Analysis of related factors of portal vein thrombosis in liver cirrhosis.

BACKGROUND AND AIMS: To investigate the usefulness of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), protein C (PC), and thromboelastography (TEG) to serve as a predictor of portal vein thrombosis (PVT) in patients with liver cirrhosis. Additionally, we examined the clinical significance of the above indicators in terms of disease progression. METHODS: A total of 123 patients with liver cirrhosis were recruited from May 2021 to December 2021, according to the imaging findings. They were divided into the PVT group (n = 52) and the non-PVT group (n = 71). Furthermore, patients with PVT were divided into plasma transfusion groups (n = 13) and non-plasma transfusion groups (n = 39). The basic general information, past medical history, laboratory, and imaging examination data were collected and analyzed. RESULTS: In univariate analysis, there was no significant difference between the two groups in IL-6, PC, reaction time (R), alpha angle (Angle), maximum amplitude, or coagulation index (CI) (P > 0.05). TNF-α in the PVT group was significantly lower than that in the non-PVT group (P = 0.001). K-time (K) in the PVT group was significantly higher than that in the non-PVT group (P = 0.031). There was no significant difference in IL-6, TNF-α, PC, or TEG between different Child-Pugh classification groups (P > 0.05). There were no significant differences in TEG between the plasma transfusion group and the non-plasma transfusion group. In Binary logistic regression analysis, TNF-α (OR = 0.9881, 95%CI = 0.971, 0.990, P < 0.001), K(OR = 1.28, 95% = 1.053, 1.569, P = 0.014), activate partial thromboplastin time (APTT) (OR = 0.753, 95%CI = 0.656, 0.865, P < 0.001), portal vein diameter (OR = 1.310, 95%CI = 1.108, 1.549, P = 0.002)and the history of splenectomy or embolism (OR = 7.565, 95%CI = 1.514, 37.799, P = 0.014)were related to the formation of PVT. CONCLUSIONS: TNF-α, K, APTT, portal vein diameter, and splenectomy or embolism history were associated with PVT formation, but IL-6 was not.

The association between Fc gamma RIIb expression levels and chronic hepatitis B virus infection progression.

BACKGROUND: Fc gamma receptor IIb (FcγRIIb) is an important inhibitory receptor that plays vital roles in regulating various immune response processes and the pathogenesis of many infectious diseases. The purpose of our research was to evaluate FcγRIIb expression in serum and liver biopsy specimens from hepatitis B virus (HBV)-infected patients and to explore the association of FcγRIIb with chronic HBV infection. METHODS: Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum FcγRIIb levels in 119 HBV-infected patients and 24 healthy controls. An immunohistochemical method was then employed to identify FcγRIIb expression in biopsy specimens from patients with chronic hepatitis B (CHB). The integrated optical density (IOD) value was measured to represent FcγRIIb expression levels. RESULTS: Serum FcγRIIb levels were decreased in CHB patients compared to controls (P < 0.001). The FcγRIIb levels in the CHB patient group were remarkably lower than those in the HBV carrier group (P < 0.001). In addition, FcγRIIb levels were negatively associated with AST and ALT (r = -0.3936, P = 0.0063; r = -0.3459, P = 0.0097, respectively). The IOD values of FcγRIIb expression in the moderate and severe CHB groups were significantly lower than those in the control group (P = 0.006 and P < 0.001, respectively). The FcγRIIb level tended to be lower with pathological changes related to hepatitis. Furthermore, correlation analysis revealed that FcγRIIb had negative correlations with AST and ALT (r = -0.688, P = 0.0016; r = -0.686, P = 0.0017, respectively) but a positive association with the platelet count (r = 0.6464, P = 0.0038). CONCLUSIONS: FcγRIIb levels are significantly related to chronic HBV infection and the progression of CHB. Changes in FcγRIIb may affect the progression of liver inflammation and fibrosis in CHB patients.

Identification of key genes and pathways associated with different immune statuses of hepatitis B virus infection.

