Gene Expression of Advanced Cirrhosis
HIV and hepatitis C and liver disease are all connected in a complex web of cause and effect. HIV, which by the way means Human Immunodeficiency Virus, weakens the immune system, making it easier for other infections like hepatitis C (HCV) to take hold. In turn, HCV can lead to liver disease and cirrhosis, which can cause serious health problems. Here’s a brief explanation: Chronic liver disease can lead to scarring of the liver in the final stage. If the liver is largely scarred, this is called cirrhosis.
The worst thing about the combination of the two infectious diseases: The body’s ability to fight off HCV is also weakened by HIV. The two viruses combined can lead to a much more severe and rapid progression of liver damage. It’s like a deadly game of dominoes, where one virus sets off a chain reaction that leads to increasingly dire consequences for the body. But with early detection, treatment and management, it is possible to prevent the progression of both HIV and HCV.
The relationship between HIV, HCV and liver disease
Let’s look a little deeper: HIV and HCV share transmission routes and both cause chronic infections, and coinfection of the two is common. Patients carrying both viruses develop cirrhosis more rapidly than patients with HCV alone. In addition, liver-related problems and deaths occur more frequently. What happens in fibrosis of the liver? Chronic hepatitis C can lead to significant changes in the liver, including inflammation and coagulopathy. Furthermore, after HCV eradication, the burden of liver cirrhosis remains substantial for a long time.
We can use transient elastography (fibroscan) to assess the degree of fibrosis and also use liquid biopsies, such as a blood sample, to identify biomarkers of infection. Yet we still know too little about what happens in the body with HIV and HCV. Now, researchers have set out to analyze the gene expression profile of peripheral blood mononuclear cells (PBMCs) in HIV/HCV-coinfected patients with varying degrees of fibrosis/cirrhosis. Peripheral blood, to briefly touch on this, is the blood flowing in the veins, which contains almost all red blood cells (erythrocytes) and platelets (thrombocytes), as well as numerous white blood cells (leukocytes). The aim of the study was to identify a gene expression signature for advanced cirrhosis at high risk for clinically significant portal hypertension.
We aimed to analyze the gene expression profile of PBMCs in HIV/HCV coinfected patients with different degrees of fibrosis/cirrhosis, measured by LSM using transient elastography, to identify a gene expression signature of advanced cirrhosis with high risk for CSPH in this population group.
Revealing the gene signature of advanced cirrhosis in HIV/HCV coinfection
The study was conducted in 68 patients with HIV and HCV co-infection. Based on measured liver stiffness, patients were divided into three groups:
Patients without cirrhosis,
patients with cirrhosis,
and patients with advanced cirrhosis and high risk for portal hypertension (high blood pressure in the portal vein system).
The researchers used RNA sequencing to analyze the gene expression of the patients. It was found that there were no differences in the respective fibrosis stages. However, the study but found a set of 60 significant differentially expressed transcripts when groups with extreme LSM values were compared, as differences were maximized.
The researchers analyzed these 60 transcripts to distinguish advanced cirrhosis at high risk for clinically significant portal hypertension. Overall, this group of transcripts was able to correctly classify patients with advanced cirrhosis at high risk for clinically significant portal hypertension. Eight of these transcripts showed good independent discriminatory performance. Five of these transcripts were also positively associated with liver stiffness. Some of these overexpressed genes have been previously observed in hepatocellular carcinoma. In conclusion assessing the expression of PBMCs is a good option because it may resemble some molecular mechanisms associated with HCV in the liver and supports the systemic nature of inflammatory signs.