Recompensation of Chronic Hepatitis C-Related Decompensated Cirrhosis Following Direct-Acting Antiviral Therapy: Prospective Cohort Study From a Hepatitis C Virus Elimination Program.

BACKGROUND & AIMS: Chronic hepatitis C-related decompensated cirrhosis is associated with lower sustained virologic response (SVR)-12 rates and variable regression of disease severity after direct-acting antiviral agents. We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients. METHODS: Between July 2018 and July 2023, patients with decompensated chronic hepatitis C-related cirrhosis after direct-acting antiviral agents treatment were evaluated for SVR-12 and then had 6-monthly follow-up. RESULTS: Of 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2 ± 11.5 years; 63% men; Model for End-stage Liver Disease-Sodium [MELD-Na]: 16.5 ± 4.6; 87% genotype 3) were enrolled. SVR-12 was 81.8% after 1 course; ultimately SVR was 90.8% after additional treatment. Decompensation events included ascites (1098; 95.3%), hepatic encephalopathy (191; 16.6%), and variceal bleeding (284; 24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284 (24.7%) at a median time of 16.5 (interquartile range, 14.5-20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin (adjusted hazard ratio [aHR], 0.6; 95% confidence interval [CI], 0.5-0.8; P < 0.001), international normalized ratio (aHR, 0.2; 95% CI, 0.1-0.3; P < 0.001), absence of large esophageal varices (aHR, 0.4; 95% CI, 0.2-0.9; P = 0.048), or gastric varices (aHR, 0.5; 95% CI, 0.3-0.7; P = 0.022) predicted recompensation. Portal hypertension progressed in 158 (13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR, 1.6; 95% CI, 1.2-2.8; P = 0.042), and presence of large varices (aHR, 2.9; 95% CI, 1.3-6.5; P < 0.001) were associated with portal hypertension progression. Further decompensation was seen in 221 (19%); 145 patients died and 6 underwent liver transplantation. A decrease in MELDNa of ≥3 was seen in 409 (35.5%) and a final MELDNa score of <10 was seen in 335 (29%), but 2.9% developed hepatocellular carcinoma despite SVR-12. CONCLUSIONS: SVR-12 in hepatitis C virus-related decompensated cirrhosis in a predominant genotype 3 population led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and hepatocellular carcinoma developed in 2.9% of patients. (ClinicalTrials.gov, Number: NCT03488485).

Evidence for the elimination of viral hepatitis B and C in Egypt: Results of a nationwide survey in 2022.

INTRODUCTION: Viral hepatitis C (HCV) and B (HBV) were at the top of Egypt's most significant public health challenges, with an estimated 14.7% of its population having antibodies to HCV in 2008. Egypt issued an ambitious action plan in 2014 to eliminate viral hepatitis through strengthening infection control and improving patient care. In 2018, an extensive HCV mass screening campaign was conducted for the entire country's population with treating more than 4 million patients with antivirals. This study aimed to evaluate the current prevalence of viral hepatitis in Egypt after all these efforts. METHODS: A cross-sectional household cluster survey was conducted in all 27 Egyptian governorates to obtain a representative sample of Egypt's population. Subjects aged 1-70 years were interviewed using a standardised questionnaire that included demographics, viral hepatitis knowledge, previous infection and risk factors data. Laboratory testing was performed for all subjects for anti-HCV and HBsAg using chemiluminescence. Subjects positive for anti-HCV were further tested for HCV-RNA by RT-PCR. Prevalence rates were calculated by demographic groups and compared to the demographic health survey 2015 results. RESULTS: Of 20 881 subjects interviewed, 48.8% were males, 20.2% were children <15 years of age, and 53.7% were residents of rural areas. Of all subjects, 92 (0.4%) were HCV-infected, 1577 (7.6%) were anti-HCV positive and 177 (0.8%) were HBV-chronically infected, including one patient who had mixed HBV and HCV current infection. The prevalence of HCV-current and HBV chronic infections decreased by 93% and 20%, respectively, compared to 2015. CONCLUSIONS: Egypt achieved the elimination of the viral hepatitis goal. To maintain low rates of viral hepatitis, community health education, in addition to maintaining infection control and blood safety programs, is essential.

Cholestatic HCV Cryoglobulinemia: A New Clinical and Pathological Entity before and after Direct-Acting Antiviral Therapies-A Case-Control Study.

