Efficacy of pharmacologic interventions on magnetic resonance imaging biomarkers in patients with nonalcoholic fatty liver disease: systematic review and network meta-analysis.

BACKGROUND AND AIM: Several agents are under investigation for nonalcoholic fatty liver disease (NAFLD). We assessed the comparative efficacy of pharmacologic interventions for patients with NAFLD focusing on magnetic resonance imaging (MRI) biomarkers. METHODS: We searched Medline, Embase, and CENTRAL. We included randomized controlled trials of more than 12 weeks of intervention that recruited patients with biopsy-confirmed or MRI-confirmed NAFLD and assessed the efficacy of interventions on liver fat content (LFC) and fibrosis by means of MRI. We performed random-effects frequentist network meta-analyses and assessed confidence in our estimates using the CINeMA (Confidence in Network Meta-Analysis) approach. RESULTS: We included 47 trials (8583 patients). Versus placebo, thiazolidinediones were the most efficacious for the absolute change in LFC, followed by vitamin E, fibroblast growth factor (FGF) analogs, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with mean differences ranging from -7.46% (95% confidence interval [-11.0, -3.9]) to -4.36% (-7.2, -1.5). No differences between drug classes were evident. Patients receiving GLP-1 RAs or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs were more likely to achieve ≥30% relative reduction in LFC. Among agents, efruxifermin produced the largest reduction in LFC compared to placebo [-13.5% (-18.5, -8.5)], followed by pioglitazone, while being superior to most interventions. The effect of interventions on magnetic resonance elastography assessed fibrosis was small and insignificant. The confidence in our estimates was low to very low. CONCLUSIONS: Several drug classes may reduce LFC in patients with NAFLD without a significant effect on fibrosis; nevertheless, trial duration was small, and confidence in the effect estimates was low.

Effects of an active lifestyle on the physical frailty of liver transplant candidates.

BACKGROUND: Liver transplantation is the most important therapeutic intervention for end-stage liver disease (ELD). The prioritization of these patients is based on the model for end-stage liver disease (MELD), which can successfully predict short-term mortality. However, despite its great validity and value, it cannot fully incor porate several comorbidities of liver disease, such as sarcopenia and physical frailty, variables that can sufficiently influence the survival of such patients. Subsequently, there is growing interest in the importance of physical frailty in regard to mortality in liver transplant candidates and recipients, as well as its role in improving their survival rates. AIM: To evaluate the effects of an active lifestyle on physical frailty on liver transplant candidates. METHODS: An observational study was performed within the facilities of the Department of Transplant Surgery of Aristotle University of Thessaloniki. Twenty liver tran splant candidate patients from the waiting list of the department were included in the study. Patients that were bedridden, had recent cardiovascular incidents, or had required inpatient treatment for more than 5 d in the last 6 mo were excluded from the study. The following variables were evaluated: Activity level via the International Physical Activity Questionnaire (IPAQ); functional capacity via the 6-min walking test (6MWT) and cardiopulmonary exercise testing; and physical frailty via the Liver Frailty Index (LFI). RESULTS: According to their responses in the IPAQ, patients were divided into the following two groups based on their activity level: Active group (A, 10 patients); and sedentary group (S, 10 patients). Comparing mean values of the recorded variables showed the following results: MELD (A: 12.05 ± 5.63 vs S: 13.99 ± 3.60; P > 0.05); peak oxygen uptake (A: 29.78 ± 6.07 mL/kg/min vs S: 18.11 ± 3.39 mL/kg/min; P < 0.001); anaerobic threshold (A: 16.71 ± 2.17 mL/kg/min vs S: 13.96 ± 1.45 mL/kg/min; P < 0.01); 6MWT (A: 458.2 ± 57.5 m vs S: 324.7 ± 55.8 m; P < 0.001); and LFI (A: 3.75 ± 0.31 vs S: 4.42 ± 0.32; P < 0.001). CONCLUSION: An active lifestyle can be associated with better musculoskeletal and functional capacity, while simultaneously preventing the evolution of physical frailty in liver transplant candidates. This effect appears to be independent of the liver disease severity.

