Efficacy of combined antiviral therapy with lamivudine and tenofovir in a liver transplanted girl with de novo hepatitis B virus infection.

The management of de novo hepatitis B (HBV) infection in children after liver transplantation is not well defined. Because this infection may induce severe liver disease in the graft liver, an efficient antiviral therapy is desirable. Here, we describe the favorable viral outcome observed in a liver transplanted girl with de novo HBV infection following combination therapy with lamivudine and tenofovir.

Ultrasound scanning in infants with biliary atresia: the different implications of biliary tract features and liver echostructure.

OBJECTIVE: To evaluate ultrasonographic features of the liver and biliary tree, including the presence of the triangular cord, in infants with biliary atresia and to analyze the correspondence between hepatic echostructure and histological aspects of the liver. MATERIALS AND METHODS: 35 consecutive infants (19 males) with documented diagnosis of biliary atresia were included. Ultrasonography evaluation, performed at a mean age of 63.1 ± 34.9 days, was focused on the extrahepatic bile ducts, characteristics of the gallbladder and liver, and the presence of the triangular cord. Liver biopsies were examined with particular regard to the presence and severity of fibrosis. RESULTS: On ultrasound, the gallbladder was not seen in 11 (31 %) cases, while in the remaining 24 patients the gallbladder was regular in 6 patients and irregular in 18 cases. The triangular cord was identified in 9 (26 %) of 35 patients. In 21 patients the liver echostructure appeared normal, while in 14 infants the liver parenchyma was more echogenic and coarse than normal. Liver biopsy showed signs of cirrhosis or fibrosis in all cases, including patients with a normal hepatic echostructure. CONCLUSION: Although the triangular cord was visualized in one-fourth of the infants with biliary atresia, abnormalities of the gallbladder on ultrasound (absence or abnormalities of length/shape) were detected in 83 % of the patients. Therefore, ultrasound evaluation of the liver and biliary tree plays an important role in suspecting biliary atresia. On the other hand, a low correspondence between liver echostructure aspects and the presence and severity of fibrosis at liver biopsy was identified. Therefore, severe liver disease in infants with biliary atresia cannot be excluded only on the basis of ultrasound findings.

Primary Prophylaxis for Gastrointestinal Bleeding in Children With Biliary Atresia and Portal Hypertension Candidates for Liver Transplantation: A Single-Center Experience.

BACKGROUND: Cirrhosis for biliary atresia (BA) is associated with risk of gastrointestinal bleeding (GB) from gastroesophageal varices due to portal hypertension. Primary prophylaxis of GB is controversial in children who are candidates for liver transplantation (LT). The aim of the study was to define the management of gastroesophageal varices and to identify the benefit of primary prophylaxis for GB in BA children waiting for LT. METHODS: A retrospective single-center study including all BA children listed for LT in 2008-2016. Clinical, endoscopical, and biochemical data were analyzed. RESULTS: Of 82 children, 50 (61%) did not receive primary prophylaxis and did not present any episode of bleeding, 16 (19.5%) underwent primary prophylaxis, and 16 (19.5%) presented spontaneous GB and received secondary prophylaxis. Children without primary prophylaxis and GB were younger than patients with primary prophylaxis and those with GB (7.7 years [range, 4.1-37.9 years] vs 11.2 years [range, 5.1-43 years]; P = .03 vs 10.7 years [range, 6.9-39.9 years], respectively; P = .004). Seventy-five percent of GB occurred in children older than 8 months. Fifteen (93.8%) children with GB presented esophageal varices (grade III = 10 [62.5%]) and 10 (62.5%) required endoscopic treatments, consisting mainly of sclerotherapy. Median time to LT was similar for children with or without bleeding (2 months [range, 0-17.7 months] vs 2.2 months [0-17.9 months], respectively; P = .89). After 45.5 months (range, 13.7-105.5 months) of follow-up, the overall patient survival was 97.6%. At the intention-to-treat analysis, the survival rate was 100% for patients without bleeding episode and 87.5% for children with GB (P = .16). CONCLUSIONS: Despite the risk of GB being not clinically predictable in children with BA waiting for LT, our experience suggests that primary prophylaxis of GB might be unnecessary in children younger than 6 months, while it should be considered in older children. Thus, the occurrence of GB does not delay the timing of transplantation.