Twenty-nine patients with HCV infection (HCV+) and mixed cryoglobulinemia (MC+) were retrospectively selected and matched for age and sex with 31 HCV+ MC- patients. Biomarkers of cholestasis (direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase), HCV-RNA and genotype, and plasma cryoprecipitates were measured before and after virus eradication; liver histology and plasma cells (aggregation and distribution), observed blinded by two pathologists, were analyzed. Sixty participants (mean age: 56.5; range: 35-77, males: 50%) with HCV infection were enrolled. Cholestasis (≥2 pathologically increased cholestasis biomarkers) was significantly higher in the MC group (p = 0.02) and correlated with cryoglobulinemia (OR 6.52; p = 0.02). At liver histological assessment, plasma cells were significantly increased in the MC+ group (p = 0.004) and tended to form aggregates more than the control group (p = 0.05). At multivariate analysis with MC, age, HCV-RNA, HBV diabetes, and cirrhosis, cholestasis was only significantly correlated to MC (OR 8.30; p < 0.05). In 25% patients, MC persisted after virus eradication with new antiviral treatment. Our study identified for the first time an association between MC, cholestasis, and an increased number of intrahepatic plasma cells in chronic hepatitis C (CHC) patients before virus eradication. Future studies are required to understand how MC contributes to liver damage and how its persistence affects the patients' follow-up after antiviral therapies.

Evaluation of the clinical and economic value of sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C in Spain during the last 5 years.

OBJECTIVE: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) represented a paradigm shift. In 2017, sofosbuvir/velpatasvir (SOF/VEL-Epclusa®) was approved, which showed a high cure rate in all patient, contributing to HCV elimination. The analysis aimed to quantify the clinical and economic value of SOF/VEL in HCV chronic patients since its approval in Spain. METHODS: An economic evaluation was elaborated adapting a Markov model that simulated the lifetime disease progression in of all HCV chronic patients treated with SOF/VEL (30,488 patients) since its launch (5-years), compared to previous therapies. Patients entered the model and were distributed between the fibrosis states (F0-to-F4) in treated and untreated. All patients (100%) were treated with SOF/VEL regardless of their fibrosis, and 49% with previous therapies in ≥F2. The average sustained viral response (SVR) rates 98.9% SOF/VEL versus 61.0% previous therapies. All parameters for the analysis were obtained from real-life data and literature. Only direct healthcare costs associated with disease management were included. The SOF/VEL value was measured as the number of hepatic complications avoided and their associated cost, and hepatic mortality compared to previous therapies. National Health System perspective and a 3% discount rate was applied. RESULTS: SOF/VEL decreased the number of liver complications, avoiding 92% decompensated cirrhosis, 80% hepatocellular carcinomas, and 87% liver transplants, as well as 85% liver-related mortality. Their cost associated was reduced, amounting to savings of 197M€. CONCLUSION: SOF/VEL adds relevant value to the HCV treatment, reducing the clinical and economic disease burden and contributing to HCV elimination in Spain.

Efficacy and safety of pan-genotypic sofosbuvir and velpatasvir in patients with hepatitis C and HIV coinfection on dolutegravir-based antiretroviral therapy.

Hepatitis C virus (HCV) infection is more prevalent in people living with HIV-AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first-line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir-based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir-based ART. Forty-five consecutive PLHA with HCV coinfection on dolutegravir-based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty-two (97.7%) of the remaining 43 patients attained SVR-12. SVR-12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan-genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir-based ART.

Microbiota and hepatitis C virus in the era of direct-acting antiviral agents.

The gut microbiota plays a fundamental role in Hepatitis C Virus (HCV)-related liver disease. Indeed, HCV infection alters the gut microbiota, whereas intestinal dysbiosis induces an underlying inflammatory state. This status may lead to liver disease progression. The advent of direct acting antivirals (DAAs) was a turning point in the history of HCV infection, which enhances the chances of recovery. Beyond the elimination of the virus, DAA therapy can affect the gut microbiota of the HCV patient. The study of the gut microbiota in the patient with HCV-related liver disease could be the first step in understanding the etiopathogenesis of hepatopathy thereby opening the way to new therapeutic opportunities. Herein we evaluate current knowledge regarding the gut microbiota in patients with HCV infection and the impact of DAA therapy.

Hepatitis C and heart transplantation: An update.

