scholarly journals Baseline Amino Acid Substitutions in the NS5A ISDR and PKR Binding Domain of Hepatitis C and Different Fibrosis Levels and Levels of Development of Hepatocellular Carcinoma in Patients Treated with DAAs

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 255
Author(s):  
Stefania Paolucci ◽  
Antonio Piralla ◽  
Federica Novazzi ◽  
Alice Fratini ◽  
Renato Maserati ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
High Frequency ◽  
Transient Elastography ◽  
Hcv Rna ◽  
Amino Acid Substitutions ◽  
Advanced Fibrosis ◽  
Ns5a Region ◽  
Advanced Liver Fibrosis

Variations in the interferon sensitivity-determining region (ISDR) within the NS5A region were related to the development of hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV). The aim of the study was to investigate a relationship between ISDR/PKR substitutions and their association with liver fibrosis or HCC development. A total of 316 patients infected with HCV and treated with DAAs were evaluated. HCV RNA was quantified and sequenced before treatment. The liver fibrosis stage was assessed by transient elastography and equalized to METAVIR scores. Multivariate analysis showed that ≥3 substitutions in ISDR and ≥6 in PKR-bd were significantly associated with advanced fibrosis. Advanced fibrosis was observed in patients with higher substitutions in ISDR and PKR-bd. A higher correlation between advanced fibrosis and a high frequency of ≥3 substitutions in ISDR and ≥6 in PKR-bd was observed in patients infected with genotype 2c. In addition, in a higher proportion of HCC patients, advanced fibrosis (40.4% vs. 88.2%; p < 0.001) and ≥6 substitutions in PKR-bd (15.4% vs. 41.2%; p = 0.01) was observed. In conclusion, a higher number of substitutions in ISDR and PKR-bd were associated with advanced liver fibrosis, suggesting a use of like predictors for progression in the liver damage. A significantly higher number of PKR-bd substitutions was observed in HCC patients; in particular, in patients infected with HCV genotype 2c.

Dynamic Evaluation of Liver Fibrosis to Assess the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Who Achieved Sustained Virologic Response

2019 ◽  
Author(s):  
Hidenori Toyoda ◽  
Toshifumi Tada ◽  
Satoshi Yasuda ◽  
Kazuyuki Mizuno ◽  
Takanori Ito ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Sustained Virologic Response ◽  
Dynamic Assessment ◽  
Predictive Ability ◽  
Virologic Response ◽  
Hcv Therapy ◽  
Number Of Patients ◽  
Advanced Liver Fibrosis

Abstract Background Liver fibrosis is an important risk factor for the development of hepatocellular carcinoma (HCC) after sustained virologic response (SVR) in patients with persistent hepatitis C virus (HCV) infection. However, as the degree of liver fibrosis changes following the eradication of HCV after SVR, it is unclear whether the prediction of HCC development based on liver fibrosis at baseline remains valid. Methods In 522 patients who achieved SVR by interferon-based anti-HCV therapy, the Fibrosis-4 Index for Liver Fibrosis (FIB-4 index) was updated annually by recalculation based on laboratory values after SVR. The incidence of HCC was reassessed annually based on the updated FIB-4 index. Results The percentage of patients with mild liver fibrosis (FIB-4 index <1.45) increased annually after SVR, whereas the percentage of patients with advanced liver fibrosis (FIB-4 index ≥3.25) decreased. The incidences of HCC based on the FIB-4 index remained constant between the time of SVR and subsequent annual updates. No patients developed HCC after SVR if the FIB-4 index decreased to <1.45. Conclusions The FIB-4 index retained its predictive ability for the risk of HCC when recalculated after SVR, despite the decrease in patients with high FIB-4 index values. Dynamic assessment of the FIB-4 index can be useful in the surveillance of HCC after SVR. Patients with a FIB-4 index <1.45 did not develop HCC even by the regression from advanced fibrosis after SVR. Further studies will be necessary to confirm these findings, which may result in a decrease in the number of patients in whom surveillance is required.

scholarly journals Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening

2020 ◽  
Author(s):  
Romina Lomonaco ◽  
Eddison Godinez Leiva ◽  
Fernando Bril ◽  
Sulav Shrestha ◽  
Lydia Mansour ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Transient Elastography ◽  
Outpatient Setting ◽  
Plasma Diagnostic ◽  
Advanced Fibrosis ◽  
Systematic Screening ◽  
Established Risk Factor ◽  
Advanced Liver Fibrosis ◽  
Clinically Significant