We aimed to identify key genes and pathways associated with different immune statuses of hepatitis B virus (HBV) infection. The gene expression and DNA methylation profiles were analysed in different immune statuses of HBV infection. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified, followed by their functional and integrative analyses. The differential expression of IgG Fc receptors (FcγRs) in chronic HBV-infected patients and immune cells during different stages of HBV infection was investigated. Toll-like receptor (TLR) signalling pathway (including TLR6) and leucocyte transendothelial migration pathway (including integrin subunit beta 1) were enriched during acute infection. Key DEGs, such as FcγR Ib and FcγR Ia, and interferon-alpha inducible protein 27 showed correlation with alanine aminotransferase levels, and they were differentially expressed between acute and immune-tolerant phases and between immune-tolerant and immune-clearance phases. The integrative analysis of DNA methylation profile showed that lowly methylated and highly expressed genes, including cytotoxic T lymphocyte-associated protein 4 and mitogen-activated protein kinase 3 were enriched in T cell receptor signalling pathway during acute infection. Highly methylated and lowly expressed genes, such as Ras association domain family member 1 and cyclin-dependent kinase inhibitor 2A were identified in chronic infection. Furthermore, differentially expressed FcγR Ia, FcγR IIa and FcγR IIb, CD3- CD56+ CD16+ natural killer cells and CD14high CD16+ monocytes were identified between immune-tolerant and immune-clearance phases by experimental validation. The above genes and pathways may be used to distinguish different immune statuses of HBV infection.

Aberrant DNA methylation profile of hepatitis B virus infection.

We aimed to study the aberrant DNA methylation profile associated with hepatitis B virus (HBV) infection and, to identify key genes and pathways associated with the HBV infection stage. A total of 54 antiviral treatment-naïve HBV-infected patients and six healthy controls were included. Genome-wide methylated DNA immunoprecipitation analysis was performed, as previously described, after which the chip data were preprocessed. Subsequently, Cytoscape software was used for the construction of a protein-protein interaction network, and a database for annotation, visualization, and integrated discovery software was used to conduct functional enrichment analysis. A total of 711 794 CpGs were obtained after data quality control, among which 152 780, 113 814, 90 747, and 175 868 CpGs showed differential methylation in acute hepatitis B (AHB) vs control, total-C vs control, CH1 vs CA1, and AHB vs total-C, respectively. Furthermore, RIPK3, PRDM10, JUN, and SNAI1 were at the center of the four associated networks, respectively. Differential methylated genes differentially methylated in these four comparisons were significantly enriched with olfactory transduction; positive regulation of transport; negative regulation of protein amino acid phosphorylation (eg, JUN), phosphorylation, phosphorus metabolic process, and phosphate metabolic process; and programmed cell death, respectively. RIPK3, PRDM10, JUN, and SNAI1 as well as olfactory transduction, positive regulation of transport, negative regulation of phosphorylation, and programmed cell death are important for the transformation associated with HBV infection stage. Moreover, JUN may be involved in HBV infection, mainly via the negative regulation of amino acid phosphorylation.

Performance of FibroScan in grading steatosis and fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis.

OBJECTIVE: Biopsy remains the gold standard for the diagnosis of Non-alcoholic fatty liver disease (NAFLD). To investigate the diagnostic value of FibroScan based on biopsy and range of cut-offs for steatosis and fibrosis, we explored the grade of steatosis and fibrosis. METHOD: A simultaneous search was performed on cohort studies published earlier than October 8, 2020,in the PubMed, Web of Science, Sinomed, CNKI, VIP, and WanFang databases. Next,we screened qualified studies. The data were mainly analysed in RevMan and complemented in STATA. RESULTS: The area under the receiver operating characteristic of FibroScan in identifying the stage of steatosis for ≥ S1 was 0.90 (sensitivity:89%; specificity:92%), that for ≥ S2 was 0.82 (sensitivity:89%;specificity:70%) and that for S3 was 0.79 (sensitivity:83%; specificity:63%).The area under the receiver operating characteristic of FibroScan in identifying the stage of fibrosis for ≥ F1 was 0.86 (sensitivity:81%;specificity:77%),that for ≥ F2 was 0.80 (sensitivity: 75%; specificity:82%), that for ≥ F3 was 0.94 (sensitivity:87%; specificity: 89%) and that for F4 was 0.97 (sensitivity: 94%; specificity:91%). CONCLUSION: FibroScan, a promising and cost-effective technique, can provide an accurate noninvasive approach for quantifying and staging hepatic steatosis and fibrosis in NAFLD, particularly for advanced fibrosis and cirrhosis. Further studies are needed to explore the relationship between steatosis and fibrosis based on the same group. Additionally, NASH is the key stage of NAFLD. Early diagnosis and intervention can help reduce the incidence of liver cirrhosis. However, no large study has investigated the significance of FibroScan in the diagnosis of NASH confirmed by pathology.