There are limited data regarding heart transplantation in the setting of hepatitis C virus (HCV) infection in either recipients or donors, as the practice was infrequent, given concerns of worse post-transplant outcomes. This changed dramatically after the development of highly effective HCV therapies, namely direct-acting antivirals (DAAs). Additionally, nucleic acid testing currently in use establishes more precisely the risk of HCV transmission from donors. As a result, chronic HCV infection in itself is no longer a barrier for heart transplant candidates, and the use of HCV-positive organs for HCV-infected and non-infected transplant candidates has increased dramatically. A review of the literature revealed that in the pre-DAA era, HCV seropositive heart transplant patients had a higher mortality than their seronegative counterparts. However, short-term data suggest that the differences in survival have been erased in the DAA era. Heart transplantation from HCV-viremic donors to HCV-uninfected recipients has become increasingly common as the number of deceased donors with HCV viremia has increased over the past years. Preliminary outcome reports are very encouraging, although further data are needed with regard to long-term safety. New information continues to be incorporated to optimize protocols that guide this practice.

Regression in hepatic fibrosis in elderly Chinese patients with hepatitis C receiving direct-acting antiviral treatment.

BACKGROUND: Patients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes. METHODS: This study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People's Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated. RESULTS: We included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9-19.9) kPa, and this value was significantly reduced to 9.7 (6.2-16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275-1.022), 3.072 (2.047-5.129) and 0.833 (0.430-1.540) to 0.231 (0.155-0.412), 2.100 (1.540-3.034) and 0.336 (0.235-0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1-16.8) kPa to 7.2 (5.3-12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly. CONCLUSION: In this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC.

Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity.

PURPOSE: It is well known that interferon-α (IFN-α), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations. METHODS: A total of 113 HCV patients, subdivided at the time of the enrollment in naïve group (n = 64) and in IFN-α group (n = 49) previously treated with pegylated interferon-α and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20-32 weeks of DAAs. RESULTS: Before starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-α group (8/49, 16.3%), while no HT cases were found in the naïve group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naïve group and 4/49 (8.2%) to IFN-α group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naïve group and 6/49 (12.2%) from IFN-α group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism. CONCLUSIONS: This study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs.

Impact of oral antiviral therapy against HCV on gut microbiota. A prospective study.

The intestinal microbiota plays a fundamental role in physiological homeostasis as well as in pathologic conditions. Hepatitis C virus is the leading cause of chronic liver diseases worldwide. The treatment of this infection has been revolutionized by the availability of direct-acting antiviral agents which guarantee a high rate (about 95%) of viral clearance. Few studies have assessed the change in the gut microbiota of patients treated with direct-acting antiviral agents against HCV, and many aspects still need to be clarified. The aim of the study was to evaluate the effects of antiviral therapy on gut microbiota. We enrolled patients with HCV-related chronic liver disease attending the Infectious Diseases Unit of the A.O.U. Federico II of Naples from January 2017 to March 2018 and treated with DAAs. For each patient, a fecal sample was collected and analyzed for the assessment of microbial diversity before the start of therapy and by SVR12 time. We excluded patients who had received antibiotics in the previous 6 months. Twelve patients were enrolled (6 male, 8 genotype 1 (1 subtype 1a), 4 genotype 2). Fibrosis scores were F0 in 1 patient, F2 in 1 patient, F3 in 4 patients and cirrhosis in the remaining 6 (all in Child-Pugh class A). All were treated with DAAs for 12 weeks (5 with Paritaprevir-Ombitasvir-Ritonavir-Dasabuvir, 3 with Sofosbuvir-Ledipasvir, 1 with Sofosbuvir-Ribavirin, 1 with Sofosbuvir-Daclatasvir, 1 with Sofosbuvir-Velpatasvir) and 100% achieved SVR12. In all patients, we observed a trend in reduction of potentially pathogenic microorganisms (i.e., Enterobacteriaceae). Furthermore, a trend of increase in α-diversity was observed in patients by SVR12 compared to baseline. This trend was markedly more evident in patients without liver cirrhosis than in those with cirrhosis. Our study shows that viral eradication obtained with DAA is associated with a trend in restoring the heterogeneity of α-diversity and in reducing the percentage of potentially pathogenic microbial species, although this benefit is less evident in patients with cirrhosis. Further studies with larger sample size are needed to confirm these data.

