SEU2-Net: multi-scale U2-Net with SE attention mechanism for liver occupying lesion CT image segmentation.

Liver occupying lesions can profoundly impact an individual's health and well-being. To assist physicians in the diagnosis and treatment of abnormal areas in the liver, we propose a novel network named SEU2-Net by introducing the channel attention mechanism into U2-Net for accurate and automatic liver occupying lesion segmentation. We design the Residual U-block with Squeeze-and-Excitation (SE-RSU), which is to add the Squeeze-and-Excitation (SE) attention mechanism at the residual connections of the Residual U-blocks (RSU, the component unit of U2-Net). SEU2-Net not only retains the advantages of U2-Net in capturing contextual information at multiple scales, but can also adaptively recalibrate channel feature responses to emphasize useful feature information according to the channel attention mechanism. In addition, we present a new abdominal CT dataset for liver occupying lesion segmentation from Peking University First Hospital's clinical data (PUFH dataset). We evaluate the proposed method and compare it with eight deep learning networks on the PUFH and the Liver Tumor Segmentation Challenge (LiTS) datasets. The experimental results show that SEU2-Net has state-of-the-art performance and good robustness in liver occupying lesions segmentation.

Histopathological Features Predicting Long-term Clinical Outcomes in Patients with Vanishing Bile Duct Syndrome.

Background and Aims: The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome (VBDS) have yet to be elucidated. The study aims to investigate these features and identify factors associated with poor prognosis. Methods: This multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022. Clinical and pathological data at time of biopsy were reviewed. Clinical outcomes including cirrhosis, decompensation events, liver transplantation (LT), and liver-related death were recorded. Cox regression analysis was used to identify the risk factors associated with poor outcomes. Results: A total of 183 patients were included. The median age was 47 years, with 77.6% being women. During a median follow-up of 4.8 years, 88 patients developed compensated or decompensated cirrhosis, 27 died, and 15 received LT. Multivariate Cox regression analysis showed that hepatocellular cholestasis (HR 2.953, 95% CI: 1.437-6.069), foam cells (HR 2.349, 95% CI: 1.092-5.053), and advanced fibrosis (HR 2.524, 95% CI: 1.313-4.851) were independent predictors of LT or liver-related deaths. A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746 (95% CI: 0.706-0.785). Conclusions: Nearly half of VBDS patients studied progressed to end-stage liver disease and 23% of them had LT or liver-related death within two years of diagnosis. Hepatocellular cholestasis, foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.

A case report of hepatitis B virus reactivation 19 months after cessation of chemotherapy with rituximab.

A 72-year-old woman presented to our hospital with elevation of serum transaminases. Her blood tests showed the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) negative. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were given for the diffuse large B-cell lymphoma. She didn't receive anti- hepatitis B virus (HBV) drug for the isolated HBcAb positive. HBV reactivation confirmed based on the serum HBV DNA detectable until 19 months after stopping R-CHOP regimen. HBV DNA became undetectable after 4 weeks therapy with Tenofovir alafenamide fumarate (TAF). Serum transaminases went down to normal 3 months later after receiving TAF. HBV reactivation is a substantial risk for patients with isolated HBcAb positive receiving rituximab-containing chemotherapy without anti- HBV drug. Regular monitoring with a frequency of 1-3 months is the basis for timely diagnosis and treatment of HBV reactivation. Serum transaminases abnormalities may be the initial manifestation of HBV reactivation.

The Emerging Role of Branched-Chain Amino Acids in Liver Diseases.

Chronic liver diseases pose a substantial health burden worldwide, with approximately two million deaths each year. Branched-chain amino acids (BCAAs)-valine, leucine, and isoleucine-are a group of essential amino acids that are essential for human health. Despite the necessity of a dietary intake of BCAA, emerging data indicate the undeniable correlation between elevated circulating BCAA levels and chronic liver diseases, including non-alcoholic fatty liver diseases (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). Moreover, circulatory BCAAs were positively associated with a higher cholesterol level, liver fat content, and insulin resistance (IR). However, BCAA supplementation was found to provide positive outcomes in cirrhosis and HCC patients. This review will attempt to address the contradictory claims found in the literature, with a special focus on BCAAs' distribution, key signaling pathways, and the modulation of gut microbiota. This should provide a better understanding of BCAAs' possible contribution to liver health.

Predictive Nomograms for Clinical Outcomes in Hepatitis B-Related Cirrhosis Patients Receiving Antiviral Therapy.

