Myeloperoxidase gene polymorphism predicts fibrosis severity in women with hepatitis C

Oxidative stress plays an important role on liver fibrosis progression in the course of hepatitis C virus (HCV) infection. Myeloperoxidase (MPO) is an enzyme released by neutrophils and macrophages, responsible for generating hypochlorous acid and reactive oxygen species (ROS) that may lead to liver injury in HCV infection. On the other hand, antioxidant enzymes such as manganese superoxide dismutase (SOD) controls ROS-mediated damage. The aim of the present study was to investigate the influence of MPO G-463A and SOD2 Ala16Val polymorphisms in the severity of liver fibrosis in individuals with chronic HCV infection. The present study included 270 patients with chronic HCV recruited from the Gastrohepatology Service of the Oswaldo Cruz University Hospital/Liver Institute of Pernambuco (Recife, Northeastern Brazil). All patients underwent liver biopsy, which was classified according METAVIR score. The SNPs were determined by real-time PCR. After multivariate analysis adjustment, the GG genotype of MPO and the presence of metabolic syndrome were independently associated with fibrosis severity in women (P = 0.025 OR 2.25 CI 1.10–4.59 and P = 0.032 OR 2.32 CI 1.07–5.01, respectively). The presence of the GG genotype seems to be a risk factor for fibrosis severity in women with HCV.     

IFNL cytokines do not modulate human or murine NK cell functions

The interferon-lambda (IFNL) cytokines have been shown to be important in HCV infection with SNPs in the IFNL3 gene associated with both natural and treatment induced viral clearance. We have recently shown that rs1299860 (an IFNL3 associated SNP) and an NK cell gene, KIR2DS3, synergised to increase the odds of chronic infection in a homogenous cohort of Irish women infected with HCV. To characterise a biological basis for the genetic synergy, we investigated for any evidence that IFNL cytokines regulate NK cell functions. Using a range of functional responses, we did not find any evidence of NK cell activation by IFNL3, IFNL1 or IFNL2 cytokines. Similar results were found using human and murine NK cells. In addition, and in contrast to our preliminary study, we did not find any evidence that IFNL cytokines inhibited NK cell cytokine production; thus, the biological basis for the genetic synergy remains to be discovered.     

Non-classical MHC-I human leukocyte antigen (HLA-G) in hepatotropic viral infections and in hepatocellular carcinoma

The human leukocyte antigen (HLA)-G is a “nonclassical” major histocompatibility complex (MHC) class Ib gene, located at chromosome 6, in the 6p21.3 region.     

Patients co-infected with hepatitis C virus (HCV) and human immunodeficiency virus recover genotype cross-reactive neutralising antibodies to HCV during antiretroviral therapy

When severely immunodeficient HIV/HCV co-infected patients are treated with antiretroviral therapy, it is important to know whether HCV-specific antibody responses recover and whether antibody profiles predict the occurrence of HCV-associated immune restoration disease (IRD). In 50 HIV/HCV co-infected patients, we found that antibody reactivity and titres of neutralising antibodies (nAb) to JFH-1 (HCV genotype 2a virus) increased over 48 weeks of therapy. Development of HCV IRD was associated with elevated reactivity to JFH-1 before and during the first 12 weeks of therapy. Individual analyses of HCV IRD and non-HCV IRD patients revealed a lack of an association between nAb responses and HCV viral loads. These results showed that increased HCV-specific antibody levels during therapy were associated with CD4⁺ T-cell recovery. Whilst genotype cross-reactive antibody responses may identify co-infected patients at risk of developing HCV IRD, neutralising antibodies to JFH-1 were not involved in suppression of HCV replication during therapy.     

Should IFN-γ, IL-17 and IL-2 be considered predictive biomarkers of acute rejection in liver and kidney transplant? Results of a multicentric study

Acute rejection (AR) remains a major challenge in organ transplantation, and there is a need for predictive biomarkers. In the present multicenter study, we prospectively examined a series of biomarkers in liver and kidney recipients. Intracellular expression of IFN-γ, IL-17 and IL-2 and IL-17 soluble production were evaluated both pre-transplantation and post-transplantation (1st and 2nd week, 1st, 2nd and 3rd month). 142 transplant patients (63 liver/79 kidney) were included in the study. Twenty-eight recipients (14 liver/14 kidney) developed AR. Pre- and post-transplantation intracellular expression of %IFN-γ⁺ in CD4⁺CD69⁺ and in CD8⁺CD69⁺ and soluble IL17 identified liver and kidney transplant patients at high risk of AR. Pre-transplantation, %IL-2⁺ in CD8⁺CD69⁺ also identified kidney patients at high risk. We constructed pre- and post-transplantation risk prediction models, based on a composite panel of biomarkers, which could provide the basis for future studies and will be a useful tool for the selection and adjustment of immunosuppressive treatments.     

Fatty liver disease

It is now widely accepted that fatty liver disease is one of the commonest causes of cirrhosis and liver cell cancer (even in the absence of cirrhosis), in its own right as well as being an important cofactor for the progression of other diseases e.g. viral hepatitis. While much work has been done on developing non-invasive techniques for assessing liver disease, the liver biopsy remains the benchmark against which these tests have to be validated as well as providing information that cannot be obtained in any other way. This review describes the histological features that alcoholic and non-alcoholic liver disease have in common (e.g. fatty change, ballooning and Mallory–Denk bodies) as well as identifying those that are more characteristic of each of them (e.g. nuclear vacuolation in non-alcoholic fatty liver disease and a florid fatty liver hepatitis in alcoholic fatty liver disease). Recent developments in the assessment of the degree of fatty change are described.