Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.
Humans ; Hepatitis C, Chronic/drug therapy* ; Antiviral Agents/therapeutic use* ; Membrane Proteins/metabolism* ; Liver Cirrhosis/diagnosis* ; Fibrosis ; Biomarkers

BACKGROUND/AIMS: Thyroid dysfunction (TD) is more likely to occur in patients with chronic hepatitis C (CHC) and is particularly associated with interferon (IFN) treatment. The purpose of this study was to investigate the incidence, outcomes, and risk factors for TD during pegylated interferon (PEG-IFN) and ribavirin (RBV) combined therapy in patients with CHC. METHODS: A total of 242 euthyroid patients with CHC treated with PEG-IFN/RBV were included. Thyroid function and autoantibodies were measured at baseline, and virologic response and thyroid function were assessed every 3 months during therapy. RESULTS: TD developed in 67 patients (27.7%) during the PEG-IFN/RBV treatment. The types of TD were subclinical hypothyroidism (50.7%), hypothyroidism (14.9%), thyroiditis (11.9%), subclinical hyperthyroidism (10.4%), and hyperthyroidism (10.4%). Most of the patients with TD recovered spontaneously; however, seven patients (10.4%) needed thyroid treatment. The sustained virological response rate was higher in patients with TD than those without (65.7% vs. 49.1%, p = 0.02). Baseline thyroid stimulating hormone (TSH) concentrations (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.96 to 8.77; p < 0.001), presence of the thyroid peroxidase antibody (OR, 8.81; 95% CI, 1.74 to 44.6; p = 0.009), and PEG-IFNalpha-2b (OR, 3.01; 95% CI, 1.43 to 6.39; p = 0.004) were independent risk factors for the development of TD. CONCLUSIONS: TD developed in 27.7% of patients with CHC during PEG-IFN/RBV treatment, and 10.4% of these patients needed thyroid treatment. TD is associated with a favorable virologic response to PEG-IFN/RBV. Assessment of TSH and thyroid autoantibodies at baseline and close monitoring of thyroid function during PEG-IFN/RBV therapy are necessary for early detection and management of IFN-induced TD.
Adult ; Aged ; Antiviral Agents/*adverse effects ; Autoantibodies/blood ; Biomarkers/blood ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnosis/*drug therapy ; Humans ; Incidence ; Interferon-alpha/*adverse effects ; Male ; Middle Aged ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Republic of Korea ; Retrospective Studies ; Ribavirin/*adverse effects ; Thyroid Diseases/*chemically induced/diagnosis/epidemiology/immunology/physiopathology ; Thyroid Gland/*drug effects/immunology/physiopathology ; Time Factors ; 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: Hepatitis C genotypes 1 and 2 are widely distributed globally. In contrast, genotype 6 is found mainly in Southeast Asia, while genotype 6 is rare in Korea. This study aims to investigate the prevalence, risk factors and clinical characteristics of patients with genotype 6 chronic hepatitis C. METHODS: We retrospectively identified 133 HCV-infected patients who underwent HCV genotype analysis between January 2012 and December 2012, and analyzed the prevalence, risk factors and clinical characteristics of patients diagnosed with genotype 6 chronic hepatitis C. RESULTS: Among 133 patients, 53 patients (39.8%) were infected with genotype 1, 62 patients (46.6%) with genotype 2, 2 patients (1.5%) with genotype 3, 14 patients (10.5%) with genotype 6, and 2 patients (1.5%) with mixed genotypes (genotype 1 and 6). The risk factors associated with genotype 6 were acupuncture (n=4, 28.6%), intravenous drug use (n=3, 21.4%), tattoo (n=2, 14.3%), and transfusion (n=2, 14.3%). Of the 14 patients with genotype 6, 6 patients were treated with pegylated interferon and ribavirin. Five patients had reached the end of treatment. All patients reaching end of treatment for genotype 6 showed early virological response and sustained virological response. CONCLUSIONS: The prevalence of genotype 6 is 10.5% and mixed infections of genotype 1 and 6 are 1.5% in patients with chronic hepatitis C. A major potential risk factor is intravenous drug use and the treatment response rate to pegylated interferon plus ribavirin is high in patients with genotype 6 chronic hepatitis C. Large scale multicenter studies are needed.
Acupuncture Therapy ; Adult ; Aged ; Antiviral Agents/therapeutic use ; Blood Transfusion ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/*genetics/isolation & purification ; Hepatitis C, Chronic/*diagnosis/drug therapy/epidemiology ; Humans ; Interferon-alpha/therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols/therapeutic use ; Prevalence ; RNA, Viral/genetics ; Recombinant Proteins/therapeutic use ; Republic of Korea ; Retrospective Studies ; Ribavirin/therapeutic use ; Risk Factors ; Tattooing

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

Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.
Antifungal Agents/therapeutic use ; Antiviral Agents/*adverse effects ; Cryptococcus neoformans/immunology/*pathogenicity ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnosis/*drug therapy/immunology ; Humans ; Immunocompromised Host ; Interferon-alpha/*adverse effects ; Meningitis, Cryptococcal/drug therapy/immunology/*microbiology ; Middle Aged ; Opportunistic Infections/diagnosis/drug therapy/immunology/*microbiology ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Ribavirin/*adverse effects ; Time Factors ; Treatment Outcome

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: The distribution of hepatitis C virus (HCV) genotypes varies geographically. In Korea, genotypes 1 and 2 comprise more than 90% of HCV infections, while genotype 6 is very rare. This study compared the clinical and epidemiological characteristics of patients with genotype 6 HCV infection with those infected with HCV genotypes 1 and 2. METHODS: This was a prospective, multicenter HCV cohort study that enrolled 1,173 adult patients, of which 930 underwent HCV genotype analysis, and only 9 (1.0%) were found to be infected with genotype 6 HCV. The clinical and epidemiological parameters of the genotypes were compared. RESULTS: The patients with genotype 6 HCV had a mean age of 41.5 years, 77.8% were male, and they had no distinct laboratory features. A sustained virologic response (SVR) was observed in four (67%) of six patients who received antiviral therapy. Risk factors such as the presence of a tattoo (n=6, 66.7%), more than three sexual partners (n=3, 33.3%), and injection drug use (n=3, 33.3%) were more common among genotype 6 patients than among genotypes 1 or 2. CONCLUSIONS: The epidemiology and treatment response of patients infected with genotype 6 HCV differed significantly from those with genotypes 1 or 2, warranting continuous monitoring.
Adult ; Antiviral Agents/therapeutic use ; Asian Continental Ancestry Group ; Cohort Studies ; Female ; Genotype ; Hepacivirus/*genetics ; Hepatitis C, Chronic/*diagnosis/drug therapy/epidemiology ; Humans ; Liver/pathology ; Male ; Middle Aged ; Prospective Studies ; RNA, Viral/blood ; Republic of Korea ; Risk Factors ; Sexual Behavior ; Substance-Related Disorders/complications ; Tattooing

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

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan(R)) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice.
Antiviral Agents/therapeutic use ; Carcinoma, Hepatocellular/epidemiology/physiopathology ; Chronic Disease ; *Elasticity Imaging Techniques ; Hepatitis B/drug therapy/physiopathology ; Hepatitis C/drug therapy/physiopathology ; Humans ; Liver Cirrhosis/*diagnosis/ultrasonography ; Liver Neoplasms/epidemiology/physiopathology ; Recurrence