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: The T-helper 1 (TH1) immune reaction is essential for the eradication of hepatitis C virus (HCV) during pegylated interferon alpha (PEG-IFN-alpha)- and ribavirin (RBV)-based therapy in chronic HCV patients. Secreted phosphoprotein 1 (SPP1) was shown to be a crucial cytokine for the initiation of a TH1 immune response. We aimed to investigate whether SPP1 single nucleotide polymorphisms (SNPs) may influence sustained virological response (SVR) rates. METHODS: Two SNPs in the promoter region of SPP1 at the -443 C>T and -1748 G>A loci were genotyped in 100 patients with chronic HCV genotype 4 infection using a TaqMan SNP genotyping assay. RESULTS: Sixty-seven patients achieved a SVR, and 33 patients showed no SVR. Patients carrying the T/T genotype at the -443 locus showed a significantly higher SVR rate than those carrying the C/T or C/C genotype (83.67% vs 50.98%, p<0.001). At the -1748 locus, the SVR rate was significantly higher in patients with the G/G genotype than in those with the A/A genotype (88.89% vs 52.63%, p=0.028) and in patients with the G/A genotype than in those with the A/A genotype (85.29% vs 52.63%, p=0.001). CONCLUSIONS: SPP1 SNPs at -443 C>T and -1748 G>A loci may be useful markers for predicting the response to PEG-IFN-alpha-2b plus RBV therapy in Egyptian patients with chronic HCV genotype 4 infection.
Adult ; Antiviral Agents/*therapeutic use ; Biomarkers/blood ; Drug Therapy, Combination ; Egypt ; Female ; Genotype ; Hepacivirus/drug effects/genetics ; Hepatitis C, Chronic/*drug therapy/virology ; Humans ; Interferon-alpha/*therapeutic use ; Male ; Middle Aged ; Osteopontin/*genetics ; Polyethylene Glycols/*therapeutic use ; Polymorphism, Single Nucleotide/genetics ; Predictive Value of Tests ; *Promoter Regions, Genetic ; Recombinant Proteins/therapeutic use ; Ribavirin/*therapeutic use ; Treatment Outcome

OBJECTIVEThe aim of this study was to explore the diagnostic value of liver stiffness measurement combined with serum high-sensitivity C-reactive protein detection in HBV-related cirrhosis patients complicated with primary liver cancer.

METHODSA total of 156 previously untreated chronic hepatitis B-related cirrhosis patients and 50 healthy subjects were included in this study. The 156 patients were divided into two groups: those with primary liver cancer (67 cases) and without liver cancer (89 cases). The 50 healthy subjects were considered as normal control group. Liver stiffness measurement (LSM) was conducted and serum high-sensitivity C-reactive protein (CRP) level was assayed in all the 156 patients and 50 normal individuals, and their measurement values were statistically compared and analyzed.

RESULTSThe LSM value was (39.72±29.05) kPa in the liver cancer patients, significantly higher than the (27.81±18.46) kPa in the cirrhosis alone patients and (4.25±0.74) kPa in the healthy controls (P<0.01 for both). Serum hs-CRP levels in the liver cancer patients was 5.81mg/L, significantly higher than 1.78 mg/L in the cirrhosis alone patients and 0.38mg/L in healthy controls, (P<0.01 for both). The higher the grade of LSM values was, the positive rate of CRP was higher in the cirrhosis patients complicated with primary liver cancer. In patients with LSM values ≥27.6 kPa, the serum CRP positive rate was 64.2% in patients with primary liver cancer, significantly higher than the 38.0% in patients with cirrhosis alone (P<0.01). In the 67 HBV-related cirrhosis patients complicated primary liver cancer, the LSM value and serum hs-CRP level in AFP-positive patients were (48.95±28.59) kPa and 4.91 mg/L, respectively, higher than those in the AFP-negative patients (28.64±26.83) kPa and 4.16 mg/L, but with a non-significant difference (P>0.05).

CONCLUSIONLiver stiffness measurement combined with serum high-sensitivity C-reactive protein detection may have potential diagnostic implications as a marker of primary liver cancer occurrence in patients with HBV-related cirrhosis.

Biomarkers ; C-Reactive Protein ; metabolism ; Elasticity Imaging Techniques ; Fibrosis ; Hepatitis B, Chronic ; complications ; metabolism ; Humans ; Liver Cirrhosis ; etiology ; metabolism ; virology ; Liver Neoplasms

OBJECTIVETo investigate the distribution of HCV genotypes in Chinese Han population with chronic hepatitis C (CHC).

METHODSThis randomized multicenter study included 1 014 CHC patients from 28 hospitals in different regions of China. SPSS 20.0 was applied to analyze the relationship among region, HCV genotype, gender and the replication level of HCV-RNA.

RESULTSHCV 1 genotype (56.80%) was the most common genotype. The majority of CHC patients were of genotype 1, 2, 3, 6 in the order of frequency, except those in southwestern, southern and central China. HCV 1, 2, 3, 6 genotypes were most common among male patients in southern China; among female patients in northern China; among male patients in northern and northwestern China and among male patients in northwestern China, respectively (all P <0.05). There was no statistical significance between different genders in other regions. The high viral load was more common than the low viral load among HCV 1, 2, 3, 6 genotype-infected patients.

CONCLUSIONThere are different distributions of HCV genotypes among the different regions. In addition, HCV genotypes are correlated with gender and HCV-RNA load.

