Primary biliary cirrhosis: lung involvement

Abstract: Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p<0.01) and with the presence of circulating anti-centromere antibodies (p<0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome. Prospective studies are needed to evaluate if these abnormalities will eventually lead to clinical symptoms and if their progression could be influenced by different therapeutic regimens for primary biliary cirrhosis.     

Role of coinfection by transfusion-transmitted virus (TTV) in patients with chronic HCV hepatitis

A novel DNA virus, associated with non A-G post-transfusion hepatitis, has been recently discovered. TTV is detectable in acute and chronic liver diseases with a variable incidence. The clinical significance of TTV coinfection in patients with chronic HCV hepatitis has not yet been defined. In this review we report the data regarding the possible pathogenetic role of TTV infection in chronic HCV hepatitis.     

Recurring duodenal ulcer. Evaluation of previous complications as a predictive factor of ulcer recurrence after eradication of Helicobacter pylori

Duodenal ulcer is a chronic disease, punctuated by acute relapses. The pathogenic mechanism in 90-100% of cases is infection by Helicobacter pylori. Two major strains exist of this bacterium: I strain, which secretes a vacuolating cytotoxin (Vac-A), and another protein named cytotoxin-associated (Cag-A) and type II strain, unable to produce both proteins and unable to produce duodenal pathology. We sought to identify the natural history of relapsing duodenal ulcer after cure of the bacterial infection. In particular, we followed the outcome of patients who repeatedly had bled from their recurrent ulcer disease, after success in eliminating the microorganism from the stomach. None of 12 repeated bleeders had an ulcer recurrence after the cure of Helicobacter pylori infection. Only 3 (5%) of 60 frequent relapser had a new episode of duodenal ulcer during a follow-up reinfection by Helicobacter pylori. We demonstrated that the cure of bacterial infection is also the cure of duodenal ulcer recurrence, but for a few cases, in the latter, event one could hypothesize a defect in the production of growth factors (Epidermal Growth Factor, Fibroblast Growth Factor) or of cellular polyamines synthesis. It is important to improve the diagnosis of reinfection by implementing the urea breath test.     

Moderate to vigorous physical activity and sedentary behavior changes in self-isolating adults during the COVID-19 pandemic in Brazil: a cross-sectional survey exploring correlates

Sport Sciences for Health - The COVID-19 pandemic imposed major changes on daily-life routine worldwide. To the best of our knowledge, no study quantified the changes on moderate to vigorous...     

Hepatitis B vaccination: current status

BACKGROUND: Hepatitis B remains a crucial Public Health problem worldwide, with a numerical impact of infected persons and long term sequences higher than other infectious diseases preventable by vaccines. Around 75% of the world population is living in areas where HBV is endemic (Africa, most of south America, eastern Europe, eastern Mediterranean basin, south-eastern Asia, China and Pacific islands except Australia, new Zealand and Japan); 5-15% of these populations are affected by chronic HBV infection. Rates of chronicity depend on the age of exposure to HBV. Newly infected adults generally clear the infection and only about 5% become chronic carriers of the virus. Infected children rarely develop clinical disease but 25-90% become chronic carriers. Over two billions of persons worldwide have been infected in their life and 350 millions are chronic carriers of HBV. About 25% of the chronic carriers will die of cirrhosis or hepatocellular carcinoma. In recent years control of the spread of HBV has been achieved by the large-scale availability of safe and effective vaccines. This review summarizes the current perspective and use of hepatitis B vaccination, with particular attention to implementation needs and results in Italy, the first country that has introduced universal vaccination against hepatitis B.     

Effect of Helicobacter pylori eradication on bulbitis and duodenal gastric metaplasia

BACKGROUND/AIMS: Duodenal gastric metaplasia seems to be linked to infection by Helicobacter pylori, to the extent of acid secretion and to bulbitis. An investigation was made of the relationship between bulbitis and duodenal gastric metaplasia, or whether bulbitis can arise along with duodenal gastric metaplasia after Helicobacter pylori eradication in an average of six years. METHODOLOGY: We compared 22 patients with duodenal ulcers [male/female 16/6; (mean age+/-SD) 55+/-12 years] Helicobacter pylori-negative after eradication, with 23 Helicobacter pylori-positive patients free from active duodenal ulcers [male/female 17/6; (mean age+/-SD) 59+/-12 years]. RESULTS: The bulbitis score was found to be lower in the Helicobacter pylori-negative than in the Helicobacter pylori-positive group (p=0.02). The duodenal gastric metaplasia score in the Helicobacter pylori-negative was higher than in the Helicobacter pylori-positive group (p=0.001). We failed to find any relationship between the presence of bulbitis and duodenal gastric metaplasia. We found a non-significant inverse correlation between the presence of duodenal gastric metaplasia and chronic body gastritis (p=0.07). CONCLUSIONS: Bulbitis and duodenal gastric metaplasia may depend on different causal factors not related to Helicobacter pylori infection. The extension of duodenal gastric metaplasia with time following recovery from peptic ulcer disease may represent a mucosal protection factor against acid.     

