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

Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs.
Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Hepatocellular/*etiology ; Hepacivirus/genetics/*pathogenicity ; Hepatitis C/complications/pathology/virology ; Humans ; Liver Neoplasms/*etiology ; Risk

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

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.
Adult ; Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blotting, Western ; End Stage Liver Disease ; genetics ; pathology ; virology ; Female ; Gene Expression ; Hepatitis, Viral, Animal ; genetics ; pathology ; virology ; Host-Pathogen Interactions ; Humans ; Interleukin-1beta ; genetics ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Leukocytes, Mononuclear ; metabolism ; virology ; Liver Failure, Acute ; genetics ; pathology ; virology ; Male ; Mice, Inbred BALB C ; Middle Aged ; Murine hepatitis virus ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Severity of Illness Index ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; blood ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Young Adult

OBJECTIVETo evaluate the clinicopathological features and prognosis of primary hepatic lymphoma (PHL).

METHODSThirty-five patients with PHL who underwent surgical resection and were confirmed by pathology in our hospital from 1982 to 2012 were re-evaluated for clinicopathological data, including their symptoms, radiological features, recurrence interval, histopathological properties and prognosis.

RESULTSOf the 35 patients, 25 were men (71.4%) and 10 were women (28.6%), with an average age of 52.6 years old (range, 17-79 years). Presented symptoms were epigastric phymatosis, abdominal pain and low-grade fever. In the present study, 21 (60.0%) patients were positive for HBsAg, 1(2.9%) patient was positive for anti-HCV, 3 patients were positive for AFP, 12 patients and 2 patients were complicated by cirrhosis and hepatocellular carcinoma, respectively. Pathologically, 35 PHL were classified into 19 DLBCL (54.3%), 13 T cell-lymphoma (37.1%), and 3 MALT lymphoma (8.6%). Patients with DCBCL showed better postoperative survival than patients with T cell-lymphoma (31.7 ± 3.2) months vs. (22.9 ± 2.2) months (P < 0.05).

CONCLUSIONSHepatitis B virus (HBV) infection may contribute to the pathogenesis of Chinese patients with PHL. Surgical resection followed by comprehensive therapy is the first-line option for PHL. The prognosis of patients with PHL is associated with PHL subtypes.

Adolescent ; Adult ; Aged ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Hepatocellular ; pathology ; therapy ; virology ; Chemotherapy, Adjuvant ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Hepatitis B ; complications ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis C Antibodies ; metabolism ; Humans ; Leukocyte Common Antigens ; metabolism ; Liver Cirrhosis ; complications ; Liver Neoplasms ; pathology ; therapy ; virology ; Lymphoma ; pathology ; therapy ; virology ; Lymphoma, B-Cell, Marginal Zone ; pathology ; therapy ; virology ; Lymphoma, Large B-Cell, Diffuse ; pathology ; therapy ; virology ; Lymphoma, T-Cell ; pathology ; therapy ; virology ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Retrospective Studies ; Survival Rate ; Vincristine ; therapeutic use ; Young Adult ; alpha-Fetoproteins ; metabolism

Antigen Presentation ; Apoptosis ; Hepatitis C ; Humans ; Lichen Planus, Oral ; etiology ; genetics ; pathology ; virology ; Polymorphism, Single Nucleotide ; T-Lymphocytes, Cytotoxic ; pathology ; T-Lymphocytes, Helper-Inducer ; pathology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo investigate viral relapse and the associated risk factors during a long-term follow-up study of chronic hepatitis C (CHC) patients who achieved end-of-treatment response (ETR) after interferon and ribavirin therapy.

METHODSThis retrospective study was conducted on 146 CHC patients treated with a combination of ribavirin and pegylated (PEG) interferon-alpha (IFNa) (n=126) or conventional IFNa (n=20) for 24 (hepatitis C virus (HCV) non-genotype 1b) or 48 (HCV genotype 1b) weeks. The main outcome measure was serum HCV RNA load. The risk factors analyzed included age, sex, HCV genotype, baseline HCV RNA load, and IFN type.

