Genotype 1b Research Articles

Study on Improvement of Liver Inflammation in Patients with Genotype 1B Chronic HCV after DAAS Antiviral Therapy under Medical Insurance Directory

Study on Improvement of Liver Inflammation in Patients with Genotype 1B Chronic HCV after DAAS Antiviral Therapy under Medical Insurance Directory

Efficacy of Glecaprevir/Pibrentasvir for Real-World HCV Infected Patients in the Northern Part of Tokyo, Japan.

Hepatis virus C (HCV) infection causes liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The objective of our study was to examine the effects of the HCV nonstructural protein (NS) 3/4A inhibitor glecaprevir/NS5A inhibitor pibrentasvir on real-world HCV patients in the northern part of Tokyo, Japan. Although 106 patients were consecutively included, a total of 102 HCV-infected patients with chronic hepatitis or compensated cirrhosis, who received 8- or 12-week combination treatment with glecaprevir/pibrentasvir and were followed up to week 12 after the end of treatment were analyzed retrospectively. Only three patients discontinued treatment due to adverse events; however, they achieved a sustained virologic response at 12 weeks (SVR12). Finally, SVR rates were 99.0% (101/102). Only one patient without liver cirrhosis was a treatment relapser who received hepatic resection for HCC approximately two years after commencement of the 8-week combination treatment with glecaprevir/pibrentasvir. After the exclusion of patients with HCV genotype 1b and P32 deletion in the HCV NS5A region, a 12-week combination of glecaprevir/pibrentasvir led to SVR12 in all nine direct-acting antiviral-experienced patients. Glecaprevir/pibrentasvir had a high efficacy and an acceptable safety profile for real-world HCV patients in a single hospital in Japan.

Retrospective Analysis of Experimental and Clinical Studies of Flakozid in Viral Hepatitis

Retrospective Analysis of Experimental and Clinical Studies of Flakozid in Viral Hepatitis

Identification of hepatitis E virus in wild sika deer in Japan

Hepatitis E virus (HEV) is a zoonotic agent mainly transmitted through the consumption of uncooked or undercooked meat products derived from infected animals. In Japan, domestic pigs and wild boars are the major animal reservoirs, and whether or not deer are an HEV reservoir remains controversial. We analyzed 395 serum and 199 liver samples from 405 sika deer (Cervus nippon) caught in the wild between 1997 and 2020 in 11 prefectures of Japan for markers of HEV infection. Overall, 17 deer had anti-HEV IgG (4.3%), while 1 (0.2%) had HEV RNA (genotype 3b), indicating the occurrence of ongoing HEV infection in wild deer in Japan. An analysis of the complete HEV genome (deJOI_14) recovered from a viremic deer in Oita Prefecture revealed only 88.8% identity with the first HEV strain in sika deer (JDEER-Hyo03L) in Japan, being closest (96.3%) to the HEV obtained from a hepatitis patient living in the same prefecture. Of note, the deJOI_14 strain was 8.7–9.0% different from the wild boar HEV strains obtained in the same habitat and the same year, suggesting that difference in infected HEV strains between boar and deer may be explained by the limited possibility of close contact with each other, although boars are a known source of HEV infection. Increased numbers of hepatitis E cases after consumption of raw or undercooked meat products of wild deer have been reported in Japan. These results suggest a low but nonnegligible zoonotic risk of HEV infection in wild deer in this country.

Co-detection of the measles vaccine and wild-type virus by real-time PCR: public health laboratory protocol.

