Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 4.752
Filter
1.
Virol J ; 21(1): 127, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38835029

ABSTRACT

BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.


Subject(s)
Alanine Transaminase , DNA, Viral , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic , Liver Cirrhosis , Humans , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/pathology , Hepatitis B, Chronic/blood , Male , Female , Adult , Liver Cirrhosis/virology , Liver Cirrhosis/blood , Liver Cirrhosis/pathology , DNA, Viral/blood , Alanine Transaminase/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Middle Aged , Viral Load , Young Adult , Liver/pathology , Liver/virology , Biopsy
2.
J Immunol Res ; 2024: 6343757, 2024.
Article in English | MEDLINE | ID: mdl-38715844

ABSTRACT

This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up to actively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5). LX-2 cells' susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-free virus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed cell death, ROS imbalance, cytokines (IL-6, TGF-ß, and TNF-α), and extracellular matrix components (collagen, α-SMA, and MMP-9). The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes. Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidative stress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redox imbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cells exhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This study highlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress, profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors. These insights offer valuable potential therapies for coinfected individuals.


Subject(s)
Bystander Effect , Coculture Techniques , Coinfection , Cytokines , HIV Infections , Hepacivirus , Hepatic Stellate Cells , Hepatitis C , Liver Cirrhosis , Humans , Hepatic Stellate Cells/metabolism , HIV Infections/complications , HIV Infections/metabolism , HIV Infections/virology , HIV Infections/immunology , Hepacivirus/physiology , Hepatitis C/metabolism , Hepatitis C/virology , Hepatitis C/complications , Hepatitis C/immunology , Jurkat Cells , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Liver Cirrhosis/etiology , Cytokines/metabolism , Hepatocytes/metabolism , Hepatocytes/virology , HIV/physiology , Oxidative Stress , Cell Communication , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Extracellular Matrix/metabolism
3.
Medicine (Baltimore) ; 103(19): e38096, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728473

ABSTRACT

To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.


Subject(s)
Antiviral Agents , Elasticity Imaging Techniques , Hepatitis C, Chronic , Liver Cirrhosis , Sustained Virologic Response , Humans , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/blood , Male , Female , Antiviral Agents/therapeutic use , Middle Aged , Prospective Studies , Liver Cirrhosis/drug therapy , Liver Cirrhosis/virology , Adult , Liver/pathology , Liver/diagnostic imaging , Aspartate Aminotransferases/blood , Aged , Treatment Outcome
4.
Sci Rep ; 14(1): 10996, 2024 05 14.
Article in English | MEDLINE | ID: mdl-38744926

ABSTRACT

Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC < middle-stage HCC < advanced-stage HCC, Class A LC < Class B LC < Class C LC. Serum ApoB/ApoA1 ratio combined diagnosis with AFP exhibited the capability of increasing the detection efficacy and specificity of AFP for HCC and AFP-negative HCC. The incidence of LC and HCC in the respective logistic regression model showed a negative correlation with the serum ApoB/ApoA1 ratio in CHB patients (P < 0.05). After all confounding factors covered in this study were regulated, the result of the restricted cubic spline analysis suggested that in a certain range, serum ApoB/ApoA1 ratio showed an inverse correlation with the prevalence of LC or HCC in CHB patients. Serum ApoB/ApoA1 ratio in CHB patients may be conducive to identifying high-risk patients for HCC or LC, such that LC and HCC can be early diagnosed and treated.


Subject(s)
Apolipoprotein A-I , Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Cirrhosis , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/virology , Carcinoma, Hepatocellular/etiology , Liver Neoplasms/blood , Liver Neoplasms/virology , Liver Neoplasms/etiology , Liver Neoplasms/diagnosis , Apolipoprotein A-I/blood , Male , Female , Middle Aged , Liver Cirrhosis/blood , Liver Cirrhosis/virology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/complications , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/blood , Adult , Apolipoprotein B-100/blood , Hepatitis B virus , ROC Curve , Case-Control Studies , Apolipoproteins B/blood
5.
Viruses ; 16(5)2024 04 26.
Article in English | MEDLINE | ID: mdl-38793565

ABSTRACT

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.


Subject(s)
Antiviral Agents , Carcinoma, Hepatocellular , Hepacivirus , Hepatitis C, Chronic , Liver Neoplasms , Propensity Score , Sustained Virologic Response , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/virology , Male , Antiviral Agents/therapeutic use , Female , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Liver Neoplasms/prevention & control , Liver Neoplasms/virology , Middle Aged , Aged , Incidence , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/complications , Liver Cirrhosis/virology , Liver Cirrhosis/epidemiology , Prospective Studies , Italy/epidemiology , Risk Factors , Cohort Studies , Adult
6.
Clinics (Sao Paulo) ; 79: 100381, 2024.
Article in English | MEDLINE | ID: mdl-38733689

ABSTRACT

OBJECTIVES: The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS: A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS: At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION: Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.


Subject(s)
Antiviral Agents , Carcinoma, Hepatocellular , Elasticity Imaging Techniques , Hepatitis C, Chronic , Liver Cirrhosis , Liver Neoplasms , Sustained Virologic Response , Humans , Elasticity Imaging Techniques/methods , Male , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/virology , Female , Middle Aged , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnostic imaging , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/virology , Follow-Up Studies , Time Factors , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/virology , Treatment Outcome , Adult , Aged , Predictive Value of Tests
7.
J Infect Dev Ctries ; 18(4): 618-626, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38728647

ABSTRACT

INTRODUCTION: Hepatitis B virus (HBV) infection is a global epidemic that can lead to several liver diseases, seriously affecting people's health. This study aimed to investigate the clinical potential of serum ß-klotho (KLB) as a promising biomarker in HBV-related liver diseases. METHODOLOGY: This study enrolled 30 patients with chronic hepatitis B (CHB), 35 with HBV-related cirrhosis, 66 with HBV-related hepatocellular carcinoma (HCC), and 48 healthy individuals. ELISA measured the levels of serum KLB in the four groups. We then compared the differences in serum KLB levels among the groups and analyzed the relationship between serum KLB and routine clinical parameters. RESULTS: The concentrations of serum KLB levels were increased sequentially among the healthy subjects, the HBV-related CHB group, the HBV-related cirrhosis group, and the HBV-related HCC group (p < 0.05). Expression of KLB was positively correlated with alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, alkaline phosphatase, total bile acid, serum markers for liver fibrosis, ascites, cirrhosis, splenomegaly, and model for end-stage liver disease sodium, while negatively correlated with platelet count, albumin, and prothrombin activity (p < 0.05). In addition, serum KLB has better sensitivity in diagnosing HCC than AFP, and serum KLB combined with AFP has higher sensitivity and specificity than AFP alone in diagnosing HCC. CONCLUSIONS: Serum KLB level is associated with the severity of HBV-related liver diseases and has important diagnostic value for HCC. Therefore, it could be a predictive biomarker for monitoring disease progression.


Subject(s)
Biomarkers , Carcinoma, Hepatocellular , Hepatitis B, Chronic , Klotho Proteins , Humans , Male , Female , Biomarkers/blood , Middle Aged , Adult , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/complications , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/virology , Glucuronidase/blood , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Liver Cirrhosis/virology , Disease Progression , Enzyme-Linked Immunosorbent Assay , Aged
8.
PLoS One ; 19(5): e0296495, 2024.
Article in English | MEDLINE | ID: mdl-38713731

ABSTRACT

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.


Subject(s)
COVID-19 , Hospital Mortality , Liver Cirrhosis , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/epidemiology , COVID-19/pathology , Italy/epidemiology , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Female , Male , Middle Aged , Retrospective Studies , Aged , SARS-CoV-2/isolation & purification , Severity of Illness Index , Aged, 80 and over , Hospitalization/statistics & numerical data , Adult
9.
EBioMedicine ; 103: 105101, 2024 May.
Article in English | MEDLINE | ID: mdl-38583259

ABSTRACT

BACKGROUND: Gut dysbiosis is present in chronic hepatitis B virus (HBV) infection. In this study, we integrated microbiome and metabolome analysis to investigate the role of gut microbiome in virological response to nucleos(t)ide analogues (NAs) treatment. METHODS: Chronic HBV patients were prospectively recruited for steatosis and fibrosis assessments via liver elastography, with full-length 16S sequencing performed to identify the compositional gut microbiota differences. Fasting plasma bile acids were quantified by liquid chromatography-tandem mass spectrometry. FINDINGS: All patients (n = 110) were characterized into three distinct microbial clusters by their dominant genus: c-Bacteroides, c-Blautia, and c-Prevotella. Patients with c-Bacteroides had a higher plasma ursodeoxycholic acids (UDCA) level and an increase in 7-alpha-hydroxysteroid dehydrogenase (secondary bile acid biotransformation) than other clusters. In NAs-treated patients (n = 84), c-Bacteroides was associated with higher odds of plasma HBV-DNA undetectability when compared with non-c-Bacteroides clusters (OR 3.49, 95% CI 1.43-8.96, p = 0.01). c-Blautia was positively associated with advanced fibrosis (OR 2.74, 95% CI 1.09-7.31, p = 0.04). No such associations were found in treatment-naïve patients. Increased Escherichia coli relative abundance (0.21% vs. 0.03%, p = 0.035) was found in on-treatment patients (median treatment duration 98.1 months) with advanced fibrosis despite HBV DNA undetectability. An enrichment in l-tryptophan biosynthesis was observed in patients with advanced fibrosis, which exhibited a positive correlation with Escherichia coli. INTERPRETATION: Collectively, unique bacterial signatures, including c-Bacteroides and c-Blautia, were associated with virological undetectability and fibrosis evolution during NAs therapy in chronic HBV, setting up intriguing possibilities in optimizing HBV treatment. FUNDING: This study was supported by the Guangdong Natural Science Fund (2019A1515012003).


Subject(s)
Gastrointestinal Microbiome , Hepatitis B virus , Hepatitis B, Chronic , Humans , Gastrointestinal Microbiome/drug effects , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/microbiology , Male , Female , Middle Aged , Adult , Hepatitis B virus/genetics , Bacteroides , Antiviral Agents/therapeutic use , Metabolome , Treatment Outcome , Liver Cirrhosis/drug therapy , Liver Cirrhosis/etiology , Liver Cirrhosis/microbiology , Liver Cirrhosis/virology , Viral Load , Bile Acids and Salts/metabolism , Bile Acids and Salts/blood , Metagenomics/methods , Nucleosides/therapeutic use , Nucleosides/analogs & derivatives
10.
Hepatol Int ; 18(3): 904-916, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38565833

ABSTRACT

BACKGROUND: Evidence has proven that liver fibrosis or even cirrhosis can be reversed by anti-HBV treatment. However, the difference of fibrosis regression rates in short-term and long-term antiviral therapy remain unclear. Therefore, we aimed to identify the dynamic changes in fibrosis regression rate in patients with three-time liver biopsies during 5 years antiviral therapy. METHODS: CHB patients with three times of liver biopsies (baseline, after 1.5-year and 5-year antiviral therapy) from a prospective cohort were enrolled. All patients were biopsy-proved Ishak stage ≥ 3 at baseline (n = 92). Fibrosis regression was defined as Ishak stage decreased ≥ 1 or predominantly regressive categorized by P-I-R score. RESULTS: Totals of 65.2% (60/92) and 80.4% (74/92) patients attained fibrosis regression after 1.5-year and 5-year therapy, respectively. Median HBV DNA level declined from 6.5 log IU/ml (baseline) to 0 log IU/ml (1.5 years and 5 years, P < 0.001). The mean level of Ishak fibrosis stage in all patients decreased from stage 4.1 (baseline) to 3.7 (1.5 years) then 3.2 (5 years). Fibrosis regression rates were 0.27 stage/year between baseline to year 1.5 and 0.14 stage/year between year 1.5 and year 5. Furthermore, for patients who attained fibrosis regression after 5-year antiviral therapy, the two-phase regression rates were 0.39 stage/year (0 year-1.5 years) and 0.20 stage/year (1.5 years-5 years). This two-phase feature of regression rate was further confirmed by fully-quantification assessment of liver fibrosis based on SHG/TPEF. CONCLUSION: During the 5 years of long-term antiviral treatment, liver fibrosis rapidly regresses in the first 1.5 years before slowing down in the following 3.5 years.