Growing challenge of post-liver transplantation non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide, with an estimated prevalence of 25%. Post-liver transplantation (LT) recurrent or de novo hepatic steatosis is a common complication in recipients, irrespective of transplantation indication. Risk factors for graft steatosis mainly include obesity, immunosuppression, donor steatosis, and genetic factors. Liver transplant recipients are at high risk of developing insulin resistance, new-onset diabetes, and post-transplantation metabolic syndrome that is highly associated with immunosuppressive treatment. Post-LT NAFLD is often underdiagnosed due to the poor sensitivity of most routine imaging methods. The gold standard for the diagnosis of hepatic steatosis is liver biopsy, which is, however, limited to more complex cases due to its invasive nature. There is no approved pharmacotherapy in NAFLD. Lifestyle modification remains the cornerstone in NAFLD treatment. Other treatment strategies in post-LT NAFLD include lifestyle modifications, pharmacotherapy, bariatric surgery, and tailored immunosuppression. However, these approaches originate from recommendations in the general population, as there is scarce data regarding the safety and efficacy of current management strategies for NAFLD in liver transplant patients. Future prospective studies are required to achieve tailored treatment for these patients.

Enhanced recovery after surgery in liver transplantation: Challenges and feasibility.

BACKGROUND: Enhanced recovery after surgery (ERAS) started a revolution that changed age-old surgical stereotypical practices regarding the overall management of the surgical patient. In the last decade, ERAS has gained significant acceptance in the community of general surgery, in addition to several other surgical specialties, as the evidence of its advantages continues to grow. One of the last remaining fields, given its significant complexity and intricate nature, is liver transplantation (LT). AIM: To investigate the existing efforts at implementing ERAS in LT. METHODS: We conducted a systematic review of the existing studies that evaluate ERAS in orthotopic LT, with a multimodal approach and focusing on measurable clinical primary endpoints, namely length of hospital stay. RESULTS: All studies demonstrated a considerable decrease in length of hospital stay, with no readmission or negative impact of the ERAS protocol applied to the postoperative course. CONCLUSIONS: ERAS is a well-validated multimodal approach for almost all types of surgical procedures, and its future in selected LT patients seems promising, as the preliminary results advocate for the safety and efficacy of ERAS in the field of LT.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Effect of golimumab on health-related quality of life, other patient-reported outcomes and healthcare resource utilization in patients with moderate-to-severe ulcerative colitis: a real-world multicenter, noninterventional, observational study in Greece.

BACKGROUND AND AIMS: This real-world study assessed the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with ulcerative colitis over 12 months in Greece. METHODS: GO-LIFE was a noninterventional, prospective, multicenter, 12-month study. Patients who had moderately-to-severely active ulcerative colitis were naïve to antitumor necrosis factor (anti-TNFα) therapy and had failed previous conventional therapy. Patients received golimumab as per label. The primary endpoint was patients achieving inflammatory bowel disease questionnaire 32-item (IBDQ-32) remission at 12 months. Secondary endpoints, at 6 and 12 months, included patients achieving IBDQ-32 response; the mean change in the treatment satisfaction questionnaire for medication (TSQM) and the work productivity and activity impairment in ulcerative colitis (WPAI:UC) questionnaires; changes in healthcare utilization; patients achieving clinical response and remission; adherence rates and the percentage of patients who discontinued golimumab. RESULTS: IBDQ-32 remission was achieved by 76.9% of patients at 12 months. Mean changes in all TSQM and WPAI:UC domain scores at 12 months were statistically significant. Clinical remission was achieved by 49.4 and 50.6% of patients at 6 and 12 months, and clinical response by 59.3 and 56.8%, respectively. All patients but one (80/81) had high adherence (≥80%) to golimumab treatment over 12 months. Ulcerative colitis-related health care resource utilization was reduced during the follow-up period. CONCLUSIONS: In real-world settings, treatment with golimumab resulted in meaningful improvements in HRQoL and other PROs, and in disease activity at 6 and 12 months in patients with moderately-to-severely active ulcerative colitis who were naïve to anti-TNFa therapy.

Red cell distribution width as a marker of activity in inflammatory bowel disease: a narrative review.