Association of aspirin and nonaspirin NSAIDs therapy with the incidence risk of hepatocellular carcinoma: a systematic review and meta-analysis on cohort studies.

According to the current research evidence, the therapy of nonsteroidal anti-inflammatory drugs (NSAIDs) might effectively decrease the risk of hepatocellular carcinoma (HCC) incidence. Investigations have been conducted on the relationship between NSAIDs (aspirin and nonaspirin NSAIDs) and the risk of HCC incidence. We searched the PubMed, Web of Science, Embase and Cochrane Library databases for cohort studies published prior to 15 March 2020 and screened eligible studies. There were a total of 12 eligible studies (published between 2012 and 2020). We observed a lower risk of HCC among aspirin users [hazard ratio 0.53; 95% confidence interval (CI), 0.43-0.65]. However, there were no statistically significant associations discovered between nonaspirin NSAID use and the risk of HCC incidence (hazard ratio 0.95; 95% CI, 0.79-1.15). Furthermore, aspirin use has also been found to reduce the risk of HCC in patients with cirrhosis or viral hepatitis compared to that in the general population (hazard ratio 0.15; 95% CI, 0.10-0.23; hazard ratio 0.65; 95% CI, 0.56-0.76, respectively). Moreover, no statistical associations were found between aspirin use and a higher risk of bleeding risk, with a hazard ratio value of 0.76 (95% CI, 0.51-1.13). In summary, the conducted meta-analysis reveals that aspirin, rather than nonaspirin NSAIDs, can significantly decrease the risk of HCC, particularly in patients with cirrhosis or viral hepatitis.

Clinical Value of TCCD for Evaluating the Prognosis of Patients with Severe Traumatic Brain Injury After Large Decompressive Craniectomy: A Retrospective Study.

INTRODUCTION: It is challenging to assess the prognosis of patients with severe traumatic brain injury (sTBI) after large decompressive craniectomy (DC). The aim of this study was to evaluate the clinical value of transcranial color-coded duplex sonography (TCCD) for assessing the prognosis of sTBI patients 6 months after large DC. METHODS: This was a retrospective observational study that consecutively enrolled 84 patients with sTBI who were followed up for prognosis until 6 months after large DC. The primary endpoint was the Glasgow Outcome Score (GOS). According to the GOS, patients were divided into an unfavorable prognosis group (GOS 1-3, n = 47) and a favorable prognosis group (GOS 4-5, n = 37). RESULTS: Significant between-group differences were found in age and hemodynamic parameters (systolic peak blood flow velocity, end-diastolic blood flow velocity, mean blood flow velocity, pulsatility index and resistance index) of the middle cerebral artery detected by TCCD (P < 0.05 for all). Subsequently, ridge regression was used to build a prognostic model for patients with large DC. Based on the cerebral hemodynamic parameters measured by TCCD and age, the mean (± standard deviation) area under the curve of the prognostic model in patients with sTBI after large DC was 0.76 ± 0.22. The sensitivity and specificity were 82.08% and 74.17%, respectively. CONCLUSIONS: The cerebral hemodynamic parameters detected by TCCD, combined with age, may be used to predict the outcomes of patients with sTBI at 6 months after large DC. As a noninvasive method, TCCD has the potential to assess the prognosis of these patients. TRIAL REGISTRATION: ChiCTR: ChiCTR1800019758. Registered 27 November 2018-retrospectively registered ( http://www.chictr.org.cn/index.aspx ).

Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population.

BACKGROUND: Recent genome-wide association studies found that genetic polymorphisms near the IL28B gene is strongly associated with sustained viral response and spontaneous viral clearance in chronically infected hepatitis C patients. AIMS: We aimed to evaluate the effects of IL28B variations on hepatitis B virus (HBV) infection in a Chinese Han population and to explore the association between IL28B polymorphisms and susceptibility to infection, viral clearance, disease progression, viral load and liver inflammation. METHODS: We determined three IL28B single gene polymorphisms (rs12979860, rs12980275 and rs8099917) in 203 individuals with chronic HBV infection, 203 individuals with self-limited HBV infection and 203 individuals negative for all HBV seromarkers. Interleukin (IL)28B serum levels were evaluated in all subjects. Additionally, peripheral blood mononuclear cells from 42 chronically HBV-infected individuals were subjected to whole-genome expression studies. RESULTS: The association among genotype, allele and haplotype frequencies of IL28B with alanine aminotransferase levels and HBV DNA was established. However, no significant differences were observed in genotype or allele frequencies among chronically HBV-infected, self-limited and healthy subjects. The serum IL28B level was lower in patients with chronic HBV infection than in the self-limited HBV-infected or healthy subjects. The serum IL28B level was correlated with the subject's genotype. Gene expression micro-array analysis showed enhanced IL28B expression in patients with low HBV viral load. CONCLUSIONS: Variability at the IL28B locus is associated with HBV viral load and hepatic inflammation. Genetic variation of IL28B may prevent HBV progression by reducing viral load and liver inflammation, providing a valuable gene therapy tool.

