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The prompt initiation of antiviral therapy is essential in patients with chronic hepatitis B (CHB), especially when severe liver inflammation is detected. However, transcutaneous liver puncture, the gold standard for assessing liver inflammation, is invasive and its widespread application is limited. Therefore, there is an urgent need for more non‐invasive markers to predict liver inflammation. In our retrospective cross‐sectional study, which included 120 CHB patients and 31 healthy subjects, we observed a significant increase in serum chemokine C‐X‐C‐motif ligand 16 (CXCL16) in CHB patients compared to healthy controls (p <.001). Notably, patients with severe inflammation (Scheuer's grade G ≥ 3, n = 26) exhibited a substantial increase in serum CXCL16 compared to those with non‐severe inflammation (Scheuer's grade G < 3, n = 96) [(median, IQR), 0.42 (0.24–0.71) ng/mL vs. 1.01 (0.25–2.09) ng/mL, p <.001]. Furthermore, we developed a predictive model that combined CXCL16 with platelet count (PLT), alanine aminotransferase (ALT) and albumin (ALB) to accurately predict liver inflammation in CHB patients. This model was more effective than ALT alone in predicting liver inflammation (AUC, 0.92 vs. 0.81, p =.015). Additionally, using an HBV‐transduced mouse model, we demonstrated that blocking CXCL16 led to a reduction in liver inflammation and impaired infiltration and function of natural killer T (NKT) and natural killer (NK) cells. These findings suggest that CXCL16 is a promising non‐invasive biomarker of liver inflammation in CHB patients and may play a role in inducing liver inflammation via a NKT and NK cell pathway. [ABSTRACT FROM AUTHOR]

Liver necroinflammation is the indicator for treating patients with chronic hepatitis B (CHB) infection. However, there is no suitable non‐invasive index for diagnosing liver necroinflammation. This study aimed to create a non‐invasive index to predict liver necroinflammation in patients who lack clear‐cut clinical inflammation parameters. Patients who were hepatitis B e antigen (HBeAg)‐negative and underwent liver histological diagnosis, had a normal or minimally increased alanine aminotransferase (ALT) level were enrolled. Liver necroinflammation was defined as histological active index ≥4. A logistic regression model (LRM) was established based on the parameters independently associated with liver necroinflammation. Of all 550 patients, 36.73% had necroinflammation. In patients with an abnormal ALT level, the rate of necroinflammation was 52.49%. The area under the curve (AUC) of the ALT level for predicting necroinflammation was 0.655 (95% confidence interval [CI], 0.609‐0.702), and that of the HBV DNA level ≥2000 IU/mL combined with an abnormal ALT level was 0.618. By using the LRM, the AUC improved to 0.769 (95% CI, 0.723‐0.815) with a Youden index of 0.519 and diagnostic accuracy of 75.3%. The cutoff value ≥0.7 in the LRM had a specificity of 97.4% and positive predictive value of 85.0% for predicting necroinflammation. By using the cutoff value <0.15 in the LRM, the presence of necroinflammation could be excluded with a negative predictive value of 90.8%. This study indicated that the LRM can be used to effectively diagnose liver necroinflammation in HBeAg‐negative patients with CHB who have normal or minimally elevated ALT levels. [ABSTRACT FROM AUTHOR]

Summary: Identifying the degree of liver inflammation is critical for therapeutic judgement of patients with chronic hepatitis B (CHB). However, we lack indexes which can accurately predict significant liver inflammation in patients with CHB. This study aimed to develop a simple predictive index for liver inflammation in CHB using routine clinical parameters. A total of 519 patients with CHB who underwent liver biopsy were enrolled and randomly divided into training (n = 346) and validation cohorts (n = 173). Based on routine clinical parameters, gamma‐glutamyl transpeptidase (GGT; P = 0.031) and platelets (PLT; P < 0.001) were identified as independent predictors of significant inflammation by multivariable analysis in the training cohort. Accordingly, the GGT to PLT ratio (GPR) was developed to amplify the opposing effects for predicting liver inflammation. In the training cohort, the AUCs of GPR in predicting significant inflammation were 0.791 (95% CI: 0.742‐0.839), 0.783 (95% CI: 0.717‐0.849) and 0.791 (95% CI: 0.716‐0.867) in the entire patients with CHB, HBeAg‐positive CHB patients and HBeAg‐negative CHB patients, respectively. The diagnostic performance of GPR for significant inflammation was significantly superior to that of alanine aminotransferase (ALT), aspartate transaminase (AST) and GGT in all patients with CHB and HBeAg‐positive CHB patients, but was comparable with ALT, AST and GGT in HBeAg‐negative CHB patients. In the validation cohort, the diagnostic performance of GPR in assessing significant liver inflammation was also superior to other indexes in all patients with CHB and HBeAg‐positive CHB patients, but was comparable with GGT in HBeAg‐negative CHB patients. Thus, GPR can be a novel and simple index for predicting significant liver inflammation in CHB, especially for HBeAg‐positive CHB. [ABSTRACT FROM AUTHOR]

