In a randomized trial of patients with primary biliary cholangitis, bezafibrate and ursodeoxycholic acid resulted in a higher rate of complete biochemical response than ursodeoxycholic acid alone. ...Bezafibrate was associated with increases in creatinine and myalgias.
Summary
Background
The accuracy of available non‐invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited.
Aim
To assess the diagnostic ...performance of paired or serial combination of non‐invasive tools in NAFLD patients.
Methods
We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB‐4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan.
Results
LSM, NFS and FIB‐4 were the best non‐invasive tools for staging F3‐F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB‐4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB‐4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB‐4 values (<−1.455 and <1.30, respectively) overall increased the diagnostic performance generating an accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to 20.4% and a rate of wrong classification ranging from 9.2% to 11.3%.
Conclusion
The serial combination of LSM with FIB‐4/NFS has a good diagnostic accuracy for the non‐invasive diagnosis of severe fibrosis in NAFLD.
Linked ContentThis article is linked to Khan paper. To view this article visit https://doi.org/10.1111/apt.14267.
In two trials involving patients with hepatitis C in whom previous treatment with direct-acting antiviral agents failed, treatment for 12 weeks with sofosbuvir, velpatasvir, and voxilaprevir achieved ...high rates of sustained virologic response.
The majority of patients who are chronically infected with hepatitis C virus (HCV) can now be successfully treated with drugs that directly target viral replication.
1
,
2
Combination regimens of direct-acting antiviral agents (DAAs) provide rates of sustained virologic response exceeding 90%, regardless of HCV genotype, disease stage, or treatment history.
3
The proportion of patients who do not have a sustained virologic response to treatment with approved regimens is small, but given the size of the infected population — estimates range up to 150 million people worldwide
4
— the absolute number of such patients is substantial and will increase as more . . .
Summary
Background
Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series.
Aim
To compare the characteristics of HBV/HCV coinfected patients to those of ...HBV‐ or HCV‐monoinfected patients in the ANRS CO22 HEPATHER cohort study.
Patients and Methods
Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti‐HCV antibody and HCV RNA positive) and were matched with 375 HBV‐ and 380 HCV‐monoinfected patients on age, gender and time since HBV or HCV diagnosis.
Results
F3‐F4 fibrosis was more frequent in coinfected patients (58%) than in HBV‐ (32%, P < .0001), but similar in HCV‐monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV‐ (2%, P = .0002) or HCV‐ (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV‐ (26%) or HCV‐monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3‐F4 fibrosis and HCV infection in HBV‐infected patients (OR = 3.84, 95% CI 1.99‐7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42‐22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22‐7.44).
Conclusions
HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV‐ or HCV‐monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients.
Linked ContentThis article is linked to Pol et al and Huang et al papers. To view these articles visit https://doi.org/10.1111/apt.14476 and https://doi.org/10.1111/apt.14445.
Background: Transient elastography (FibroScan) is a new, non-invasive, rapid, and reproducible method allowing evaluation of liver fibrosis by measurement of liver stiffness. In cirrhotic patients, ...liver stiffness measurements range from 12.5 to 75.5 kPa. However, the clinical relevance of these values is unknown. The aim of this prospective study was to evaluate the accuracy of liver stiffness measurement for the detection of cirrhosis in patients with chronic liver disease. Methods: A total of 711 patients with chronic liver disease were studied. Aetiologies of chronic liver diseases were hepatitis C virus or hepatitis B virus infection, alcohol, non-alcoholic steatohepatitis, other, or a combination of the above aetiologies. Liver fibrosis was evaluated according to the METAVIR score. Results: Stiffness was significantly correlated with fibrosis stage (r = 0.73, p<0.0001). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.80 (0.75–0.84) for patients with significant fibrosis (F>2), 0.90 (0.86–0.93) for patients with severe fibrosis (F3), and 0.96 (0.94–0.98) for patients with cirrhosis. Using a cut off value of 17.6 kPa, patients with cirrhosis were detected with a positive predictive value and a negative predictive value (NPV) of 90%. Liver stiffness was significantly correlated with clinical, biological, and morphological parameters of liver disease. With an NPV >90%, the cut off values for the presence of oesophageal varices stage 2/3, cirrhosis Child-Pugh B or C, past history of ascites, hepatocellular carcinoma, and oesophageal bleeding were 27.5, 37.5, 49.1, 53.7, and 62.7 kPa, respectively. Conclusion: Transient elastography is a promising non-invasive method for detection of cirrhosis in patients with chronic liver disease. Its use for the follow up and management of these patients could be of great interest and should be evaluated further.