Subject(s)
Antiviral Agents , Hepatitis B, Chronic , Liver Cirrhosis , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Liver Cirrhosis/drug therapy , Antiviral Agents/therapeutic use , Male , Female , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/pathology , Hepatitis B, Chronic/complications , Biopsy/methods , Middle Aged , Adult , Prospective Studies , Liver/pathology , DNA, Viral/analysis , DNA, Viral/blood , Hepatitis B virus/genetics , Treatment Outcome
11.
Viruses ; 16(4)2024 04 16.
Article in English | MEDLINE | ID: mdl-38675959

ABSTRACT

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.


Subject(s)
Comorbidity , Hepatitis B virus , Humans , Hepatitis B virus/physiology , Hepatitis B/epidemiology , Hepatitis B/complications , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/epidemiology , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/virology , Liver Neoplasms/epidemiology , Liver Neoplasms/virology , Liver Cirrhosis/epidemiology , Liver Cirrhosis/virology , Cost of Illness , Antiviral Agents/therapeutic use , Prevalence
12.
Front Cell Infect Microbiol ; 14: 1371429, 2024.
Article in English | MEDLINE | ID: mdl-38650735

ABSTRACT

Background: Achieving sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) reduces all-cause mortality. However, the mechanisms and risk factors for liver fibrosis and portal hypertension post-SVR remain incompletely understood. In the gut-liver axis, mucosa-associated microbiota (MAM) substantially influence immune and metabolic functions, displaying spatial heterogeneity at the anatomical intestinal site. We analyzed MAM composition and function to isolate the locoregional MAM involved in chronic liver disease progression in HCV post-SVR patients. Methods: We collected MAM samples from three intestinal sites (terminal ileum, ascending colon, and sigmoid colon) via brushing during colonoscopy in 23 HCV post-SVR patients and 25 individuals without liver disease (controls). The 16S rRNA of bacterial DNA in specimens collected with a brush and in feces was sequenced. The molecular expression of intestinal tissues and hepatic tissues were evaluated by quantitative real-time PCR. Results: In the post-SVR group, the microbial ß-diversity of MAM, especially in the ascending colon, differed from the control group and was associated with liver fibrosis progression. In PICRUSt analysis, MAM in the ascending colon in the liver cirrhosis (LC) group showed compromised functions associated with the intestinal barrier and bile acid production, and FGF19 expression was markedly decreased in the terminal ileum biopsy tissue in the LC group. At the genus level, six short-chain fatty acid (SCFA)-producing bacterial genera, Blautia, Alistipes, Roseburia, Agathobaculum, Dorea, and Pseudoflavonifractor were reduced in the ascending colon of post-SVR LC patients. Conclusion: In patients of HCV post-SVR, we identified the association between the degree of liver fibrosis and dysbiosis of mucosa-associated SCFA-producing bacterial genera that may be related to intestinal barrier and bile acid production in the ascending colon.


Subject(s)
Colon, Ascending , Dysbiosis , Gastrointestinal Microbiome , Intestinal Mucosa , Liver Cirrhosis , RNA, Ribosomal, 16S , Sustained Virologic Response , Humans , Liver Cirrhosis/virology , Liver Cirrhosis/microbiology , Male , Middle Aged , Female , RNA, Ribosomal, 16S/genetics , Colon, Ascending/microbiology , Colon, Ascending/pathology , Intestinal Mucosa/microbiology , Intestinal Mucosa/virology , Hepacivirus/genetics , Feces/microbiology , Feces/virology , Aged , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/microbiology , Hepatitis C, Chronic/virology , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Adult , DNA, Bacterial/genetics , Bile Acids and Salts/metabolism
13.
Dig Dis Sci ; 69(5): 1551-1561, 2024 May.
Article in English | MEDLINE | ID: mdl-38580885

ABSTRACT

Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5 g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.


Subject(s)
Antiviral Agents , Hepatitis C, Chronic , Liver Cirrhosis , Humans , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/complications , Liver Cirrhosis/virology , Liver Cirrhosis/drug therapy , Drug Therapy, Combination , Hepacivirus/genetics , Hepacivirus/drug effects , Sustained Virologic Response , Sofosbuvir/therapeutic use
14.
Asian Pac J Cancer Prev ; 25(4): 1325-1332, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38679993

ABSTRACT

OBJECTIVES: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Cytokeratins are a marker of hepatic progenitor cells and act as a key player in tumor invasion. Herein, we sought to develop a novel score based on the combination of cytokeratin 18 (CK18) and cytokeratin 19 (CK19) with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Serum CK18, CK 19, α-fetoprotein, albumin and platelets count were assayed in HCC patients (75), liver cirrhosis patients (55) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CK-HCC = CK 19 (ng/ml)×0.001+ CK18 (ng/ml)×0.004 + AFP (U/L)×5.4 - Platelets count (×109)/L×0.003 - Albumin (g/L)×0.27-36 was developed. CK-HCC score produces AUC of 0.919 for differentiating patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.3 (i.e., less than 1.3 the case is considered cirrhotic, whereas above 1.3 it is considered HCC. CONCLUSION: CK-HCC score could replace AFP during screening of HCV patients and early detection of HCC.


Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular , Hepacivirus , Keratin-18 , Keratin-19 , Liver Neoplasms , alpha-Fetoproteins , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/virology , Liver Neoplasms/diagnosis , Liver Neoplasms/blood , Liver Neoplasms/virology , Biomarkers, Tumor/blood , Female , Male , Middle Aged , Keratin-18/blood , Hepacivirus/isolation & purification , Keratin-19/blood , Case-Control Studies , alpha-Fetoproteins/analysis , alpha-Fetoproteins/metabolism , Liver Cirrhosis/diagnosis , Liver Cirrhosis/blood , Liver Cirrhosis/virology , Hepatitis C/diagnosis , Hepatitis C/virology , Hepatitis C/blood , Hepatitis C/complications , Prognosis , Follow-Up Studies , Adult , Aged
15.
Eur J Gastroenterol Hepatol ; 36(6): 735-741, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38683191

ABSTRACT

BACKGROUND: Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE: We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS: A Google form document was sent to those HGs from May to September 2021. RESULTS: A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION: Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.


Subject(s)
Gastroenterologists , Hepatitis D , Hepatitis Delta Virus , Practice Patterns, Physicians' , Adult , Female , Humans , Male , Middle Aged , Antiviral Agents/therapeutic use , Biopsy , France , Gastroenterology , Health Knowledge, Attitudes, Practice , Hepatitis B Surface Antigens/blood , Hepatitis Delta Virus/isolation & purification , Hepatitis Delta Virus/genetics , Liver Cirrhosis/virology , Practice Patterns, Physicians'/statistics & numerical data , Hepatitis D/blood , Hepatitis D/diagnosis , Hepatitis D/drug therapy , Hepatitis D/epidemiology
16.
Diagn Microbiol Infect Dis ; 109(2): 116264, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38493510

ABSTRACT

This study was performed to investigate the frequency of angiogenic T cells (CD4+ Tang cells) among CD4+ T cells in patients with hepatitis B-induced liver cirrhosis (HBV-LC) and to evaluate the predictive role of these cells in the clinical outcome. In total, 185 patients with HBV-LC were recruited to measure the frequency of CD4+ Tang cells and chemokine levels using flow cytometry. RESULTS: There was 11.4% of death after 3-momth follow-up. The AUC for the ability of the frequency of CD4+ Tang cell to predict death was 0.724 (higher than those for the MELD score, FIB-4 score, and Child-Pugh classification). Cox regression analysis revealed an association between the frequency of CD4+ Tang cells and a 3-month survival chance. CONCLUSIONS: The lower frequency of CD4+ T ang cells was correlated with the severity of HBV-LC and may serve as a prognostic predictor.


Subject(s)
CD4-Positive T-Lymphocytes , Liver Cirrhosis , Humans , Male , Female , Liver Cirrhosis/virology , Prognosis , Middle Aged , CD4-Positive T-Lymphocytes/immunology , Adult , Hepatitis B/complications , Flow Cytometry , Chemokines/blood , Hepatitis B, Chronic/complications , Aged
17.
United European Gastroenterol J ; 12(4): 516-525, 2024 May.
Article in English | MEDLINE | ID: mdl-38520063

