The Role of Metformin in the Management of NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Its prevalence ranges 10–24% in the general population, reaching 60–95% and 28–55% in obese and diabetic patients, respectively. Although the etiology of NAFLD is still unclear, several lines of evidences have indicated a pathogenetic role of insulin resistance in this disorder. This concept has stimulated several clinical studies where antidiabetic drugs, such as insulin sensitizers including metformin, have been evaluated in insulin-resistant, NAFLD patients. These studies indicate that metformin might be of benefit in the treatment of NAFLD, also in nondiabetic patients, when associated to hypocaloric diet and weight control. However, the heterogeneity of these studies still prevents us from reaching firm conclusions about treatment guidelines. Moreover, metformin could have beneficial tissue-specific effects in NAFLD patients irrespective of its effects as insulin sensitizer

Surveillance Study of Hepatitis E Virus (HEV) in Domestic and Wild Ruminants in Northwestern Italy

In industrialized countries, increasing autochthonous infections of hepatitis E virus (HEV) are caused by zoonotic transmission of genotypes (Gts) 3 and 4, mainly through consumption of contaminated raw or undercooked pork meat. Although swine and wild boar are recognized as the main reservoir for Gt3 and Gt4, accumulating evidence indicates that other animal species, including domestic and wild ruminants, may harbor HEV. Herein, we screened molecularly and serologically serum and fecal samples from two domestic and four wild ruminant species collected in Valle d'Aosta and Piemonte regions (northwestern Italy. HEV antibodies were found in sheep (21.6%), goats (11.4%), red deer (2.6%), roe deer (3.1%), and in Alpine ibex (6.3%). Molecular screening was performed using different primer sets targeting highly conserved regions of hepeviruses and HEV RNA, although at low viral loads, was detected in four fecal specimens (3.0%, 4/134) collected from two HEV seropositive sheep herds. Taken together, the data obtained document the circulation of HEV in the geographical area assessed both in wild and domestic ruminants, but with the highest seroprevalence in sheep and goats. Consistently with results from other studies conducted in southern Italy, circulation of HEV among small domestic ruminants seems to occur more frequently than expected

Nonalcoholic Fatty Liver: A Possible New Target for Type 2 Diabetes Prevention and Treatment

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed

Emerging Respiratory Viruses of Cats

In recent years, advances in diagnostics and deep sequencing technologies have led to the identification and characterization of novel viruses in cats as protoparviruses and chaphamaparvoviruses, unveiling the diversity of the feline virome in the respiratory tract. Observational, epidemiological and experimental data are necessary to demonstrate firmly if some viruses are able to cause disease, as this information may be confounded by virus- or host-related factors. Also, in recent years, researchers were able to monitor multiple examples of transmission to felids of viruses with high pathogenic potential, such as the influenza virus strains H5N1, H1N1, H7N2, H5N6 and H3N2, and in the late 2019, the human hypervirulent coronavirus SARS-CoV-2. These findings suggest that the study of viral infections always requires a multi-disciplinary approach inspired by the One Health vision. By reviewing the literature, we provide herewith an update on the emerging viruses identified in cats and their potential association with respiratory disease

Detection and characterization of bopiviruses in domestic and wild ruminants

Highly divergent picornaviruses (PVs) classified in the genus Bopivirus have been recently discovered on faecal samples from sheep and goats in Hungary and from fallow and red deer in Australia. In this study, we investigated the epidemiology of these novel viruses in domestic and wild ruminants from Northwestern Italian Alps by testing archival faecal samples collected from 128 sheep, 167 goats, 61 red deer (Cervus elaphus), 77 roe deer (Capreolus capreolus), 43 chamois (Rupicapra rupicapra) and 32 Alpine ibex (Capra ibex). Bopivirus RNA was detected in a total of 19 animals, including 14 sheep (10.9%), 2 red deer (3.3%), 1 roe deer (1.3%), 1 chamois (2.3 %) and 1 Alpine ibex (3.3 %), but not in goats. Upon sequence analysis of the 3D(RdRp) region, the sequences generated from chamois, roe deer, Alpine ibex and ovine faecal samples showed the highest nucleotide identity (96.8-100%) to bopiviruses detected in goats and sheep from Hungarian farms, whereas strains found in red deer displayed the closest relatedness (90.8%-91.2%) to bopiviruses identified in fallow and red deer in Australia. The nearly complete genome sequence of strains 12/2020/ITA (ON497046) and 14-73/2020/ITA (ON497047) detected in an Alpine ibex and in a sheep, respectively, was determined by combining a modified 3'-RACE protocol with Oxford Nanopore Technologies sequencing platform. On phylogenetic analysis based on the complete polyprotein, both strains segregated into the candidate species Bopivirus B along with ovine and caprine strains detected in Hungary (90.0-94.6% nucleotide and 94.6-98.0% amino acid identities). The findings of this study expand the host range of these novel viruses and hint to a possible virus circulation between domestic ruminants and wild animals

