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Aiming at investigating the potential effect of minimal dietary changes in NAFLD patients with non-significant fibrosis, 55 patients with NAFLD were enrolled in a randomized controlled clinical trial. Patients were assigned into two isocaloric dietary treatment groups for 24 weeks: (a) nutritional counseling (Control arm, N = 27), (b) nutritional counseling with currants included (two fruit servings, 36 g per day), substituting snacks of similar caloric content (Currant arm, N = 28). Clinical tests, anthropometrics, inflammatory and oxidative stress markers were conducted pre- and post-intervention. A total of 50 patients completed the trial. Significant differences between the two arms post-intervention were observed in fasting glucose and in IL-6 levels, these being significantly decreased only in Currant patients. Body weight, BMI, HbA 1c , CRP and EUS values decreased in both arms, differences being insignificant between the two arms post-intervention. Participants in the Currant arm had significantly reduced total body fat, WC and trunk fat. Ultrasound scanning improved significantly in patients snacking currants daily. Also, volunteers enrolled in the Currant arm showed a reduced intake of saturated fatty acids. Because BW regulation has been officially recognised as a treatment approach in NAFLD an additional analysis was repeated in patients adhering to this. Post-intervention, the decrease in IL-6 and in fasting glucose was significantly higher in Currant patients who lost BW compared to their counterparts in the Control arm. Conclusively, minimal modifications in snacking choices, such as the inclusion of dried grapes in diet, are beneficial in NAFLD patients with non-significant fibrosis.

Cirrhotic cardiomyopathy, a cardiac dysfunction presented in patients with cirrhosis, represents a recently recognized clinical entity. It is characterized by altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, in particular prolongation of the QT interval. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, including impaired function of beta-receptors, altered transmembrane currents, and overproduction of cardiodepressant factors, like nitric oxide, tumor necrosis factor α, and endogenous cannabinoids. Diastolic dysfunction is the first manifestation of cirrhotic cardiomyopathy and reflects the increased stiffness of the cardiac mass, which leads to delayed left ventricular filling. On the other hand, systolic incompetence is presented later, is usually unmasked during pharmacological or physical stress, and predisposes to the development of hepatorenal syndrome. The prolongation of QT is found in about 50 % of cirrhotic patients, but rarely leads to fatal arrhythmias. Cirrhotics with blunted cardiac function seem to have poorer survival rates compared to those without, and the risk is particularly increased during the insertion of transjugular intrahepatic portosystemic shunt or liver transplantation. Till now, there is no specific treatment for the management of cirrhotic cardiomyopathy. New agents, targeting to its pathogenetical mechanisms, may play some role as future therapeutic options.

Background: The cardiac dysfunction presented in cirrhotic patients is already known as cirrhotic cardiomyopathy. The pathogenesis of this entity is not fully understood., Aims: The aim of this study was to evaluate the frequency and characteristics of cirrhotic cardiomyopathy and to investigate the possible role of bacterial endotoxemia on its aggravation., Methods: Forty-five cirrhotics were studied by a tissue Doppler imaging echocardiography at rest and after stress. The diagnosis of left ventricular diastolic dysfunction was based on the latest guidelines of the American Society of Echocardiography, whereas its severity was defined by the E/e'av ratio. Endotoxemia was estimated by measuring the serum levels of lipopolysaccharide-binding protein (LBP) and cytokines., Results: None of the patients had systolic dysfunction, but 17/45 (37.8 %) had a diastolic one. Patients with grade II diastolic dysfunction had significantly longer QTc (p = 0.049), larger left atrium volume (p = 0.013), higher Brain Natriuretic Peptide levels (p = 0.007) and higher LBP levels (p = 0.02), compared to those with normal cardiac function, without differences in the systemic hemodynamics and the cytokines' levels. Moreover, the severity of diastolic dysfunction as reflected by the E/e'av. was significantly correlated with the LBP levels (p = 0.002). On the multivariate analysis, the LBP was independently associated with the presence of diastolic dysfunction., Conclusions: Cirrhosis is commonly complicated by cardiac dysfunction. Patients with severe cirrhotic cardiomyopathy have higher LBP levels, which are significantly correlated with the degree of diastolic dysfunction. Our findings support a potential role of bacterial endotoxemia on the aggravation of cardiomyopathy in cirrhotic patients.

