Effect of Periodontitis and Periodontal Therapy on Oral and Gut Microbiota.

Mounting evidence indicates that periodontitis-related oral bacteria may contribute to gut microbial dysbiosis. This clinical study aimed to explore the oral-gut microbial signatures associated with periodontitis and to longitudinally evaluate the effect of periodontal treatment on the oral and gut microbial composition. Stool and saliva samples from generalized stage III/IV periodontitis patients (n = 47) were collected and analyzed by 16S ribosomal RNA gene amplicon sequencing, before and 3 mo after steps I to II of periodontal therapy. Periodontally healthy matched subjects (n = 47) were used as controls. Principal component analysis was carried out to identify oral-gut microbial profiles between periodontitis patients at baseline and healthy subjects; periodontitis samples were longitudinally compared before and after treatment. ß-Diversity of gut microbial profiles of periodontitis patients before treatment significantly differed from healthy controls (P < 0.001). Periodontal therapy was associated with a significant change in gut microbiota (P < 0.001), with post-treatment microbial profiles similar to healthy volunteers. A higher abundance of Bacteroides, Faecalibacterium, Fusobacterium, and Lachnospiraceae was noted in fecal samples of periodontitis patients at baseline compared to healthy controls. In contrast, Lactobacillus was the only genus more abundant in the latter. Additionally, periodontal therapy led to a parallel reduction in the salivary carriage of periodontal pathobionts, as well as gut Bacteroides, Lachnoclostridium, Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae, to levels similar to healthy controls. Collectively, discriminating oral-gut microbial signatures of periodontitis were found. Periodontal treatment both mitigated oral dysbiosis and altered gut microbial composition, signifying potential broader implications for gastrointestinal health and disease.

Treatment of hepatitis D: an unmet medical need.

BACKGROUND: Therapy of chronic hepatitis D (CHD) is still based on interferon alpha (IFNα), introduced in clinical practice 30 years ago: results are modest and better therapies are an urgent medical need. AIMS: This article provides a critical overview of the new therapies under investigation for CHD. SOURCES: Review of the recently published medical literature. CONTENT: New therapeutic efforts aim to deprive the hepatitis D virus (HDV) of functions provided to its life cycle by the hepatitis B Virus (HBV) or by the host. Three therapeutic strategies are in evaluation: a) Myrcludex B, a myristolated lipopeptide of the pre-S1 domain of the HBsAg that blocks the entry of the HDV into hepatocyes and controls infection by preventing the spreading of the virus to liver cells not infected by the HBV; b) Lonafarnib, an inhibitor of a host farnesyl-transferase that hinders morphogenesis of the HDV by preventing the farnesylation of the large HD-antigen, necessary for virion assembly; c) REP 2139, a nucleic acid polymer that prevents export of the mature HDV by the presumed inhibition of the synthesis of subviral HBsAg particles with which the virion is coated. Myrcludex B and Lonafarnib increase therapeutic efficacy in combination with Peg-IFNα. In a pilot study, REP 2139 in combination with Peg-IFNα induced the clearance of serum HDV RNA and of the HBsAg in about half of 12 treated patients. IMPLICATIONS: Long-term therapies with either Myrcludex B or Lonafarnib in combination with Peg-IFNα are required to achieve clinical control of CHD. However, with prolonged therapies tolerance becomes a problem; studies are on the way to determine whether Peg-IFN lambda may be better tolerated that Peg-IFNα. The promising preliminary data of REP 2139 in combination with Peg-IFNα await confirmation of the original pilot study.

Endocrine manifestations of chronic HCV infection.

Chronic hepatitis C virus (HCV) infection has been associated with a great number of extra-hepatic manifestations (EHMs), including several endocrine disorders. Currently available epidemiological, clinical and experimental data do not show a link between HCV and all EHMs. Thyroid disorders (TD) and type 2 diabetes, for example, are the most frequent endocrine alterations in patients with chronic HCV infection, but there are only weak evidences that HCV could be involved in hypothalamic-pituitary axis perturbation, bone metabolism alteration and sexual dysfunctions induction. Thus, this issue needs further investigation. Prospective studies have also shown that interferon (IFN)-based therapy for chronic HCV infection can induce or worsen EHMs. In particular, IFN has been associated with development of autoimmunity and/or TD in up to 40% of chronic HCV infected patients. Hence, a careful monitoring of thyroid function should be performed in such patients. The recent approval of direct-acting antiviral agents in IFN-free regimens for chronic hepatitis C treatment will dramatically reduce not only liver-related mortality but also morbidity due to EHMs.

MicroRNAs in HBV-related hepatocellular carcinoma: functions and potential clinical applications.

Hepatitis B virus (HBV) infection is still a relevant problem worldwide and many cases of hepatocellular carcinoma (HCC) are related to HBV. The prognosis of HBV-related HCC is poor, particularly for advanced stage diagnosis. Although follow-up strategies were adopted for patients at risk, there is need for an optimal early biomarker for the screening purpose. MicroRNAs (miRNAs) are small non-coding RNAs, tightly connected to cell type and differentiation status and act as genetic regulator which can be involved in oncogenic processes. The alteration in miRNA expression pattern may represent a new opportunity for HBV-related HCC diagnosis and therapies. Some studies focused on miRNA polymorphism responsible for HCC susceptibility; others found several miRNAs deregulated by HBV X protein as well as miRNAs altered in HBV-related HCC tissue and cells. A high variability among results emerged, probably due to different techniques employed, biological substrates, experimental procedures, criteria of miRNAs selection and ethnic provenience of the included patients. Interestingly, circulating miRNAs have been studied as potential HCC-biomarkers but the reported accuracy is still not convincing, particularly in distinguishing patients with HCC from patients with cirrhosis. Hence, the use of miRNAs remains in an experimental phase and more studies are required to define their role in the clinical practice.

Chronic hepatitis B therapy: available drugs and treatment guidelines.

There are currently several drugs approved for the treatment of chronic hepatitis B including recombinant interferons, such as interferon-α and its pegylated formulation, and the nucleos(t)ide analogues, such as lamivudine, adefovir, telbivudine, entecavir and tenofovir. Pegylated-interferon is an immune-modulatory agent that works mainly by enhancing the innate immune response while nucleos(t)ide analogues are oral drugs with direct inhibition of viral replication. Each agent has its own advantages and drawbacks. Pegylated-Interferon treatment has a finite duration without induction of drug resistance but only a limited number of patients achieve a sustained virological response to therapy. On the other hand, the care with nucleos(t)ide analogues requires a long-term treatment with a potential risk of induction of drug resistance, but higher rates of viral replication suppression are achieved. Nevertheless, second generation nucleos(t)ide analogues, such as Entecavir and Tenofovir, have both high genetic barrier to resistance and potent antiviral action. This review describes the mechanisms of antiviral activity and the efficacy of viral suppression of the different available drugs for chronic hepatitis B treatment, considering the recent clinical guidelines for an optimal management of chronic HBV infection.