Hepatitis C virus (HCV) RNA can be cleared from the blood circulation by direct antiviral treatment to achieve sustained virologic response (SVR). Studies have shown that SVR after direct antiviral therapy can reduce the incidence of hepatocellular carcinoma; however, monitoring for hepatocellular carcinoma is still needed. This review briefly summarizes and discusses the existing studies on the possible causes of hepatitis C secondary to HCC after antiviral therapy, which is mainly divided into epigenetic alterations and abnormal DNA methylation, HCV-related cirrhosis and abnormal DNA amplification, HBV reactivation, several aspects of occult HCV infection, and the effect of direct antiviral treatment on hepatocellular carcinoma recurrence. In few cases, direct antiviral treatment cannot completely prevent the occurrence and recurrence of hepatitis C-related hepatocellular carcinoma. Therefore, its mechanism needs to be studied and explored, and clinicians should also approach it with caution.
Antiviral Agents/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Hepatitis C/drug therapy* ; Hepatitis C, Chronic/drug therapy* ; Humans ; Liver Neoplasms/etiology* ; Sustained Virologic Response

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.
Amylases/analysis ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnostic imaging/*drug therapy ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Lipase/analysis ; Middle Aged ; Pancreatitis/*etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; Recombinant Proteins/adverse effects/therapeutic use ; Republic of Korea ; Ribavirin/therapeutic use ; Tomography, X-Ray Computed

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

Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy.
Aged ; Creatinine/blood ; Foot/pathology ; Gangrene/*etiology ; Hepatitis C, Chronic/complications ; Humans ; Liver Cirrhosis/complications/diagnosis ; Liver Diseases/*diagnosis/drug therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Osteomyelitis/*etiology ; Severity of Illness Index ; Toe Phalanges/radiography ; Vasoconstrictor Agents/*adverse effects/therapeutic use

OBJECTIVETo evaluate the therapeutic effects and influencing factors of common antiviral therapy (low-dose interferon plus ribavirin, IFN+RBV) in patients with hepatitis C virus (HCV)-decompensated cirrhosis following splenectomy.

METHODSTwelve patients were treated post-surgery with low-dose IFN (300-500 MIU QOD) or pegylated (Peg)-IFN (50 mug/w) and RBV (0.6-0.9 g/d) for 72 weeks if carrying the lb genotype or 48 weeks if carrying the 2a genotype. All patients were followed-up for 24 weeks after treatment completion to determine the virological response (VR) rates, measured as rapid (R)VR, complete early (cE)VR, 24 hr (24)VR, and sustained (S)VR. Statistical comparisons were made using the t-test or rank sum test, and correlation analyses were made using the Chi-square test. Differences were considered significant at P less than 0.05.

RESULTSAll 12 patients completed the treatment course and follow-up. Three patients could not tolerate the Peg-IFN and were switched to IFN, and six patients developed hemolysis that required RBV dose adjustment. The VR rates were: 25.0%, RVR; 50.0%, cEVR; 16.7%, 24VR; 86.0%, SVR. Only one patient was a non-responder, and only one relapsed. Of the patients who achieved SVR, 100% had shown RVR, 83.3% showed cEVR, and 50.0% showed 24VR, suggesting that RVR and cEVR may effectively predict SVR.

CONCLUSIONSome HCV-decompensated cirrhosis patients may benefit from antiviral therapy following surgical resolution of hypersplenism. The occurrence of RVR and cEVR in these patients is positively correlated with achieving SVR. Physician-patient communication during early antiviral treatment and close clinical monitoring accompanied by psychological counseling throughout promotes success of the treatment approach.

