• Elastography
• Kidney
• Liver
• Mechanical properties
• Minimally invasive surgery
• Young's modulus

• Animals
• Swine
• Elasticity Imaging Techniques/methods
• Finite Element Analysis
• Elastic Modulus
• Silicones
• Minimally Invasive Surgical Procedures

Diagnosis of significant liver fibrosis is essential to facilitate the optimal treatment decisions and improve prognosis in patients with chronic hepatitis B (CHB). We aimed to evaluate the value of inflammatory indicators and construct a nomogram that effectively predicts significant liver fibrosis among CHB patients. 563 CHB patients from two centers in China from 2014 to 2019 were divided into three cohorts (development, internal validation, and independent validation cohorts), assigned into cases with significant fibrosis (liver fibrosis stages ≥2) and those without. Multiple biochemical and serological inflammatory indicators were investigated. Inflammatory indicators, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly associated with significant liver fibrosis in CHB patients but limited predictive performance, and then we combined them with prothrombin time activity percentage (PTA) and liver stiffness measurement (LSM) were identified by multivariate logistic regression analysis. Based on these factors, we constructed the nomogram with excellent performance. The area under the receiver operating characteristic curve (AUROC) for the nomogram in the development, internal validation, and independent validation cohorts were 0.860, 0.877, and 0.811, respectively. Our nomogram based on ALT and AST that had excellent performance in predicting significant fibrosis of CHB patients were constructed.

• chronic hepatitis B
• diagnosis
• inflammatory indicators
• liver fibrosis
• predicting tool

• Biomarker
• Cirrhosis
• PET/CT
• [¹¹C] choline

• nanobiotechnology
• sensors and probes

• Animals
• Female
• Male
• Biocompatible Materials
• Biomechanical Phenomena
• Feasibility Studies
• Hydrogels
• Kidney
• Liver
• Mice, Inbred C57BL
• Nanotechnology/methods
• Spleen
• Uterus
• Vascular Stiffness
• Mice

• Deutsche Forschungsgemeinschaft (DFG)
• Projekt DEAL

HIV infection exacerbates the prognosis of HCV infection, with a faster progression of hepatitis. Hepatic fibrosis is the major disruption of the hepatic tissue architecture characterized by anarchic deposition and excess of the extracellular matrix. The objective of this study was to evaluate hepatic fibrosis in HIV/HCV co-infected individuals as compared to HCV mono-infected.

A total of 97 participants (mean age 60.2 ± 14.3 years and 0.76 male/female sex ratio) was enrolled in a study conducted in Yaoundé, Cameroon from November 2018 to January 2019. Liver fibrosis was assessed by the APRI score (Aspartate Aminotransferase or AST/Platelet Ratio Index) which identifies the stage of fibrosis as classified by the Metavir system (F0 to F4). CD4 counts and plasmatic HIV viral load of HIV/HCV co-infected individuals were determined and the correlation between hepatic fibrosis and immuno-virological status established. Statistical analysis was done using Microsoft Excel 2016 and EpiInfo7 software.

A high proportion (63.6%) of HIV/HCV co-infected participants had an abnormal AST level: 73.6 ± 45.8 IU/L as compared to 58.5 ± 39.3 IU/L (59.3%) among HCV mono-infected participants. The frequency of thrombocytopenia was 63.6% with a mean platelet count of 137 ± 50 ×  10³ IU/L in HIV/HCV co-infected participants as compared to 176 ± 67 × 10³ IU/L in HCV mono-infected participants (38.4%). The progression of hepatic fibrosis in participants with clinically significant fibrosis: F2, F3 and F4 was higher among HIV/HCV co-infected and the mean APRI score was 1.7 ± 1.4 versus 1 ± 0.8 among HCV mono-infected (26.7%). All participants (100%) with detectable HIV viral load had clinically significant fibrosis compared to 33.4% in those with undetectable HIV viral load (p = 0.55). Only 42.9% participants with CD4 >  500 cells/μL had clinically significant fibrosis (p = 0.72) while 100% participants with CD4 <  200 cells/μL had clinically significant fibrosis (p = 0.58).

A high level of AST combined with thrombocytopenia (APRI score > 1.5) is an indicator of hepatic fibrosis in HIV/HCV co-infected individuals. Because of its non-invasive and less costly nature, the APRI score can be a suitable biomarker to monitor hepatic fibrosis in HIV/HCV co-infected individuals in resource constrained settings.

• APRI score
• HIV/HCV co-infection
• Liver fibrosis
• Resource constrained settings
• Thrombocytopenia

• chronic hepatitis C
• genotype 3
• glecaprevir
• hepatitis C virus
• pibrentasvir
• ribavirin
• sofosbuvir
• velpatasvir

Non-invasive methods are the first choice for liver fibrosis evaluation in chronic liver diseases, but few studies investigate the ability of combined methods to predict outcomes.

591 chronic hepatitis C patients with baseline liver stiffness (LSM) by FibroScan and hyaluronic acid measurements were identified retrospectively. The patients were grouped by baseline LSM: < 10kPa, 10–16.9kPa, and 17-75kPa. Primary outcomes were all-cause mortality and liver-related mortality, analyzed using cox regression and competing risk regression models, respectively.