Barriers to HCV micro-elimination in a cohort of people living with HIV (PLWH).

To achieve the World Health Organization goal of hepatitis C virus (HCV) eradication, barriers to treatment should be investigated and overcome. The aim of this study was to identify those barriers and describe the strategies adopted to achieve HCV micro-elimination in a cohort of coinfected people living with HIV (PLWH-HCV). Adult PLWH-HCV followed at our hospital with detectable serum HCV-RNA in 2018 were enrolled. After a three-year follow-up, barriers to HCV treatment were investigated and strategies to overcome them were described. Of 492 PLWH-HCV seen in 2018, 29 (5.9%) had detectable serum HCV-RNA. Eight out of 29 (27.6%) were excluded because they were already under treatment, while 2 others were excluded because they moved to other outpatient clinics. Among the remaining 19 study participants, the most common barriers to treatment were poor adherence to therapies and follow-up visits (n=9, 47%), recent HCV diagnosis awaiting proper staging (n=3, 16%) and treatment hesitancy (n=2, 10%). During the following three years, direct-acting antivirals (DAAs) treatment was completed in 11/19 (58%) cases, with achievement of sustained virological response in 100% of cases. For the remaining cases, 2/19 (10.5%) were lost to follow-up, 2/19 (10.5%) died before treatment initiation and 4/19 (21.0%) are still awaiting treatment. Despite 3 years of effort, HCV micro-elimination has not been achieved at our center. We observed that poor adherence and treatment hesitancy were the main barriers to treatment. Strategies addressing these issues need to be implemented.

Declining incidence of hepatitis C related hepatocellular carcinoma in the era of interferon-free therapies: A population-based cohort study.

BACKGROUND & AIMS: The impact of interferon (IFN)-free therapies on the epidemiology of hepatitis C virus (HCV) related hepatocellular carcinoma (HCC) is not well understood at a population level. Our goal was to bridge this evidence gap. METHODS: This study included all patients in Scotland with chronic HCV and a diagnosis of cirrhosis during 1999-2019. Incident cases of HCC, episodes of curative HCC therapy, and HCC-related deaths were identified through linkage to nationwide registries. Three time periods were examined: 1999-2010 (pegylated interferon-ribavirin [PIR]); 2011-2013 (First-generation DAA); and 2014-2019 (IFN-free era). We used regression modelling to determine time trends for (i) number diagnosed and living with HCV cirrhosis, (ii) HCC cumulative incidence, (iii) HCC curative treatment uptake and (iv) post-HCC mortality. RESULTS: 3347 cirrhosis patients were identified of which 381 (11.4%) developed HCC. After HCC diagnosis, 140 (36.7%) received curative HCC treatment and there were 202 deaths from HCC. The average annual number of patients diagnosed and living with HCV cirrhosis was approximately seven times higher in the IFN-free versus the PIR era, whereas the number of incident HCCs was four times higher. However, the cumulative incidence of HCC was significantly lower in the IFN-free versus PIR era (sdHR: 0.65; 95%CI:0.47-0.88; P = .006). Among HCC patients, diagnosis in the IFN-free era was not associated with improved uptake of curative treatment (aOR:1.18; 95%CI:0.69-2.01; P = .54), or reduced post-HCC mortality (sdHR: 0.74; 95%CI:0.53-1.05; P = .09). CONCLUSIONS: The cumulative incidence of HCC is declining in HCV cirrhosis patients, but uptake of curative HCC therapy and post-HCC survival remains suboptimal.

Effects of direct-acting antiviral treatment on reducing mortality among Medicare beneficiaries with HIV and HCV coinfection.

Hepatitis C virus (HCV) infection is common among people living with HIV. HIV and HCV coinfected patients have higher overall mortality rates compared with HIV mono-infected patients. With its high cure rate of HCV infection, direct-acting antiviral (DAA) treatment provides an opportunity to improve the survival of the HIV/HCV coinfected population. The objective of this study is to investigate the association between DAA treatment and all-cause mortality among HIV/HCV coinfected people. The study included 7103 Medicare beneficiaries in the United States who were infected with both HIV and HCV between 2014 and 2017. Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) of death for patients with and without DAA treatment while controlling for patient characteristics. During the study period, 1675 patients initiated DAA treatment (23.6%). The adjusted hazard ratio (aHR) of all-cause mortality between patients with and without DAA treatment was 0.37 (95% CI, 0.29-0.48), regardless of cirrhosis status. DAA treatment was associated with a smaller reduction in all-cause mortality for females (aHR, 0.50 [95% CI, 0.30-0.85]) compared with males (aHR, 0.34 [95% CI, 0.25-0.46]). DAA treatment was associated with improved survival among all HIV/HCV coinfected patients regardless of sex or HCV disease progression.

