This study aims to explore the effects of various hepatic steatosis conditions on histological outcomes in patients with significant inflammation and fibrosis in chronic hepatitis B (CHB) and analyze their impact on HBV virological suppression outcomes and biochemical improvement.

This retrospective study included 219 chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogues therapy. Each of these patients underwent two liver biopsies. Patients were categorized into four groups based on hepatic steatosis status: sustained non-hepatic steatosis (n = 118), new-onset hepatic steatosis (n = 33), sustained hepatic steatosis (n = 37), and disappeared hepatic steatosis (n = 31). We compared the liver biochemical parameters and histological changes before and after treatment. Logistic regression analysis was performed to evaluate characteristics associated with the improvement of significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2), and the persistence of hepatic steatosis.

After treatment, the sustained non-steatosis group exhibited the highest rate of improvement in baseline significant inflammation (75.31%), while the sustained steatosis group had the lowest (42.31%, p = 0.008). The sustained steatosis group also had the highest rate of inflammation progression (15.38%, p = 0.020) and was identified as a risk factor for inadequate baseline inflammation improvement (p = 0.006, OR = 0.244, 95% CI 0.090-0.665). In terms of baseline significant liver fibrosis improvement, the sustained non-hepatic steatosis group showed the highest improvement rate (67.14%), while the sustained hepatic steatosis group had the lowest (28.00%, p = 0.006). The new-onset steatosis group had the highest rate of liver fibrosis progression (15.00%, p = 0.027), and sustained hepatic steatosis was a risk factor for poor baseline fibrosis improvement (p = 0.001, OR = 0.180, 95% CI 0.064-0.507). Furthermore, the sustained hepatic steatosis group showed the smallest decrease in liver enzyme markers ALT, GGT, and ALP post-treatment, with reductions of 22.11% (p = 0.023), 13.86% (p = 0.003), and 1.98% (p = 0.025), respectively. Logistic regression analysis revealed that high baseline BMI and LDL-C levels were significantly associated with persistent fatty liver, with high BMI (p = 0.042, OR = 1.109, 95% CI 1.004-1.226) and high LDL-C (p < 0.001, OR = 2.570, 95% CI 1.524-4.332).

In CHB patients with significant inflammation and fibrosis, the persistence of hepatic steatosis during antiviral treatment may impede the improvement of inflammation and fibrosis, leading to disease progression and biochemical abnormalities.

We evaluated the diagnostic accuracy of various international guideline criteria for identifying HBeAg-positive chronic HBV infection patients with no significant liver disease. A total of 1108 HBeAg-positive CHB patients were retrospectively enrolled. The guidelines assessed included those from the European Association for the Study of the Liver (EASL) 2017, the American Association for the Study of the Liver Disease (AASLD) 2018, the Asian Pacific Association for the Study of the Liver (APASL) 2015 and the Chinese Society of Hepatology (CSH) 2022. The CSH criteria demonstrated a higher proportion of patients with G0-1 and S0-1 (82.9%) compared to the EASL (75.9%), AASLD (75.3%) and APASL groups (58.8%). Additionally, the CSH criteria exhibited a significantly higher predictive value (AUC 0.782, 95% CI 0.754-0.809) than the EASL (AUC 0.765, 95% CI 0.737-0.793), AASLD (AUC 0.749, 95% CI 0.720-0.778) and APASL (AUC 0.720, 95% CI 0.690-0.750) criteria for identifying G0-1 and S0-1. Adding quantitative HBsAg levels (> 104 IU/mL) to the EASL, AASLD and APASL criteria improved diagnostic performance. Consequently, the CSH guideline thresholds showed higher accuracy in identifying Chinese HBeAg-positive patients with no significant liver disease compared to EASL, AASLD and APASL criteria, emphasising the importance of considering quantitative HBsAg in the evaluation of HBeAg-positive chronic HBV infection.