In rare cases vaccination with the measles virus vaccine genotype A (MeVA) may cause a vaccine reaction with clinical signs similar to infection with wild-type measles virus (MeVwt). Rapid differentiation between MeVA and MeVwt infection is important for taking adequate public health measures. Recently, a few MeVA real-time reverse-transcription quantitative PCR methods (RT-qPCRs) were described that can distinguish between MeVA and MeVwt. However, detection of MeVA does in theory not exclude infection with MeVwt. In the present study, we established a protocol for determination of co-infections with MeVA and MeVwt. To this end, MeVA RT-qPCRs were used in combination with the routine measles virus (MeV) RT-qPCR, and the results suggested that the differences between the RT-qPCR Ct values (delta Ct, ∆Ct) could be used as criteria. Subsequently, we tested samples from vaccine-associated measles cases that were confirmed by genotyping. In addition, experimental mixtures of MeVA and MeVwt were tested in different concentrations. All tested MeVA clinical samples had ∆Ct ≤3.6. The results of experimental mixtures showed a mean ∆Ct ≤2.8 for genotype A alone and >3.2 when combined with either genotype B3 or D8. The results of a receiver operator characteristic analysis indicated that the optimum ∆Ct for use as a cut-off value was 3.5, while with ∆Ct values of 2.9 and 3.7 sensitivity and specificity were respectively 1.00. Thus, ∆Ct could be used to exclude the presence of MeVwt if MeVA is detected and ∆Ct is <2.9, while ∆Ct >3.7 were highly suggestive of co-infection and ≥2.9 ∆Ct <3.7 warranted additional confirmation, such as next-generation sequencing. This RT-qPCR-based protocol could be used for the exclusion of infection with MeVwt in cases with vaccine-associated measles reaction, crucial for the timely implementation of public health prevention and control measures.

Biological Characterization of Hepatitis B virus Genotypes: Their Role in Viral Replication and Antigen Expression.

Hepatitis B virus (HBV) inter-host evolution has resulted in genomic diversification reflected in the existence of nine genotypes (A-I) and numerous subgenotypes. There is growing evidence that genotypes influence HBV natural history, clinical outcomes, and treatment response. However, the biological characteristics underlying these differences have not yet been established. By transfecting HuH-7 cells with unit-length constructs of genotypes A2, B2, C1, D1, and F1b, we identified major differences in HBV replicative capacity and antigen expression across genotypes. Genotypes B2 and F1b showed a 2-fold increase in cccDNA levels compared to the other genotypes (p<0.005). Genotype A2 expressed the lowest pgRNA levels, with a 70-fold decrease in relation to the other genotypes (p<0.0001), while genotype B2 showed the lowest Precore RNA levels, with a 100-fold reduction compared to genotype A2 (p<0.0001). The highest intracellular HBV DNA levels were observed for genotype B2 and the lowest for genotypes A2 and C1 (p<0.0001). Regarding antigen expression, genotype F1b secreted the highest HBsAg levels and genotype D1 the lowest (p<0.0001), while genotypes A2 and B2 showed the highest intracellular HBsAg levels (p<0.0001). Interestingly, genotype C1 secreted the highest HBeAg levels, while genotype A2 showed the highest intracellular levels (p<0.0001). Finally, the analysis of the intra/extracellular antigen ratios revealed that most genotypes retained intracellularly 5–20% of the antigens, except the genotype A2 that retained 50% of the total expressed antigens. In conclusion, this study provides new insights into the biological characteristics of HBV genotypes, being the first study to comparatively analyze European (A and D) and Asian (B and C) genotypes with the Latin American (F) genotype. The differences in HBV replication and antigen expression might contribute to understand the differential role of genotypes in pathogenesis.

Twenty-year follow-up of an outbreak of hepatitis C in a small rural town of Argentina: The O'Brien Project

Introduction and objectivesIn 1999, a population-based survey showed a 5.6 % (102/1832) prevalence of HCV infection in O'Brien, a small rural town of Argentina. The aim of this study was to assess the impact of screening, clinical evaluation and antiviral therapy on elimination of HCV after 20 years of follow-up. Patients and methodsHCV+ subjects (n=102) underwent clinical, biochemical and histological evaluation to assess the presence and severity of liver disease. Antiviral therapy included pegylated interferon + ribavirin in 2005 and direct antiviral agents from 2017. ResultsAll viremic subjects (n=84) had genotype 1b with 90%-97.5% sequence homology scores, suggesting the existence of a common source of infection (use of unsafe injections administered by the same health professional). Liver biopsy (n=55) showed chronic hepatitis in all patients. The prevalence of cirrhosis was 28% overall (29/102) and 34.5% among viremic patients. Sustained virological response (SVR) was obtained in 20/34 (59%) patients treated with interferon. From 2005 to 2017, when oral antivirals became available 37/50 untreated patients died. Median age of this group in 2005 was 67 years. Six interferon non-responders and five naive subjects received direct antiviral agents and all developed SVR. Only 1/31 patient (3.2%) with SVR died and none developed decompensated cirrhosis or HCC. In 2019, a new population-based study showed that the prevalence of HCV in O'Brien decreased 20-fold, from 5.6% to 0.28% (3/1070). ConclusionsDespite the high mortality rate precluding timely access to direct antiviral agents, the O'Brien Project is a good example of HCV micro-elimination studies

Safety and efficacy of grazoprevir/elbasvir in the treatment of acute hepatitis C in hemodialysis patients.

