• hepatitis C
• liver fibrosis
• shear wave elastography

• Fibrosing cholestatic hepatitis
• HCV
• Liver transplantation
• Recurrence
• Treatment, Pathology

Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.

• Hepatitis C, Comorbidities, Screening and treatment policy
• Hepatitis C virus
• Review

• Elimination
• Epidemic
• Hepatitis C virus
• Liver disease
• Modeling
• Opioid substitution therapy (OST)
• People who inject drugs (PWID)
• Prevention
• Public health
• Treatment

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023–0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.

• direct-acting antiviral drugs
• hepatitis C
• hepatocellular carcinoma
• liver stiffness
• liver ultrasound elastography

• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/epidemiology
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Humans
• Liver/diagnostic imaging
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/etiology
• Liver Neoplasms/drug therapy
• Liver Neoplasms/epidemiology

• infectious diseases
• hepatology
• nutrition
• quality of life
• target validation

• Adult
• Aged
• Antiviral Agents/therapeutic use
• Body Mass Index
• Case-Control Studies
• Female
• Follow-Up Studies
• Hepacivirus/drug effects
• Hepacivirus/immunology
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/epidemiology
• Hepatitis C, Chronic/immunology
• Hepatitis C, Chronic/virology
• Humans
• Male
• Metabolic Diseases/physiopathology
• Middle Aged
• Neoplasms/drug therapy
• Neoplasms/pathology
• Obesity/physiopathology
• Prognosis
• Quality of Life
• Young Adult

• fibrosis
• hepatitis C
• liver stiffness
• treatment

Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations in UGT1A1 gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association of UGT1A1 TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse.

Genetic testing of UGT1A1 TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging.

UGT1A1*28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p=0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence of UGT1A1*28 genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation of UGT1A1*28 genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence of UGT1A1*28 genotype in CHC patients with severe liver injury.

Frequencies of UGT1A1*28 genotype are high in both Serbian CHC patients and healthy subjects. The presence of UGT1A1*28 genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.

• Gilbert syndrome
• UGT1A1
• hepatitis C
• hyperbilirubinemia
• late relapse

• chronic hepatitis C
• controlled attenuation parameter
• fibroscan
• hepatitis C virus
• steatosis

• Adult
• Aged
• Brazil/epidemiology
• Cross-Sectional Studies
• Elasticity Imaging Techniques
• Female
• Hepatitis C, Chronic/diagnostic imaging
• Hepatitis C, Chronic/epidemiology
• Hepatitis C, Chronic/pathology
• Hepatitis C, Chronic/physiopathology
• Humans
• Liver/diagnostic imaging
• Liver/pathology
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/diagnostic imaging
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/pathology
• Non-alcoholic Fatty Liver Disease/physiopathology
• Predictive Value of Tests
• Prevalence
• Retrospective Studies
• Risk Factors

• Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
• Conselho Nacional de Desenvolvimento Científico e Tecnológico, (CNPq)

• Addiction
• Alcohol
• Behavioral
• Hepatitis C
• Integrated care
• Therapy

• Humans
• Alcohol Abstinence
• Alcohol Drinking
• Alcoholism/epidemiology
• Alcoholism/therapy
• Carcinoma, Hepatocellular/epidemiology
• Cognitive Behavioral Therapy/methods
• Comorbidity
• Cost-Benefit Analysis
• Hepatitis C, Chronic/epidemiology
• Liver Cirrhosis/epidemiology
• Liver Neoplasms/epidemiology
• Motivational Interviewing/methods
• Psychotherapy, Group
• Quality-Adjusted Life Years
• Randomized Controlled Trials as Topic
• Risk Reduction Behavior
• Multicenter Studies as Topic

• P30 AI064518 NIAID NIH HHS
• R01 AA021133 NIAAA NIH HHS

• Agentes antivirales de acción directa
• Consenso
• Consensus
• Direct-acting antiviral agents
• Interferon-free regimens
• Regímenes libres de interferón
• Ribavirin
• Ribavirina

• Antiviral Agents/therapeutic use
• Consensus
• Evidence-Based Medicine
• Hepatitis C/drug therapy
• Hepatitis C/therapy
• Humans
• Mexico

• Biomarker
• Cirrhosis/cirrhotics
• Fibrosis
• Hepatitis C virus
• Tenascin-C

• Herth Hope Index
• depression
• employment
• fatigue
• health-related quality of life
• hepatitis C
• hope
• injecting drug use
• nursing care
• stigma

• Diagnosis
• Hepatocellular carcinoma
• Staging
• Surveillance
• Treatment

• age-standardized death rate
• cirrhosis mortality
• hepatocellular carcinoma mortality
• liver disease mortality

CXCL9-11 polymorphisms are related to various infectious diseases, including hepatitis C virus (HCV) infection. In this study, we analyzed the association between CXCL9-11 polymorphisms and liver fibrosis in HCV-infected patients.

We performed a cross-sectional study in 389 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using the Sequenom’s MassARRAY platform. The primary outcome variable was the liver stiffness measurement (LSM). We established three cut-offs of LSM: LSM ≥ 7.1 kPa (F ≥ 2—significant fibrosis), LSM ≥ 9.5 kPa (F ≥ 3—advanced fibrosis), and LSM ≥ 12.5 kPa (F4—cirrhosis).