Red blood cell distribution width is a parameter measured automatically in every complete blood count that actually reflects the degree of anisocytosis of the red blood cell population. It is a cost-effective tool used in everyday clinical practice along with other parameters to define and narrow the cause of anemia. In a series of pathologic entities, such as cardiovascular diseases, autoimmune diseases, malignancy, chronic renal diseases and chronic respiratory diseases, where inflammation and oxidative stress comprise the major pathophysiologic insults, red cell distribution width behaves as a significant and competent marker able to predict and assess disease activity and severity. A number of clinical studies based on these observations have aimed to evaluate its potential utility as an index of activity in inflammatory bowel disease. In this narrative review we present data from the international literature regarding its ability to express disease activity and we look into its relation with clinical, laboratory and endoscopic indices used to identify active disease. According to the results of published clinical trials, red cell distribution width is considerably correlated with disease activity and might serve as an index to differentiate Crohn's disease from ulcerative colitis.

Comparison of the Uptake of Screening Colonoscopy between Physicians and the General Population in Greece.

AIM: To evaluate the uptake of screening colonoscopy among physicians as compared to the general population. METHODS: Asymptomatic physicians, aged 45-67 years, at average risk for colorectal cancer (CRC), working in the participating National Health System hospitals were asked to complete a questionnaire regarding the uptake of screening colonoscopy. The results were compared to those in a background healthy population, aged 50-75 years, inhabitants of a Greek county, who were offered a free access to a screening colonoscopy program for CRC. High-risk adenomas were those ≥10 mm in diameter or any adenoma, regardless of size, with villous histology or high-grade dysplasia. RESULTS: Overall, 267 of 782 physicians and 402 of 6,534 nonphysicians underwent a screening colonoscopy (uptake rates 34.2 and 6.2% respectively, p = 0.00001). Screening colonoscopy has yielded 4 adenocarcinomas (1.6%), 14 high-risk adenomas (5.5%), and 61 low-risk adenomas (25.7%) in the physicians' group. Corresponding figures in the nonphysician arm were 4 (1), 26 (6.5), and 107 (26.6%), respectively. The main reason among physicians for nonadherence was indifference/negligence (n = 213). CONCLUSION: The proportion of physicians undergoing screening colonoscopy for CRC is significantly higher compared to the general population; however, it does remain suboptimal.

Free Cortisol Is a More Accurate Marker for Adrenal Function and Does Not Correlate with Renal Function in Cirrhosis.

BACKGROUND: The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated. AIM: The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function. METHODS: Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography. RESULTS: Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child-Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II-III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child-Pugh and MELD score compared to those with normal GFR. CONCLUSIONS: Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio-renal hypothesis.

Tofacitinib for induction of remission in ulcerative colitis: systematic review and meta-analysis.

BACKGROUND: The aim of the study was to assess the efficacy and safety of tofacitinib and its impact on quality of life in patients with moderate-to-severe ulcerative colitis. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tofacitinib with placebo or any active comparator. We searched Medline, Embase, the Cochrane Library and gray literature for articles published up to May 2017. We synthesized data using a fixed-effect model. We conducted subgroup analysis based on prior exposure to anti-tumor necrosis factor (TNF). We summarized the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included three trials with 1220 participants. Compared with placebo, tofacitinib was effective in inducing clinical remission (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.29-6.44, I2: 41%, GRADE: moderate), clinical response (OR 2.95, 95%CI 2.21-3.95, I2: 0%, GRADE: high), mucosal healing (OR 2.70, 95%CI 1.81-4.03, I2: 0%, GRADE: high). Tofacitinib was effective in both anti-TNF-naïve and -experienced patients. Tofacitinib had a favorable effect on quality of life. There were no significant differences in the safety profile in terms of the incidence of any or serious adverse events compared to placebo. The risk for infections was increased (OR 1.51, 95%CI 1.05-2.19, I2: 0%, GRADE: moderate), but the incidence of serious infections did not differ between tofacitinib and placebo. CONCLUSION: In patients with moderate-to-severe ulcerative colitis, short-term treatment with tofacitinib is effective for induction of remission and improvement of quality of life.

Everolimus with or without mycophenolate mofetil in a liver transplantation setting: a single-center experience.