Time to complete hepatitis C cascade of care among patients identified during mass screening campaigns in rural Rwanda: a retrospective cohort study.

BACKGROUND: Since the discovery of direct-acting antivirals, treatment for hepatitis C virus (HCV) is increasingly accessible in low-resource settings, but quality of care in these settings is not known. We described progression through the cascade of care among individuals who screened positive for HCV antibodies during a mass screening campaign in Kirehe and Kayonza, two rural Rwandan districts, in September 2019. METHODS: This retrospective cohort study used routine clinical data to assess proportions of participants completing each stage of the cascade of care, including: (a) screening positive on rapid diagnostic test; (b) return of initial viral load results; (c) detectable viral load; (d) treatment assessment; (e) treatment initiation; (f) return of sustained virological response (SVR12) results; and (g) achieving SVR12. We proposed three indicators to assess timely care provision and used medians and interquartile ranges (IQR) to describe the time to complete the cascade of care. RESULTS: Overall, 666 participants screened HCV positive, among them, 452 (68.1%) were female and median age was 61 years (IQR: 47, 70). Viral load results were returned for 537 (80.6%) participants of whom 448 (83.4%) had detectable viral loads. Of these, 398 (88.8%) were assessed for treatment, 394 (99%) were initiated, but only 222 (56.3%) had results returned for SVR12. Among those with SVR12 results, 208 (93.7%) achieved SVR12. When assessing timely care provision, we found 65.9% (95% CI: 62.0, 69.7) of initial viral load results were returned ≤ 30 days of screening; 45% (95% CI: 40.1, 49.8) of people with detectable viral load completed treatment assessment ≤ 90 days of initial viral load results; and 12.5% (95% CI: 9.2, 16.3) of SVR12 results were returned ≤ 210 days of treatment initiation among those who initiated treatment. The overall median time from screening to SVR12 assessment was 437 days. CONCLUSION: Despite high rates of SVR12 among those who completed all stages of the cascade of care, we identified gaps and delays in the treatment cascade. Improving communication between viral load testing hubs and health facilities could reduce the turn-around time for viral load testing, and actively monitor timeliness of care provision could improve quality of HCV care.

The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. METHODS: Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. RESULTS: Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. CONCLUSIONS: HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. TRIAL REGISTRATION: This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients' medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).

The clinical impact of direct-acting antiviral treatment on patients affected by hepatitis C virus-related oral lichen planus: a cohort study.

OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease. Literature supports an association between OLP and Hepatitis C virus (HCV) infection. The current treatment for HCV infection with direct-acting antivirals (DAAs) is highly effective and safe. The aim of this study is to evaluate the clinical impact of viral eradication with DAAs in patients with HCV and OLP. MATERIALS AND METHODS: For this cohort observational study, 18 patients with HCV and OLP were recruited; all patients received DAAs. Nineteen patients with OLP without HCV were recruited as controls. Both groups received an oral clinical examination, taking photographs of the oral mucosa, at three time points. Size and type of lesions, clinical and efficacy scores, were evaluated at each time point with ImageJ software. Changes were assessed by a general linear model repeated measures analysis. Kruskal-Wallis H and Mann-Whitney U tests were used to evaluate the differences between subgroups. RESULTS: All patients of the study group reached a sustained virological response. The study group showed a correlation between viral load and clinical status (p < 0.05), higher clinical scores at baseline (p = 0.001) and higher efficacy index than controls (p < 0.001), improving over time (p < 0.001); controls did not show significant changes (p = 0.196). One patient of the experimental group developed oral squamous cell carcinoma (OSCC) of the tongue during the DAAs treatment. CONCLUSIONS: In this study, patients with HCV and OLP showed a worst clinical oral status than controls at baseline. However, treatment for virus eradication can improve the oral lichen planus clinical course. CLINICAL RELEVANCE: HCV eradication can improve the clinical course of patients with HCV-related OLP.

Re-purposing of hepatitis C virus FDA approved direct acting antivirals as potential SARS-CoV-2 protease inhibitors.

