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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.)

Background and Aim: Daclatasvir combined with asunaprevir is the first all-oral, ribavirin-free treatment of hepatitis C virus genotype 1b infection in Japan. This study compared the efficacy and safety of daclatasvir plus asunaprevir versus telaprevir plus peginterferon/ribavirin in Japanese treatment-naive patients infected with hepatitis C virus genotype 1b., Methods: Treatment-naive patients (20-70 years; baseline viral load, ≥ 100,000 IU/mL) were randomly assigned (stratified by IL28B rs8099917 TT/non-TT status) to receive either daclatasvir 60 mg tablets once daily and asunaprevir 100 mg softgel capsules twice daily for 24 weeks or telaprevir 750 mg (3 × 250 mg tablets) three times daily for 12 weeks and peginterferon/ribavirin per Japanese prescribing information for 24 weeks. A cohort of prior relapsers to peginterferon/ribavirin (20-75 years; baseline viral load, ≥ 100,000 IU/mL) received daclatasvir plus asunaprevir., Results: In treatment-naive patients, sustained virologic response at post-treatment week 12 in daclatasvir plus asunaprevir recipients was non-inferior (treatment difference, +25.8% in favor of daclatasvir plus asunaprevir) and higher (89.1%, 106/119) than telaprevir plus peginterferon/ribavirin recipients (62.2%, 69/111); sustained viral response was achieved in 95.5% (n = 21/22) of relapsers. Numerically, fewer patients receiving daclatasvir plus asunaprevir compared with telaprevir plus peginterferon/ribavirin experienced serious adverse events (4.2% vs. 5.4%), adverse events leading to discontinuation of any drug (5.0% vs. 62.2%), grade 3/4 treatment-related adverse events (14.3% vs. 72.1%), rash-related events (0% vs. 13.5%), or anemia (0% vs. 47.7%)., Conclusion: Marked differences were observed in the efficacy and safety profile of daclatasvir in combination with asunaprevir, compared with telaprevir plus peginterferon/ribavirin., (© 2015 Bristol-Myers Squibb. Journal of Gastroenterology and Hepatology published by Wiley Publishing Asia Pty Ltd. and Journal of Gastroenterology and Hepatology Foundation.)

Background: There are few detailed clinical reports about extrahepatic metastases of hepatocellular carcinoma (HCC). The purpose of the present study was to elucidate the clinical features of extrahepatic metastases of HCC., Methods: The clinical records of 482 patients who had been diagnosed as having HCC during the period from January 1995 to March 2001 were retrospectively reviewed. Extrahepatic metastases had been detected in 65 patients. Clinical features of those 65 patients were analyzed., Results: Patients with extrahepatic metastases had more advanced intrahepatic tumors at the first diagnosis of HCC: 73.8% of the patients with extrahepatic metastases had tumors of intrahepatic tumor stage T3 or T4 according to the TNM classification, while only 28.5% of the patients without extrahepatic metastases had tumors of T3 or T4 (P < 0.001). Vessel invasion was also detected at the first diagnosis of HCC more frequently in the patients with extrahepatic metastasis (P < 0.001). The frequent metastatic sites were lung (53.8%), bone (38.5%), and lymph node (33.8%). Other metastatic sites were the adrenal gland, peritoneum, skin, brain and muscle. The median survival time and 1-year survival rate were 7 months (range: 1-59 months) and 24.9%, respectively. Patients with Child-Pugh grade B and C (P = 0.0018) and patients with positive serum alpha-fetoprotein (P = 0.011) had significantly poor prognosis., Conclusions: Extrahepatic metastases of HCC are not rare. The possibility of extrahepatic metastases and the clinical features of extrahepatic metastases should be considered when examining patients with HCC, particularly those with advanced intrahepatic tumors, to enable precise evaluation of the spread of HCC and determination of the appropriate treatment method., ((c) 2005 Blackwell Publishing Asia Pty Ltd.)

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)