Asian Continental Ancestry Group ; China ; Female ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; virology ; Humans ; Male ; Randomized Controlled Trials as Topic ; Viral Load

Peg-interferon and ribavirin has been the standard therapy of chronic hepatitis C for the past 15 years in Korea. However, the treatment paradigm is changing. Direct acting agents (DAAs) are oral pills that can be easily taken. In addition, DAAs are more effective and have less adverse reactions compared to the previously used drugs. Chronic hepatitis C is hard to treat because the virus is error-prone virus. Host immunity is helpless against the hepatitis C virus since it evades the host immunity through various complex mechanisms. There are 6 genotypes. Quasispecies can co-exist even in the same patients. The treatment strategy is based on the combination of the individual drug corresponding to each step of viral replication process. NS5B nucleosides are the most powerful and effective drug available until now. Other drugs with different mechanisms of action can be used to provide synergy. NS5A and NS5B inhibition drugs currently belong to the leading group amongst many DAAs. These drugs will soon be available in Korea. We have to know the merits and adverse drug reactions of the new drug.
Antiviral Agents/*therapeutic use ; Drug Therapy, Combination ; Enzyme Inhibitors/therapeutic use ; Genotype ; Guidelines as Topic ; Hepacivirus/genetics ; Hepatitis C, Chronic/*drug therapy/immunology/virology ; Humans ; Viral Nonstructural Proteins/antagonists & inhibitors/metabolism

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

OBJECTIVETo investigate the clinical features and rate of natural viral clearance in patients with hepatitis C virus (HCV) infection acquired by blood transfusion from a single donor.

METHODSNinety-six patients who acquired HCV infection between January 1998 and December 2002, upon receipt of donated blood from a single infected individual in Guizhou,were included in this retrospective cross-sectional study. Patients were clinically assessed to determine levels of anti-HCV antibodies, HCV RNA and biochemical indicators of liver function,as well as features of liver structure (by abdominal B ultrasonography and elastography). HCV genetic testing was used to determine the virus genotype. Measurement data were expressed as mean ± standard deviation. Count data were analyzed by the x² test,with P less than 0.05 indicating statistical significance.

RESULTSAll 96 patients tested positive for antiHCV antibodies. The majority of patients (70%; 34:33 male:female) had HCV RNA more than or equal to 1.0 * 103 copies/ml. All patients carried the same HCV genotype as the single blood donor:genotype lb. The overall rate of natural HCV clearance was 30.2%. but males had a significantly lower rate (19.0% (8/42) vs. females:38.9% (21/54);x²=4.41,P=0.023) as did older patients (more than 40 years-old:16.1% (5/31) vs .less than or equal to 40 years-old:36.9% (24/65);x²=4.30,P=0.028). The overall rate of chronic HCV infection (CHC) was 69.8%,but the rate was significantly lower in younger patients (less than or equal to 40 years-old:63.1% (41/65) vs. more than 40 years-old:83.9% (26/31);x²=6.67,P=0.028). Among the 67 patients with CHC,12 had symptoms of mild weakness,anorexia and abdominal distention,11 had elevated serum alanine aminotransferase (116.25 +/- 24.65 U/L) and stage 3 or 4 fibrosis (liver elasticity values more than or equal to 5.1 kPa),and three had mildly abnormal serum bilirubin (32.56 ± 5.28 mumol/L). Fifteen patients showed signs of chronic hepatitis and one patient showed signs of cirrhosis by abdominal B ultrasonography. None of the patients showed signs of hepatocellular carcinoma.

CONCLUSIONThe course of blood transfusion acquired HCV infection is largely unknown and natural viral clearance rate may be associated with sex-and age-related factors.

Adolescent ; Adult ; Aged ; Blood Donors ; Child ; Cross-Sectional Studies ; Female ; Genotype ; Hepacivirus ; genetics ; physiology ; Hepatitis C ; epidemiology ; virology ; Hepatitis C Antibodies ; blood ; Hepatitis C, Chronic ; epidemiology ; virology ; Humans ; Male ; Middle Aged ; RNA, Viral ; blood ; Remission, Spontaneous ; Retrospective Studies ; Transfusion Reaction ; Young Adult

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 investigate the variations of hepatitis C virus (HCV) quasispecies and the changes in their composition in untreated patients with chronic hepatitis C.

METHODSEleven patients chronic hepatitis C without previous specific anti-HCV treatment were tracked for disease progression and blood samples were collected at multiple time points. The major clinical parameters of liver function and viral load were tested. A fragment of HCV hypervariable region 1 (HVR1) was amplified and cloned, and the positive clones were sequenced and subsequently analyzed to determine the composition variation of HCV quasispecies during disease progression in relation to the major clinical parameters.

RESULTSA total of 631 HVR1 sequences were acquired from the positive clones. The evolution of HCV HVR1 quasispecies in untreated chronic hepatitis C patients featured 3 patterns of variation in quasispecies composition, namely stable, fast and slow changes during the natural course of chronic hepatitis C. The genetic distance of the quasispecies was found to inversely correlated with ALT (R=-0.438, P=0.011) and AST level (R=-0.500, P=0.003), and sense mutation rate was also inversely correlated with ALT level (R=-0.387, P=0.026) and AST level (R=-0.410, P=0.018). No significant association was found between HCV load and any clinical or virological parameters.

CONCLUSIONDue to individual differences and immune pressure, HCV quasispecies can present with different patterns of evolution in the natural disease progression of chronic hepatitis C. HCV quasispecies evolution, due to its close correlation with the biochemical parameters, can be used to evaluate the severity and prognosis of chronic hepatitis C.

Base Sequence ; Disease Progression ; Genetic Variation ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; virology ; Humans ; Viral Load