Liver fibrosis is a wound-healing response to liver injury caused by various factors such as viral hepatitis, alcohol abuse, and non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD). Though liver fibrosis is a reversible process, advanced liver fibrosis can result in cirrhosis, liver failure and hepatocellular carcinoma (HCC). It is important to assess fibrosis stage. Liver biopsy has been considered the gold standard for diagnosing liver fibrosis, however it is invasive and can cause serious complications [10, 11]. Transient elastography is a noninvasive tool for staging liver fibrosis, but the Fibroscan device is expensive. Furthermore the diagnostic accuracy of the method was poorer for significant fibrosis [12]. Recently GPR and GLR were reported to be predictors of liver fibrosis, cirrhosis and hepatocellular carcinoma [2,3,4,5,6,7,8,9]. However, it has remained unknown about the reference ranges of GPR and GLR in healthy adults.
In present study we measured the GPR and GLR in 2400 Chinese healthy adults. We found that the 95% reference range of GPR in normal male and female are 0.09~0.54 and 0.08~0.55, GLR are 4.55~29.64 and 3.52~23.08, respectively. The GPR and GLR were affected by sex and age.
GGT, a cell-membrane-bound protease, has long been regarded as a marker of liver disease [13]. Recent evidences have shown the association between GGT and cancer [14, 15], cardiovascular diseases, lung inflammation and neurological diseases [16]. Moreover it has been found that GPR and GLR are associated with significant liver fibrosis, cirrhosis and liver cancer [2,3,4,5,6,7,8,9]. There was significant positive correlation between GPR and fibrosis stage. The optimal cut-off value of GPR for significant fibrosis and cirrhosis was 0.32 and 0.56, respectively [2]. High GPR (> 0.23) was an independent risk factor for hepatocellular carcinoma development in chronic hepatitis patients [17]. High GLR was also an independent prognostic factor of hepatocellular carcinoma and intrahepatic cholangiocarcinoma [8, 9].
It has been demonstrated that there are significant male-female differences in the reference range for serum or plasma GGT [18], platelet and lymphocyte cell counts [19]. Furthermore, the geographic and ethnic difference of platelet counts was significant [20,21,22]. These studies showed that GPR and GLR varied significantly among sex, geographic region and race.
Though GPR and GLR were used widely in many diseases, the cut-off points for risk stratification varied in these studies, which were affected by the disease category, age, and race of patients. In the studies from West Africa a lower cut-off value of GPR for predicting significant liver fibrosis was suggested than that in China (0.32 vs. 0.448). The optimal cut-off value of GLR was 33.7 for predicting prognosis of intrahepatic cholangiocarcinoma while 56 for hepatocellular carcinoma [8, 9]. In present study, we found that GPR and GLR varied with age and sex, which suggested that factors affecting GPR and GLR should be considered when the cut-off values for risk stratification were determined.
There are a few limitations in present study. First, the study is a retrospective study and routine blood analyses were collected from healthy population in the checkup center of hospital, the effects of high alcohol consumption and use of enzyme-inducing drugs on GGT can not be excluded [18]. Secondly, owing to the geographic and ethnic difference of platelet counts [20,21,22], the reference range of GPR in healthy population from Han population in Chaoshan region may be different from other races in local region or other regions in China.
In summary, we found that the reference ranges of GPR and GLR in male were different from in female from Chaoshan region in South China. The GPR and GLR varied with age and sex.