Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.
Antiviral Agents/therapeutic use* ; Carbamates ; Drug Therapy, Combination ; Genotype ; Hepacivirus/genetics* ; Hepatitis C/drug therapy* ; Hepatitis C, Chronic/drug therapy* ; Heterocyclic Compounds, 4 or More Rings ; Humans ; Liver Cirrhosis/complications* ; Prospective Studies ; RNA ; Ribavirin/therapeutic use* ; Sofosbuvir/adverse effects* ; Sustained Virologic Response ; Treatment Outcome

BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSIONS: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.
Aged ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Aspartate Aminotransferases/blood ; Drug Administration Schedule ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/*genetics/isolation & purification ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Imidazoles/*therapeutic use ; Isoquinolines/*therapeutic use ; Liver/diagnostic imaging ; Liver Cirrhosis/complications ; Male ; Middle Aged ; RNA, Viral/blood ; Retrospective Studies ; Sulfonamides/*therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: The previous standard treatment for chronic hepatitis C (CHC) patients, comprising a combination of pegylated interferon (IFN) and ribavirin, was associated with suboptimal efficacy and severe adverse reactions. A new era of direct-acting antivirals is now dawning in Korea. Early experience of applying sofosbuvir-based therapy to CHC patients in Korea is reported herein. METHODS: Data on efficacy and safety were collected for CHC patients treated with a combination of sofosbuvir plus ribavirin or sofosbuvir/ledipasvir with or without ribavirin. RESULTS: This retrospective study included 25 consecutive patients who received sofosbuvir-based therapy (19 with genotype 1b and 6 with genotype 2) at Seoul National University Hospital from May 2014 to April 2015. A virologic response was achieved at week 4 by 85.7% and 80% of the patients with genotypes 1b and 2, respectively. The HCV-RNA level decreased more slowly in IFN-experienced than in treatment-naive patients with genotype 1b. However, the sustained virologic response at week 12 (SVR12) rate did not differ among these patients, and was as high as 100%. The presence of cirrhosis significantly increased the risk of a virologic response failure at week 4 (OR, 11.0; P=0.011) among patients with HCV genotype 1b. Only five patients (20%) experienced minor adverse events, including grade 1 fatigue and headache. The hemoglobin level decreased slightly after sofosbuvir-based therapy, but there was no case of premature discontinuation of this therapy. CONCLUSIONS: In a real clinical practice, sofosbuvir-based therapy for CHC patients in Korea achieved optimal antiviral efficacy with insignificant adverse events. Long-term follow-up data are warranted to ensure the sustained antiviral efficacy and long-term safety of sofosbuvir-based IFN-free therapy.
Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Fatigue/etiology ; Female ; Genotype ; Headache/etiology ; Hemoglobins/analysis ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/complications/diagnosis ; Male ; Middle Aged ; RNA, Viral/blood ; Republic of Korea ; Retrospective Studies ; Ribavirin/therapeutic use ; Sofosbuvir/adverse effects/*therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon alpha-2a plus ribavirin for CHC in hemophilia. METHODS: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests. RESULTS: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naive patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis. CONCLUSIONS: Peginterferon alpha-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.
Adult ; Aged ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Fatigue/etiology ; Female ; Genotype ; Headache/etiology ; Hemophilia A/*complications ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Liver/pathology ; Male ; Middle Aged ; Neutropenia/etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; RNA, Viral/blood ; Recombinant Proteins/adverse effects/therapeutic use ; Recurrence ; Republic of Korea ; Ribavirin/adverse effects/*therapeutic use ; Treatment Outcome

No abstract available.
Antiviral Agents/*therapeutic use ; Female ; Hemophilia A/*complications ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon-alpha/*therapeutic use ; Male ; Polyethylene Glycols/*therapeutic use ; Ribavirin/*therapeutic use