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome in a patient with paroxysmal nocturnal hemoglobinuria: a case report.

Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is frequently associated with extrahepatic autoimmune disorders. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disease that is characterized by complement-mediated hemolysis due to erythrocyte membrane defects. However, autoimmune liver disease was not previously reported to be associated with PNH. A 37-year-old female patient was referred to our hospital with elevated liver enzymes and hematuria. On the basis of the symptoms and results of laboratory tests, radiographic studies, and pathologic results, she was diagnosed with PBC-AIH overlap syndrome and PNH. She was treated with a combination of ursodeoxycholic acid and prednisolone. The patient was symptom-free, with laboratory findings within near-normal range. The patient had recovered well at the 24-month follow-up evaluation. While we acknowledge that this was a single case, these findings expand our knowledge of immunological diseases that are associated with PNH and suggest an immune-mediated pathogenic pathway between PNH and PBC-AIH overlap syndrome. The combination of ursodeoxycholic acid and prednisolone can achieve therapeutic success. Routine follow-up of these patients is necessary to document disease progression.

LINC00346 Acts as a Competing Endogenous RNA Regulating Development of Hepatocellular Carcinoma via Modulating CDK1/CCNB1 Axis.

Hepatocellular carcinoma (HCC) is one of the important types of liver cancer. LncRNA is an important regulatory factor that regulates many biological processes such as tumor cells during tumorigenesis and metastasis. LINC00346 has been associated with various types of liver cancer, but its role and regulatory mechanism in HCC remain unclear. In our study, we found the LINC00356-miR-199a-3p-CDK1/CCNB1 axis through bioinformatics analysis. The expressions of LINC00356, miR-199a-3p, CDK1, and CCNB1 in HCC and normal hepatocytes were determined by qRT-PCR and WB. The results showed that LINC00356, CDK1 and CCNB1 were highly expressed in HCC, while miR-199a-3p was lowly expressed. Dual luciferase reporter gene assay, RIP and RNA-pull down assays demonstrated the targeted binding relationship of LINC00346-miR-199a-3p-CDK1/CCNB1. Overexpressing LINC00460 and silencing miR-199a-3p promoted cell invasion, inhibited apoptosis of HCC, and arrested the cell cycle in S phase while opposite results were obtained when silencing LINC00346, CDK1, and CCNB1. LINC00346 indirectly affects liver cancer by promoting the expression of CDK1/CCNB1 through competitive adsorption of miR-199a-3p. In addition, the study also demonstrated that overexpression of LINC00346 indirectly inhibited the expression of p53 and p21 proteins by promoting CDK1/CCNB1 expressions, thereby blocking the p53 signaling pathway. These results proved that LINC00346 could regulate the expression of CDK1/CCNB1 through the competitive adsorption of miR-199a-3p, thereby affecting the p53 signaling pathway and finally regulating the apoptosis, invasion and cell cycle of HCC cells. In conclusion, LINC00346 can be used as a tumor promoter and potential therapeutic target for HCC metastasis and prognosis.

Silencing of hsa_circ_0101145 reverses the epithelial-mesenchymal transition in hepatocellular carcinoma via regulation of the miR-548c-3p/LAMC2 axis.