Normal serum transaminases and immunoglobulin G (IgG) levels are surrogate markers for hepatic histologic disease activity in autoimmune hepatitis (AIH). This study aimed to evaluate liver inflammation in patients with AIH with normal serum alanine aminotransferase (ALT) and IgG levels.

Two hundred and five AIH patients who underwent liver biopsy in four medical centers were included. Logistic regression analysis was used to identify risk factors associated with advanced inflammation.

One hundred and thirty-one (63.9 %) AIH patients had advanced liver inflammation, and 108 (52.7 %) patients had advanced liver fibrosis. 60.0 % of patients with normal ALT and 51.7 % of patients with normal ALT and IgG had advanced inflammation. However, 76.7 % and 35.0 % of patients with or without advanced fibrosis with normal ALT had advanced inflammation, while the corresponding proportions of advanced inflammation were 78.6 % and 26.7 % in patients with normal ALT and IgG, respectively. Moreover, 81.0 % and 44.8 % of patients with and without cirrhosis with normal ALT had advanced inflammation, while the corresponding proportions were 83.3 % and 29.4 % in patients with normal ALT and IgG, respectively. Red cell distribution width (OR = 1.325, 95%CI 1.045-1.681, P = 0.020) and PT (OR = 1.514, 95%CI 1.138-2.014, P = 0.004) were independent factors associated with advanced inflammation.

High proportion of advanced inflammation was found in AIH patients with normal ALT and IgG levels despite without advanced fibrosis. Although using non-invasive methods may contribute to rule out liver fibrosis in AIH patients with normal ALT and IgG levels, liver biopsy is encouraged to assess liver inflammation.

The predominantly progressive, indeterminate, and predominantly regressive (P-I-R) classification extends beyond staging and provides information on dynamic changes of liver fibrosis. However, the prognostic implication of P-I-R classification is not elucidated. Therefore, in the present research, we investigated the utility of P-I-R classification in predicting the on-treatment clinical outcomes.

In an extension study on a randomized controlled trial, we originally enrolled 1000 patients with chronic hepatitis B and biopsy-proven histological significant fibrosis, and treated them for more than 7 years with entecavir-based therapy. Among the 727 patients with a second biopsy at treatment week 72, we compared P-I-R classification and Ishak score changes in 646 patients with adequate liver sections for the histological evaluation. Progressive, indeterminate, and regressive cases were observed in 70%, 17%, and 13% of patients before treatments and 20%, 14%, and 64% after 72-week treatment, respectively, which could further differentiate the histological outcomes of patients with stable Ishak scores. The 7-year cumulative incidence of HCC was 1.5% for the regressive cases, 4.3% for the indeterminate cases, and 22.8% for the progressive cases ( p <0.001). After adjusting for age, treatment regimen, platelet counts, cirrhosis, Ishak fibrosis score changes, and Laennec staging, the posttreatment progressive had a HR of 17.77 (vs. posttreatment regressive; 95% CI: 5.55-56.88) for the incidence of liver-related events (decompensation, HCC, and death/liver transplantation).

The P-I-R classification can be a meaningful complement to the Ishak fibrosis score not only in evaluating the histological changes but also in predicting the clinical outcomes.

The present letter to the editor is related to the review with the title "Past, present, and future of long-term treatment for hepatitis B virus." Chronic hepatitis B (CHB) represents an important and pressing public health concern. Timely identification and effective antiviral therapy hold the potential to reduce liver-related mortality attributable to chronic infection with hepatitis B virus (HBV) substantially. However, the current global treatment rates for CHB remain conspicuously low, with the excessively stringent treatment criteria advocated by national CHB guidelines being a contributing factor to these low rates. Nevertheless, recent strides in comprehending this malady and the emergence of novel antiviral agents prompt the imperative re-evaluation of treatment standards to extend the sphere of potential beneficiaries. An impending need arises for a novel paradigm for the classification of patients with CHB, the expansion of antiviral treatment eligibility for HBV-infected individuals, and even the streamlining of the diagnostic process for CHB to amplify cost-effectiveness and augment survival prospects.

