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Hepatitis C virus (HCV) is a primary hepatotropic pathogen responsible for acute and chronic hepatitis C, however, it can also cause “occult” infection (OCI), defined as the presence of the virus’ genetic material in hepatocytes and/or peripheral blood cells, but not in plasma/serum. Assessment of the sustained virologic response (SVR) after treatment with direct-acting antivirals (DAA) is based exclusively on HCV-RNA testing in plasma/serum, which may preclude the diagnosis of post-treatment OCI. Possible clinical consequences of OCI were described previously, but its occurrence after DAA-based antiviral treatment programs and determinants of the virus persistence are not fully elucidated. The aim of this study was to assess the incidence of post-treatment OCI after successful DAA-based treatment and to identify clinical and immunological factors associated with this phenomenon. In 97 patients treated with DAA, HCV-RNA was tested by RT-PCR in peripheral blood mononuclear cells (PBMC) at baseline (i.e., before the onset of treatment) and at the time of SVR assessment. Before treatment, HCV-RNA was detectable in all patients’ PBMC. All subjects responded to therapy according to the clinical criteria, but 9 (9.3%) patients revealed the HCV-RNA in PBMC at SVR. In most of these cases, post-DAA OCI was related to switch of the dominant infecting genotype. Post-treatment OCI was characterized by significantly lower pre-treatment HCV viral load and lower expression of Tim-3 (T-cell immunoglobulin and mucin domain-containing protein 3) on CD8 + T-cells. Our results imply that post-treatment OCI may be related to lower pretreatment viral load as well as distinct pre-existing immune exhaustion status.

Hepatitis C virus (HCV) is a global public health problem, but advancements in HCV treatment have improved the cure rate. This study evaluated the effectiveness of direct-acting antivirals (DAAs) in HCV-infected patients from May 2021 to April 2023 in collaboration with tertiary care hospitals in West Bengal. The HCV viral load was monitored via qRT-PCR. Sanger sequencing was performed to determine the HCV genotypes. The clinicians prescribed the patient treatment regime. The maximum number of patients in the study population (N = 398) were compensated cirrhosis patients (46.28%). The overall SVR rate of the study population was 94.47%. The decompensated cirrhosis patients experienced the lowest SVR rate (88.89%). The maximum number of patients were prescribed sofosbuvir/daclatasvir (63.77%), and the lowest SVR rate (93.23%) was observed with this treatment regime. In the study population, GT-3 was the predominant (67.43%) circulating genotype, followed by GT-1 and -4. Among 398 patients, 22 (5.53%) were non-responsive to DAA treatment. Out of these 22 non-responder patients, 77.27% (n = 17) were GT-3-infected (3a:10; 3b:07), followed by GT-1 (1c: 04; 1b: 01). Thus, increasing numbers of DAA non-responsive cases among HCV GT-3-infected and decompensated cirrhosis patients may pose serious threats in the future.

Background: Hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and hepatocellular carcinoma globally. The advent of direct-acting antivirals (DAAs) with high cure rates provides an opportunity to reduce the rising HCV disease burden. However, few studies have explored the side effects and physiological benefits of DAA therapy in rural areas. The aim of this study was to investigate the subjective reports of discomfort, patient feedback about the course of treatment, and physiological changes after DAA treatment in HCV patients. Methods: A descriptive, prospective, comparative cohort study was conducted from January to August 2019 in western coastal Yunlin County, Taiwan. Data regarding demographic characteristics, subjective discomfort levels, and physiological responses were collected through face to face interviews and from medical records by a cooperating hospital. Results: Six-hundred-and-twenty-three participants with an active HCV infection were identified; 555 (89.1%) had completed treatment, and sustained virologic response was achieved in 99.6% (n = 553). The mean age was 64.9 (standard deviation = 13.1) years, and 35% of patients experienced discomfort during DAA treatment, including fatigue, itching, and dizziness. After three months of treatment, physiological markers, including body weight (p < 0.001), waist circumference (p < 0.05), blood pressure (p < 0.001), alanine aminotransferase (p < 0.001), and aspartate aminotransferase (p < 0.001), had significantly improved. Almost all participants provided positive feedback about the treatment experience and reported manageable side effects. Conclusions: The findings showed that, in an endemic rural area, DAA treatment had a high cure rate and improved physiological markers with few discomforts. These results can be used to reduce the barriers HCV patients face in adopting new medications.