Treatment of hepatitis C virus (HCV) infection with direct‐acting antiviral agents (DAAs) in hemodialysis patients requires extensive consideration. At present, studies regarding DAAs for acute HCV infection in such patients are limited. The present study aims to evaluate the efficacy and safety of grazoprevir (GZR) plus elbasvir (EBR) treatment in acute hepatitis C (AHC) patients undergoing hemodialysis. Patients undergoing hemodialysis who had a nosocomial acute HCV infection were enrolled. All patients received GZR 100 mg/EBR 50 mg once daily for 12 weeks and were followed up for 12 weeks. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and HCV RNA levels were monitored during treatment and follow‐up periods. Sustained virologic response at 12 weeks after treatment cessation and treatment‐emergent adverse events (AEs) were assessed. A total of 68 AHC patients were enrolled. All patients were infected with HCV genotype 1b and achieved SVR12. Decreasing ALT, AST, and TBIL were observed over time in the first 4 weeks and became steady thereafter. Forty‐eight (70.59%) patients reported at least one AEs. The most common AEs were fatigue, headache, and nausea. Two AHC patients discontinued treatment due to serious but drug‐unrelated AEs. In conclusion, GZR/EBR has a high efficacy and safety profile in hemodialysis‐dependent patients with genotype 1b AHC.

CYP3A4 *1B Gene Polymorphism in Coronary Artery Disease Patients with Obesity Undergoing Statin Treatment

Objective: Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide and statins are frequently prescribed in the treatment of CAD to help lower blood cholesterol levels. Since the main enzyme involved in the metabolism of statins is CYP3A4, we aimed to investigate the effect of CYP3A4 * 1B genotypes on plasma lipid profile in Turkish cardiovascular disease subjects with and without obesity taking statin. Materials and Methods: The study group consisted of 85 cardiovascular disease patients who were prescribed statins and had routine biochemical analysis data. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) assay was performed for genotyping of CYP3A4 *1B (rs2740574) polymorphism. Results: Genotype distribution of CYP3A4 *1B polymorphism was found for homozygous wild (AA) and homozygous polymorphic (GG) genotypes as 94.1% and 5.9%, respectively. We did not detect patients with heterozygous genotype in our study group. We found that the mean LDL-c, TG and TC levels were higher in patients with CYP3A4 *1B GG compared to the AA genotype. The frequency of CYP3A4 *1B GG genotype frequency (9.5%) was detected higher in the obese patients compared to the non-obese patients (7.7%) (χ2=0.037, p=0.85). Conclusions: Our results demonstrate that CYP3A4 *1B homozygous polymorphic genotype distribution tends to be higher in obese patients compared to non-obese patients with cardiovascular disease which may point to *1B allele having a slight effect on serum lipids during statin therapy. Additional studies with higher samples are needed for evaluating the role of CYP3A4 *1B on lipids in patients under statin therapy.

Serum Peptidyl-prolyl Cis-trans Isomerase NIMA-interacted 1 (Pin1) as a Non-invasive Marker for Liver Fibrosis due to Chronic Hepatitis C Virus.