BACKGROUND: This study evaluated the efficacy, safety, and impact on renal function of everolimus in patients after liver transplantation (LT) with or without mycophenolate mofetil (MMF). METHODS: We evaluated LT recipients with calcineurin inhibitor (CNI)-related renal dysfunction after everolimus initiation. Laboratory data, including evaluation of renal function based on glomerular filtration rate (GFR) at baseline (i.e., everolimus initiation) and at the end of follow up, were analyzed. RESULTS: Fifty consecutive patients started taking everolimus at 30 months post-LT (range: 1-240), 6 as monotherapy and 44 in combination with MMF. After 30.5 months (range: 6-112), all patients were alive, without any biochemical evidence of a rejection episode or recurrence of hepatocellular carcinoma. The mean GFR, based on the Modification of Diet in Renal Disease equation, was 53±13 mL/min at baseline and 59±12 mL/min at the end of follow up (P=0.031). Eleven (22%) of the patients had GFR <60 mL/min at baseline but returned to GFR >60 mL/min by the end of follow up. In multivariate analysis, the time between the development of renal dysfunction and everolimus initiation was the only factor independently associated with GFR improvement (odds ratio [OR] 0.85, 95% confidence interval [95%CI] 0.76-0.96; P=0.007). Everolimus was stopped in 11 patients (22%) at the end of follow up because of adverse events. CONCLUSION: A CNI-free everolimus-based regimen was effective in LT recipients with renal dysfunction and was associated with an improvement in GFR.

Can Serum Uric Acid Lowering Therapy Contribute to the Prevention or Treatment of Nonalcoholic Fatty Liver Disease?

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western countries with potential progression to nonalcoholic steatohepatitis (NASH) and cirrhosis, is associated with cardiovascular disease (CVD) mortality. Several studies have reported a relationship between uric acid and NAFLD/NASH and it seems that serum uric acid (SUA) is a significant independent factor for the development of NAFLD. Potential mediating mechanisms include insulin resistance, endothelial dysfunction, and activation of inflammasome, especially NLRP3. Moreover, emerging evidence indicates a strong association between elevated SUA, metabolic syndrome (MetS), NAFLD, and CVD. The emphasis of the present review is whether common therapy of elevated SUA levels and NAFLD can improve compliance. There are several drugs with "off target" properties that show some separate benefit on SUA reduction (e.g. losartan) or NAFLD/NASH (pioglitazone); however, there is no randomized controlled trial (RCT) of a single drug with beneficial outcome for both diseases. Allopurinol reduces SUA levels and ameliorates NAFLD/NASH; however, no RCTs have been performed up to now to explore potential survival benefits. Atorvastatin, which has proven safe in NAFLD/NASH, reduces SUA levels, ameliorates NAFLD/NASH, prevents liver fibrosis, and above all substantially reduces CVD morbidity and mortality in comparison with those on statins but without NAFLD/NASH. This drug could be a solution to improve compliance in both diseases, which are prevalent and becoming even more common with the obesity, MetS, and type 2 diabetes mellitus epidemic.

Diagnostic Accuracy of Fecal Immunochemical Test in Patients at Increased Risk for Colorectal Cancer: A Meta-analysis.

Importance: The potential role of the fecal immunochemical test (FIT) for screening patients at increased risk for colorectal cancer (CRC) has not yet been elucidated. Objective: To assess the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in asymptomatic patients at above-average risk. Data Sources: MEDLINE, EMBASE, Cochrane Library, and gray literature sources through August 2016. Study Selection: Diagnostic studies evaluating the accuracy of FIT for CRC or AN in patients with a personal or familial history of CRC using colonoscopy as the reference standard. Data Extraction and Synthesis: Two authors (A.K. and P.P.) independently extracted data and evaluated study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, and evaluated the quality of the body of evidence by means of GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Hierarchical models were used to synthesize available evidence. Main Outcomes and Measures: The primary outcome was the diagnostic performance of FIT for detecting CRC or AN. Results: We included 12 studies (6204 participants). Seven studies were deemed at high or unclear risk of bias. The average sensitivity of FIT for CRC was 93% (95% CI, 53%-99%), and the average specificity was 91% (95% CI, 89%-92%), yielding a positive likelihood ratio (LR+) of 10.30 (CI 7.7-13.9) and a negative likelihood ratio (LR-) of 0.08 (95% CI, 0.01-0.75) (GRADE: very low). The average sensitivity of FIT for AN was 48% (95% CI, 39%-57%); and the average specificity was 93% (95% CI, 91%-94%), yielding an LR+ of 6.55 (95% CI, 5.0-8.5) and an LR- of 0.57 (95% CI, 0.48-0.67) (GRADE: very low). Subgroup analyses indicated that FIT cutoff values between 15- and 25-µg/g feces provided the best combination of sensitivity and specificity for the diagnosis of CRC (93% and 94%, respectively). Quantitative and 1-sample FIT showed adequate test performance, but data on other FIT brands and multiple samples were insufficient. Conclusions and Relevance: The FIT has high overall diagnostic accuracy for CRC but moderate accuracy for AN in patients at above-average personal or familial risk. Heterogeneity and wide confidence intervals limit the trustworthiness of our findings.