Treatment of recurrent hepatitis C virus infection after liver transplantation

Therapeutic strategies were designed based on experience from the treatment options of the last 10 years in the ordinary clinical setting. Interferon was the first treatment used. This monotherapy was discontinued with the arrival of ribavirin. Ribavirin monotherapy has also been shown to have a limited effect and in recent years the combination of interferon and ribavirin has become the first line therapy.     

Characterization of von Willebrand factor in primary pulmonary hypertension

Summary The aim of this study was to determine the value of von Willebrand factor (vWF), a well-characterized endothelial cell protein secretion, as a marker for prognosis in patients with primary pulmonary hypertension (PPH). Venous and arterial blood samples were obtained from 18 clinically diagnosed PPH patients and 12 case controls matched for age and sex. Plasma vWF antigen was determined by enzymelinked immunosorbent assay (ELISA). The patients' multimeric vWF pattern was analyzed by sodium dodecylsulfate (SDS)-agarose-acrylamide electrophoresis, Western blot, and densitometric analysis. vWF sialic acid content was determined by a lectin-based ELISA. The PPH patients showed a higher content of vWF antigen in venous (P = 0.0026) and arterial (P = 0.0094) blood samples than controls. The mean vWF sialic acid content of the PPH patients corresponded to 37.7% of the mean value for the control group. On the basis of the hemodynamic response to vasodilator trial, the PPH patients were grouped as responders or nonresponders. The latter group showed a significantly higher plasma vWF antigen antecubital vein/radial artery ratio, an increased number of unusually large vWF multimers, and a diminished content of vWF sialic acid in comparison with the first group. We believe that our results establish the nature of vWF alterations that are related to endothelial cell damage in patients with primary pulmonary hypertension and that this could be of value when establishing the prognosis in this group of patients.     

Natural killer response to exogenous interferon in delta hepatitis: boost or depression defined within the first week of therapy

Six patients with hepatitis B surface antigen (HBsAg)-positive chronic active liver disease and superimposed delta virus infection were followed up for changes of natural killer (NK) cell function during a 3-month course with median doses of recombinant leukocyte alpha interferon (rIFN). Careful record of the off-therapy NK function means revealed that 3 subjects were boosted, 2 were depressed, and 1 was unchanged. The NK activity patterns showed that after the start of therapy the maximal shift from the off-therapy mean was concentrated in the first week; then the trend, although confirmed, had a gentler slope on the follow-up. This indicated that the first week reflects the availability of rIFN-sensitive NK cells and characterizes the immunological competence of the patient; whilst later in follow-up, suppressive control mechanisms or loss of receptor affinity tend to blur the response. The serum levels of delta RNA dropped in the NK-boosted patients; persistently negative RNA together with clearance of intrahepatic delta antigen was demonstrated solely in that 1 patient showing 164% NK cell function increment in the first week. This study shows that paradoxical responses to exogenous rIFN are not confined to cancer patients, as indicated so far, but may appear in other subjects as well, and reflect the peculiar response of the individual; whenever an NK-dependent clearance of virus-infected cells is required, recognition of the early pattern of reactivity would be useful.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulatory Agilities in the Time of COVID-19: Overview,Trends, and Opportunities

PurposeCrucial steps have been adopted by health and regulatory authorities around the world to respond to the COVID-19 pandemic. This review aims to highlight these steps by providing an overview of the regulatory approaches adopted during the onset of the pandemic, provide an assessment of observed trends, and offer some reflections and proposals to leverage learnings and opportunities from this current pandemic.MethodsDocuments and informational materials on regulating the development and management of medical products during the COVID-19 pandemic were collected and classified. These materials were sourced from official websites and press releases from health authorities and international bodies from selected markets across the globe, and covered the period between January and July 2020. Additional information to support this study was gathered through a literature review and analysis of related data available from the public domain, and was complemented with the authors' personal experience.FindingsCommunication has been vital in addressing the impact of COVID-19. A total of 1705 documents and informational materials related to health or regulatory response to the COVID-19 pandemic were gathered. Of these, 343 (around 20%) were identified as regulatory agilities. These agile approaches were classified into 3 categories, namely, where health and regulatory authorities had: (1) facilitated product management across the entire lifecycle, notably in expediting medical product use for COVID-19, ensuring the continuity of clinical trials, and addressing supply chain issues; (2) strengthened international cooperation; and (3) addressed regulatory burden with the adoption of electronic and digital tools.ImplicationsWhile many regulatory measures have been introduced temporarily as a response to the COVID-19 crisis, there are opportunities for leveraging an understanding from these approaches in order to collectively achieve more efficient regulatory systems and to mitigate and address the impact of COVID-19 and further future-proof the regulatory environment.