This study aimed to investigate the role of immunocompetence in chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) levels and negative hepatitis B e antigen (HBeAg) in the risk assessments of the progression of liver fibrosis.

We collected the clinical data of 57 patients with CHB, with normal ALT levels and negative HBeAg from December 2020 to December 2022. With hepatitis B virus (HBV) DNA > 20 IU/mL and ALT ≤ 40 U/L, these patients had never undergone antiviral therapy. The levels of CD4+ , CD4+ CD25+ , CD8+ , and CD4+ CD25+ CD127LOW regulatory T cells (Tregs) in the patients were detected using flow cytometry; the liver stiffness measurement (LSM) values of the patients were detected using Fibroscan.

There was a statistically significant difference between the levels of fibrosis-4 (FIB-4) and hepatitis B surface antigen (HBsAg) when the cutoff point was HBsAg ≥ 1500 (p < .001). FIB-4 was negatively correlated with HBsAg (R = -0.291, p = .028) and positively correlated with age (R = 0.787, p < .001). LSM was negatively correlated with Treg but this correlation was not statistically significant (p > .05). Findings based on the analysis using logistic regression were as follows: (i) age was the independent risk factor when FIB-4 was used as the indicator for assessing liver fibrosis; (ii) Treg was the independent risk factor when LSM was used as the indicator for assessing liver fibrosis. When Treg was used to predict liver fibrosis, the cutoff value, diagnostic efficacy, area under the receiver operating characteristic (ROC) curve, and p value of the ROC curve were 6.875, 0.641, 0.84, and .027, respectively.

Age and Treg are independent risk factors for progressive liver fibrosis. The cutoff value of Treg > 6.81 indicates the need for timely antiviral treatment and can serve as an indicator for evaluating liver fibrosis.

The upper limits of normal (ULNs) for alanine aminotransferase (ALT) are different among international guidelines for chronic hepatitis B (CHB). We aimed to investigate the proportion of significant histological disease in Asian patients with CHB with detectable hepatitis B virus (HBV) DNA under diverse ALT ULNs.

Consecutive patients with CHB and detectable HBV DNA who underwent liver biopsy were retrospectively included from four tertiary hospitals. Above grade 2 inflammation and stage 2 fibrosis were defined as significant inflammation and significant fibrosis, respectively. Significant histological disease was defined as above grade 2 inflammation or stage 2 fibrosis.

Among the 414 patients with detectable HBV DNA and normal ALT, the proportion of those with significant histological disease was lower (59.7%) according to the ULN for ALT at 30/19 U/L (male/female), while the corresponding proportions were 66.7% and 62.3% according to the ULNs of 40 U/L and 35/25 U/L (male/female), respectively. In patients with detectable HBV DNA and normal ALT levels without significant fibrosis, the proportions of significant inflammation were comparable among different ULNs of ALT at 40 U/L (30.7%), 35/25 U/L (27.3%) and 30/19 U/L (25.0%). The proportion of significant histological disease was significantly lower in patients with normal ALT for 2 determinations at least 6 months apart compared to patients with normal ALT once.

Although a more stringent ALT ULN may reduce the risk of the presence of significant histological disease in patients with detectable HBV DNA, the rates of significant histological disease remain high. Persistently normal ALT levels are more important for excluding patients with CHB with a high probability of significant histological disease.

To investigate the immune status of Chinese chronic hepatitis B (CHB) pregnant women and their clinical characteristics.

About 1544 CHB pregnant women without antiviral therapy from 2013 to 2018 were selected from the hospital records. The definition of immune status is based on American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidance, and those who did not meet any criteria of the immune status were referred to in the gray zones (GZ).