Background/aims: Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension., Methods: We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >or=10 mm Hg treated with oral lamivudine (100mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications., Results: At 12 months, a significant reduction was observed in ALT (p=0.001), HBV DNA (p=0.002), Child-Pugh (p=0.012) and MELD score (p=0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4+/-3.9 and 12 months: 12.4+/-3.3 mm Hg (p=0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >or=12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough., Conclusion: In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved.

Background and Aim: We evaluated the effect of infection on the short- and long-term outcome of cirrhotic patients with upper gastrointestinal bleeding (UGIB), in a series of patients not submitted to antibiotic prophylaxis., Methods: The cirrhotic patients hospitalized for UGIB were prospectively followed up until the last visit, death, or transplantation. A standard screening protocol was used for bacterial infection at admission., Results: In total, 205 patients were included in the study. Antibiotics were administered in 79 (38.5%) patients and an infection was documented in 64 (31.4%) patients. In total, 130 (63.4%) patients died after a mean (SD) follow up of 23.8 (30.9) months. Six-week mortality was higher in the infected patients (P < 0.0001). The mortality of patients who were alive 6 weeks after admission was not different between the infected and non-infected patients. Antibiotic use or bacterial infection, the Child-Pugh score, hepatocellular carcinoma, and creatinine were the independent predictors of 6-week mortality. Age and the Child-Pugh score were the only predictors of mortality of the patients who had survived for more than 6 weeks after acute bleeding. In total, 51 (24.9%) patients rebled, 37 (18.1%) within 5 days of admission. Rebleeding was more frequent (41.8% vs 14.3%, P < 0.0001) in infected patients, mostly due to differences in early rebleeding (31.6% vs 9.5%, P = 0.0001)., Conclusion: Bacterial infection is associated with failure to control UGIB and early mortality in cirrhotic patients, but does not seem to affect the outcome of patients who overcome the bleeding episode.

During variceal bleeding, several factors may increase portal pressure, which in turn may precipitate further bleeding. This study investigates the early effects of endoscopic injection sclerotherapy (EIS) and endoscopic band ligation (EBL) on hepatic venous pressure gradient (HVPG) during acute bleeding and the possible influence in outcome. In 50 cirrhotic patients with bleeding esophageal varices treated with EIS (n = 25) or EBL (n = 25), we performed repeated HVPG measurements before and immediately after endoscopic treatment (time 0) and every 24 hours for a 5-day period. Endotherapy was continued until the varices were too small for further treatment. Both groups were comparable with regard to age, gender, Child-Turcotte-Pugh grade, and HVPG. In the EBL and EIS groups, a significant (P <.0001) increase was observed in mean portal pressure (20.7 mm Hg +/- 4.4 SD and 21.5 mm Hg +/- 4.5 SD, respectively) immediately after treatment (time 0) as compared with pretreatment (18.1 +/- 4.5 and 18.1 +/- 4.0). However, HVPG in the EBL group returned to baseline values within 48 hours after treatment, while in the EIS group it remained high during the 120-hour study period (P <.0001). Bleeding stopped in all patients after endotherapy. During the 42-day follow-up period, the rebleeding rate over time was lower in the EBL group compared with the EIS group (P =.024). Patients with an initial HVPG greater than 16 mm Hg had, despite endoscopic treatment, a significantly higher likelihood of death (P =.024) and overall failure (P =.037) [correction]. In conclusion, during acute variceal bleeding EIS, but not EBL, causes a sustained increase in HVPG, which is followed by a higher rebleeding rate.