Background: Hepatitis C virus (HCV) may remain asymptomatic or cause liver fibrosis and cirrhosis. Objectives: We aimed to assess the relationship between serum peptidyl-prolyl cis-trans isomerase NIMA-interacted 1 (Pin1) levels and liver fibrosis due to HCV. Methods: Serum samples of successive patients with HCV genotype 1b and healthy volunteers were collected, and Pin1 levels were measured using ELISA kits. Liver fibrosis stages were calculated by the Ishak Scoring System and subdivided into two groups; stage &lt; 3 (mild fibrosis) and ≥ 3 (advanced fibrosis). Correlation and area under receiver operating characteristics (AUROC) analysis were used to investigate the relationship between Pin1 and clinical and histopathological properties of HCV infection. Results: Ninety-four patients with HCV and 47 age- and sex-matched volunteers were included. The median age of the participants was 52, and 55% of whom were females. The mean (SD) of Pin1 serum level was significantly higher in the HCV group compared with healthy volunteers (33.94 (21.15) vs. 26.82 (8.85) pg/mL, respectively, P = 0.007). Seventy-seven (82%) and 17 (18%) of the participants showed mild and advanced fibrosis, respectively. Pin1 serum levels were significantly lower in the mild compared with advanced fibrosis group (29 (17.88) vs. 43.59 (7.98) pg/mL, respectively, P &lt; 0.001). We found a significantly positive correlation between Pin1 serum level and liver fibrosis stage (r = 0.71, P &lt; 0.001). The cut off of 33.04 pg/mL of Pin1 serum level showed the best sensitivity (100%) and specificity (68.4%) (AUROC = 0.81 [95% confidence interval: 0.72 - 0.90], P &lt; 0.001) for distinguishing advanced from mild liver fibrosis. Conclusions: Serum Pin1 level may be a relevant marker for predicting liver fibrosis in HCV infected patients.

S2592 Misleading Hepatitis C Viral Counts During COVID-19 Infection: A Case Report and Discussion

Introduction: COVID-19 infection is associated with liver injury that increases in severity in sicker patients. This is thought to be due to the cytokine storm phenomenon which can paradoxically suppress other underlying chronic viral infections. We report the 1st case of suppressed HCV viral load and undetectable HCV genotype in the setting of COVID-19. Case Description/Methods: A 77-year-old man with chronic hepatitis C (HCV) secondary to intravenous drug use was seen at the gastroenterology clinic for initiation of HCV treatment. Four months prior to presentation, HCV screening showed a positive HCV antibody and HCV viral load of 127330 IU/mL. Further testing for initiation of HCV therapy was remarkable for a markedly decreased HCV viral load of 31 IU/mL. Genotype could not be evaluated as the test requires a viral load of ≥1000 IU/mL. FibroSure revealed F1 fibrosis. Around that time, the patient reported body aches, fevers, and an exposure to a person with upper respiratory tract symptoms. Four days later, he tested positive for COVID-19, then quarantined and recovered. As the marked drop in HCV viral load was felt to be secondary to cytokine response in COVID-19 infection, a decision was made to repeat HCV viral load and genotyping 3 months later. The results revealed a viral load of 9010000 IU/ml and genotype 2b. The patient's liver function tests and INR remained normal and he was initiated on glecaprevir/pibrentasvir. Discussion: While liver injury from cytokine storm in COVID-19 is well recognized, there is paucity of data on its effect on chronic viral infections. This is the first report of documented transient reduction in HCV viral load in COVID-19, presumably secondary to the cytokine response. It is notable that the HCV viral load reduction in this case was to such an extent that genotyping was not possible. Therefore, we believe that reductions to below the lower limit of detection are possible resulting in false negative HCV PCR results. Since it is standard practice to interpret a one-time negative HCV viral load to be indicative spontaneous viral clearance, such a result could lead to a mistaken diagnosis. Clinicians need to be mindful of the coexistent clinical conditions while interpreting HCV PCR results. Additionally, there may be a role for repeating HCV PCR after an interval if a negative result was obtained during a period of widespread community transmission of COVID- 19 or other viral epidemics. Further research is required to validate the appropriateness of such a testing strategy. (Figure Presented).

Genetic Characterizations and Molecular Evolution of the Measles Virus Genotype B3's Hemagglutinin (H) Gene in the Elimination Era.

Measles virus (MeV) genotype B3 is one globally significant circulating genotype. Here, we present a systematic description of long-term evolutionary characterizations of the MeV genotype B3’s hemagglutinin (H) gene in the elimination era. Our results show that the B3 H gene can be divided into two main sub-genotypes, and the highest intra-genotypic diversity was observed in 2004. MeV genotype B3’s H gene diverged in 1976; its overall nucleotide substitution rate is estimated to be 5.697 × 10−4 substitutions/site/year, and is slowing down. The amino acid substitution rate of genotype B3’s H gene is also decreasing, and the mean effective population size has been in a downward trend since 2000. Selection pressure analysis only recognized a few sites under positive selection, and the number of positive selection sites is getting smaller. All of these observations may reveal that genotype B3’s H gene is not under strong selection pressure, and is becoming increasingly conservative. MeV H-gene or whole-genome sequencing should be routine, so as to better elucidate the molecular epidemiology of MeV in the future.