Median follow-up was 46.1 months. Prevalence of cirrhosis at baseline was 107/591 (18.1%). Median LSM was 6.8kPa (IQR 5.3–11.6) and divided into groups, 404/591 (68.4%) had a LSM < 10kPa, 100/591 (16.9%) had a LSM between 10–16.9kPa and 87/591 (14.7%) had a LSM between 17-75kPa. There were 69 deaths, 27 from liver-related disease. 26 patients developed cirrhosis and 30 developed complications of cirrhosis. The mortality rate in the 17-75kPa group was 9.7/100 person-years, compared to 2.2/100 person-years and 1.1/100 person-years in the 10–16.9kPa and <10kPa groups (p<0.005). Liver-related mortality increased 10-fold for each group (p<0.005). Cirrhotic complications occurred almost exclusively in the 17-75kPa group, with an incidence of 10.3/100 person-years, compared to 1.8/100 person-years and 0.2/100 person-years in the 10–16.9kPa and <10kPa groups (p<0.005). Median hyaluronic acid in the 17-75kPa group was approximately 200ng/mL. Patients with a LSM 17-75kPa had significantly higher risks of death, liver-related death, and complications to cirrhosis if their hyaluronic acid measurement was more than or equal to 200ng/mL at baseline, with hazard ratios of 3.25 (95% CI 1.48–7.25), 7.7 (95% CI 2.32–28), and 3.2 (95% CI 1.35–7.39), respectively.

The combination of LSM and circulating hyaluronic acid measurements significantly improved prognostic ability, relative to LSM alone. Combined static and dynamic markers of liver fibrosis could provide superior risk prediction.

• Adult
• Elasticity Imaging Techniques
• Female
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/metabolism
• Hepatitis C, Chronic/mortality
• Humans
• Hyaluronic Acid/blood
• Liver/diagnostic imaging
• Liver/pathology
• Liver Cirrhosis/diagnostic imaging
• Liver Cirrhosis/epidemiology
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/mortality
• Male
• Middle Aged
• Prevalence
• Prognosis
• Regression Analysis
• Retrospective Studies

• Fibrosis
• Hepatitis B virus
• Hepatitis C virus
• Human immunodeficiency virus
• Stiffness
• Treatment

• Antiviral Agents/therapeutic use
• Coinfection/drug therapy
• Coinfection/epidemiology
• Coinfection/pathology
• Coinfection/virology
• Comorbidity
• Disease Progression
• Drug Therapy, Combination
• HIV/immunology
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• HIV Infections/pathology
• HIV Infections/virology
• Hepacivirus/immunology
• Hepatitis B/drug therapy
• Hepatitis B/epidemiology
• Hepatitis B/pathology
• Hepatitis B/virology
• Hepatitis B virus/immunology
• Hepatitis C/drug therapy
• Hepatitis C/epidemiology
• Hepatitis C/pathology
• Hepatitis C/virology
• Humans
• Liver/pathology
• Liver/virology

• K01 AA026864 NIAAA NIH HHS
• R24 OD018546 NIH HHS

• Direct acting antivirals
• HIV progression
• HIV/HCV co-infection
• Hepatitis C virus
• Interferons

Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake.

We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness.

Liver stiffness ranged from 3.0–34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated.

Our findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations.

• Ageing
• Antiretroviral therapy
• Bayesian model averaging
• Elasticity imaging techniques
• HIV
• Lipodystrophy
• Liver fibrosis

Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12–3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23–6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01–11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.

We observed high mortality and liver disease progression associated primarily driven by untreated HIV and chronic hepatitis C as well as alcohol use in a cohort of PWID in India. Interventions to reduce HIV and HCV burden are needed.

Background. There are limited data on clinical outcomes of hepatitis C virus (HCV) infection from low- and middle-income countries. We characterize mortality and liver disease progression in a cohort of people who inject drugs (PWID) with high HCV burden.

Methods. In a cohort of PWID in Chennai, India, 851 persons were observed semiannually. Information on death was obtained through verbal autopsy and liver disease progression, which was defined as an incident liver stiffness measurement of ≥12.3 kPa if it was <12.3 at baseline. Poisson and Cox regression were used to identify factors associated with mortality and disease progression, respectively.

Results. At baseline, 36.9% of cases were infected with HCV, 16.7% were infected with human immunodeficiency virus (HIV), 71.6% had no or mild stiffness, 14.9% had moderate stiffness, and 13.5% had severe stiffness or cirrhosis. Mortality was significantly higher among those with moderate (mortality rate ratio [MRR] = 2.31) and severe stiffness (MRR = 4.86) at baseline, those with ongoing substance use, those who were HIV monoinfected and not on antiretroviral therapy (ART) (MRR = 6.59), and those who were HIV/HCV coinfected regardless of ART status (MRR for no ART = 5.34; MRR for ART = 4.51). Of those with no or mild stiffness, 25.9% and 6.4% had evidence of progression to moderate and severe stiffness or cirrhosis, respectively; 38.3% of those with moderate stiffness had evidence of progression to severe stiffness or cirrhosis. Factors associated with progression included age, alcohol use, body mass index, and chronic HCV infection.

Conclusions. We observed significant morbidity and mortality primarily driven by untreated HIV, HIV/HCV coinfection, and alcohol use. Even with improved access to HIV treatment, in the absence of HCV treatment, outcomes are unlikely to improve for HIV/HCV-coinfected persons.

• HIV/AIDS
• hepatitis C virus
• liver stiffness
• low- and middle-income settings
• mortality

• Cohort Studies
• Community Health Services
• Elasticity Imaging Techniques
• Female
• Humans
• Liver/diagnostic imaging
• Liver Cirrhosis/diagnostic imaging
• Male
• Middle Aged
• Taiwan

• HIV coinfection
• alanine aminotransferase
• aspartate aminotransferase
• hepatitis C virus
• liver fibrosis