Obalon intragastric balloon in the treatment of paediatric obesity: a pilot study.

BACKGROUND: Lifestyle interventions are often ineffective in the treatment of pediatric obesity. Weight loss devices have been introduced for the temporary nonsurgical treatment of morbid obesity. OBJECTIVE: The aim of the study is to evaluate the efficacy of Obalon Intragastric Balloon on weight loss and on metabolic and cardiovascular parameters in a pediatric population with severe obesity. METHODS: We enrolled 10 children with severe obesity. In all patients anthropometric parameters, biochemical tests, ultrasound liver examination and blood pressure monitoring were evaluated at the time of insertion and after removal of device. RESULTS: The Obalon had a positive effect on decrease of weight, body mass index and percentage of excess body weight within 3 months from placement. Moreover, this safe minimally invasive device improves the cardio-metabolic profiles of obese children. CONCLUSIONS: The Obalon could be a useful tool in the difficult management of pediatric patients with morbid obesity, inducing in short-term a meaningful weight loss.

The association between retinal microvascular changes, metabolic risk factors, and liver histology in pediatric patients with non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: The prevalence of childhood obesity is increasing worldwide. Studies in adult populations show that retinal microvascular changes are associated with obesity and components of the metabolic syndrome. In our study we have assessed the effect of body mass index (BMI), metabolic parameters, and adiposity on the retinal microvasculature in children. METHODS: Fifty-four consecutive children with biopsy-proven NAFLD were enrolled in this study. Anthropometric and laboratory parameters were obtained using standardized protocols. Retinal caliber was quantified from digital retinal images using well-known computer-based programs. Twenty-four-hour ambulatory blood pressure monitoring was measured using a standard protocol. RESULTS: In our population, the prevalence of retinopathy was of 53 % (13 males). The 29 patients with retinopathy (mean age 10.91 ± 3.10) showed significantly higher values of triglycerides (mg/day) (105.57 vs. 90.20, p = 0.04), basal insulin (mUI/ml) (17.20 vs. 12.97, p = 0.02), and HOMA-IR (3.37 vs. 2.76, p = 0.04). The patients with a HOMA-IR >2.5 (OR = 3.34, p = 0.02; 95 % IC, 1.07-10.39), and systolic non-dipping (OR 4.16, p = 0.028, 95 % IC, 1.11-13.67), have an increased risk of retinopathy. Moreover, the study of correlation between all stages of liver biopsy (CRN criteria) and the grade of retinopathy showed a positive correlation with fibrosis (r = 0.31) and an NAS score (r = 0.28). CONCLUSIONS: We found an association between metabolic parameters and nocturnal blood pressure on the retinal microvasculature among the obese children with NAFLD. Furthermore, for the first time, we report the positive relationship between hepatic fibrosis in pediatric NAFLD patients and the degree of retinopathy signs.

Non-alcoholic fatty liver disease and hepatocellular carcinoma in a 7-year-old obese boy: coincidence or comorbidity?

BACKGROUND: Hepatocellular carcinoma (HCC) may develop from non-alcoholic fatty liver disease (NAFLD) either in the presence or in the absence of established cirrhosis. Non-cirrhotic patients with NAFLD-related HCC are usually adult, male and obese. However, this association has not been reported yet in younger age groups. Objectives In the present study, the clinical case of a 7-yaer-old obese boy with steatosis and HCC is presented. METHODS: A 7-year-old boy, with no evidence of chronic liver disease, was admitted for assessment of a liver mass. Preliminary assessment was suggestive of a combined and severe liver steatosis together with a malignant disease. RESULTS: A biopsy confirmed the suspected diagnosis of HCC; interestingly, the non-neoplastic liver was surrounded and characterized by the presence of steatosis and ballooning, and being absent of lobular inflammation and fibrosis. Chemotherapy and diet changes were conducted successfully with ultrasound characteristics suggesting improvements on both aspects: conventional liver mass resection could take place. CONCLUSIONS: This case report suggests that HCC might develop in paediatric age patients with obesity-related NAFLD, even in the absence of fibrosis.