Recessive, overdominant and codominant models of inheritance showed significant values, but the overdominant model was the best fitting our data. In this case, CXCL9 rs10336 AG, CXCL10 rs3921 CG and CXCL11 rs4619915 AG were mainly associated with lower values of LSM [(adjusted GMR (aGMR) = 0.85 (p = 0.005), aGMR = 0.84 (p = 0.003), and aGMR = 0.84 (p = 0.003), respectively]. Patients with CXCL9 rs10336 AG genotype had lower odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 0.59 (p = 0.016)], advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 0.54 (p = 0.010)], and cirrhosis (LSM ≥ 12.5 kPa) [aOR = 0.56 (p = 0.043)]. Patients with CXCL10 rs3921 CG or CXCL11 rs4619915 AG genotypes had lower odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 0.56 (p = 0.008)], advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 0.55 (p = 0.013)], and cirrhosis (LSM ≥ 12.5 kPa) [aOR = 0.57 (p = 0.051)]. Additionally, CXCL9-11 polymorphisms were related to lower liver stiffness under a codominant model of inheritance, being the heterozygous genotypes also protective against hepatic fibrosis. In the recessive inheritance model, the CXCL9 rs10336 AA, CXCL10 rs3921 CC and CXCL11 rs4619915 AA were associated with higher LSM values [(adjusted GMR (aGMR) = 1.19 (p = 0.030), aGMR = 1.21 (p = 0.023), and aGMR = 1.21 (p = 0.023), respectively]. Moreover, patients with CXCL9 rs10336 AA genotype had higher odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 1.83 (p = 0.044)] and advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 1.85 (p = 0.045)]. Furthermore, patients with CXCL10 rs3921 CC or CXCL11 rs4619915 AA genotypes had higher odds of advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 1.89 (p = 0.038)].

CXCL9-11 polymorphisms were related to likelihood of having liver fibrosis in HCV-infected patients. Our data suggest that CXCL9-11 polymorphisms may play a significant role against the progression of CHC and could help prioritize antiviral therapy.

• CXCL9-11
• Chronic hepatitis C
• Cirrhosis
• Liver fibrosis
• Liver stiffness
• SNPs

Increased risk of both cardiovascular disease (CVD) and bleeding has been found in patients with chronic hepatitis C (CHC) infection, and a re-balanced hemostasis has been proposed. The aim of this study was to investigate functional whole blood coagulation and platelet function in CHC infection. The prospective study included 82 patients with CHC infection (39 with advanced liver fibrosis and 43 with no or mild liver fibrosis) and 39 healthy controls. A total of 33 patients were treated for CHC infection and achieved sustained virological response (SVR). Baseline and post-treatment blood samples were collected. Hemostasis was assessed by both standard coagulation tests and functional whole blood hemostatic assays (thromboelastograhy (TEG), and platelet aggregation (Multiplate). Patients with CHC and advanced fibrosis had impaired platelet aggregation both compared to patients with no or mild fibrosis and to healthy controls. Patients with CHC and advanced fibrosis also had lower antithrombin, platelet count, and coagulation factors II-VII-X compared to healthy controls. In contrast, TEG did not differ between groups. In treated patients achieving SVR, post-treatment platelet count was higher than pre-treatment counts (p = 0.033) and ADPtest, ASPItest, and RISTOhightest all increased post treatment (all p < 0.05). All Multiplate tests values, however, remained below those in the healthy controls. CHC-infected patients displayed evidence of rebalanced hemostasis with only partly hemostatic normalization in patients achieving SVR. The implications of rebalanced hemostasis and especially the impact on risk of CVD and bleeding warrants further studies.

• HCV
• hemostasis
• platelet aggregation

Hepatitis B and C viruses (HBV and HCV), both cause serious chronic infections leading to fatal liver diseases. The prototype therapy for both HBV and HCV was based on IFN-α with or without ribavirin. The advent of direct-acting antivirals (DAA) for both HBV and HCV has remarkably improved the standard of treatment for both infections. While HCV can be eliminated following combination DAA therapy, HBV persists even after treatment, requiring life-long therapy with DAAs. Treatment with DAAs is also associated with high cost, the development of resistance and side effects. There is ample published evidence that both HBV and HCV can be eliminated from infected host cells through non-cytolytic immune mechanisms. We need to identify the mechanisms behind this successful elimination of replicating viruses and develop them into novel immunotherapeutic regimens. Moreover, a synergy of, chemo- and immuno-therapeutic strategies will be necessary to eradicate HBV or HCV from a host.

• Hepatitis C virus
• Hepatitis B virus
• Direct-acting antiviral
• Chemotherapy
• Immunotherapy

• Antiviral Agents/pharmacology
• Antiviral Agents/therapeutic use
• Drug Therapy, Combination
• Hepacivirus/drug effects
• Hepatitis B virus/drug effects
• Hepatitis B, Chronic/drug therapy
• Hepatitis C, Chronic/drug therapy
• Humans
• Immunologic Factors/pharmacology
• Immunologic Factors/therapeutic use
• Virus Replication/drug effects