There were 284 patients in the immune-tolerance phase, 72 patients in the HBeAg-positive immune active phase, 553 patients in the inactive phase, 61 patients in the HBeAg-negative immune active phase. Of note, 574 (37.18%) patients did not fit into any of the above phases were defined as the GZ. Patients with elevated ALT had a higher rate of intrahepatic cholestasis of pregnancy (ICP). Mother to child HBV transmission was rare (only two cases) and occurred in mothers in the immune-tolerant phase.

Our data showed that more than one-third of CHB pregnant women were classified into the GZ. In standard stages, advanced age is associated with HBeAg-negative and a higher cesarean rate in the inactive phase. The incidence of ICP was higher in immune active phases, including GB and GD. The probability of mother-to-child transmission in gray zones is low.

Concurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic HBV infection. But the impact of fatty liver on the histologic progression of HBV infection remains controversial.

Consecutive HBV-infected patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G ≥ 2), significant fibrosis (S ≥ 2) and advanced fibrosis (S ≥ 3).

Among the 871 HBV-infected patients, hepatic steatosis was prevalent in 255 patients (29.28%). Significant liver inflammation was present in 461 patients (52.93%). Significant fibrosis was observed in 527 patients (60.51%), while advanced liver fibrosis was observed in 171 patients (19.63%). Patients with concomitant NAFLD were more likely to have significant liver inflammation and advanced fibrosis. Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict the development of fibrosis. Especially, in HBV-infected patients with persistent normal ALT (immune tolerant and inactive carrier phase), the presence of significant liver inflammation was higher in NAFLD than those without NAFLD. The prevalence of advanced liver fibrosis was higher in NAFLD than non-NAFLD only in the immune tolerant phase, while NAFLD did not increase fibrosis burden in other stages of HBV infection. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760.

NAFLD is independently associated with significant liver inflammation, and increases the burden of advanced liver fibrosis in HBV-infected patients. The influence of NAFLD on the degree of liver inflammation and fibrosis is different in distinct clinical phases of chronic HBV infection.

The clinical and histological features of chronic hepatitis B (CHB) patients who fall into the "grey zone (GZ)" and do not fit into conventional natural phases are unclear.

To explore the impact of varying the threshold of alanine aminotransferase (ALT) levels in identifying significant liver injury among GZ patients.

This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy. The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines. GZ CHB patients were classified into four groups: GZ-A (HBeAg positive, normal ALT levels, and HBV DNA ≤ 107 IU/mL), GZ-B (HBeAg positive, elevated ALT levels, and HBV DNA < 104 or > 107 IU/mL), GZ-C (HBeAg negative, normal ALT levels, and HBV DNA ≥ 2000 IU/mL), and GZ-D (HBeAg negative, elevated ALT levels, and HBV DNA ≤ 2000 IU/mL). Significant hepatic injury (SHI) was defined as the presence of notable liver inflammation (≥ G2) and/or significant fibrosis (≥ S2).

The results showed that 50.22% of patients were classified as GZ, and 63.7% of GZ patients developed SHI. The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria (35 U/L for men and 25 U/L for women) can more accurately identify patients with significant liver damage in the GZ phases. In total, the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 64.86% [(221 + 294)/794]. When we lowered the ALT treatment threshold to the new criteria (30 U/L for men and 19 U/L for women), the same outcome was revealed, and the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 75.44% [(401 + 198)/794]. Additionally, the proportion of SHI was 49.1% in patients under 30 years old and increased to 55.3% in patients over 30 years old (P = 0.136).

These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.

In recent years, liver experts have conducted in-depth discussions on whether it is necessary to expand the indication of antiviral therapy for patients with chronic hepatitis B (CHB). Currently, the guidelines are too strict in treating CHB patients. With the deepening understanding of the natural history of hepatitis B virus infection, there is more and more evidence challenging the view that there is no disease progression and no treatment in the immune tolerance period and inactive period. As the price of antiviral agents for CHB has decreased significantly, the availability of antiviral agents for CHB has been considerably improved. Therefore, expanding the indications for antiviral treatment of CHB is of great significance in achieving the goal of eliminating the public health threat of viral hepatitis by 2030, as the World Health Organization has proposed.