Objectives: We have evaluated the efficacy of long-term lamivudine monotherapy in patients with decompensated HBeAg-negative/HBV-DNA positive cirrhosis., Methods: We analyzed the clinical course and outcome of lamivudine treatment in 30 consecutive cirrhotics and compared with 30 HBV untreated historical HBeAg-negative controls matched for age and gender., Results: Significant clinical improvement, defined as a reduction of at least two points in Child-Pugh score was observed in 23 of the 30 treated patients (76.6%) versus none of the 30 patients in the control group (p < 0.0001) after a mean follow-up of 20.6 +/- 12.1(+/-SD) months. There were 10 deaths in the treated group versus 24 in the control group (p= 0.07). Liver-related deaths occurred in five of the eight patients soon after the development of biochemical breakthrough. Patients with clinical improvement had better survival than patients with no improvement (p= 0.04) or those who developed biochemical breakthrough due to YMDD mutants (p= 0.001)., Conclusions: Lamivudine significantly improves liver function in HBeAg-negative decompensated cirrhosis. However, the development of the biochemical breakthrough due to YMDD mutants is associated with fatal outcome.

Background: Bacterial infections have been postulated as a trigger for variceal bleeding in cirrhotic patients, and impair coagulation evaluated by thrombelastography (TEG). Endogenous heparinoids have been detected after variceal bleeding and during liver transplantation in some cirrhotics using heparinase-modified-TEG., Aim: To assess if bacterial infection is associated with endogenous heparinoids in cirrhotics, thus impairing coagulation., Methods: Native and heparinase-modified-TEG (cleavage of heparin and heparan-sulphate) was performed in 60 cirrhotics (Grade A, 2; B, 30; C, 28): 30 infected [septicaemia, 6 (culture positive); 6 (culture negative); spontaneous bacterial peritonitis, 10; chest infection, 4; others, 4], 30 not infected, and five infected patients without liver diseases, comparing TEG parameters r, alpha, and ma. Eight cirrhotics were studied before and after infection. The diagnosis of presence and type of infection was based on international standard criteria., Results: A significant heparin effect was found only in infected cirrhotics (28 of 30) with significant changes in r (P=0.0003), alpha (P<0.0001), and ma (P<0.0001), but in none of those not infected. This effect completely reversed in the eight evaluated after resolution of infection. There was no heparin effect in infected non-cirrhotics., Conclusions: A heparin effect was only found in cirrhotic patients with infection, further confirming that infection significantly modifies coagulation in cirrhotic patients.

Background: We estimated the frequency of cirrhotic cardiomyopathy (CC) using all of the proposed diagnostic criteria, to describe the whole spectrum of cardiac alterations, and to investigate the role of stress in unmasking latent cases of CC. Methods: Ninety consecutive patients were recruited. CC was evaluated using the Montreal, the American Society of Echocardiography 2009 criteria, and the 2019 modified criteria of the CCM consortium. A dobutamine stress test was also performed. Results: Left ventricular diastolic dysfunction (LVDD) was identified in 72 (80%), 36 (40%), and 10 (11.1%) patients based on the above criteria, respectively. None of the patients had right ventricular systolic dysfunction, either at rest or after stress. The dobutamine stress test revealed left systolic dysfunction in 4 (4.5%) patients. There was agreement among the 3 criteria that the presence of LVDD was not associated with the severity of liver disease, using Child-Pugh stage. However, patients with Child-B/C had longer QTc intervals (P=0.004), higher levels of brain natriuretic peptide (P=0.016), and greater echocardiographic E/e' ratio (P<0.001) and E/e'(s) (P=0.003), compared to Child-A patients, while a significant correlation was demonstrated between Child-Pugh score and E/e' (P<0.001), or E/e'(s) (P=0.002). Conclusions: The prevalence of LVDD seems to be lower than previously considered. Right ventricular function seems to remain unimpaired. A dobutamine stress uncovered only a small percentage of patients with left systolic dysfunction. Nevertheless, the aggravation of several sonographic variables during stress, particularly in Child-B/C patients, potentially indicates a higher risk for clinical heart failure during stressful invasive interventions. [ABSTRACT FROM AUTHOR]