Reducing the treatment duration for chronic hepatitis C could be an important tool in the effort to reach the elimination goals set by the World Health Organization. The current challenge is to predict the target group who will achieve sustained virological response at week 12 (SVR12) with shorter treatment duration. The aim of this exploratory study was to characterize immune subsets with focus on inhibitory receptors in patients who experienced SVR12 or virological relapse following four weeks treatment with glecaprevir/pibrentasvir with or without ribavirin. A total of 32 patients were included in this study of whom 21 achieved SVR12 and 11 had virological relapse. All available samples at baseline (n = 31) and end of treatment (EOT) (n = 30) were processed for flow cytometric analysis in order to measure the expression of PD-1, 2B4, BY55, CTLA-4, TIM-3 and LAG-3 on 12 distinct T cell subsets. At baseline, patients with SVR12 (n=21) had numerically lower frequencies of inhibitory receptors for 83% (60/72) of the investigated T-cell subtypes. The most significant difference observed between the two groups was a lower frequency of stem cell-like memory T-cells CD4 + PD1 + in the SVR group (p = 0.007). Furthermore, we observed a significant positive correlation between baseline viral load and the expression of PD-1 on the total CD8 + T-cells and effector memory T-cells CD4 + and CD8 + for patients with virological relapse. This study suggests a measurable immunologic phenotype at baseline of patients achieving SVR12 after short treatment compared to patients with virological relapse.

Background Combination therapy of interferon and ribavirin has traditionally been used to eradicate hepatitis C virus. The sustained virologic response achieved with interferon-related therapy is persistent, and late relapses after achieving sustained virologic response at 24 weeks using this therapy are reportedly rare (< 1%). In 2014, interferon-free therapy with direct-acting antivirals was developed, and the rate of sustained virologic response was improved. However, the persistence thereof remains uncertain, and the appropriate follow-up period for hepatitis C virus-positive patients is under discussion. Case presentation A 74-year-old Japanese man who had hepatitis C virus–related hepatocellular carcinoma and was successfully treated with radiofrequency ablation four times underwent direct-acting antiviral therapy with daclatasvir and asunaprevir; sustained virologic response at 24 weeks was confirmed. However, although he had no high risk factors for reinfection, hepatitis C virus ribonucleic acid was detected again 6 months after achieving sustained virologic response at 24 weeks. Moreover, he developed active hepatitis with an increased viral load. Five months after development of hepatitis, recurrent hepatocellular carcinoma emerged in segment II, where we had performed radiofrequency ablation 17 months previously. The recurrent hepatocellular carcinoma enlarged quite rapidly and induced multiple peritoneal disseminations and lung metastases. He died 3 months after the abrupt recurrence. A sarcomatous change in the hepatocellular carcinoma was identified during the autopsy. Conclusions Although sustained virologic response at 24 weeks has generally been regarded to denote complete eradication of hepatitis C virus, we present a patient in whom hepatitis C virus recurred 6 months after achieving sustained virologic response at 24 weeks with direct-acting antiviral therapy. In addition, a sarcomatous change in hepatocellular carcinoma emerged 5 months after active hepatitis developed due to late hepatitis C virus relapse in this case. The sarcomatous change in hepatocellular carcinoma is generally thought to be related to anticancer therapies, such as radiofrequency ablation. However, in this case, late viral relapse and active hepatitis in addition to the previous radiofrequency ablation could have been the trigger. There may be a need for follow-up of hepatitis C virus ribonucleic acid beyond sustained virologic response at 24 weeks with direct-acting antiviral therapy, owing to the possibility of late viral relapse and tumorigenesis.

