Serum Asprosin Tracks Sex, Not Fibrosis, in Chronic Hepatitis C

Non-fasting serum asprosin levels in people with chronic hepatitis C virus infection differ between the sexes but do not reflect the severity of liver fibrosis, cirrhosis, diabetes, hepatic steatosis, or virological features, according to a prospective single-center study published in the Egyptian Liver Journal. The hormone-like adipokine, produced mainly by fat tissue, remained stable throughout direct-acting antiviral therapy and at sustained virological response twelve weeks after treatment ended. Instead of tracking liver disease, the protein showed consistent positive correlations with circulating phospholipids, particularly phosphatidylinositol, both before and after viral cure, pointing toward a possible role in lipid metabolism that the authors say merits further investigation.

Asprosin is generated when the protease furin cleaves profibrillin-1, releasing a 140-amino-acid C-terminal fragment alongside mature fibrillin-1. Although adipose tissue is its primary source, the molecule is also expressed in the liver and kidney, though immunohistochemical studies have failed to detect it in hepatocytes in liver samples from healthy controls and patients with hepatitis B or C. Physiologically, asprosin regulates appetite and maintains blood glucose during fasting by stimulating hepatic glucose production. Pathologically elevated levels contribute to hyperinsulinemia and the development of metabolic and cardiovascular disease, and the protein has been shown to promote lipid accumulation in the liver and induce hepatic inflammation by activating nuclear factor kappa B. One study in rats on a high-fat diet, however, reported protective effects on liver health, underscoring that its role in liver disease remains contested.

Previous research had given reason to suspect a connection with liver disease severity. Serum asprosin rises with body weight, averaging around 17 nanograms per milliliter in normal-weight individuals and nearly 40 nanograms per milliliter in obese subjects, and it correlates positively with the controlled attenuation parameter, a FibroScan measure of liver steatosis, across weight categories. Elevated levels have been reported in metabolic liver steatosis, in type 2 diabetes, and in diabetic patients with metabolic dysfunction-associated fatty liver disease compared with diabetic patients without it. On the other hand, one study found no difference between healthy controls and patients with chronic liver disease of various etiologies, while noting that levels decreased significantly in cirrhosis and correlated negatively with liver stiffness among non-cirrhotic patients. Because asprosin is strongly induced by fasting, sampling conditions may matter considerably when interpreting such findings.

The new study set out to determine whether non-fasting serum asprosin reflects fibrosis stage before viral cure, and whether it varies with diabetes, hepatic steatosis, sex, and obesity status before therapy and after sustained virological response. Researchers at a German university hospital enrolled treatment-naïve adults with chronic HCV infection eligible for direct-acting antiviral therapy between September 2014 and February 2017. Only compensated cirrhosis was permitted, and patients co-infected with hepatitis B or HIV were excluded. Paired serum specimens were obtained from 195 of 217 enrolled patients at baseline, during treatment, and at sustained virological response. Because serum volumes varied across time points, the present analysis drew on samples from 96 treatment-naïve patients at baseline, 107 patients after four weeks of therapy, 91 patients at twelve weeks, and 85 patients at sustained virological response.

Blood was drawn during the day without fasting, and asprosin was measured in duplicate with a commercial enzyme-linked immunosorbent assay with a detection range of 0.156 to 10 nanograms per milliliter. Fibrosis was staged non-invasively by shear-wave elastography performed on three ultrasound systems with eight to twelve valid measurements per participant, and by the fibrosis-4 score, which combines routine laboratory parameters with age. Cirrhosis was identified through a multifactorial approach integrating sonographic characteristics with laboratory parameters, and liver biopsy was reserved for diagnostically uncertain cases. Hepatic steatosis was assessed by the conventional sonographic criterion of increased liver echogenicity relative to the renal cortex, a feature with roughly 64 percent sensitivity and 97 percent specificity, rising to about 91 percent when steatosis exceeds 30 percent, since quantitative attenuation techniques were not available at the center during the study period.

Levels correlated negatively with age. Across the whole cohort, asprosin showed no significant relationship with body mass index, and levels did not differ significantly among normal-weight, overweight, and obese patients. A sex-stratified analysis, however, revealed an asymmetry: in men, obese patients had higher asprosin levels than normal-weight and overweight individuals, with the latter difference reaching statistical significance, whereas no such pattern appeared among women. When obese patients were excluded, women exhibited higher levels than men, indicating a sex-specific upregulation that emerges only in the non-obese range.