RESULTSThe mean follow-up time for all patients was 33.45+/-16.41 months (range: 12-85 months). The cumulative relapse rate during follow-up was 14.80%. The relapse rate within six months (8.90%) was significantly higher than other periods during two years of follow-up, and no relapse occurred after 30 months. Of all relapsers (n=20), 65% occurred within six months, followed by 35% within 7-24 months after antiviral therapy. The relapse rates in patients with HCV genotype 1b and non-1b were not significantly different (20.37% vs. 12.12%, X2 =1.517, P=0.315). The mean baseline HCV RNA load was significantly higher in the relapsers than that in the non-relapsers (t=0.915, P=0.362). Relapse rates were similar in patients treated with PEG-IFNa-2b, PEG-IFNa-2a and IFNa (12.12% vs. 13.97% vs. 15.00%, respectively; X2=0.104, p=0.949). The mean age of relapsers was significantly higher than that of non-relapsers (P less than 0.005).

CONCLUSIONThe maximum probability of relapse for CHC patients exists within six months from when ETR is achieved by interferon and ribavirin therapy. A lower risk for relapse persists past this period. Thus, ETR CHC patients, especially older patients, should be carefully monitored during the two years after cessation of antiviral therapy. Standard antiviral therapy based on HCV genotype eliminates the influence of viral factors on treatment-response.

Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis C, Chronic ; drug therapy ; pathology ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; RNA, Viral ; Recurrence ; Retrospective Studies ; Ribavirin ; therapeutic use ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease. METHODS: Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR. RESULTS: Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity. CONCLUSIONS: Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.
Adult ; Aged ; Cohort Studies ; DNA, Viral/analysis ; Female ; Genotype ; Hepatitis B/*complications/*diagnosis ; Hepatitis B Core Antigens/blood/immunology ; Hepatitis B Surface Antigens/blood/immunology ; Hepatitis B virus/*genetics ; Hepatitis C, Chronic/*complications/genetics/*pathology ; Humans ; Liver/virology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Severity of Illness Index

Parvovirus B19 infection is known to cause chronic anemia in immunocompromised hosts, including organ transplant recipients. We report the first case of liver transplant recipient with parvovirus B19-induced pure red cell aplasia in Korea. A 57-yr-old female patient with hepatocellular carcinoma due to hepatitis C virus received a liver transplantation. Two months later, anemia developed and she received periodic red blood cell transfusions. However, chronic anemia persisted and bone marrow examination was performed 8 months after transplantation. Bone marrow aspiration smears showed markedly reduced erythroid precursors with atypical giant pronormoblasts and nuclear remnants with viral inclusions, and characteristic lantern cells were observed in biopsy sections. In addition, parvovirus B19 DNA PCR was positive. She was diagnosed as parvovirus B19-induced pure red cell aplasia and her anemia was improved following intravenous immunoglobulin therapy.
Blood Transfusion ; Bone Marrow/pathology ; Carcinoma, Hepatocellular/etiology/therapy ; DNA, Viral/analysis ; Female ; Hepatitis C/complications/diagnosis ; Humans ; Immunocompromised Host ; Immunoglobulins/therapeutic use ; Liver Neoplasms/etiology/therapy ; Liver Transplantation ; Middle Aged ; Parvoviridae Infections/complications/*diagnosis ; *Parvovirus B19, Human/genetics ; Red-Cell Aplasia, Pure/*diagnosis/therapy/virology

Adenovirus Infections, Human ; pathology ; virology ; Glomerulonephritis, Membranous ; pathology ; virology ; HIV Infections ; pathology ; virology ; Hepatitis B ; pathology ; virology ; Hepatitis C ; pathology ; virology ; Herpes Zoster ; pathology ; virology ; Herpesvirus 3, Human ; isolation & purification ; Humans ; Kidney ; pathology ; virology ; Kidney Diseases ; pathology ; virology ; Nephritis, Interstitial ; pathology ; virology ; Parvoviridae Infections ; pathology ; virology ; Parvovirus B19, Human ; isolation & purification