Antiviral Agents ; therapeutic use ; Female ; Hepatitis C, Chronic ; complications ; drug therapy ; Humans ; Interferons ; therapeutic use ; Liver Cirrhosis ; drug therapy ; etiology ; Male ; Middle Aged ; Postoperative Period ; Ribavirin ; therapeutic use ; Splenectomy ; Treatment Outcome

Insulin resistance is frequently associated with chronic liver disease, and the interaction between hepatitis C virus (HCV) infection and insulin resistance is a major public health issue, bound to increase in the near term. Because of their potential synergism on liver disease severity, a better understanding of the clinical consequences of the relationship between HCV infection and insulin resistance is needed. This translates into accelerated liver disease progression, reduced response to anti-viral agents and, in susceptible individuals, increased risk of developing type 2 diabetes. HCV may also cause hepatic steatosis, especially in patients infected with genotype 3, although the clinical impact of viral steatosis is debated. Little is known regarding the effect of anti-diabetic agents on HCV infection, and a possible association between use of exogenous insulin or a sulfonylurea agents and the development of hepatocellular carcinoma has recently been reported. Thus, modified lifestyle and pharmacological modalities are urgently warranted in chronic hepatitis C with metabolic alterations.
Antiviral Agents/therapeutic use ; Diabetes Mellitus, Type 2/complications/drug therapy/metabolism ; Genotype ; Hepatitis C, Chronic/*drug therapy/etiology/metabolism ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin/therapeutic use ; *Insulin Resistance ; Liver Cirrhosis/etiology ; Liver Neoplasms/etiology ; Sulfonylurea Compounds/therapeutic use

Pegylated interferon and ribavirin combination therapy is accepted as the standard antiviral treatment for chronic hepatitis C regardless of HCV genotype. This combination therapy achieves higher response rates than previous therapy, but, nevertheless, a large proportion of patients suffer from treatment failure or adverse events. Recent clinical studies of viral kinetics during antiviral treatment have led to the introduction of response-guided therapy, the concept of 'customized therapy depending on viral response', which focuses on modulation of the treatment period depending on the viral response to create a sustained viral response without unnecessary medication and costs. New upcoming direct-acting antivirals (DAAs) maximize response rate, and triple therapy including DAAs along with pegylated interferon and ribavirin combination therapy could soon be the standard therapy. In this article, we reviewed the factors affecting treatment, response guided treatment, retreatment after failure of standard treatment, management of adverse events during treatment, and new treatment options.
Anemia, Hemolytic/drug therapy/etiology ; Antiviral Agents/adverse effects/*therapeutic use ; Erythropoietin/therapeutic use ; Hepatitis C, Chronic/*drug therapy ; Humans ; Individualized Medicine ; Interferon-alpha/adverse effects/therapeutic use ; Polyethylene Glycols/adverse effects/therapeutic use ; Protease Inhibitors/therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/adverse effects/therapeutic use ; Ribavirin/adverse effects/therapeutic use

Adult ; Antiviral Agents ; therapeutic use ; Female ; Hair Diseases ; drug therapy ; etiology ; Hepatitis C, Chronic ; complications ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Recombinant Proteins ; therapeutic use

BACKGROUNDMixed cryoglobulinemia (MC) is one of the most common and severe symptoms in chronic hepatitis C patients. The aim of this study was to investigate whether mixed cryoglobulinemia is a factor associated with sustained virological response in chronic hepatitis C patients treated with combination therapy of pegylated interferon alpha-2a and ribavirin.

METHODSThis is a single-center study including 57 chronic hepatitis C patients who received combination treatments of pegylated interferon alfa-2a and ribavirin. Serum cryoglobulin was detected by cryoprecipitation prior to treatment. Serum hepatitis C virus (HCV) RNA levels were checked before treatment, during the fourth and 12th week of treatment, and during the 24th week after cessation of treatment. The genotype of HCV was determined at baseline. Logistic regression analysis was used to assess the factors associated with sustained virological response.

RESULTSTwenty-five patients were with MC (43.9%). Twenty-four weeks after cessation of antiviral treatment, sustained virological response achievement in MC(+) patients was significantly lower than that in MC(-) patients (32.0% vs. 75.0%, P = 0.001). Univariate Logistic regression analysis and multivariate Logistic regression analysis found that only MC (odds ratio: 6.375; 95% CI: 1.998- 20.343, P = 0.002) was negatively associated with sustained virological response achievement.

CONCLUSIONMC is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients treated with pegylated interferon alpha-2a and ribavirin.

Adolescent ; Adult ; Aged ; Cryoglobulinemia ; etiology ; metabolism ; Cryoglobulins ; metabolism ; Female ; Hepatitis C, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Ribavirin ; therapeutic use ; Young Adult