Hepatocellular carcinoma (HCC) is a primary cause of cancer-related deaths globally. While there have been advancements in HCC treatment and diagnosis, incidence and mortality rates continue to rise. One study found that circular RNAs functioned as competing endogenous RNAs, and constructed a gene-based nomogram to estimate overall survival of HCC patients. Previous studies using high-throughput sequencing suggested that hsa_circ_0101145 is abnormally expressed in HCC, but the underlying mechanism is unknown. We performed RT-qPCR to determine hsa_circ_0101145 and miR-548c-3p expression in HCC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0101145 expression and hsa_circ_0101145 subcellular localization in HCC tissues. hsa_circ_0101145 expression in HCC cells was selectively regulated. We determined LAMC2 and EMT mRNA and protein levels by RT-qPCR and western blotting analysis, respectively. We employed flow cytometry, and CCK8, Transwell, and wound healing assays to monitor the cell cycle, cell proliferation, invasion, and migration, respectively. We employed dual-luciferase reporter and RNA pulldown assays to verify the relationship among hsa_circ_0101145, miR-548c-3p, and LAMC2. We examined the effects of hsa_circ_0101145 on HCC cell metastasis and proliferation in vivo using a subcutaneous xenograft model as well as intravenous tail injection of nude mice. The data demonstrated that hsa_circ_0101145 was significantly upregulated in both HCC tissues and cell lines. High hsa_circ_0101145 expression was correlated with aggressive HCC phenotypes. Downregulation of hsa_circ_0101145 suppressed HCC proliferation as well as metastasis by targeting the miR-548c-3p/LAMC2 axis, which was examined using luciferase reporter and RNA pulldown assays. Silencing of hsa_circ_0101145 suppressed the epithelial-mesenchymal transition in HCC. Downregulation of miR-548c-3p or overexpression of LAMC2 restored migration and proliferation abilities of HCC cells following hsa_circ_0101145 silencing. LAMC2 overexpression reversed miR-548c-3p-induced cell migration and growth inhibition in vitro. In summary, the findings illustrated that hsa_circ_0101145 silencing suppressed HCC progression by functioning as an miR-548c-3p sponge to enhance LAMC2 expression. Therefore, hsa_circ_0101145 could be an HCC treatment target.

The long-term outcomes of deceased-donor liver transplantation for primary biliary cirrhosis: a two-center study in China.

BACKGROUND & AIMS: Factors that influence the outcomes after deceased-donor liver transplantation (DDLT) for primary biliary cirrhosis (PBC) are not well known. We aimed to clarify these effects on the outcomes after DDLT. METHODS: We retrospectively analyzed patients with PBC who underwent DDLT from March 2006 to July 2018 at the organ transplantation center of the First Hospital of Jilin University and the First Central Hospital of Tianjin. Changes in liver function were assessed posttransplantation. Recurrence, survival rate, and complications were recorded at follow-up. The effect of liver transplantation on survival and recurrence was evaluated using univariate and/or multivariate Cox regression analyses. RESULTS: In total, 69 patients with PBC undergoing DDLT were included in this study. At 4 weeks posttransplant, all liver function tests were normal. During a median follow-up time of 32 months, 5-year overall survival and recurrence rates were estimated as 95.1% and 21.8%, respectively. A recipient aspartate aminotransferase-to-platelet ratio index (APRI) greater than 2 was negatively associated with survival (P = 0.0018). Multivariate regression analysis demonstrated that age younger than 48 years was an independent risk factor for recurrent PBC in recipients undergoing liver transplantation (hazard ratio 0.028, 95% confidence interval 0.01-0.71, P = 0.03). Posttransplant infections (62%) and biliary tract complications (26%) were the most common complications. CONCLUSION: Liver transplantation is an effective treatment for patients with PBC. Liver function normalizes by 4 weeks posttransplant. Although posttransplant survival rate is high, recurrence is possible. To some extent, survival rate and recurrence rate can be predicted by APRI and age, respectively.

Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis.

Background and Aims: Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. Methods: We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment. Results: Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy. Conclusions: The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.

Computational analysis of naturally occurring resistance-associated substitutions in genes NS3, NS5A, and NS5B among 86 subtypes of hepatitis C virus worldwide.