OBJECTIVE: Many scores have been constructed to predict liver-related events in chronic hepatitis B, while most of them are based on baseline clinical parameters. The objective of this study was to develop nomograms based on on-treatment improvement in established scores to predict clinical outcomes in patients with hepatitis B virus (HBV)-related cirrhosis who are receiving antiviral therapy. METHODS: The Cox proportional hazards regression model was used. Nomograms were constructed for the prediction of liver-related events, hepatocellular carcinoma (HCC), and liver-related mortality risk during long-term antiviral therapy. RESULTS: A total of 277 treatment-naive patients with HBV-associated cirrhosis were enrolled from January 2010 to December 2013. After a median follow-up of 63.3 months, 95 patients developed liver-related events, including 59 patients with liver-related death. Multivariate Cox analysis showed that the albumin-bilirubin score at year 1 was an independent predictor of liver-related events, liver-related mortality, and HCC. Age, decompensation, and delayed virological remission were independent factors for liver-related mortality. Age was also a risk factor for liver-related events. The concordance index values of event-nomogram, mortality-nomogram, and HCC-nomogram were 0.742 (95% confidence interval [CI], 0.691~0.793), 0.799 (95% CI, 0.748~0.850), and 0.613 (95% CI, 0.540~0.686), respectively. The calibration plots showed an agreement between the predicted and observed incidences, which indicates good calibration of the model of event-nomogram and mortality-nomogram. CONCLUSION: The nomograms achieved an optimal preoperative prediction of liver-related events, mortality, and HCC development in patients with HBV-related cirrhosis receiving antiviral therapy. These findings may help to identify high-risk patients for further optimal surveillance and intervention strategies.

Clinical Aspects of Gut Microbiota in Hepatocellular Carcinoma Management.

Liver cancer, predominantly hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths worldwide. Emerging data highlight the importance of gut homeostasis in the pathogenesis of HCC. Clinical and translational studies revealed the patterns of dysbiosis in HCC patients and their potential role for HCC diagnosis. Research on underlying mechanisms of dysbiosis in HCC development pointed out the direction for improving the treatment and prevention. Despite missing clinical studies, animal models showed that modulation of the gut microbiota by probiotics may become a new way to treat or prevent HCC development.

Human immune repertoire in hepatitis B virus infection.

Hepatitis B virus (HBV) infection is a public health threat that affects 257 million people worldwide and can progress to liver cirrhosis, liver failure, and hepatocellular carcinoma. The HBV antigen- induced adaptive immune response plays an important role in HBV clearance. Immune repertoire sequencing (IRS) has been used to investigate the molecular mechanisms behind the immune system, find novel ways to treat HBV infection, and evaluate the genetic responses and immune characteristics of individuals infected by HBV or immunized by HBV vaccine. This review summarizes the human immune repertoire analysis methodology, and the application of the IRS in the prediction of HBV infection progression, treatment, and vaccination.

Chinese guidelines on the management of liver cirrhosis (abbreviated version).

Based on reviews of the literature and experts' consensus, the Chinese Society of Hepatology developed guidelines for the diagnosis and treatment of liver cirrhosis, in order to improve clinical practice. In addition to what has been covered in previously published guidelines on the management of cirrhosis complications, these guidelines add new sections and provide updates. The guidelines emphasize the early diagnosis of the cause and assessment of complications. Comprehensive treatments including etiological treatment and complication management should be initiated immediately. In addition, regular monitoring, especially surveillance of hepatocellular carcinoma, is crucial for managing patients.

Dysregulated microRNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Potential as Biomarkers and Therapeutic Targets.

MicroRNAs (miRNAs) are non-coding small RNAs that can function as gene regulators and are involved in tumorigenesis. We review the commonly dysregulated miRNAs in liver tumor tissues and plasma/serum of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. The frequently reported up-regulated miRNAs in liver tumor tissues include miR-18a, miR-21, miR-221, miR-222, and miR-224, whereas down-regulated miRNAs include miR-26a, miR-101, miR-122, miR-125b, miR-145, miR-199a, miR-199b, miR-200a, and miR-223. For a subset of these miRNAs (up-regulated miR-222 and miR-224, down-regulated miR-26a and miR-125b), the pattern of dysregulated circulating miRNAs in plasma/serum is mirrored in tumor tissue based on multiple independent studies. Dysregulated miRNAs target oncogenes or tumor suppressor genes involved in hepatocarcinogenesis. Normalization of dysregulated miRNAs by up- or down-regulation has been shown to inhibit HCC cell proliferation or sensitize liver cancer cells to chemotherapeutic treatment. miRNAs hold as yet unrealized potential as biomarkers for early detection of HCC and as precision therapeutic targets, but further studies in diverse populations and across all stages of HCC are needed.