The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement.

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.

A fully covered self-expandable metal stent anchored by a 10-Fr double pigtail plastic stent: an effective anti-migration technique.

BACKGROUND: Fully covered self-expandable metal stents (FCSEMS) have been used successfully in the treatment of malignant and benign biliary strictures. However, stent migration is a major complication. We investigated the efficacy of anchoring FCSEMS with a 10-Fr double-pigtail plastic stent to prevent migration in patients with biliary strictures. METHODS: Between January 2012 and May 2013, 10 patients with malignant biliary strictures and one patient with a suprapapillary benign biliary stenosis were enrolled in the study. The primary endpoint of the study was to record the migration rate of FCSEMS. RESULTS: The placement of FCSEMSs and the anchoring with a 10-Fr double-pigtail plastic stent were successful in all patients. During a median follow-up period of eight months, proximal or distal migration of FCSEMS was not observed. No procedural complications related to the placement of FCSEMS and/or the anchoring plastic stent were recorded. CONCLUSIONS: The placement of an anchoring 10-Fr double-pigtail stent is a simple and effective anti-migration technique for FCSEMS in patients with malignant biliary strictures.

Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome.

AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis (NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH. METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome (MetS) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients received lifestyle advice and were treated for a 12 mo period with rosuvastatin (10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid (SUA), high sensitivity C reactive protein (hsCRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values. RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20(th), which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3(rd) treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6(th) treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3(rd) treatment month. No patient had MetS by the 9(th) treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group. CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve MetS within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.

Effect of rosuvastatin on non-alcoholic steatohepatitis in patients with metabolic syndrome and hypercholesterolaemia: a preliminary report.

BACKGROUND: There is no widely accepted treatment for non-alcoholic fatty liver disease (NAFLD) or its advanced form, non-alcoholic steatohepatitis (NASH). METHODS: We administered rosuvastatin (10 mg/day) for 1 year in patients with metabolic syndrome (MetS), NASH on liver biopsy and dyslipidaemia (but without diabetes or arterial hypertension). Patients also received lifestyle advice. RESULTS: We report preliminary results for 6 patients. The second biopsy (at the end of the study) showed complete resolution of NASH in 5 patients, while the 6(th), which had no improvement, developed arterial hypertension and substantial rise in triglyceride levels during the study. We suspect alcohol abuse despite advice to abstain. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were reduced by 76 and 61%, respectively (p < 0.001 for both), during treatment, while γ-glutamyl transpeptidase (γ-GT), and alkaline phosphatase (AP) showed smaller non significant reductions. Fasting plasma glucose and glycated haemoglobin (HbA1c) were significantly reduced (p<0.05). Lipid values were totally normalised and liver ultrasonography showed a complete resolution of NASH in 5 patients. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed to treatment with rosuvastatin. A substantial limitation of the study is the small number of patients. CONCLUSIONS: These preliminary findings suggest that rosuvastatin could ameliorate NASH within a year of treatment in MetS patients with dyslipidaemia.

Lipoprotein-associated phospholipase A2 and arterial stiffness evaluation in patients with inflammatory bowel diseases.