BACKGROUND AND OBJECTIVE: Direct-acting antivirals (DAA) facing resistance continue to be used in some areas worldwide. Thus, identifying hepatitis C virus (HCV) genotypes/subtypes and loci with certain prevalent resistance-associated substitutions (RASs) deserves attention. We investigated the global and regional frequencies of naturally occurring RASs among all confirmed HCV subtypes (n=86) and explored co-occurring and mutually exclusive RAS pairs within and between genes NS3, NS5A, and NS5B. METHODS: A total of 213,908 HCV sequences available as of July 10, 2019 were retrieved from the NCBI nucleotide database. After curation, 17,312 NS3, 8,478 NS5A, and 25,991 NS5B sequence fragments from DAA-naïve patients were screened for RASs. MEGA 6.0 was used to translate aligned nucleotide sequences into amino acid sequences, and RAS pairs were identified by hypergeometric analysis. RESULTS: RAS prevalence varied significantly among HCV subtypes. For example, D168E, highly resistanct to all protease inhibitors except voxilaprevir, was nearly absent in all subtypes except in 43.48% of GT5a sequences. RASs in NS3 exhibiting significantly different global distribution included Q80K in GT1a with the highest frequency in North America (54.49%), followed by in Europe (22.66%), Asia (6.98%), Oceania (6.62%), and South America (1.03%). The prevalence of NS3 S122G in GT1b was highest in Asia (26.6%) and lowest in Europe (2.64%). NS5A L28M, R30Q, and Y93H in GT1b, L31M in GT2b, and NS5B C316N in GT1b was most prevalent in Asia. A150V in GT3a, associated with sofosbuvir treatment failure, was most prevalent in Asia (44.09%), followed by Europe (31.19%), Oceania (24.29%), and North America (19.05%). Multiple mutually exclusive or co-occurring RAS pairs were identified, including Q80K+R155K and R155K+D168G in GT1a and L159F+C316N and R30Q (NS5A)+C316N (NS5B) in GT1b. CONCLUSION: Our data may be of special relevance for those countries where highly effective antivirals might not be available. Considering the specific RASs prevalence will help the clinicians to make optimal treatment choices. The RASs pairs would benefit anti-HCV drug development.

Primary cutaneous amyloidosis associated with autoimmune hepatitis-primary biliary cirrhosis overlap syndrome and Sjögren syndrome: A case report.

RATIONALE: Primary cutaneous amyloidosis (PCA) is a localized skin disorder characterized by the abnormal deposition of amyloid in the extracellular matrix of the dermis. The association between PCA and other diseases, although rare, has been documented for various autoimmune diseases. PCA associated with autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome and Sjögren syndrome (SS) has not been previously reported in the literature. PATIENT CONCERNS: A 50-year-old woman presented with progressive abnormal liver enzyme levels and was referred to our department. DIAGNOSES: Due to the patient's symptoms, laboratory test results, radiographic findings, and pathologic results, she was diagnosed with PCA associated with AIH-PBC overlap syndrome and SS. INTERVENTIONS: She was subsequently treated with a combination of ursodeoxycholic acid (UDCA), prednisone, and azathioprine. OUTCOMES: While this treatment can achieve therapeutic success, it cannot prevent complications from cirrhosis. This patient remains alive but experienced an emergent gastrointestinal hemorrhage. LESSONS: While we acknowledge that this is a single case, these findings extend our knowledge of immunological diseases associated with PCA and suggest a common, immune-mediated pathogenic pathway between PCA, AIH-PBC overlap syndrome, and SS. After 12 years of follow up, clinical manifestations have developed, and these autoimmune diseases have progressed. The combination of UDCA, prednisone, and azathioprine can achieve therapeutic success but cannot prevent disease progression. Routine follow up for this patient is necessary to document disease progression.

Pernicious anemia associated with cryptogenic cirrhosis: Two case reports and a literature review.

RATIONALE: Pernicious anemia (PA) is an autoimmune gastritis that results from the destruction of gastric parietal cells and the associated lack of an intrinsic factor to bind ingested vitamin B12. While an association between PA and various liver diseases has been rarely reported, reports of associated diseases include primary biliary cholangitis, autoimmune hepatitis, and Interferon-treated hepatitis C. We present 2 cases of PA associated with cryptogenic cirrhosis (CC), which has not been previously reported in the literature. PATIENT CONCERNS: A 42-year-old man presented with fatigue, pallor, and sustained abdominal distension that had persisted for 15 days. An 87-year-old man was admitted to the hospital for an unsteady gait and loss of appetite that had persisted for 20 days. DIAGNOSES: Symptoms, laboratory tests, and imaging findings for both patients were indicative of PA and CC.Both had neurological and psychiatric symptoms during hospitalization that were ultimately linked to a vitamin B12 deficiency but not hepatic encephalopathy. INTERVENTIONS: Both patients received intramuscular injections of vitamin B12. OUTCOMES: Hemoglobin levels of the 2 patients increased gradually, and their neurological symptoms were alleviated. LESSONS: PA associated with a liver disease is rare, and the underlying mechanism can only now be clarified. We speculate that autoimmune dysfunction and chronic vitamin B12 deficiency caused by PA might be unique causes of liver cirrhosis. Additional investigations are needed to verify these findings.

Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation.

Natural killer (NK) cells play an important role in hepatitis B virus (HBV) infection control, and are regulated by a complex network of activating and inhibitory receptors. However, NK cell activity in HBV patients remains poorly understood. The objective of this study was to investigate the phenotypic and functional characteristics of circulating NK cells in patients during different chronic hepatitis B (CHB) infection stages. We investigated NK cell phenotypes, receptor expression and function in 86 CHB patients and 20 healthy controls. NK cells were purified and NK cell subsets were characterized by flow cytometry. Cytotoxic activity (CD107a) and interferon-gamma (IFN-γ) secretion were examined, and Natural Killer p46 (NKP46) blockade and spontaneous NK cell cytolytic activity against K562, HepG2 and HepG2.215 cell lines was studied. Activating NKp46 receptor expression was higher in inactive HBsAg carriers when compared with other groups (p = 0.008). NKp46 expression negatively correlated with HBV DNA (R = -0.253, p = 0.049) and ALT (R = -0.256, p = 0.045) levels. CD107a was higher in immune-activated groups when compared with immune-tolerant groups (p = 0.039). CD107a expression was related to viral load (p = 0.02) and HBeAg status (p = 0.024). In vitro NKp46 blockade reduced NK cell cytolytic activity against HepG2 and HepG2.215 cell lines (p = 0.02; p = 0.039). Furthermore, NK cells from high viral load CHB patients displayed significantly lower specific cytolytic activity against anti-NKp46-loaded K562 targets (p = 0.0321). No significant differences were observed in IFN-γ secretion (p > 0.05). In conclusion, NKp46 expression regulates NK cell cytolytic function. NKp46 may moderate NK cell activity during HBV replication suppression and HBV-associated liver damage and may be critical for NK cell activity during CHB infection.

Replication Inhibition of Hepatitis B Virus and Hepatitis C Virus in Co-Infected Patients in Chinese Population.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infections contributes to a substantial proportion of liver disease worldwide. The aim of this study was to assess the clinical and virological features of HBV-HCV co-infection. METHODS: Demographic data were collected for 3238 high-risk people from an HCV-endemic region in China. Laboratory tests included HCV antibody and HBV serological markers, liver function tests, and routine blood analysis. Anti-HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBsAg-positive samples were tested for HBV DNA. RESULTS: A total of 1468 patients had chronic HCV and/or HBV infections. Among them, 1200 individuals were classified as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were classified as co-infected. The HBV-HCV co-infected patients not only had a lower HBV DNA positive rate compared to HBV mono-infected patients (84.1% versus 94.4%, respectively; P < 0.001). The median HCV RNA levels in HBV-HCV co-infected patients were significantly lower than those in the HCV mono-infected patients (1.18[Interquartile range (IQR) 0-5.57] versus 5.87[IQR, 3.54-6.71] Log10 IU/mL, respectively; P < 0.001). Furthermore, co-infected patients were less likely to have detectable HCV RNA levels than HCV mono-infected patients (23.4% versus 56.5%, respectively; P < 0.001). Those HBV-HCV co-infected patients had significantly lower median HBV DNA levels than those mono-infected with HBV (1.97[IQR, 1.3-3.43] versus 3.06[IQR, 2-4.28] Log10 IU/mL, respectively; P < 0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection group, and similar to that of the HCV mono-infected group. CONCLUSION: These results suggest that co-infection with HCV and HBV inhibits the replication of both viruses. The serologic results of HBV-HCV co-infection in patients suggests more liver injury compared to HBV mono-infected patients, but is similar to HCV mono-infection.

Factors associated with spontaneous clearance of hepatitis C virus in Chinese population.

Hepatitis C virus (HCV) infections spontaneously clear in approximately 15-45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

A novel t(8;13)(q21;q22) translocation in a pediatric lipoma.

Pediatric lipomas are rare and their etiology is unknown. As in adult lipomas, a segment of 12q13-q15 has been documented as a common chromosomal rearrangement region. Here, we report a pediatric lipoma case without rearrangement of 12q13-q15 but with an apparently balanced translocation involving chromosomes 8 and 13 [t(8;13)(q21;q22)] detected by routine cytogenetic analysis, and small deletions on 5q21.1 and 8q21.11 detected by array comparative genetic hybridization. The small deletion on 8q21.11 is possibly due to chromosomal instability at the breakpoint of the translocation.