Hepatitis B virus (HBV) infection can activate macrophages to accelerate liver disease progression, including inflammation and fibrosis. However, the exact mechanism remains undetermined. The present study assessed the effects of macrophage polarization and the related cytokines on Th‑17 differentiation in HBeAg positive individuals with a HBV infection, and also evaluated the potential association of Th‑17 cell frequency with the severity of liver injury. A cross‑sectional study design was used to collect the clinical parameters, blood samples and liver tissue samples of patients with alanine transaminase £2x upper limit of normal and confirmed hepatitis B who underwent liver puncture in Qishan Hospital between January 2019‑December 2021. Macrophage and Th‑17 cell related factors were assayed using ELISA. The expression and quantification of cell surface antigen and intracellular markers in cells were assessed using flow cytometry. Pathological staining, including hematoxylin and eosin, reticular fiber staining and immunohistochemical staining were used to assess inflammation and fibrosis in the liver tissue. In the peripheral blood of patients with HBV infection, the number of CD14⁺ macrophages was significantly increased compared with the healthy control, especially in the hepatitis B e antigen (HBeAg) positive group. CD14⁺ macrophages were predominantly of the M1 type based on the assessment of the phenotype using flow cytometry and cytokine secretion. Furthermore, the percentage of M1 phenotype and related cytokines were positively correlated with Th‑17 differentiation. IL‑17A secreted by Th‑17 was positively correlated with the degree of liver inflammation and fibrosis, as well as with the severity of liver disease, which indicated that the differentiation of Th‑17 may be involved in the progression of liver disease. HBeAg may promote Th‑17 differentiation and IL‑17A production by M1 macrophages to accelerate the pathogenesis of liver inflammation and fibrosis in CHB patients.

Significant histopathologic changes of hepatic injury (SHCHI) play a decisive role in evaluating the condition and initiating antiviral in hepatitis B virus (HBV)-infected patients, especially those with normal or mildly elevated alanine transaminase levels. Considering that non-invasive methods were established through experience with chronic hepatitis C, the aim of this study was to establish and verify a nomogram based on hepatitis B for diagnosing SHCHI.

Three hundred eighty-four patients who fulfilled requirements for participation were randomly assigned to training cohort (n=270) and validation cohort (n=114) according to 7:3. The selection criteria for clinical factors were based on the previous research papers. SHCHI was subgrouped as followed: grade ≥ G2 inflammation and/or stage ≥ S2 fibrosis. The predictive accuracy and discriminative ability of nomogram were determined by a concordance index (C-index), calibration curve and the area under the receiver-operating characteristic curve (AUROC). We also compared diagnostic value of nomogram with model for AST-to-PLT ratio index (APRI) score and model for Fibrosis-4 (FIB-4) score.

Two hundred and two patients (74.44%) and 87 patients (76.32%) were diagnosed as SHCHI, in the training and validation cohort. Logistic regression analysis illustrated that hepatitis B e antigen (HBeAg), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and prothrombin time (PT) all independently served as risk factors for SHCHI (P<0.05) and were thus utilized to create the nomogram. The nomogram had well-fitted calibration curves and attained excellent concordance indices of 0.80 and 0.75. The sensitivity of nomogram in the diagnosis of SHCHI was 79.7%, the specificity was 68.1%. The area under the curve {AUC; 0.80 [95% confidence interval (CI): 0.74-0.86]} for diagnosing SHCHI by the nomogram was greater in comparison to that of APRI [0.78 (95% CI: 0.71-0.84)], and FIB-4 [0.76 (95% CI: 0.69-0.82)]. Patients with nomogram scores less than 119 were considered to have a lower risk of SHCHI.