<b>Objective:</b> Assess the prevalence of NAFLD and of liver fibrosis associated with nonalcoholic steatohepatitis (NASH) in unselected patients with T2DM. <p><b>Research Design and Methods:</b> 561 patients with T2DM (age: 60±11; BMI: 33.4±6.2 kg/m<sup>2</sup>; HbA1c: 7.5±1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by CAP (≥274 dB/m) and LSM (≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as APRI and FIB-4, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.</p> <p><b>Results:</b> The prevalence of steatosis was 70% and of fibrosis 21% (LSM≥7.0 kPa). Moderate fibrosis (F2: LSM≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3-4: LSM≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Non-invasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 U/L were present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4, APRI).</p> <p><b>Conclusions: </b>Moderate-to-advanced fibrosis (F≥2), an established risk factor for cirrhosis and overall mortality, affects at least one-out-of-six (15%) patients with T2DM. These results support the ADA guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.</p>

scholarly journals Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening

2021 ◽  
Author(s):  
Romina Lomonaco ◽  
Eddison Godinez Leiva ◽  
Fernando Bril ◽  
Sulav Shrestha ◽  
Lydia Mansour ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Transient Elastography ◽  
Outpatient Setting ◽  
Plasma Diagnostic ◽  
Advanced Fibrosis ◽  
Systematic Screening ◽  
Established Risk Factor ◽  
Advanced Liver Fibrosis ◽  
Clinically Significant

<b>Objective:</b> Assess the prevalence of NAFLD and of liver fibrosis associated with nonalcoholic steatohepatitis (NASH) in unselected patients with T2DM. <p><b>Research Design and Methods:</b> 561 patients with T2DM (age: 60±11; BMI: 33.4±6.2 kg/m<sup>2</sup>; HbA1c: 7.5±1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by CAP (≥274 dB/m) and LSM (≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as APRI and FIB-4, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.</p> <p><b>Results:</b> The prevalence of steatosis was 70% and of fibrosis 21% (LSM≥7.0 kPa). Moderate fibrosis (F2: LSM≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3-4: LSM≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Non-invasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 U/L were present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4, APRI).</p> <p><b>Conclusions: </b>Moderate-to-advanced fibrosis (F≥2), an established risk factor for cirrhosis and overall mortality, affects at least one-out-of-six (15%) patients with T2DM. These results support the ADA guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.</p>

scholarly journals Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics

2021 ◽  
Vol 22 (14) ◽  
pp. 7411
Author(s):  
Jingjing Jiao ◽  
Jessica I. Sanchez ◽  
Erika J. Thompson ◽  
Xizeng Mao ◽  
Joseph B. McCormick ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Fibrosis ◽  
Somatic Mutations ◽  
Advanced Fibrosis ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Significant Difference ◽  
Advanced Liver Fibrosis

Hispanics are disproportionally affected by liver fibrosis and hepatocellular carcinoma (HCC). Advanced liver fibrosis is a major risk factor for HCC development. We aimed at identifying somatic mutations in plasma cell-free DNA (cfDNA) of Hispanics with HCC and Hispanics with advanced liver fibrosis but no HCC. Targeted sequencing of over 262 cancer-associated genes identified nonsynonymous mutations in 22 of the 27 HCC patients. Mutations were detected in known HCC-associated genes (e.g., CTNNB1, TP53, NFE2L2, and ARID1A). No difference in cfDNA concentrations was observed between patients with mutations and those without detectable mutations. HCC patients with higher cfDNA concentrations or higher number of mutations had a shorter overall survival (p < 0.001 and p = 0.045). Nonsynonymous mutations were also identified in 17 of the 51 subjects with advanced liver fibrosis. KMT2C was the most commonly mutated gene. Nine genes were mutated in both subjects with advanced fibrosis and HCC patients. Again, no significant difference in cfDNA concentrations was observed between subjects with mutations and those without detectable mutations. Furthermore, higher cfDNA concentrations and higher number of mutations correlated with a death outcome in subjects with advanced fibrosis. In conclusion, cfDNA features are promising non-invasive markers for HCC risk prediction and overall survival.

scholarly journals Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening

2021 ◽  
Author(s):  
Romina Lomonaco ◽  
Eddison Godinez Leiva ◽  
Fernando Bril ◽  
Sulav Shrestha ◽  
Lydia Mansour ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Transient Elastography ◽  
Outpatient Setting ◽  
Plasma Diagnostic ◽  
Advanced Fibrosis ◽  
Systematic Screening ◽  
Established Risk Factor ◽  
Advanced Liver Fibrosis ◽  
Clinically Significant