A new coronavirus strain called as SARS-CoV-2 has emerged from Wuhan, China in late 2019 and it caused a worldwide pandemic in a few months. After the Second World War, it is the biggest calamity observed as there is no specific US Food and Drugs Administration (USFDA) approved drug or vaccine available globally for the treatment. Several clinical trials are ongoing for therapeutic alternatives, however with little success rate. Considering that the time is crucial, the drug repurposing and data obtained from in silico models are one of the most important approaches to identify possible lead inhibitors against SARS-CoV-2. More recently, the Direct Acting Antivirals (DAAs) are emerged as the most promising drugs to control viral infection. The Main Protease (Mpro), a key enzyme in the SARS-CoV-2 replication cycle, is found close homolog to the Hepatitis C Virus (HCV) protease and could be susceptible of blocking its activity by DAAs. In the current study, the DAAs were investigated as antivirals using structure based computational approach against Mpro of SARS-CoV-2 to propose them as new therapeutics. In total, 20 DAAs of HCV, including a reference compound O6K were docked against Mpro. The docked structures were examined and resulted in the identification of six highly promising DAAs i.e. beclabuvir, elbasvir, paritaprevir, grazoprevir, simeprevir, and asunapevir exhibiting high theoretical binding affinity to Mpro from SARS-CoV-2 in comparison to other DAAs. Furthermore, the post docking analysis revealed that Cys145, Glu166, His163, Thr26, His41, and Met165 played potential role for the binding of these DAAs inside binding site of Mpro. Furthermore, the correlation between binding energies were found in accord with the results from the reported IC50s for some DAAs. Overall, the current study provides insight to combat COVID-19 using FDA-approved DAAs as repurposed drugs.

[Chronic hepatitis B virus infection: current and future treatment strategies]. / Chronische Hepatitis-B-Virusinfektion: aktuelle und zukünftige Therapieansätze.

For the treatment of chronic hepatitis B virus (HBV) infection, pegylated interferon-alfa and nucleoside/nucleotide analogs (entecavir and tenofovir) are currently available. These drugs allow viral suppression and normalization of the liver enzyme alanine aminotransferase (ALT) and prevent the liver disease from progressing. However, several therapeutic strategies that are still in clinical development aim at a functional cure. Their aim is that the HBV envelope protein HBsAg is no longer detectable in the serum ("resolved" hepatitis B). This review article provides an overview of current and possible future antiviral therapies against chronic HBV infection. A literature search paying special attention to the current guidelines as well as current conference contributions served as the basis.The currently available antiviral therapies only very rarely lead to the elimination of HBsAg (functional cure). It is also largely unclear in which patients discontinuation of long-term therapy with entecavir or tenofovir is feasible. New therapeutic strategies in clinical development lead to a functional cure in a higher proportion of patients. However, a combination of several antiviral strategies is likely required to achieve a functional cure in the majority of patients. Such therapies may presumably be available in the next 5-10 years.

Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus-Infected Patients With or Without Human Immunodeficiency Virus Coinfection.

BACKGROUND: The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)-infected patients with or without human immunodeficiency virus (HIV) is unclear. METHODS: We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. RESULTS: Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. CONCLUSIONS: This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.

Thyroid gland and direct-acting antivirals (DAAs) used to treat chronic hepatitis C. Is it a safe regimen?

Hepatitis C virus (HCV) infection is widespread in the world and it has a diverse clinical manifestation. As a result of chronic infection, a patient may experience many health complications. Autoimmune thyroid disorders (AITD) occur more often among HCV-infected patients compared with healthy population. HCV treatment has changed over the years. It results from discovering of more and more new drugs. With the advent of the new generation of drugs, the frequent of endocrine adverse effects decreased. The review considers the latest articles on thyroid diseases caused by direct-acting antiviral drugs (DAAs) against HCV. Based on the available literature, we can find out that DAAs are well tolerated by patients and rarely lead to thyroid disorders. The most common thyroid side effect associated with using one of DAAs in the therapeutic regimen is hypothyroidism. It's worth noting that the information collected from past medical history, especially about thyroid disease in the family of patients are very important. Population studies confirm a strong genetic influence on the development of AITD. Physicians should evaluate thyroid hormone parameters before, during and after treatment with using DAAs. In addition, symptoms of hypothyroidism should be quickly detected and then appropriate diagnosis and treatment initiated.