Hepatitis C infection (HCV) and menopause are associated with insulin resistance (IR), and IR accelerates HCV-induced liver disease. The relationship between menopause and IR has not been studied in this population. This study aimed to assess the impact of menopause on IR and metabolic syndrome in HCV. One hundred and three (69 men, 16 premenopausal, 18 postmenopausal women) noncirrhotic, nondiabetic HCV-infected adults underwent IR measurement via steady-state plasma glucose during a 240-min insulin suppression test. Metabolic syndrome was defined by at least three of five standard laboratory/clinical criteria. The patient characteristics were as follows: mean age 48 years, waist circumference 94.4 ± 12.4 cm and 37.9% Caucasian. SSPG was higher in postmenopausal than premenopausal women or men (mean difference 18, 95% CI −41 to 76 and 35, 95% CI −3 to 72 mg/dL; respectively). After adjusting for waist circumference, female gender, nonwhite race and triglycerides were positively associated and high-density lipoprotein negatively associated with steady-state plasma glucose. Compared to men, both pre- (Coef 48, 95% CI 12-84) and postmenopausal women (Coef 49, 95% CI 17-82) had higher steady-state plasma glucose. Compared to premenopausal women, men (OR 2.0, 95% CI 0.38-10.2) and postmenopausal women (OR 2.9, 95% CI 0.46-18.8) had higher odds of metabolic syndrome, but this was statistically nonsignificant. Both liver inflammation (OR 7.9) and nonwhite race (OR 6.9) were associated with metabolic syndrome. We conclude that women are at inc-reased risk for IR in HCV. There may also be an increased risk of metabolic syndrome postmenopause. Along with lifestyle modification and weight loss, women with metabolic abnormalities represent an especially at-risk group warranting HCV treatment to prevent adverse metabolic outcomes. [ABSTRACT FROM AUTHOR]

. Although hepatitis C (HCV) is associated with diabetes, few studies have examined pre-diabetes in this population. We aimed to evaluate factors associated with pre-diabetes in HCV-infected patients, including direct measurement of insulin action. Ninety-seven non-cirrhotic, non-diabetic and HCV-infected patients underwent clinical evaluation and oral glucose tolerance testing (OGTT). Insulin sensitivity was measured directly by steady-state plasma glucose (SSPG) concentration during insulin suppression test. Early phase and total insulin secretion were determined using OGTT. Rates of pre-diabetes were as follows: 21% impaired fasting glucose (IFG), 7% impaired glucose tolerance (IGT) and 9% combined IFG/IGT. Twelve percent of Caucasians, 50% of African Americans and 70% of Latinos had pre-diabetes ( P = 0.002). Patient characteristics among the glucose metabolism categories were similar except those with combined IFG/IGT had a higher body mass index (BMI) vs normal glucose tolerance (NGT) (30 vs 26 kg/m2, P = 0.007) and lower LDL vs NGT and IGT (74, 104 and 112 mg/dL, respectively, P ≤ 0.01). On multivariable analysis, non-Caucasian race (OR 23.1, P = 0.003), BMI (OR 3.4, P = 0.02) and greater liver inflammation (OR 7.9, P = 0.03) predicted IFG, whereas non-Caucasian race (OR 14.8, P = 0.01) and SSPG (OR 1.1 per 10 units, P = 0.01) predicted IGT. Early and total insulin secretion adjusted for the degree of insulin resistance was decreased in pre-diabetes compared with NGT ( P = 0.01 and P = 0.02, respectively). Pre-diabetes is highly prevalent among HCV-infected patients, and in some instances, coincides with host responses to the virus. In most cases, however, factors that are associated with pre-diabetes in HCV-infected patients are similar to those observed in the non-HCV population. [ABSTRACT FROM AUTHOR]