Pathogenesis and treatment of oral candidosis

Oral infections caused by yeast of the genus Candida and particularly Candida albicans (oral candidoses) have been recognised throughout recorded history. However, since the 1980s a clear surge of interest and associated research into these infections have occurred. This has largely been due to an increased incidence of oral candidosis over this period, primarily because of the escalation in HIV-infection and the AIDS epidemic. In addition, changes in medical practice leading to a greater use of invasive clinical procedures and a more widespread use of immunosuppressive therapies have also contributed to the problem. Whilst oral candidosis has previously been considered to be a disease mainly of the elderly and very young, its occurrence throughout the general population is now recognised. Candida are true ‘opportunistic pathogens’ and only instigate oral infection when there is an underlying predisposing condition in the host. Treatment of these infections has continued (and in some regards continues) to be problematic because of the potential toxicity of traditional antifungal agents against host cells. The problem has been compounded by the emergence of Candida species other than C. albicans that have inherent resistance against traditional antifungals. The aim of this review is to give the reader a contemporary overview of oral candidosis, the organisms involved, and the management strategies that are currently employed or could be utilised in the future

S-Adenosyl-Methionine and Betaine Improve Early Virological Response in Chronic Hepatitis C Patients with Previous Nonresponse

Treatment of chronic hepatitis C (CHC) with pegylated interferon (pegIFN ) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFN signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFN signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFN on HCV replicons. We have performed a clinical study with the aim to evaluate efficacy and safety of the addition of SAMe and betaine to treatment of CHC with pegIFN /ribavirin

Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva

AIMS: To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. METHODS AND RESULTS: Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. CONCLUSIONS: The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. SIGNIFICANCE AND IMPACT OF THE STUDY: To understand the expression of virulence factors in Candida dual-species systems.This work was supported by Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BPD/20987/2004 attributed to Claudia Botelho

Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, treatment options are limited and often inefficient. The aim of this study was to determine current survival rates for patients diagnosed with HCC and to identify prognostic factors, which will help in choosing optimal therapies for individual patients. A retrospective analysis of medical records was performed on 389 patients who were identified through the central tumour registry at our institution from 1998 to 2003. Clinical parameters, treatments received and survival curves from time of diagnosis were analysed. Overall median survival was 11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170 patients received transarterial chemoembolisation (TACE) and/or percutaneous ethanol injections (PEI) with a median survival rate of 16 months for patients receiving TACE, 11 months for patients receiving PEI and 24 months for patients receiving TACE followed by PEI. Independent negative prognostic parameters for survival were the presence of portal vein thrombosis, advanced liver cirrhosis (Child–Pugh score B or C) and a score of >2. This study will help to estimate survival rates for patients with HCC according to their clinical status at diagnosis and the treatments received

The Novel Immunosuppressive Protein Kinase C Inhibitor Sotrastaurin Has No Pro-Viral Effects on the Replication Cycle of Hepatitis B or C Virus

The pan-protein kinase C (PKC) inhibitor sotrastaurin (AEB071) is a novel immunosuppressant currently in phase II trials for immunosuppression after solid organ transplantation. Besides T-cell activation, PKC affects numerous cellular processes that are potentially important for the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV), major blood-borne pathogens prevalent in solid organ transplant recipients. This study uses state of the art virological assays to assess the direct, non-immune mediated effects of sotrastaurin on HBV and HCV. Most importantly, sotrastaurin had no pro-viral effect on either HBV or HCV. In the presence of high concentrations of sotrastaurin, well above those used clinically and close to levels where cytotoxic effects become detectable, there was a reduction of HCV and HBV replication. This reduction is very likely due to cytotoxic and/or anti-proliferative effects rather than direct anti-viral activity of the drug. Replication cycle stages other than genome replication such as viral cell entry and spread of HCV infection directly between adjacent cells was clearly unaffected by sotrastaurin. These data support the evaluation of sotrastaurin in HBV and/or HCV infected transplant recipients

Population screening for liver fibrosis: towards early diagnosis and intervention for chronic liver diseases

Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy non-invasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using non-invasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate -18 to 27%- in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression

Molecular therapy for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Conventional cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. Recently, a number of new drugs targeting molecular mechanisms involved in liver cell transformation have entered into clinical trials and led to encouraging results. In this review we summarise this data and point to a number of new compounds, which are currently being tested and can potentially broaden our therapeutic arsenal even further

IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study

Background and purpose: Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients. Methods: A total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records. Results: 2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G) 1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection. Conclusion: This large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle EastF. Hoffmann-La Roche Ltd, Basel, Switzerlan