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Background and AimsPatients with chronic hepatitis B virus infection (CBI) with concurrent nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common in clinical practice, and it is quite important to identify the etiology when hepatitis occurs. A noninvasive diagnostic model was constructed to identify patients who need antihepatitis B virus (HBV) therapies [histologic activity index (HAI) ≥ 4] in patients with CBI with concurrent NAFLD by analyzing clinical routine parameters.Approach and ResultsIn total, 303 out of 502 patients with CBI with concurrent NAFLD proven by liver biopsy from January 2017 to December 2020 in the Tianjin Second People's Hospital were enrolled and they were divided into the HBV-related inflammation (HBV-I) group (HAI ≥ 4,176 cases) and the non-HBV-I group (HAI < 4,127 cases) according to hepatic pathology. The univariate analysis and multivariate logistic regression analysis were performed on the two groups of patients, and then the HBV-I model of patients with CBI with concurrent NAFLD was constructed. The areas under receiver operating characteristic curves (AUROCs) were used to evaluate the parameters of the regression formula. Another 115 patients with CBI with concurrent NAFLD proven by liver biopsy from January 2021 to January 2022 were enrolled as the validation group. There were some statistical differences in demographic data, biochemical indicators, immune function, thyroid function, virology indicator, and blood routine indicators between the two groups (P < 0.05) and liver stiffness measurement (LSM) in the HBV-I group was significantly higher than those in the non-HBV-I group (P < 0.05). While controlled attenuation parameters (CAP) in the HBV-I group were lower than those in the non-HBV-I group (P < 0.05); (2) We developed a novel model by logistic regression analysis: HBV-I = −0.020 × CAP + 0.424 × LSM + 0.376 × lg (HBV DNA) + 0.049 × aspartate aminotransferase (AST) and the accuracy rate was 82.5%. The area under the receiver operating characteristic (AUROC) is 0.907, the cutoff value is 0.671, the sensitivity is 89.30%, the specificity is 77.80%, the positive predictive value is 90.34%, and the negative predictive value is 81.89%; (3) The AUROC of HBV-I in the validation group was 0.871 and the overall accuracy rate is 86.96%.ConclusionOur novel model HBV-I [combining CAP, LSM, lg (HBV DNA), and AST] shows promising utility for predicting HBV-I in patients with CBI with concurrent NAFLD with high sensitivity, accuracy, and repeatability, which may contribute to clinical application.

LINKED CONTENT This article is linked to Myojin.et al's paper. To view this article, visit https://doi.org/10.1111/apt.16691 and https://doi.org/10.1111/apt.16862.

To the editor, We read with great interest the article published in Hepatology by Wang et al. [1] This study developed a novel, easy-to-use nomogram model to predict biochemical nonresolution (BNR) in patients with chronic druginduced liver injury (DILI), named BNR-6, and patients with significant hepatocellular inflammation are at greater risk of BNR. This is a large, retrospective, and multicenter cohort study, which is significant for the guiding of clinical practice, because it is estimated [2] that China is the country with the largest disease burden of DILI. However, there are issues requiring further clarification.First, with regard to the use of the Roussel Uclaf Causality Assessment Method (RUCAM) score (only >6 points, probably), the investigators failed to completely exclude other liver diseases given that not all patients underwent a liver biopsy first. In addition, there are currently no exact diagnostic criteria for chronic DILI, and drugs could also induce fatty liver or autoimmune hepatitis (AIH) [3] ; so, we believe that the investigators should describe the type of hepatic histopathology in detail.Second, the meaning of liver biochemistry abnormalities varies widely. [4] The problem is, however, that not only could liver inflammation cause an elevation of liver enzymes, but also other types of organ damage, especially injury to the myocardium and skeletal muscle. [3] Thus, it would be better to explain this clearly in the article. Furthermore, even if patients do have liver inflammation after 1 year, it is necessary to carry out another liver biopsy to determine whether the cause is still chronic DILI rather than other causes, because DILI can induce an autoimmune liver disease such as AIH, which is hard to detect without hepatic histopathology. In addition, the prevalence of NAFLD in China is ~29.88%, so the case of combining with NAFLD or the progression of NAFLD likely occurs in the DILI recovery period, and a liver biopsy is also necessary to determine or exclude an association with NASH. [3,5] Hence, the definition of BNR should be thoughtfully discussed to obtain the best clinical value.