BACKGROUND/AIMS: The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate. METHODS: Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients. RESULTS: The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234). CONCLUSIONS: The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC.
Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/therapeutic use ; Carcinoma, Hepatocellular/complications/*pathology/radiography ; Demography ; Female ; Hepatitis B, Chronic/*complications/drug therapy ; Hepatitis C, Chronic/*complications/drug therapy ; Humans ; Linear Models ; Liver Neoplasms/complications/*pathology/radiography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Staging ; Republic of Korea ; Retrospective Studies ; Tertiary Care Centers ; Tomography, X-Ray Computed

Hepatitis C virus (HCV) is one of the main viral causes of hepatocellular carcinoma (HCC) and is associated with lymphoproliferative disorder such as non-Hodgkin's lymphoma (NHL). However, there are only few case reports on concomitantly induced NHL and HCC by HCV. Herein, we report a case of synchronous NHL and HCC in a patient with chronic hepatitis C which was unexpectedly diagnosed during liver transplantation surgery. This case suggests that although intrahepatic lymph node enlargements are often considered as reactive or metastatic lymphadenopathy in chronic hepatitis C patients with HCC, NHL should also be considered as a differential diagnosis.
Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/complications/*diagnosis/radiotherapy ; Drug Therapy, Combination ; Embolization, Therapeutic ; Fluorodeoxyglucose F18 ; Gadolinium DTPA ; Genotype ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/complications/*diagnosis/*virology ; Humans ; Liver Neoplasms/complications/*diagnosis/radiotherapy ; Lymph Nodes/pathology ; Lymphoma, Non-Hodgkin/complications/*diagnosis/drug therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed

OBJECTIVETo evaluate the effect of antiviral therapy on the quality of life (QOL) of patients with chronic hepatitis C (CHC) and cirrhosis during the 5-year period following splenectomy to treat hypersplenism.

METHODSData of patients with CHC and cirrhosis who had undergone treatment for hypersplenism were retrospectively selected from the hospital database of medical records. The patients were first grouped according to the hypersplenism treatment: splenectomy (group A, 28 cases) and conservative/non-operative (group B, 30 cases). Sub-grouping was carried out according to the CHC treatment: interferon-alpha-2a and ribavirin (15 cases in the A1 group, and 19 cases in the B1 group) and non-antiviral (13 cases in the A2 group, and 11 cases in the B2 group). To determine the intergroup differences in QOL during the 5-year period following the hypersplenism treatment, the QOL was assessed by chronic liver disease questionnaire (CLDQ), listing of specific symptoms (SS), and the World Health Organization QOL scale (WHOQOL-BREF).

RESULTSBetween-group statistical comparison of the subjective feeling, physiological status, mental state, and social life relationship of the patients showed no significant differences among the patients who received splenectomy compared to those who received the conservative treatment. However, the QOL of splenectomy-treated patients who received non-antiviral CHC treatment was worse than that of the patients who were given conservative treatment for the hypersplenism and antiviral therapy for the CHC. The patients who received splenectomy and antiviral therapy had better QOL than the other patient group(3.69 +/- 0.75 vs 2.15 +/- 0.98, P = 0.0003).

CONCLUSIONSplenectomy followed by antiviral therapy may improve the QOL of patients with CHC-related cirrhosis and hypersplenism.

Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis C, Chronic ; complications ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; virology ; Male ; Middle Aged ; Quality of Life ; Retrospective Studies ; Splenectomy ; Treatment Outcome

OBJECTIVETo determine whether patients infected with chronic hepatitis C (CHC) show a differential distribution profile of IL-28B polymorphisms according to the presence of concomitant cryoglobulinemia.

METHODSSixty-two consecutive CHC patients were enrolled in the study between December 2008 and December 2010. All patients received combination therapy of pegylated interferon alpha-2a (weekly, 180 g, subcutaneous injection) plus ribavirin (daily, 10to15 mg/kg body weight, oral) for 48 weeks, with individualized dosage adjustments according to the patient's clinical situation. Cryoglobulins were detected visibly by separation of cryoprecipitates in patient serum samples. Three IL-28B SNPs (rs8099917, rs12979860, and rs12980275) were detected by sequencing. Response to treatment was assessed by measuring serum levels of HCV RNA by quantitative PCR at baseline (prior to treatment initiation), during treatment (4 and 12 weeks after treatment initiation), end of therapy (48 weeks after treatment initiation), and post-treatment (24 weeks after end of therapy). The significance of between-group differences were assessed by the Chi-square and Fisher's exact tests.