A novel controlled attenuation parameter (CAP) has been developed for Fibroscan® to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy ...in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan® and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S0: steatosis in <10% of hepatocytes, S1: 11–33%, S2: 34–66% and S3: 67–100%. Performances of CAP and liver stiffness were determined using receiver operating characteristic (ROC) curve analysis and cross‐validated using the bootstrap method. The Obuchowski measure was used to assess overall accuracy of CAP and to differentiate between steatosis grades. In multivariate analysis, CAP was related to steatosis (P < 10−15) independently of fibrosis stage (which was related to LSM). The areas under ROC curves using CAP to detect steatosis were 0.80 (95% CI, 0.75–0.84) for S ≥ S1, 0.86 (0.81–0.92) for S ≥ S2 and 0.88 (0.73–1) S = S3. CAP exhibited a good ability to differentiate steatosis grades (Obuchowski measure = 0.92). Performance of LSM for fibrosis assessment confirmed results from previous studies. CAP is a novel tool to assess the degree of steatosis and both fibrosis and steatosis can be evaluated noninvasively during the same procedure using Fibroscan®, in patients with CHC.
Summary
Background
In chronic hepatitis C, the European Association for the Study of the Liver and the Asociacion Latinoamericana para el Estudio del Higado recommend performing transient ...elastography plus a blood test to diagnose significant fibrosis; test concordance confirms the diagnosis.
Aim
To validate this rule and improve it by combining a blood test, FibroMeter (virus second generation, Echosens, Paris, France) and transient elastography (constitutive tests) into a single combined test, as suggested by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.
Methods
A total of 1199 patients were included in an exploratory set (HCV, n = 679) or in two validation sets (HCV ± HIV, HBV, n = 520). Accuracy was mainly evaluated by correct diagnosis rate for severe fibrosis (pathological Metavir F ≥ 3, primary outcome) by classical test scores or a fibrosis classification, reflecting Metavir staging, as a function of test concordance.
Results
Score accuracy: there were no significant differences between the blood test (75.7%), elastography (79.1%) and the combined test (79.4%) (P = 0.066); the score accuracy of each test was significantly (P < 0.001) decreased in discordant vs. concordant tests. Classification accuracy: combined test accuracy (91.7%) was significantly (P < 0.001) increased vs. the blood test (84.1%) and elastography (88.2%); accuracy of each constitutive test was significantly (P < 0.001) decreased in discordant vs. concordant tests but not with combined test: 89.0 vs. 92.7% (P = 0.118). Multivariate analysis for accuracy showed an interaction between concordance and fibrosis level: in the 1% of patients with full classification discordance and severe fibrosis, non‐invasive tests were unreliable. The advantage of combined test classification was confirmed in the validation sets.
Conclusions
The concordance recommendation is validated. A combined test, expressed in classification instead of score, improves this rule and validates the recommendation of a combined test, avoiding 99% of biopsies, and offering precise staging.
Linked ContentThis article is linked to Trivedi and Lai, and Calès and Boursier papers. To view these articles visit https://doi.org/10.1111/apt.14011 and https://doi.org/10.1111/apt.14032
Summary
Background
The area under the receiver operating characteristic (ROC) curve is widely used as an estimate of the diagnostic value for fibrosis markers. Biopsy length and fragmentation are ...known as risk factors of false positive or false negative of biopsy but their quantitative impact on area under the receiver operating characteristic curve variability has not been assessed.
Aim
To assess these relationships to better compare the fibrosis markers.
Methods
The area under the ROC curves of FibroTest for the diagnosis of fibrosis was estimated in patients with chronic hepatitis C using an integrated database including 1312 patients with FibroTest and biopsy. To take into account the biopsy length, we used two adjustment factors: one in which an observed area under the ROC curve could be adjusted according to the relative area under the receiver operating characteristic curve of a biopsy of a given length vs. the entire liver and one taking into account the prevalence of each fibrosis stage defining advanced and non‐advanced fibrosis.
Results
The mean biopsy length was smaller for cirrhosis (F4, 16 mm) vs. F3, (18 mm, P = 0.01) and F0 (19 mm, P = 0.01). The mean number of fragments was higher for cirrhosis (F4 = 4.1 fragments) vs. all the other stages (F0 = 1.9, F1 = 1.9, F2 = 1.9, F3 = 2.3; P < 0.001 vs. F4). The FibroTest area under the ROC curves for the diagnosis of advanced fibrosis, adjusted for stages’ prevalence, ranged from 0.80 to 0.98 depending on biopsy length and fragmentation, respectively.
Conclusion
The comparison of the area under the ROC curves of fibrosis markers should take into account the biopsy length and fragmentation.
The existence of extrahepatic sites of hepatitis C virus (HCV) replication has been proposed as a mechanism responsible for the poor antiviral immune response found in chronic infection. Dendritic ...cells (DCs), as unique antigen-presenting cells able to induce a primary immune response, are prime targets of persistent viruses. From 24 blood samples obtained from HCV-seropositive patients, peripheral blood DCs (PBDCs) were purified. HCV genomic sequences were specifically detected by reverse-transcription polymerase chain reaction in 6 of 24 PBDC pellets, and replicative-strand RNA also was found in 3 of 24 cell purifications. Analysis of the HCV quasi-species distribution in the PBDC population of 1 patient showed the presence of a dominant variant different from that found in plasma with respect to the primary amino-acid sequence and physicochemical profile of the hypervariable region 1 of glycoprotein E2. These data strongly suggest that PBDCs constitute a reservoir in which HCV replication takes place during natural infection
PDF