ABSTRACT

BACKGROUND AND OBJECTIVE: The prevalence of Hepatitis Delta Virus (HDV) is underestimated and the assessment of fibrosis is recommended for this infection. We tested the diagnostic impact of an annual screening for HDV serology in Hepatitis B Surface Antigen (HBs Ag) chronic carriers and followed the progression of fibrosis in these patients. METHODS: Between January 2014 and October 2021, we annually tested all chronic HBs Ag-positive patients for HDV antibody (HDV Ab). Each HDV Ab positive patient underwent annually repeated elastometry. Patients with detectable HDV RNA levels (group 1) were compared to those with undetectable HDV RNA (group 2). RESULTS: We identified 610 chronic HBs Ag-positive patients, and repeated screening for HDV Ab was performed in 534 patients. Sixty (11%) patients were HDV Ab positive at baseline and were considered as "coinfected". Seven cases of HDV superinfection were diagnosed through repeated screening. In co-infected patients, cirrhosis was initially diagnosed in 12/60 patients and developed in six patients during follow-up. HDV RNA PCR was performed in 57/67 patients and 27 had detectable levels (group 1). Cumulative incidence of cirrhosis at 7 years was 13.8% (95% CI 0-30) in group 1 and 0 (95% CI 0-0) in group 2 (p = 0.026). CONCLUSION: A systematic screening for HDV in chronic HB Ag carriers revealed a high prevalence of HDV Ab. Repeated serological screening enables the diagnosis of superinfections in asymptomatic patients. Regular assessment of fibrosis using elastometry leads to the identification of incidental cirrhosis in patients with detectable HDV RNA.


Subject(s)
Carrier State , Hepatitis B Surface Antigens , Hepatitis B, Chronic , Hepatitis D , Hepatitis Delta Virus , Liver Cirrhosis , Mass Screening , Humans , Liver Cirrhosis/virology , Liver Cirrhosis/diagnosis , Male , Female , Hepatitis Delta Virus/genetics , Hepatitis Delta Virus/immunology , Hepatitis Delta Virus/isolation & purification , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/virology , Middle Aged , Hepatitis D/diagnosis , Hepatitis D/complications , Hepatitis D/epidemiology , Hepatitis B Surface Antigens/blood , Mass Screening/methods , Carrier State/diagnosis , Adult , RNA, Viral/blood , Coinfection/diagnosis , Disease Progression , Hepatitis Antibodies/blood , Prevalence , Elasticity Imaging Techniques , Aged , Incidence
18.
Aliment Pharmacol Ther ; 59(11): 1387-1401, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38501893

ABSTRACT

BACKGROUND: Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. AIM: To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. METHODS: We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. RESULTS: 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. CONCLUSION: HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.


Subject(s)
Antiviral Agents , Body Composition , Hepatitis C, Chronic , Muscle, Skeletal , Sarcopenia , Humans , Hepatitis C, Chronic/drug therapy , Antiviral Agents/therapeutic use , Male , Middle Aged , Female , Longitudinal Studies , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiopathology , Aged , Sarcopenia/drug therapy , Body Composition/drug effects , Hand Strength , Muscle Strength/drug effects , Liver Cirrhosis/drug therapy , Liver Cirrhosis/virology
19.
Aliment Pharmacol Ther ; 59(10): 1223-1235, 2024 May.
Article in English | MEDLINE | ID: mdl-38425096

ABSTRACT

BACKGROUND: Risk of hepatocellular carcinoma (HCC) persists after hepatitis B surface antigen (HBsAg) seroclearance in patients with chronic hepatitis B (CHB). AIMS: To identify risk factors and construct a predictive model for HCC development. METHODS: We retrospectively analysed patients with CHB with HBsAg seroclearance. Primary outcome was HCC development. Factors identified from a multivariate Cox model in the training cohort, consisting of 3476 patients from two Korean hospitals, were used to construct the prediction model. External validation was performed using data from 5255 patients in Hong Kong. RESULTS: In the training cohort, HCC occurred in 102 patients during 24,019 person-years of observation (0.43%/year). Risk scores were assigned to cirrhosis (C:3), age ≥50 years (A:2), male sex (M:3) and platelet count <150,000/mm3 (P:1); all were independently associated with an increased risk of HCC in multivariate analysis The time-dependent area under receiver operating characteristic curves for 5, 10 and 15 years in the training and validation cohorts were 0.782, 0.817 and 0.825 and 0.785, 0.771 and 0.796, respectively. In the validation cohort, 85 patients developed HCC (0.24%/year). The corresponding incidence of HCC in the low-, intermediate- and high-risk groups were 0.07%, 0.37% and 0.90%, respectively. CONCLUSIONS: The CAMP-B score (cirrhosis, age ≥50 years, male sex and platelet count <150,000/mm3/L) was significantly associated with HCC development after HBsAg seroclearance. CAMP-B score can be easily implemented in real-world clinical practice and helps stratify HCC risk in patients with CHB following HBsAg seroclearance.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B Surface Antigens , Hepatitis B, Chronic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/epidemiology , Male , Hepatitis B, Chronic/complications , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Female , Middle Aged , Hepatitis B Surface Antigens/blood , Retrospective Studies , Risk Factors , Adult , Aged , Liver Cirrhosis/virology , Hong Kong/epidemiology , Republic of Korea/epidemiology , Risk Assessment , Platelet Count , Age Factors
20.
J Hepatol ; 80(6): 868-881, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38311121