The constructed nomogram is suitable to serve as a SHCHI screening tool in chronic HBV-infected patients. But the dependability of the nomogram will necessitate further confirmation in a prospective study and further external validation is needed.

Interleukin-2 (IL-2) can be used as an adjuvant therapy when pegylated interferon alpha (Peg-IFN-α) does not effectively promote hepatitis B surface antigen (HBsAg) loss, but the relevant timing, kinetic patterns, and prognostic associations of this intervention are unclear.

A total of 115 patients with chronic hepatitis B (CHB) treated at our institution between October 2018 and March 2021 were included in this retrospective analysis. They were divided into two kinetic patterns by using K-medoids cluster analysis. Profile and prognostic associations were statistically analyzed between the two patterns.

After baseline standardization, before the intervention, the relative HBsAg level showed a continuously increasing trend, but after the intervention, it showed a continuously decreasing trend. Based on the relative change in the HBsAg level, two kinetic patterns, namely, a fluctuation platform pattern and a stepwise growth pattern, were identified by using K-medoids cluster analysis for all 115 patients before IL-2 intervention. Profile analysis showed that there were statistically significant differences between the two patterns before IL-2 intervention (p < 0.05), but their profiles showed the same trend after 2 weeks of IL-2 intervention. Prognostic association analysis showed that CD8+ T cells, alanine transaminase (ALT), age, natural killer (NK) cells, neutrophils, and course of treatment before IL-2 intervention were the six main indicators affecting the relative decrease in the HBsAg level.

For CHB patients who have received continuous Peg-IFN-α treatment, IL-2 intervention should be given as early as possible when the HBsAg level has not decreased for four consecutive weeks or a fluctuation platform pattern is observed. After the intervention, a downward relative change in the HBsAg level can be maintained over 4 weeks. CD8+ T cells, ALT, NK cells, and neutrophils are baseline indicators closely related to the prognosis of this intervention.

In clinical practice, a substantial proportion of chronic hepatitis B virus (HBV) infections that do not fit into any of the usual immune states are considered to be in the "grey zone (GZ)". This study aimed to investigate the effect of the change in antiviral therapy indication on identifying significant hepatic injury among GZ patients.

Patients with chronic HBV infections and a persistent normal alanine aminotransferase (ALT) level (PNALT) who underwent ultrasonography-guided percutaneous liver biopsy were examined retrospectively. Evidenced hepatic injury (EHI) was defined as an inflammation grade ≥2 (≥G2) and/or fibrosis stage ≥2 (≥F2). Complete clinical data, liver inflammation, and fibrosis grades were collected, and the levels of cytokines were detected by the Luminex technique, all of which were analysed to investigate the immune and histopathology states of the liver.

A total of 347 patients with chronic HBV infections and PNALT were categorized into immune tolerant (IT, n = 108), inactive HBV surface antigen (HBsAg) carrier (IHC, n = 61), GZ-1 (HBeAg positive in GZ, n = 92), and GZ-2 (HBeAg negative in GZ, n = 68) phases. Among them, 51.3% were in the GZ phase, and 50.1% presented with EHI. The IL-6 levels were higher in the EHI group than in the non-EHI group (2.77 vs. 1.53 pg/ml, Z = -13.32, p = 0.028). The monocyte chemoattractant protein 1 (MCP-1) level was positively correlated with HBV DNA (R = 0.64, p < 0.001) and HBeAg (R = 0.5, p < 0.001) but negatively correlated with fibrosis grade (R = -0.26, p = 0.048). The ratio of EHI in the GZ phase was 60.55%, which was significantly higher than that in patients in the IT (39.8%) and IHC phases (37.7%) (χ2 = 10.4, p = 0.006). A total of 46.69% of all patients exceeded the new ALT antiviral treatment threshold (30 U/L for men and 19 U/L for women). The EHI values in the IT and IHC phases below the new ALT threshold were 32.6% and 37.8%, respectively, whereas higher EHI values of 67.4% and 68.4% were seen in GZ-1 and GZ-2 patients, respectively, exceeding the new ALT threshold, and the difference was statistically significant (χ2 = 11.13, p < 0.001; χ2 = 14.22, p = 0.002). The median age in our cohort was 38.91 years, and only 21.03% were less than 30 years old. The EHI values in the IT and IHC patients <30 years old were 32.4% and 35.8%, respectively, while the ratio of EHI increased to 43.2% once patients were older than 30 years but still in the IT and IHC stages.