Host and Viral Genetic Variation in HBV-Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the second leading cause of cancer deaths globally. The high prevalence of HCC is due in part to the high prevalence of chronic HBV infection and the high mortality rate is due to the lack of biomarkers for early detection and limited treatment options for late stage HCC. The observed individual variance in development of HCC is attributable to differences in HBV genotype and mutations, host predisposing germline genetic variations, the acquisition of tumor-specific somatic mutations, as well as environmental factors. HBV genotype C and mutations in the preS, basic core promoter (BCP) or HBx regions are associated with an increased risk of HCC. Genome-wide association studies have identified common polymorphisms in KIF1B, HLA-DQ, STAT4, and GRIK1 with altered risk of HBV-related HCC. HBV integration into growth control genes (such as TERT), pro-oncogenic genes, or tumor suppressor genes and the oncogenic activity of truncated HBx promote hepatocarcinogenesis. Somatic mutations in the TERT promoter and classic cancer signaling pathways, including Wnt (CTNNB1), cell cycle regulation (TP53), and epigenetic modification (ARID2 and MLL4) are frequently detected in hepatic tumor tissues. The identification of HBV and host variation associated with tumor initiation and progression has clinical utility for improving early diagnosis and prognosis; whereas the identification of somatic mutations driving tumorigenesis hold promise to inform precision treatment for HCC patients.

Relationship between virological response and FIB-4 index in chronic hepatitis B patients with entecavir therapy.

AIM: To investigate whether long-term low-level hepatitis B virus (HBV) DNA influences dynamic changes of the FIB-4 index in chronic hepatitis B (CHB) patients receiving entecavir (ETV) therapy with partial virological responses. METHODS: We retrospectively analyzed 231 nucleos(t)ide (NA) naïve CHB patients from our previous study (NCT01926288) who received continuous ETV or ETV maleate therapy for three years. The patients were divided into partial virological response (PVR) and complete virological response (CVR) groups according to serum HBV DNA levels at week 48. Seventy-six patients underwent biopsies at baseline and at 48 wk. The performance of the FIB-4 index and area under the receiver operating characteristic (AUROC) curve for predicting fibrosis were determined for the patients undergoing biopsy. The primary objective of the study was to compare the cumulative probabilities of virological responses between the two groups during the treatment period. The secondary outcome was to observe dynamic changes of the FIB-4 index between CVR patients and PVR patients. RESULTS: For hepatitis B e antigen (HBeAg)-positive patients (n = 178), the cumulative probability of achieving undetectable levels at week 144 was 95% and 69% for CVR and PVR patients, respectively (P < 0.001). In the Cox proportional hazards model, a lower pretreatment serum HBV DNA level was an independent factor predicting maintained viral suppression. The cumulative probability of achieving undetectable levels of HBV DNA for HBeAg-negative patients (n = 53) did not differ between the two groups. The FIB-4 index efficiently identified fibrosis, with an AUROC of 0.80 (95%CI: 0.69-0.89). For HBeAg-positive patients, the FIB-4 index was higher in CVR patients than in PVR patients at baseline (1.89 ± 1.43 vs 1.18 ± 0.69, P < 0.001). There was no significant difference in the reduction of the FIB-4 index between the CVR and PVR groups from weeks 48 to 144 (-0.11 ± 0.47 vs -0.13 ± 0.49, P = 0.71). At week 144, the FIB-4 index levels were similar between the two groups (1.24 ± 0.87 vs 1.02 ± 0.73, P = 0.06). After multivariate logistic regression analysis, a lower baseline serum HBV DNA level was associated with improvement of liver fibrosis. In HBeAg-negative patients, the FIB-4 index did not differ between the two groups. CONCLUSION: The cumulative probabilities of HBV DNA responses showed significant differences between CVR and PVR HBeAg-positive CHB patients undergoing entecavir treatment for 144 wk. However, long-term low-level HBV DNA did not deteriorate the FIB-4 index, which was used to evaluate liver fibrosis, at the end of three years.

[The histopathologic and clinical analysis of viral chronic hepatitis patients with negative serological viral markers].

OBJECTIVE: To analyze the histopathological and clinical features of viral chronic hepatitis patients with negative serological viral markers. METHODS: 62 hepatitis patients with negative serological markers were assayed with serological viral hepatitis markers, liver function test and liver biopsies were enrolled in the study. Serum HBV DNA of HBV cases was analyzed by PCR. Liver specimens were examined by immunohistochemistry for HBsAg and HBcAg. RESULTS: The fit rate of histopathological diagnosis with clinical diagnosis is 53.2%, the fit rate is 69.1% in moderate chronic hepatitis group. The immunohistochemistry showed that HBsAg and/or HBeAg positive rate was 45.2%, 53.6% had moderate chronic hepatitis and 25% had mild hepatitis. 13 (46.4%) had G1 hepatitis, 10 (35.7%) had G2 hepatitis, 3 (10.8%) had G3 hepatitis and 2 (7.1%) had G4 hepatitis, and serum HBV DNA positive rate was 35.7%. There were no differences in HBV DNA levels between different hepatitis group and fibrosis stage group (P > 0.05). There were no differences in all indexes between HBV DNA negative group and HBV DNA positive group (P > 0.05). There were no differences in all indexes between HBV patients and other patients (P > 0.05). CONCLUSION: Occult HBV infection may account for a high proportion of the cases with chronic hepatitis of unknown etiology. Most patients are chronic mild hepatitis, but they still have HBV replication and can progress to liver cirrhosis. Serum PCR test, liver biopsy and immunohistochemistry are helpful for the diagnosis.