RESULTSCryoglobulinemia was detected in 43.5% (27/62) of the CHC patients and showed a female bias (59.3% vs. males: 34.3%, P = 0.05). Compared to CHC patients without cryoglobulinemia, the CHC patients with cryoglobulinemia showed significantly higher levels of HCV RNA at baseline (5.64+/-1.20 vs. 6.37+/-0.67, P less than 0.05) but lower frequencies of the IL28B rs8099917 TT genotype (94.3% vs. 63.0%, P = 0.002), rs8099917 T allele (97.1% vs. 81.5%, P = 0.003), and rs12979860 C allele (94.3% vs. 83.3%, P = 0.048). CHC patients with cryoglobulinemia and having the rs8099917 TT, rs12979860 CC, or rs12980275 AA genotype achieved a higher rate of sustained virological response.

CONCLUSIONCryoglobulinemia in CHC patients is associated with a differential distribution of IL-28B polymorphisms, and certain polymorphisms may be related to anti-viral treatment response.

Adult ; Alleles ; Antiviral Agents ; therapeutic use ; Cryoglobulinemia ; blood ; complications ; Female ; Genotype ; Hepatitis C, Chronic ; blood ; complications ; drug therapy ; genetics ; Humans ; Interleukins ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; RNA, Viral ; blood

OBJECTIVETo investigate the relation of thyroid function with hashimoto thyroiditis (HT, an autoimmune disease of unknown etiology also known as chronic lymphocytic thyroiditis) in patients with chronic hepatitis C (CHC) receiving treatment with pegylated-interferon-alpha (Peg-IFNa) based on the observation that HT is common among individuals undergoing IFN-based therapy.

METHODSOne-hundred-and-seven patients with chronic hepatitis C were enrolled for study between January 2008 and December 2010. Thyroid function was assessed by electrochemiluminescence assays to detect serum levels of anti-thyroid peroxidase (A-TPO) antibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) prior to initiation of the IFN-based therapy. The treatment strategies (drugs, doses, schedules) were designed according to HT status (CHC with HT, or CHC without HT). Patients were monitored during the 24 weeks of treatment (including measuring serum alanine aminotransferase (ALT), TSH, and FT4 every two to four weeks, and HCV RNA every four weeks) so that the IFNa dose could be adjusted and thyroid medications (levothyroxine sodium or methimazole) added as necessary. The response rate at end of treatment (week 24) was assessed.

RESULTSTwenty-one of the CHC patients were diagnosed with HT, and the incidence of thyroid dysfunction among the CHC patients with HT was 71.4% (15/21); among the CHC patients with no HT, the incidence of thyroid dysfunction was significantly lower (30.2% (26/86), X2 = 12.1995, P less than 0.01). In the CHC patients with HT, 90.5% (19/21) had serum levels of A-TPO antibodies that were more than or equal to 2-times higher than the normal value at the end of treatment. Of the 15 CHC patients with HT and thyroid dysfunction, 73.3% (11/15) continued to show thyroid dysfunction at the end of treatment. Hypothyroidism was the most common form of thyroid dysfunction observed (4/11), and all of those patients responded to levothyroxine sodium treatment. The virological response rates of the two groups (CHC with HT and CHC without HT) were not significantly different at any time point examined (treatment week 4, 12, and 24, P more than 0.05).

CONCLUSIONThe incidence of thyroid dysfunction is significantly higher among CHC patients with HT than among CHC patients without HT. If suspected, these patients should be carefully monitored because the clinical symptoms of thyroid dysfunction are not obvious and the drug therapy should be carefully adjusted to minimize the thyroid dysfunction while maximizing the antiviral effect.

Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Female ; Hashimoto Disease ; complications ; drug therapy ; Hepatitis C, Chronic ; complications ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Ribavirin ; therapeutic use ; Young Adult