Blockade of ß-adrenoceptors restores the GRK2-mediated adrenal α(2) -adrenoceptor-catecholamine production axis in heart failure.

BACKGROUND AND PURPOSE: Sympathetic nervous system (SNS) hyperactivity is characteristic of chronic heart failure (HF) and significantly worsens prognosis. The success of ß-adrenoceptor antagonist (ß-blockers) therapy in HF is primarily attributed to protection of the heart from the noxious effects of augmented catecholamine levels. ß-Blockers have been shown to reduce SNS hyperactivity in HF, but the underlying molecular mechanisms are not understood. The GPCR kinase-2 (GRK2)-α(2) adrenoceptor-catecholamine production axis is up-regulated in the adrenal medulla during HF causing α(2) -adrenoceptor dysfunction and elevated catecholamine levels. Here, we sought to investigate if ß-blocker treatment in HF could lower SNS activation by directly altering adrenal GRK2 levels. EXPERIMENTAL APPROACH: Four weeks after myocardial infarction-induced HF, adult rats were randomized to 10-week treatment with vehicle (HF/C) or bisoprolol (HF/B). Cardiac function and dimensions were measured. In heart and adrenal gland, GRK2 levels were assessed by RT-PCR and Western blotting and adrenoceptors studied with radioligand binding. Catecholamines and α(2) adrenoceptors in adrenal medulla chromaffin cell cultures were also measured. KEY RESULTS: Bisoprolol treatment ameliorated HF-related adverse cardiac remodelling and reduced plasma catecholamine levels, compared with HF/C rats. Bisoprolol also attenuated adrenal GRK2 overexpression as observed in HF/C rats and increased α(2) adrenoceptor density. In cultures of adrenal medulla chromaffin cells from all study groups, bisoprolol reversed HF-related α(2) adrenoceptor dysfunction. This effect was reversed by GRK2 overexpression. CONCLUSION AND IMPLICATIONS: Blockade of ß-adrenoceptors normalized the adrenal α(2) adrenoceptor-catecholamine production axis by reducing GRK2 levels. This effect may contribute significantly to the decrease of HF-related sympathetic overdrive by ß-blockers.

Myocardial ß(2) -adrenoceptor gene delivery promotes coordinated cardiac adaptive remodelling and angiogenesis in heart failure.

BACKGROUND AND PURPOSE: We investigated whether ß(2) -adrenoceptor overexpression could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodeling of the failing heart. EXPERIMENTAL APPROACH: We explored the angiogenic effects of ß(2) -adrenoceptor overexpression in a rat model of post-myocardial infarction (MI) heart failure (HF). Cardiac adenoviral-mediated ß(2) -adrenoceptor overexpression was obtained via direct intramyocardial injection 4-weeks post-MI. Adenovirus(Ad)-GFP and saline injected rats served as controls. Furthermore, we extended our observation to ß(2) -adrenoceptor -/- mice undergoing MI. KEY RESULTS: Transgenes were robustly expressed in the LV at 2 weeks post-gene therapy, whereas their expression was minimal at 4-weeks post-gene delivery. In HF rats, cardiac ß(2) -adrenoceptor overexpression resulted in enhanced basal and isoprenaline-stimulated cardiac contractility at 2-weeks post-gene delivery. At 4 weeks post-gene transfer, Ad-ß(2) -adrenoceptor HF rats showed improved LV remodeling and cardiac function. Importantly, ß(2) -adrenoceptor overexpression was associated with a markedly increased capillary and arteriolar length density and enhanced in vivo myocardial blood flow and coronary reserve. At the molecular level, cardiac ß(2) -adrenoceptor gene transfer induced the activation of the VEGF/PKB/eNOS pro-angiogenic pathway. In ß(2) -adrenoceptor-/- mice, we found a ~25% reduction in cardiac capillary density compared with ß(2) -adrenoceptor+/+ mice. The lack of ß(2) -adrenoceptors was associated with a higher mortality rate at 30 days and LV dilatation, and a worse global cardiac contractility compared with controls. CONCLUSIONS AND IMPLICATION: ß(2) -Adrenoceptors play an important role in the regulation of the angiogenic response in HF. The activation of VEGF/PKB/eNOS pathway seems to be strongly involved in this mechanism.