Short-term changes of liver fibrosis in patients with HCV genotype 1b – related compensated cirrhosis after sustained virologic response

Several studies suggested a regression of liver fibrosis (LF) over time after successful therapy in HCV infected patients. The aim of this study was to assess the changes of fibrosis occurring after successful direct acting antiviral (DAA) treatment using transient elastography (TE) and FIB-4 score in patients with HCV genotype 1 b compensated cirrhosis. Material and methods: LF were evaluated by TE and FIB-4 at baseline, sustained virological response (SVR) and 12 months after end of treatment (EOT). LF regression was defined as an improvement of ≥ 30% in Fibroscan® score at follow-up compared to baseline. Results: There were 98 patients with HCV-related compensated liver cirrhosis who achieved SVR after DAAs, most female (65.3%), aged 60.64 ± 9.56 years. Overall, LF had a significant improvement with a median (IQR) regression of 4.5 (1.8-7.8) from baseline to SVR and 5.1 (2.5-8.65) from baseline to 12 months after EOT (p &lt;0.001). Also, the FIB-4 score significantly decreased at SVR and 12 months after EOT, similar to LSM values [median (IQR) at SVR 2.27 (1.55-3.26) and 2.21 (1.51-3.28) at 12 months after EOT (p &lt;0.001)]. Conclusions: We demonstrated that achieving SVR with DAA-based regimens was associated with significant improvement of liver stiffness measured by TE, and liver function monitored by FIB-4 index, but the regression of fibrosis must be constantly evaluated in dynamic thus further studies are warranted to confirm these findings in other populations.

Genotype-specific versus pangenotypic regimens in patients infected with hepatitis C virus genotype 1b in real-world settings.

Introduction: The introduction of direct-acting antivirals (DAAs) has provided us with hope to eliminate hepatitis C virus (HCV) infection as a significant public health problem in the coming years. Objective: Our study aimed to compare the effectiveness and safety of genotype-specific and pangenotypic regimens in genotype 1b–infected patients treated in real-world settings. Patients and methods: Patients were selected from 990 HCV-infected individuals treated with DAAs in the Department of Infectious Diseases in Kielce, Poland, who had the therapy initiated between July 1, 2015 and December 31, 2020. Results: A total of 795 genotype 1b–infected patients with a median age of 51 years, female predominance (55%), and a 21.1% rate of cirrhosis were included in the analysis. A total of 69.9% of patients were treated with genotype-specific regimens. Those patients were significantly older, more often were treatment experienced, and had advanced liver fibrosis and cirrhosis compared with patients assigned to pangenotypic regimens. An overall sustained virologic response rate of 97.9% in the intention-to-treat (ITT) analysis and 99% after excluding nonvirologic nonresponders was achieved, with no significant difference between patients in the 2 treatment arms. Significantly higher proportions of men (P = 0.001) and DAA-experienced patients (P = 0.049) were documented among virologic nonresponders. Conclusions: We confirmed very high effectiveness and a good safety profile of both genotype-specific and pangenotypic regimens used in patients with genotype 1b HCV infection, and we found no differences between these 2 generations of medications. Male sex and previous treatment with DAAs were identified as negative predictors for therapy effectiveness.

Direct-Acting Antiviral Use for Genotype 1b Hepatitis C Patients with Associated Hematological Disorders from Romania.