ABSTRACT

BACKGROUND & AIMS: Persons with chronic HBV infection coinfected with HIV experience accelerated progression of liver fibrosis compared to those with HBV monoinfection. We aimed to determine whether HIV and its proteins promote HBV-induced liver fibrosis in HIV/HBV-coinfected cell culture models through HIF-1α and TGF-ß1 signaling. METHODS: The HBV-positive supernatant, purified HBV viral particles, HIV-positive supernatant, or HIV viral particles were directly incubated with cell lines or primary hepatocytes, hepatic stellate cells, and macrophages in mono or 3D spheroid coculture models. Cells were incubated with recombinant cytokines and HIV proteins including gp120. HBV sub-genomic constructs were transfected into NTCP-HepG2 cells. We also evaluated the effects of inhibitor of HIF-1α and HIV gp120 in a HBV carrier mouse model that was generated via hydrodynamic injection of the pAAV/HBV1.2 plasmid into the tail vein of wild-type C57BL/6 mice. RESULTS: We found that HIV and HIV gp120, through engagement with CCR5 and CXCR4 coreceptors, activate AKT and ERK signaling and subsequently upregulate hypoxia-inducible factor-1α (HIF-1α) to increase HBV-induced transforming growth factor-ß1 (TGF-ß1) and profibrogenic gene expression in hepatocytes and hepatic stellate cells. HIV gp120 exacerbates HBV X protein-mediated HIF-1α expression and liver fibrogenesis, which can be alleviated by inhibiting HIF-1α. Conversely, TGF-ß1 upregulates HIF-1α expression and HBV-induced liver fibrogenesis through the SMAD signaling pathway. HIF-1α small-interfering RNA transfection or the HIF-1α inhibitor (acriflavine) blocked HIV-, HBV-, and TGF-ß1-induced fibrogenesis. CONCLUSIONS: Our findings suggest that HIV coinfection exacerbates HBV-induced liver fibrogenesis through enhancement of the positive feedback between HIF-1α and TGF-ß1 via CCR5/CXCR4. HIF-1α represents a novel target for antifibrotic therapeutic development in HBV/HIV coinfection. IMPACT AND IMPLICATIONS: HIV coinfection accelerates the progression of liver fibrosis compared to HBV monoinfection, even among patients with successful suppression of viral load, and there is no sufficient treatment for this disease process. In this study, we found that HIV viral particles and specifically HIV gp120 promote HBV-induced hepatic fibrogenesis via enhancement of the positive feedback between HIF-1α and TGF-ß1, which can be ameliorated by inhibition of HIF-1α. These findings suggest that targeting the HIF-1α pathway can reduce liver fibrogenesis in patients with HIV and HBV coinfection.


Subject(s)
Coinfection , HIV Infections , Hepatitis B virus , Hypoxia-Inducible Factor 1, alpha Subunit , Liver Cirrhosis , Signal Transduction , Transforming Growth Factor beta1 , Animals , Transforming Growth Factor beta1/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mice , Liver Cirrhosis/metabolism , Liver Cirrhosis/virology , Liver Cirrhosis/pathology , Humans , HIV Infections/complications , HIV Infections/metabolism , HIV Infections/pathology , Hepatitis B virus/genetics , Coinfection/virology , Mice, Inbred C57BL , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/metabolism , Hepatitis B, Chronic/pathology , Hepatitis B, Chronic/virology , HIV Envelope Protein gp120/metabolism , Hepatocytes/metabolism , Hepatocytes/virology , Hepatocytes/pathology , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/virology , Disease Models, Animal , Hep G2 Cells , Male
SELECTION OF CITATIONS
SEARCH DETAIL
...