Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.
Carcinoma, Hepatocellular/complications ; DNA, Viral/analysis ; Hepacivirus/genetics ; Hepatitis B/*complications/*diagnosis/drug therapy ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/*complications/*diagnosis/drug therapy ; Humans ; Interferon-alpha/therapeutic use ; Liver/virology ; Liver Neoplasms/complications

BACKGROUND/AIMS: Cross-sectional studies have documented that 2-10% of patients who are chronically infected with hepatitis C virus (HCV) are also positive for hepatitis B virus (HBV) surface antigen (HBsAg). Data related to HCV-HBV coinfection are lacking in Korea. This study evaluated the clinical characteristics, the treatment efficacy of peginterferon alfa plus ribavirin, and the changes induced by such treatment in HBV status in chronic hepatitis C (CHC) patients coinfected with HBV. METHODS: Eighteen (2.37%) HBsAg-positive CHC patients were selected from among the 758 subjects from the K(G)yeonggi-Incheon Peginterferon alfa and ribavirin in chronic hepatitis C Treatment (KIPECT) study, which evaluated the treatment efficacy and safety of peginterferon alfa plus ribavirin in CHC patients. Data on changes in the status of HBV infections were obtained. RESULTS: HCV genotype 1b was the most common (44%). The overall sustained virologic response rate was 72% in all patients, and 60% and 87.5% in genotypes 1 and 2, respectively. Two of the 18 patients were positive for HBeAg, and 15 had baseline HBV DNA level of less than 2,000 IU/mL. Two of the three whose levels exceeded this threshold showed no detectable DNA after treatment. After the completion of treatment, serum HBV DNA levels were increased in the two patients whose baseline HBV DNA levels were less than 2,000 IU/mL. CONCLUSIONS: The prevalence of HBV coinfection in CHC patients was 2.37% and most of the patients were inactive carriers. The treatment efficacy was similar to that of HCV mono-infection. Reactivation of HBV replication was observed in some patients after CHC treatment.
Adult ; Antiviral Agents/*therapeutic use ; Cross-Sectional Studies ; DNA, Viral/blood ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/*complications/genetics ; Hepatitis C, Chronic/complications/*drug therapy/pathology ; Humans ; Interferon-alpha/*therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols/*therapeutic use ; Recombinant Proteins/therapeutic use ; Ribavirin/*therapeutic use

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

Pegylated interferon (PEG-IFN) is now the standard treatment for chronic hepatitis C. But, there are few reports about patients with end stage renal disease, and treatment protocol for HCV infection has not been determined, particularly in patients on peritoneal dialysis. We experienced a case of a peritoneal dialysis patient with chronic hepatitis C who was successfully treated with PEG-IFN monotherapy. A 50-year old man was undergoing peritoneal dialysis because of diabetic nephropathy. Considering that his HCV genotype was 2, we decided to treat him with PEG-IFN alpha-2a monotherapy 4 month after the beginning of peritoneal dialysis. We adopted a 90 microg of PEG-IFN administration. After the injection of PEG-IFN, dialysate concentration of PEG-IFN did not change significantly. HCV-RNA disappeared at the 4th week and sustatined virus response was achieved thereafter. No side effects were observed during the treatment of 24 weeks. PEG-IFN monotherapy with dose modification may be a safe and effective treatment for HCV infection in patients undergoing peritoneal dialysis.
Antiviral Agents/*therapeutic use ; Diabetic Nephropathies/complications ; Genotype ; Hepatitis C, Chronic/complications/*drug therapy/genetics ; Humans ; Interferon-alpha/*therapeutic use ; Male ; Middle Aged ; Peritoneal Dialysis ; Polyethylene Glycols/*therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/therapeutic use

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

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

OBJECTIVETo perform a Meta-analysis on peginterferon with interferon in treatment of HIV patients coinfected with refractory genotype HCV.

METHODSA literature search of Medline was conducted to identify eligible randomized controlled trials. Meta analysis was conducted to evaluate peginterferon and interferon in treatment of coinfected HCV genotype 1 or 4 in HIV patients.

RESULTSix trials of 88 matched the selection criteria. Total 1,131 patients with coinfection of HCV genotype 1 or 4 and HIV were included. Sustain viral response was higher in patients treated with peginterferon plus ribavirin compared with that of interferon plus ribavirin (26 % compared with 8 %) or peginterferon alone (26 % compared with 13 %). Severe adverse effects and withdrawal rates were similar for patients treated with peginterferon and patients treated with interferon.

CONCLUSIONPeginterferon plus ribavirin in treatment of patients with coinfection of genotype 1 or 4 HCV and HIV can achieve higher sustain viral response and the likelihoods of serious adverse effects and withdrawal rates are similar to other therapies.

Adult ; Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Female ; Genotype ; HIV Infections ; complications ; drug therapy ; immunology ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; complications ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; Male ; Polyethylene Glycols ; administration & dosage ; Randomized Controlled Trials as Topic ; Recombinant Proteins ; Ribavirin ; administration & dosage

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: Chronic hepatitis C patients with advanced fibrosis have unsatisfactory sustained virological response (SVR) rates. Few data demonstrating the efficacy of combination therapy in chronic hepatitis C patients with advanced fibrosis in South Korea are available. The purpose of this study was to assess whether the stage of fibrosis impacts the efficacy of combination therapy for chronic hepatitis C. METHODS: We retrospectively reviewed data for a total of 109 patients with chronic hepatitis C, treated with peginterferon alfa and ribavirin. SVR according to the stage of liver fibrosis assessed by pretreatment liver biopsy and genotype results were analyzed. RESULTS: Data from 66 genotype 1 patients (60.6%) and 43 genotype 2 or 3 patients (39.4%) among the 109 patients were analyzed. SVR rates for the genotype 1 patients were significantly lower for the stage 3-4 group (32.1%) than the stage 0-2 group (78.9%; P<0.001). SVR rates (92.0% for stage 0-2, 77.8% for stage 3-4, P=0.184) of genotype 2 or 3 patients were not significantly different according to fibrosis stage. Likewise, the frequency of adverse events was not significantly different according to fibrosis stage. CONCLUSIONS: Compared to patients without advanced fibrosis, we can anticipate good SVR rates for genotype 2 or 3 patients with advanced fibrosis and they did not show an inferior tolerability for peginterferon and ribavirin combination therpy. Our results suggest that active treatment is needed for genotype 2 or 3 patients with advanced fibrosis.
Adult ; Age Factors ; Antiviral Agents/therapeutic use ; Blood Platelets/cytology ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/genetics ; Humans ; Interferon-alpha/therapeutic use ; Liver Cirrhosis/complications/*pathology ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Polyethylene Glycols/therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/therapeutic use ; Retrospective Studies ; Ribavirin/therapeutic use ; Severity of Illness Index ; 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