Setting 30 years old as a cut-off and lowering the ALT threshold could facilitate screening for the presence of significant liver injury, especially for GZ patients. IL-6 was a good indicator of EHI, and MCP-1 was significantly positively correlated with HBV DNA but negatively correlated with liver fibrosis.

Patients with chronic liver diseases (CLDs) develop acute liver injury and/or acute decompensation under the attack of various precipitants and present with significantly elevated alanine aminotransferase and/or total bilirubin levels, liver failure, or acute decompensation of liver cirrhosis, which is called acute-on-CLD (AoCLD). AoCLD accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AoCLD is complicated by various clinical types, the severity of the disease, and may pose a high risk of death. To date, the definition of AoCLD is still vague, and a consensus concept of the clinical classification is lacking. This review aimed to define the concept and clinical types of AoCLD based on related studies and the literature.

4-Hydroxy-2-nonenal (HNE) is one of the most important products of lipid peroxidation which induces inflammation. In order to investigate the effect of rice protein (RP) on suppressing HNE-induced inflammation and the role of methionine in regulating the anti-inflammatory function of RP, Wistar rats (male, weighing180-200 g) were ad libitum fed either a pellet diet with oral administration of methionine or ad libitum fed RP for two weeks. RP and methionine significantly reduced HNE levels and effectively suppressed the expressions of cyclooxygenase-2, tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase. The anti-inflammatory action of RP was evident from the upregulation of IL-10 and glutathione S-transferase, which played a role in the detoxification of HNE. The results show that the molecular mechanism responsible for the anti-inflammatory function of RP is the inhibition of nuclear factor-κB activation by the downregulation of protein kinase B/phosphoinositide 3 kinase. Further, this study demonstrates that methionine availability contributes to the suppression of HNE-induced inflammation through up-regulating IL-10 and GST in rats fed RP. Novelty: RP suppresses HNE-induced inflammation. Met plays a role in up-regulating IL-10 and GST. Met availability regulates the inhibition of NF-κB by RP.

The purpose of this study was to assess the diagnostic value of multifrequency MR elastography for grading necro-inflammation in the liver. Fifty participants with chronic hepatitis B or C were recruited for this institutional review board-approved study. Their liver was examined with multifrequency MR elastography. The storage, shear and loss moduli, and the damping ratio were measured at 56 Hz. The multifrequency wave dispersion coefficient of the shear modulus was calculated. The measurements were compared to reference markers of necro-inflammation and fibrosis with Spearman correlations and multiple regression analysis. Diagnostic accuracy was assessed. At multiple regression analysis, necro-inflammation was the only determinant of the multifrequency dispersion coefficient, whereas fibrosis was the only determinant of the storage, loss and shear moduli. The multifrequency dispersion coefficient had the largest AUC for necro-inflammatory activity A ≥ 2 [0.84 (0.71-0.93) vs. storage modulus AUC: 0.65 (0.50-0.79), p = 0.03], whereas the storage modulus had the largest AUC for fibrosis F ≥ 2 [AUC (95% confidence intervals) 0.91 (0.79-0.98)] and cirrhosis F4 [0.97 (0.88-1.00)]. The measurement of the multifrequency dispersion coefficient at three-dimensional MR elastography has the potential to grade liver necro-inflammation in patients with chronic vial hepatitis.