<b>Objective:</b> Assess the prevalence of NAFLD and of liver fibrosis associated with nonalcoholic steatohepatitis (NASH) in unselected patients with T2DM. <p><b>Research Design and Methods:</b> 561 patients with T2DM (age: 60±11; BMI: 33.4±6.2 kg/m<sup>2</sup>; HbA1c: 7.5±1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by CAP (≥274 dB/m) and LSM (≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as APRI and FIB-4, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.</p> <p><b>Results:</b> The prevalence of steatosis was 70% and of fibrosis 21% (LSM≥7.0 kPa). Moderate fibrosis (F2: LSM≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3-4: LSM≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Non-invasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 U/L were present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4, APRI).</p> <p><b>Conclusions: </b>Moderate-to-advanced fibrosis (F≥2), an established risk factor for cirrhosis and overall mortality, affects at least one-out-of-six (15%) patients with T2DM. These results support the ADA guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.</p>

scholarly journals Non-Invasive Indirect Markers of Liver Fibrosis after Interferon-Free Treatment for Hepatitis C

2021 ◽  
Vol 10 (17) ◽  
pp. 3951
Author(s):  
Dagmara Przekop ◽  
Jakub Klapaczynski ◽  
Agnieszka Grytczuk ◽  
Ewa Gruszewska ◽  
Andrzej Gietka ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Transient Elastography ◽  
Histopathological Examination ◽  
Hcv Rna ◽  
Significant Fibrosis ◽  
Non Invasive ◽  
Free Treatment ◽  
Ap Index

The effectiveness of interferon-free therapy during the course of HCV infection has already been confirmed. Liver fibrosis can be assessed in several ways, from biopsies to imaging tests. The present study evaluates the usefulness of non-invasive indirect biomarkers of liver fibrosis (APRI, GAPRI, FORNS, FIB-4, the AP index and HUI score) as markers of the effective treatment of HCV with the 3D regimen. Blood samples were collected from 70 patients suffering from chronic hepatitis C. Patients received the 3D AbbVie regimen for hepatitis C. All patients had HCV genotype 1b. The APRI, GAPRI, FIB-4, FORNS, HUI and AP index (age–platelet score) values were calculated with their respective algorithms. The stage of fibrosis was evaluated on the basis of a liver biopsy and confirmed by FibroScan-based transient elastography. An undetectable level of HCV RNA after 12 weeks of treatment with the 3D regimen indicates 100% eradication of hepatitis C virus. After the treatment, non-invasive indirect markers of liver fibrosis achieved levels below the limit for significant fibrosis, Thus, non-invasive indirect biomarkers of hepatic fibrosis failed to detect the presence of significant fibrosis, which was proved in histopathological examination. However, the eradication of hepatitis C virus by means of the 3D regimen treatment does not mean that patients were completely cured.

scholarly journals Clinical and epidemiological overview of liver fibrosis and hepatocellular carcinoma in patients infected with the hepatitis C virus

2020 ◽  
Vol 9 (7) ◽  
pp. e688974645
Author(s):  
Joao Victor Cordeiro Farias ◽  
Isabela Cristina Cordeiro Farias ◽  
Penelopy Rodrigues Macedo ◽  
Patrícia Muniz Mendes Freire de Moura
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Chronic Infection ◽  
Detection Methods ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hcv Rna ◽  
Medical Centers ◽  
Direct Acting

About 2.4 million people die each year worldwide as a result of chronic infection with the hepatitis C virus (HCV). HCV is a worldwide problem, more than 170 million people are infected with the virus worldwide, corresponding to about 3% of the population. Some common signs for patients chronically infected with HCV are: increased liver enzyme activity and chronic liver diseases, such as fibrosis, cirrhosis, and hepatocellular carcinoma. The present study consists of a literature review, of a qualitative nature which aims to approach the main clinical and epidemiological aspects of the chronic infection caused by the HCV. HCV detection is carried out by screening for antibodies by enzyme-linked immunosorbent assay (ELISA) and screening for HCV-RNA through polymerase chain reaction (PCR). The current detection methods are not viable for all medical centers and outpatient clinics, making it necessary to develop new detection methods, since the technological apparatus for screening HCV-RNA, as well as ELISA, is a distant reality for the vast majority of the global health system. The development of direct-acting antivirals (DAAs) increased the viral response, reaching up to 92.7% success rate. It is necessary to monitor post-treatment patients, as well as to treat patients who are still affected by the virus worldwide, to ensure that there is no progression of liver fibrosis in cirrhosis, nor the development of HCC. Additionally, vigilance should be maintained for possible mutations and the emergence of viral resistance to DAAs.

Sign in / Sign up

Export Citation Format

Share Document