Background: The primary goal of the treatment of the Hepatitis C Virus (HCV) is to eradicate the disease, which is determined by achieving sustained virologic response (SVR), defined as an undetectable quantitative HCV RNA level 12 weeks after completion of therapy. This lab value is required to assess the outcome of therapy and is important to stakeholders, including primary payors, to determine the value of care provided. Objectives: This study sought to determine the impact of a specialty-pharmacy led intervention on adherence with required post-treatment SVR labs Methods: This was a single center, retrospective, observational study, comparing patient adherence to SVR lab work from baseline data to data collected once the pharmacy intervention was initiated and implemented. The intervention was multidisciplinary and engaged functions of the pharmacy technicians, clinic staff, and the specialty pharmacists. The pharmacy technician was instructed to place fluorescent stickers on the packaging of the medication during the initial fill and the last fill of therapy, instructing the patient to call the Hepatitis C clinic. When the patient called the clinic, they would be provided with further instructions about lab dates and reminders about the importance of adherence. The patient would receive three to six phone calls from the specialty pharmacist while on therapy, depending on the length of therapy and adherence obstacles. The pharmacist would remind the patient of all required lab dates during these phone calls. The pharmacist would call the patient one to two times during the SVR window to remind the patient to complete lab work. Any adherence concerns with the medication or adherence issues with lab work were referred to the clinic for further outreach. Data was reviewed quarterly to assess the impact of the intervention. Baseline data were collected between 1 January 2016 and 30 June 2016. The quarterly reviews were performed from July 2016 to September 2016 (Quarter 1), October 2016 to December 2016 (Quarter 2), January 2017 to March 2017 (Quarter 3), and April 2017 to June 2017 (Quarter 4). Results: After implementation of the intervention SVR completion rates for Quarter 1, Quarter 2, Quarter 3, and Quarter 4 were 86.1% (31/36), 79.4% (27/34), 79.1% (34/43), and 87.5% (49/56), respectively. The overall SVR lab adherence rate increased from 62.8% at baseline to 83% post-intervention (p = .0054). This amounts to an overall increase in adherence to SVR lab work by 33%. Conclusions: Following the initiation of a multidisciplinary, specialty pharmacy-led intervention, SVR lab completion rates rose by approximately 20.7%, indicating a 33% improvement in adherence to required lab monitoring. These results demonstrate the importance and necessity of a multidisciplinary team, including pharmacists and pharmacy technicians in addressing adherence issues and ensuring the delivery of value-driven healthcare.

(1) Background: Direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection is associated with high sustained virologic response (SVR) and overcomes negative predictive factors, including steatosis, in patients without human immunodeficiency virus (HIV) coinfection. The impact of steatosis on SVR in patients with HIV–HCV coinfection is unknown. (2) Methods: A retrospective analysis of patients treated with direct-acting antivirals was performed. Demographic, laboratory and direct-acting antiviral regimen data were prospectively collected. Metabolic syndrome and its components—diabetes mellitus, hypertension, dyslipidemia and obesity—were assessed. Hepatic steatosis (≥5%) was defined by liver biopsy or controlled attenuation parameter (CAP) measurement during vibration-controlled transient elastography (VCTE). (3) Results: A total of 151 HIV–HCV-coinfected patients on combined antiretroviral therapy and direct-acting antiviral therapy were included in this analysis. Prevalence of steatosis by liver biopsy (n = 34) or CAP (≥263 db/m) during VCTE (n = 92) was 27% and was independently associated with obesity (OR 3.11; 95% CI 1.43–6.82; p = 0.004) and the metabolic syndrome (OR 1.08; 95% CI 1.01–0.15; p = 0.01). The overall SVR rate (n = 148) was 95% and was not impacted by the presence of steatosis (p = 0.42). (4) Conclusions: Hepatic steatosis is common in HIV–HCV coinfection, correlates with obesity and the metabolic syndrome and does not impact SVR.

Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality among thalassemic patients. Direct-acting antiviral agents (DAAs) are highly effective and well-tolerated by chronic HCV patients. The mean age of our patients was 29 years. Sustained virologic response (SVR) at 12 and 24 weeks was achieved in all patients (100%). The most common side effects were fatigue (18%), anemia (13.63%), and headache (4.5%). There was no statistically significant difference in the hemoglobin level before and after treatment (p = 0.48). There was a significant improvement in serum bilirubin and mean ALT levels after treatment compared to baseline data (p < 0.0005 each). DAAs, namely, sofosbuvir plus daclatasvir or sofosbuvir plus ledipasvir, are effective and well-tolerated regimens in thalassemic patients with chronic HCV.

The drugs currently licensed for treatment of hepatitis C are pegylated interferon and ribavirin. Variation of treatment length and dose modification of these drugs are the strategies that have been so far investigated to optimize the outcomes of treatment in patients with genotypes 2 and 3. The different design of the studies on shortening treatment duration and the rates of SVR, according to RVR, are reported and discussed in this chapter. Moreover, additional factors besides RVR that may improve patients' outcomes, reducing the rate of relapse after a short course of treatment, are analyzed. Finally, we focus on how drug dosing can influence treatment outcomes, increasing the efficacy of treatment.