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Introduction and Objectives: Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index., Material and Methods: Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45-3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis., Results: Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 10 4 /mm 3 ), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 10 4 /mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index., Conclusions: Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Aim: Since the advent of direct-acting antiviral (DAA) therapy, the total eradication of hepatitis C virus has been achievable with the recovery of hepatic reserve after achievement of sustained virologic response (SVR). Hence, here, we examined the factors affecting the recovery of hepatic reserve., Methods: We followed up 403 patients (male: 164, female: 239; genotype 1: 299, genotype 2: 104; median age: 69 years) for at least 3 years after they achieved SVR to DAA therapy. Of these patients, 75 (18.6%) had a history of hepatocellular carcinoma (HCC). Biochemical tests were periodically performed, and the hepatic reserve was evaluated based on the albumin-bilirubin grade. We examined background factors such as age, biochemical test results, HCC occurrence and portosystemic shunt by computed tomography., Results: At the start of treatment, the albumin-bilirubin grades were grades 1, 2, and 3 in 241, 157, and 5 patients, respectively, and 3 years later, 117 of 162 (72%) patients with grade 2 or 3 improved to grade 1. Multivariate analysis identified the HCC occurrence after achievement of SVR (hazard ratio [HR]: 3.08, P < 0.0138), male sex (HR: 3.45, P = 0.0143), hemoglobin level of <11.5 g/dL (HR: 4.19, P = 0.0157), the presence of a portosystemic shunt (HR: 3.07, P = 0.0349), and alanine aminotransferase levels <45 U/L (HR: 2.67, P = 0.0425) as factors inhibiting improvement to grade 1. However, old age was not an inhibitory factor., Conclusion: Our results demonstrate that hepatic reserve could be improved even in elderly patients over a long course of time., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

We aimed to examine the relationship between renal dysfunction and anaemia that may develop during combination therapy involving pegylated interferon, ribavirin and telaprevir (PEG-IFN/RBV/TVR) for the treatment of chronic hepatitis C. Sixty-eight patients with genotype 1b high viral loads were treated with PEG-IFN/RBV/TVR. Peg-IFN and RBV doses were administered according to body weight. TVR was prescribed at 2250 mg/day for 44 patients and at 1500 mg/day for 24 patients who had low haemoglobin level (<12 g/dL). When anaemia had developed, the RBV dose was decreased. The serum TVR concentration at day 8 was measured, and the serum RBV concentration was measured serially. The estimated glomerular filtration rate (eGFR) was estimated to assess renal function. At week 1, serum TVR concentration was not correlated with a decrease in eGFR; however, the TVR dose, on a weight basis (mg/kg), and eGFR were correlated (r = 0.2691; P = 0.0265). Moreover, there was a negative correlation between eGFR and RBV serum concentration (r = −0.3694; P = 0.0025), and the serum RBV concentration and decrease in the haemoglobin were significantly correlated from week 1 to week 8. In triple therapy, the TVR dose per weight is correlated with a decline in renal function. Thus, the serum concentration of RBV increases, with a concomitant decrease in haemoglobin. It is important to adjust the doses of TVR and RBV to avoid excessive serum RBV levels and the development of severe anaemia, to achieve a good clinical effect.

Background/aims: Anemia is commonly observed as a side effect in a treatment with protease inhibitors combined with peginterferon alpha and ribavirin for hepatitis C virus infection. This study assessed the safety, tolerability, viral kinetics, and selection of variants in telaprevir monotherapy for 24 weeks, and outcomes of the off-study treatment with peginterferon alpha-2b and ribavirin among Japanese female patients at a median age of 54 years who were difficult to treat with the standard therapy (peginterferon alpha-2b and ribavirin) alone in Japan., Methods: Four treatment-naïve patients with chronic hepatitis C virus subtype 1b infection received telaprevir (750 mg every 8 h) alone for 24 weeks. All patients then started the off-study treatment with peginterferon alpha-2b and ribavirin. Safety, tolerability, hepatitis C virus RNA levels, and emergence of telaprevir-resistant variants were monitored., Results: During the 24 weeks of telaprevir monotherapy, there was no discontinuation due to adverse events, but 2 patients stopped the intake at weeks 6 and 15 because of viral breakthrough. Emergence of telaprevir-resistant variants was observed in 3 patients who showed viral breakthrough. These variants were eliminated by the off-study treatment, and sustained virological response was achieved in all patients., Conclusions: Anemia was manageable by carefully adjusting the ribavirin dosage in the standard therapy that followed telaprevir monotherapy. This sequential regimen seems to be safer and more tolerable than the triple combination of telaprevir, peginterferon alpha, and ribavirin, especially among elderly females with low baseline hemoglobin.

Background and Aims: Recently, hepatitis C virus (HCV) dynamics during interferon (IFN) therapy have been studied in detail. We examined factors that regulate the viral kinetics and the relationship between the viral kinetics and clinical effect of IFN therapy., Methods: Eighty-eight patients with chronic hepatitis C entered this study. All patients had been treated with 3 MU of IFN-beta twice a day for the first 2-4 weeks, then IFN-alpha for the next 20-22 weeks (three injections per week). The levels of serum HCV RNA were determined by Amplicor HCV Monitor version 1.0, before and 24 h after the first injection of IFN; then the decline of HCV was calculated. Liver inflammation and fibrosis were scored as 0 (none), 1 (mild), 2 (moderate) or 3 (severe) using biopsy specimens., Results: The decline of serum HCV RNA was 1.42 +/- 0.65 log copies/mL in genotype 1b and 1.83 +/- 0.72 in genotype 2a or 2b (P < 0.01). By a logistic regression model, genotype (1b, 2a or 2b) and hepatic fibrosis (0 or 1, 2 or 3) associated with 24-h decline of serum HCV RNA, independently. As the predictor of IFN therapy, the decline of serum HCV RNA and serum HCV RNA levels before IFN therapy were the independent significant factors (P < 0.001)., Conclusions: The decline of serum HCV RNA during the first 24 h of IFN therapy was regulated by genotypes and hepatic fibrosis. The decline of serum HCV RNA and initial HCV load were independent factors that can be the predictor of the subsequent sustained viral response to IFN therapy., (Copyright 2003 Blackwell Publishing Asia Pty Ltd)