Background and objectives: this study assessed variations in the blood parameters of patients with hematological disorders infected with HCV throughout a 12-week interferon-free treatment regimen. Materials and methods: We followed a total of 344 patients suffering from chronic hepatitis C, infected with the 1b genotype and concomitant hematological disorders, who benefited from the direct-acting antiviral (DAA) therapy in our clinic. Seven of the most routinely checked blood parameters were analyzed, namely, hemoglobin, leucocyte count, neutrophils, erythrocyte count, platelet count, ALT, and total bilirubin level. In total, 129 patients received a treatment scheme comprising ombitasvir, paritaprevir, ritonavir, and dasabuvir, while the 215 other patients received a sofosbuvir and ledipasvir regimen. Results: Patients enrolled in the study showed remarkably increased ALT levels in the first four weeks of DAA treatment, normalizing to levels below 40 U/L by the end of regimen. There were no other blood parameters that worsened throughout the 12-week regimen to levels below our laboratory’s normal range. After 12 weeks of DAA therapy, 309 patients (90%) achieved SVR. Conclusions: Our findings are consistent in evaluating the efficacy and tolerability of direct-acting antivirals for 1b genotype HCV infected patients with associated hematological malignancies under remission, and other hematological disturbances, that were previously unsuccessfully treated with a pegylated interferon regimen. Thus, paving a pathway for government-funded programs being implemented in this direction.

Effectiveness, tolerability and safety of Direct Acting Antivirals in Mexican individuals with Hepatitis C virus genotype-1 and previous pegylated interferon and ribavirin therapy.

BackgroundDirect Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy.MethodsA descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment.ResultsSVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction.ConclusionsDAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.

Mutation of the sixth amino acid of the Rep protein has no effect on porcine circovirus 2b but enhances porcine circovirus 2d replication in vitro.

Porcine circovirus type 2 (PCV2) is the etiological agent of post-weaning multisystemic wasting syndrome (PMWS). The original prevalent genotype, PCV2a, has been replaced by genotypes 2b and 2d in the swine population worldwide. The Rep protein is critical for viral replication. Comparison of a large number of Rep protein amino acid (aa) sequences showed that three sites distinguish genotype 2b from genotype 2d. In order to analyze the effect of exchanging the amino acids (asparagine and serine) at position 6 in the Rep proteins of PCV2b and PCV2d, two wild-type and two mutant viruses were rescued. Real-time quantitative PCR and a one-step growth curve were used to determine the viral load to assess the replication ability of the rescued viruses. The results showed that there was no significant difference in in vitro performance between the wild-type PCV2b and the mutated virus, while the mutation of PCV2d enhanced viral replication.

The Discovery of Conformationally Constrained Bicyclic Peptidomimetics as Potent Hepatitis C NS5A Inhibitors.

HCV NS5A inhibitors are the backbone of directly acting antiviral treatments against the hepatitis C virus (HCV). While these therapies are generally highly curative, they are less effective in some specific HCV patient populations. In the search for broader-acting HCV NS5A inhibitors that address these needs, we explored conformational restrictions imposed by the [7,5]-azabicyclic lactam moiety incorporated into daclatasvir (1) and related HCV NS5A inhibitors. Unexpectedly, compound 5 was identified as a potent HCV genotype 1a and 1b inhibitor. Molecular modeling of 5 bound to HCV genotype 1a suggested that the use of the conformationally restricted lactam moiety might have resulted in reorientation of its N-terminal carbamate to expose a new interaction with the NS5A pocket located between amino acids P97 and Y93, which was not easily accessible to 1. The results also suggest new chemistry directions that exploit the interactions with the P97–Y93 site toward new and potentially improved HCV NS5A inhibitors.

Distribution of hepatitis C virus (HCV) genotypes in a Saudi Arabian hospital during the 2015-2020 period.

Hepatitis C virus (HCV) is the leading cause of chronic liver disease. HCV genotypes and subtypes are important predictors of disease progression and antiviral treatment response. To our knowledge, there had been limited studies of HCV genotypes in Qatif, Saudi Arabia. This study aims to assess the distribution of HCV genotypes in Qatif Central Hospital, Qatif, Saudi Arabia. This is a retrospective study of adult patients with HCV infection between January 2015 and December 2020. Only patients with documented HCV genotyping were included. A total of 356 HCVinfected patients fulfilled the inclusion criteria and were included in further analysis. Of those patients, 179 (50.3%) were males, and most were Saudi (N=347, 97.5%). The median age was 60 years, and 191 (53.7%) were 50-69 years of age. Genotype 2 was present in 118 (33.1%) of the patients, followed by genotype 4 in 92 (25.8%), genotype 1B in 62 (17.4%), and genotype 1A in 37 (10.4%). The study showed that HCV genotype 2 is the predominant variant among chronic HCV patients in the study population. Monitoring the epidemiology of HCV genotypes may provide guidance in treatment decisions.

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

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.