Metabolic comorbidities left the adipokine untouched. Levels did not differ between the 16 diabetics and non-diabetics, nor between the 46 patients with and 50 without ultrasound-detected liver steatosis, and these null findings held among patients with a body mass index at or below 30 and in sex-specific analyses. Fibrosis staging was equally uninformative. Shear-wave elastography classified 30 patients as having no fibrosis, 12 as F1, 2 as F2, 15 as F3, and 37 as F4 fibrosis or cirrhosis, with no differences in asprosin across these stages. The fibrosis-4 score grouped 29 patients as free of fibrosis, 21 with intermediate values, and 46 with fibrosis, again with similar levels. The 37 patients with ultrasound-diagnosed cirrhosis had asprosin concentrations comparable to those without, and all of these null results persisted after excluding obese patients. Asprosin was also unrelated to liver function markers, the Model for End-Stage Liver Disease score, HCV viral load, and genotype, although it correlated negatively with creatinine and positively with glomerular filtration rate before therapy.

Direct-acting antiviral therapy eliminated HCV in the 59-patient subcohort followed longitudinally, with aminotransferases falling, procalcitonin declining, albumin improving, and LDL rising at sustained virological response. Yet asprosin remained flat across baseline, four weeks, twelve weeks of therapy, and SVR12, with reported medians of 1.38, and 1.30 nanograms per milliliter at twelve weeks, and 1.32 nanograms per milliliter at SVR12, a stability that persisted after excluding obese patients. The authors argue this argues against asprosin as a marker of treatment response or liver disease severity. Sex differences did surface at later time points: at therapy end, the 40 women had higher levels than the 51 men, and at SVR12 the difference among 38 women and 47 men was nearly significant. Notably, the association between obesity and higher asprosin in men was no longer apparent at SVR12, suggesting viral clearance may attenuate or mask the sex-specific pattern, though the small number of obese patients means this observation requires confirmation in larger cohorts.

The most consistent signal concerned lipids. Asprosin did not correlate with LDL before therapy, but correlated positively with LDL at the end of treatment and at SVR12, associations that survived exclusion of cirrhotic patients, who have characteristically low LDL, and of obese patients. At therapy end, asprosin correlated with phosphatidylcholine, ceramides, sphingomyelin, phosphatidylinositol, total cholesterol, and triglycerides, with the strongest relationship for phosphatidylinositol, where the coefficient of determination indicated that asprosin explained about 36 percent of its variance, compared with 25 percent for phosphatidylcholine, 13 percent for ceramides, 11 percent for cholesterol, and 9 percent for LDL. Phosphatidylinositol also predicted asprosin levels in untreated and treated patients in regression models. The authors note that the absence of the LDL association before therapy may reflect the well-documented reduction of LDL during active HCV infection and its normalization after viral eradication, but they caution that these correlations do not imply causality.

The authors acknowledge several limitations. The observational design precludes causal inference, glucose metabolism measures were not documented, and the absence of a healthy control group, the use of non-fasting rather than fasting samples, and the single-center design may limit generalizability. They also contrast their findings with a recent study that used fasting samples and reported lower asprosin in cirrhosis, proposing that the fasting-related rise in asprosin may be impaired in cirrhosis even though non-fasting levels remain unchanged, an interpretation they urge be made cautiously. Overall, the study concludes that serum asprosin in chronic hepatitis C shows sex-specific differences but does not track diabetes, hepatic steatosis, fibrosis, cirrhosis, or virological features, and that its positive relationship with circulating phospholipids before and after treatment points to a potential role in lipid homeostasis that warrants further investigation.

Subject of Research: Serum asprosin levels in chronic hepatitis C infection in relation to sex, fibrosis, metabolic comorbidities and antiviral therapy

Article Title: Preliminary evidence that non-fasting serum asprosin differs by sex but not by fibrosis stage in chronic hepatitis C

Article References: Peschel, G., Weigand, K., Müller, M., & Buechler, C. (2026). Preliminary evidence that non-fasting serum asprosin differs by sex but not by fibrosis stage in chronic hepatitis C. Egyptian Liver Journal, 16(1), Article 81. https://doi.org/10.1186/s43066-026-00567-8

Image Credits: AI Generated

DOI: 10.1186/s43066-026-00567-8

Keywords: asprosin, chronic hepatitis C, liver fibrosis, cirrhosis, adipokine, direct-acting antivirals, phospholipids, shear-wave elastography, FIB-4 score, hepatic steatosis, sex differences, lipid metabolism