THE ROLE OF ELASTOGRAPHY IN CLINICALLY SIGNIFICANT PORTAL HYPERTENSION

ABSTRACT This is a narrative review that aims to discuss the importance of elastographic methods in the evaluation of clinically significant portal hypertension (CSPH) in cirrhotic patients, where the authors propose an algorithm for evaluating these patients. In compensated advanced chronic liver disease, the goal is to prevent the development of CSPH and, in those already with CSPH, prevent the appearance of gastroesophageal varices (GEV) and other complications of portal hypertension. In compensated cirrhosis, the prevalence of GEV is 30-40%, of which 10-20% are at risk of bleeding. Therefore, using non-invasive methods would exempt the patient from the need of an endoscopy. Hepatic Elastography is a non-invasive, safe, reproducible method, available through many techniques: Vibration-Controlled Transient Elastography (VCTE), Shear Wave Elastography (SWE) and Magnetic Resonance Elastography (MRE). The Baveno VII presented the “rule of 5” for VCTE: liver stiffness measurement (LSM) ≤15 kPa and platelets >150.000/mm3 exclude CSPH, while an LSM ≥25 kPa is highly suggestive of CSPH. Also, the “rule of 4” for SWE has been proposed: patients with ≥17 kPa could be considered as having CSPH. At last, spleen stiffness measurement (SSM) has been proposed as a more specific technique to predict the presence of CSPH. In conclusion, elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH

Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database

AIM: To evaluate the occurrence of resistant mutations in treatment-naïve hepatitis C virus (HCV) sequences deposited in the European hepatitis C virus database (euHCVdb). METHODS: The sequences were downloaded from the euHCVdb (https://euhcvdb.ibcp.fr/euHCVdb/). The search was performed for full-length NS3 protease, NS5A and NS5B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5A and 535 NS5B sequences from HCV genotypes 1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents (DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioEdit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis. RESULTS: The Q80K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V (3.21%) in genotype 1a, and Y56F (15.93%), V132I (23.28%) and I170V (65.20%) in genotype 1b. For the NS5A, 2.21% of the genotype 1a sequences have the P58S mutation, 5.95% of genotype 1b sequences have the R30Q mutation, 15.79% of subtypes 2a sequences have the Q30R mutation, 23.08% of subtype 2b sequences have a L31M mutation, and in subtype 3a sequences, 23.08% have the M31L resistant variants. For the NS5B, the V321L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142T variant was observed in 0.32% of subtype 1b sequences. The C316Y, S556G, D559N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes. CONCLUSION: HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome

Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database

AIM: To evaluate the occurrence of resistant mutations in treatment-naïve hepatitis C virus (HCV) sequences deposited in the European hepatitis C virus database (euHCVdb). METHODS: The sequences were downloaded from the euHCVdb (https://euhcvdb.ibcp.fr/euHCVdb/). The search was performed for full-length NS3 protease, NS5A and NS5B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5A and 535 NS5B sequences from HCV genotypes 1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents (DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioEdit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis. RESULTS: The Q80K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V (3.21%) in genotype 1a, and Y56F (15.93%), V132I (23.28%) and I170V (65.20%) in genotype 1b. For the NS5A, 2.21% of the genotype 1a sequences have the P58S mutation, 5.95% of genotype 1b sequences have the R30Q mutation, 15.79% of subtypes 2a sequences have the Q30R mutation, 23.08% of subtype 2b sequences have a L31M mutation, and in subtype 3a sequences, 23.08% have the M31L resistant variants. For the NS5B, the V321L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142T variant was observed in 0.32% of subtype 1b sequences. The C316Y, S556G, D559N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes. CONCLUSION: HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome

Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database

AIM: To evaluate the occurrence of resistant mutations in treatment-naïve hepatitis C virus (HCV) sequences deposited in the European hepatitis C virus database (euHCVdb). METHODS: The sequences were downloaded from the euHCVdb (https://euhcvdb.ibcp.fr/euHCVdb/). The search was performed for full-length NS3 protease, NS5A and NS5B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5A and 535 NS5B sequences from HCV genotypes 1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents (DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioEdit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis. RESULTS: The Q80K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V (3.21%) in genotype 1a, and Y56F (15.93%), V132I (23.28%) and I170V (65.20%) in genotype 1b. For the NS5A, 2.21% of the genotype 1a sequences have the P58S mutation, 5.95% of genotype 1b sequences have the R30Q mutation, 15.79% of subtypes 2a sequences have the Q30R mutation, 23.08% of subtype 2b sequences have a L31M mutation, and in subtype 3a sequences, 23.08% have the M31L resistant variants. For the NS5B, the V321L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142T variant was observed in 0.32% of subtype 1b sequences. The C316Y, S556G, D559N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes. CONCLUSION: HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome

LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts