordant findings for 54 nodules (87%), including 46 hypervascular on both examinations and 8 that were consistently hypovascular. Two of the latter nodules were hepatocellular carcinomas. The other eight nodules displayed arterial hypervascularity on only one of the studies. Six of these (75%) were hepatocellular carcinomas, including five that were negative in the contrast-enhanced ultrasound study. Conclusion: Computed tomography and contrast-enhanced ultrasound show high agreement in the vascular classification of small nodules detected by ultrasound in cirrhotic livers, although the former technique was slightly more sensitive in the detection of arterial hypervascularization. [Copyright &y& Elsevier]

Abstract: Background/aim: We aimed to evaluate safety and efficacy of granulocyte-colony stimulating factor treatment in patients with acute on chronic liver failure and the effect of granulocyte-colony stimulating factor on the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4. Methods: Twenty-four patients with acute on chronic liver failure were randomised to receive standard therapy, standard therapy+granulocyte-colony stimulating factor (5μg/kg/day for 6 days) and standard therapy+granulocyte-colony stimulating factor (15μg/kg/day s.c. for 6 days). Data on CD34+cell mobilisation were compared to age-matched peripheral blood haematopoietic stem cell donors treated with granulocyte-colony stimulating factor. On day third of treatment, the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4 was analysed in mobilised CD34+ cells. Results: CD34 cell count increased after the second day of granulocyte-colony stimulating factor injection in both treatment groups compared to the linear increase observed in control. After the fifth day the increase was significantly higher in healthy donors versus patients with acute on chronic liver failure. A decrease in the expression of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor compared to premobilisation values was observed. No major side effects were observed. Conclusions: Granulocyte-colony stimulating factor treatment is able to induce CD34 mobilisation in patients with acute on chronic liver failure. The expression pattern of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor suggests that these molecules are involved in the granulocyte-colony stimulating factor-induced stem cell mobilisation. [Copyright &y& Elsevier]