To investigate the Hepatitis C virus (HCV) mediated disturbance of the intestinal environment in detail, a research group comprising Professor Yasuhito Tanaka of Kumamoto University Graduate School of Life Sciences, Professor Takako Inoue of Nagoya City University Graduate School of Medical Sciences, and Professor Jiro Nakayama of Kyushu University Faculty of Agriculture analyzed the balance of fecal bile acid, a metabolite, and clarified its characteristics.
More than 100 trillion bacteria live in the human gut. Together, they constitute the intestinal flora ecosystem, which is involved in maintaining health. Intestinal bacteria synthesize a variety of metabolites from compounds supplied in the diet or synthesized in the body. Some of these metabolites are absorbed from the intestine and circulate throughout the body via the bloodstream. Metabolites produced by disturbed intestinal flora have been related to a variety of systemic diseases.
Remarkable progress has been made in the treatment of hepatitis C, enabling the elimination of HCV using a combination of orally administered, direct-acting antiviral agents. However, in advanced stages of hepatitis C, when patients have developed decompensated liver cirrhosis, countermeasures for complications, such as hyperammonemia and edema, become necessary during treatment. Since the intestine is connected to the liver through the bloodstream, in decompensated cirrhosis, attempts have sought to improve the intestinal flora using antibiotics for prevention and treatment of hyperammonemia.
The research group analyzed the intestinal flora of patients at different stages of infection reported in previous studies. Changes in the intestinal flora due to HCV were evident early in the disease. As the disease progressed, the number of bacterial species comprising the intestinal flora decreased and the number of streptococci, which are indigenous in the oral cavity, increased. As a consequence, the intestinal flora was disrupted. The authors predicted that the intestinal flora was disturbed as the disease progressed and that the bacteria that grew abnormally in the intestine increased the production of ammonia. In this study, to investigate the disturbance of the intestinal environment caused by hepatitis C in detail, the balance of fecal bile acid, a metabolite, was analyzed and its characteristics were investigated.
Stool samples were collected from 23 healthy individuals and 100 patients with hepatitis C at different stages [9 HCV carriers with persistently normal alanine aminotransferase (PNALT), 60 chronic hepatitis patients, 17 patients with cirrhosis, and 14 liver cancer patients]. Fecal bile acids were analyzed using liquid chromatography-mass spectrometry and the composition of stool from these various groups was compared. The balance of bile acids in the feces changed in the early stage of the disease. The level of one bile acid (deoxycholic acid) decreased. This feature was found to be more pronounced as the disease progressed (PNALT, chronic hepatitis, cirrhosis, and liver cancer).
"The current problem with hepatitis C is that some individuals will develop liver cancer or cirrhosis and these conditions will not be alleviated after elimination of the virus," Dr. Inoue stated. "Taking into account environmental factors, such as alcohol, obesity, and diabetes mellitus, for each case, the future challenge will be to identify individuals at high risk of disease deterioration and possibly prevent this by characterizing changes in the intestinal bacteria and fecal bile acid balance, genetic factors, and gene expression patterns."
■ Disturbance of the intestinal flora refers to a decrease in bacterial species diversity (simplification) due to abnormalities in the bacterial species that constitute the flora, an abnormal increase in bacterial species that should be present at low levels, and a decrease in bacterial species that should be present at high levels.
■ Decompensated cirrhosis refers to a condition in which the necessary liver function is lost due to severe cirrhosis. Various complications (symptoms) appear.
■ HCV carrier with persistently normal alanine aminotransferase (PNALT): A state in which the patient is infected with HCV, but the ALT value, a measure of liver function, is continuously below the standard value (normal).
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