Exploring the Enteric Virome of Cats with Acute Gastroenteritis

Viruses are a major cause of acute gastroenteritis (AGE) in cats, chiefly in younger animals. Enteric specimens collected from 29 cats with acute enteritis and 33 non-diarrhoeic cats were screened in PCRs and reverse transcription (RT) PCR for a large panel of enteric viruses, including also orphan viruses of recent identification. At least one viral species, including feline panleukopenia virus (FPV), feline enteric coronavirus (FCoV), feline chaphamaparvovirus, calicivirus (vesivirus and novovirus), feline kobuvirus, feline sakobuvirus A and Lyon IARC polyomaviruses, was detected in 66.1% of the samples.. Co-infections were mainly accounted for by FPV and FCoV and were detected in 24.2% of the samples. The virome composition was further assessed in eight diarrhoeic samples, through the construction of sequencing libraries using a sequence-independent single-primer amplification (SISPA) protocol. The libraries were sequenced on Oxford Nanopore Technologies sequencing platform. A total of 41 contigs (>100 nt) were detected from seven viral families infecting mammals, included Parvoviridae, Caliciviridae, Picornaviridae, Polyomaviridae, Anelloviridae, Papillomaviridae and Paramyxoviridae, revealing a broad variety in the composition of the feline enteric virome

Current Knowledge of Hepatitis E Virus (HEV) Epidemiology in Ruminants

Hepatitis E virus (HEV) infection represents an emerging public health concern worldwide. In industrialized countries, increasing numbers of autochthonous cases of human HEV infection are caused by zoonotic transmission of genotypes 3 and 4, mainly through the consumption of contaminated raw or undercooked meat of infected pigs and wild boars, which are considered the main reservoirs of HEV. However, in the last few years, accumulating evidence seems to indicate that several other animals, including different ruminant species, may harbor HEV. Understanding the impact of HEV infection in ruminants and identifying the risk factors affecting transmission among animals and to humans is critical in order to determine their role in the epidemiological cycle of HEV. In this review, we provide a summary of current knowledge on HEV ecology in ruminants. A growing body of evidence has revealed that these animal species may be potential important hosts of HEV, raising concerns about the possible implications for public health

Serological and Molecular Survey on Domestic Dog Hepadnavirus in Household Dogs, Italy

The discovery of hepadnaviruses in cats (domestic cat hepadnavirus, DCH) and of a DCH-like virus in dogs has raised several questions regarding the role of these viruses in pets, with particular emphasis on their potential impact on animal health and epidemiology, as well as possible zoonotic implications. In this study, by screening an age-stratified collection of 600 canine serum samples for DCH with an ELISA assay based on the recombinant core antigen (DCHCAg), specific antibodies were found with an overall prevalence of 10.0% (60/600), with a higher prevalence in younger and older dogs. By retesting the canine DCHCAbs-positive sera with an ELISA test based on the recombinant surface protein of DCH (DCHSAg), a total of 18 sera (30%, 18/60) also contained IgG anti-DCHSAg. All the sera were also assessed molecularly using either a consensus hepadnavirus PCR or a specific real-time PCR for DCH. Hepadnavirus DNA was detected in four seronegative dogs, with a prevalence rate of 0.7% (4/600). On sequence analysis of the polymerase region amplified with pan-hepadnavirus primers, the amplicons displayed the highest nucleotide identity (97.3–99.6%) to DCH sequences detected in cats and to the domestic dog hepadnavirus recently identified in a canine serum sample from Italy