BACKGROUND AND AIMS: The association between inflammatory bowel diseases (IBD) and cardiovascular disease (CVD) remains equivocal. Arterial stiffness, as assessed by pulse wave velocity (PWV), and lipoprotein-associated phospholipase A2 (Lp-PLA2) are surrogates of CVD risk. AIM: The aim of this study was to assess carotid-femoral PWV and Lp-PLA2 in patients with IBD without history of CVD. METHODS: Established CVD risk factors, IBD characteristics, PWV and Lp-PLA2 activity were assessed in 44 patients with IBD, 29 with Crohn's disease (CD) and 15 with ulcerative colitis (UC), and 44 matched controls. RESULTS: IBD patients had lower total and low density lipoprotein cholesterol (LDL-C) levels. There was no difference in PWV between patients and controls (6.8 vs. 6.4m/s), but patients with CD had higher PWV compared to those with UC (7 vs. 6.3m/s; p=0.044), and to controls. Smoking rates were significantly higher among CD patients. Factors associated with PWV were age, mean arterial pressure and smoking. Lp-PLA2 activity was significantly lower in patients with IBD (46.8 vs. 53.9 nmol/mL/min; p=0.011). There was no difference in Lp-PLA2 between CD and UC patients. LDL-C was the only significant predictor of Lp-PLA2. CONCLUSIONS: Our study showed lower Lp-PLA2 activity in patients with IBD compared with controls, reflecting lower LDL-C in the former. There was no difference in PWV between the two groups. Arterial stiffness was higher in patients with CD, which is likely related to higher smoking rates. These findings challenge a possible association between IBD and CVD, but further studies are required.

Carotid intima-media thickness in patients with inflammatory bowel disease: a systematic review.

We systematically reviewed the available data on carotid intima-media thickness (cIMT) in patients with inflammatory bowel diseases (IBDs) without history of cardiovascular disease (CVD) and its associated factors. A total of 6 studies met the inclusion criteria including 217 patients with Crohn's disease (CD) and 85 with ulcerative colitis (UC). Two studies included only patients with CD. The prevalence of traditional CVD risk factors and the inflammatory burden (IBD duration and activity) varied greatly among patients and studies. Factors that correlated with cIMT were age, male gender, body mass index, arterial hypertension, as well as cholesterol and homocysteine levels. The current data on cIMT in patients with IBD are inconclusive. This is probably due to small number of patients, population heterogeneity with regard to inflammatory burden and smoking habits, and lack of strict matching with controls. In order to elucidate any potential association between IBD and CVD risk, larger prospective studies are required.

Everolimus-based immunosuppression in liver transplant recipients: a single-centre experience.

PURPOSE: Everolimus, a mammalian target of rapamycin inhibitor, has been shown to reduce growth factor-mediated cell proliferation, but data regarding its effectiveness and impact on renal function and recurrence of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients are limited. METHODS: We evaluated LT recipients with a calcineurin inhibitor (CNI)-based immunosuppression regimen in whom everolimus treatment was initiated. The changes in laboratory data, including glomerular filtration rate (GFR), compared to the baseline (i.e. the day of everolimus conversion), were assessed. RESULTS: Totally, 44 consecutive patients (32 men, age 55 ± 7 years) were commenced on everolimus [indications: renal dysfunction post-LT (16 patients, group 1); prevention of HCC recurrence (21 patients) or others (7 patients), group 2] at 6 months (range 1-206) post-LT. After 48 (range 12-76) months, all patients were alive without any rejection episodes. Compared to group 2 patients, group 1 patients had significantly greater improvement in renal function (DGFR: 12 ± 5 vs. -0.4 ± 0.2 ml/min, p = 0.02). GFR at baseline (OR 0.08, p = 0.002) and the combination of everolimus + MMF (OR 0.14, p = 0.024) were the factors independently associated with improvement in renal function. Finally, HCC recurrence was observed less frequently in the everolimus group of patients (n = 21) compared to the CNI-historical control group (n = 22) with HCC before LT [0/21 (0 %) vs. 4/22 (18.5 %), log rank p = 0.055), although the two groups of recipients had similar baseline characteristics and follow-up. CONCLUSIONS: Everolimus is effective and is associated with low rates of HCC recurrence and improvement of renal function in LT recipients.