Hepatitis C virus (HCV), a non-cytopathic positive-stranded RNA virus, is one of the most common causes of chronic liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Upon HCV infection, the majority of patients fail to clear the virus and progress to chronic hepatitis C. Chemokines are small chemotactic cytokines that direct the recruitment of immune cells and coordinate immune responses upon viral infection. Chemokine production during acute HCV infection contributes to the recruitment of immune cells with antiviral effector functions and subsequent viral clearance. In chronic HCV infection, however, continuous production of chemokines due to persistent viral replication might result in incessant recruitment of inflammatory cells to the liver, giving rise to persistence of chronic inflammation and liver injury. In this review, we will summarize the roles of chemokines in acute and chronic settings of HCV infection and the clinical relevance of chemokines in the treatment of hepatitis C.
Antiviral Agents/therapeutic use ; Chemokines/*metabolism ; Hepatitis C/drug therapy/*immunology/*metabolism ; Hepatitis C, Chronic/drug therapy/*immunology/*metabolism ; Humans

Background/Aims: Proton pump inhibitors (PPIs) increase gastric pH and alter the gut microbiome. An increased risk for infectious diseases has been reported in PPI users. However, little is known about the association of PPI use with pyogenic liver abscess (PLA) incidence risk. Methods: We conducted a population-based cohort study using data from a nationwide representative sample of the Korean general population followed up for 10 years (January 1, 2003 to December 31, 2013). We identified PPI prescriptions and considered PPI as a timevarying variable. Proportional hazards regression model was used for incident PLA comparing PPI use versus non-use. Propensity score matching was also conducted. Results: During the 4 209 229 person-years of follow-up, 58 595 participants had at least 1 PPI prescription and 541 patients developed liver abscess. The age-, sex-, residential area-, and income-adjusted hazard ratio for PLA incidence with PPI use was 4.19 (95% CI, 2.54-6.92). The association was observed in fully adjusted models (hazard ratio 3.88; 95% CI, 2.33-6.44). The positive association between PPI use and PLA was consistent in all subgroups analyzed and in propensity score matching group. Conclusion The present data indicate that PPI use is associated with an increased PLA risk. Therefore, it is necessary to prescribe PPIs with clear indication and to avoid improper use of PPIs.

Background/Aims: Proton pump inhibitors (PPIs) increase gastric pH and alter the gut microbiome. An increased risk for infectious diseases has been reported in PPI users. However, little is known about the association of PPI use with pyogenic liver abscess (PLA) incidence risk. Methods: We conducted a population-based cohort study using data from a nationwide representative sample of the Korean general population followed up for 10 years (January 1, 2003 to December 31, 2013). We identified PPI prescriptions and considered PPI as a timevarying variable. Proportional hazards regression model was used for incident PLA comparing PPI use versus non-use. Propensity score matching was also conducted. Results: During the 4 209 229 person-years of follow-up, 58 595 participants had at least 1 PPI prescription and 541 patients developed liver abscess. The age-, sex-, residential area-, and income-adjusted hazard ratio for PLA incidence with PPI use was 4.19 (95% CI, 2.54-6.92). The association was observed in fully adjusted models (hazard ratio 3.88; 95% CI, 2.33-6.44). The positive association between PPI use and PLA was consistent in all subgroups analyzed and in propensity score matching group. Conclusion The present data indicate that PPI use is associated with an increased PLA risk. Therefore, it is necessary to prescribe PPIs with clear indication and to avoid improper use of PPIs.

Bortezomib, an inhibitor of 26S proteosome, is recently approved treatment option for multiple myeloma. Thalidomide, a drug with immunomodulating and antiangiogenic effects, has also shown promise as an effective treatment in multiple myeloma. Pulmonary complications are believed to be rare, especially interstitial lung disease. Here, we describe a patient with dyspnea and diffuse pulmonary infiltrates while receiving bortezomib and thalidomide in combination with dexamethasone for treatment-naive multiple myeloma. Bronchoalveolar lavage demonstrated a significant decrease in the ratio of CD4 : CD8 T lymphocytes (CD4/8 ratio, 0.54). Extensive workup for other causes, including infections, was negative. A lung biopsy under video-assisted thorascopic surgery revealed a diagnosis of nonspecific interstitial pneumonitis. The symptoms and imaging study findings improved after initiating steroid treatment. Physicians should be aware of this potential complication in patients receiving the novel molecular-targeted antineoplastic agents, bortezomib and thalidomide, who present with dyspnea and new pulmonary infiltrates and fail to improve despite treatment with broad-spectrum antibiotics.
Aged ; Boronic Acids/*adverse effects/therapeutic use ; Dexamethasone/therapeutic use ; Humans ; Lung Diseases, Interstitial/*chemically induced ; Male ; Multiple Myeloma/*drug therapy ; Pyrazines/*adverse effects/therapeutic use ; Thalidomide/*adverse effects/therapeutic use

This study aimed to analyze the overall survival period of adult lymphoblastic lymphoma patients treated with various therapeutic regimens, and to assess the determinants affecting survival outcome. Twenty-five adult patients with lymphoblastic lymphoma who had been treated at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea from June 1996 to June 2005 were analyzed retrospectively. As an initial remission induction chemotherapy, the hyper-CVAD regimen was performed in eight patients, the Stanford/Northern California Oncology Group (NCOG) regimen in five, the CAVOP regimen in four, the m-BACOP regimen in three, and the CHOP regimen in one patient. Patients were divided into two groups according to their therapeutic modalities. Twenty patients received conventional chemotherapy alone and five received subsequent PBSCT after conventional chemotherapy. Four patients of the PBSCT group underwent autologous PBSCT and one underwent allogeneic PBSCT. The overall response rate was 80% (60% showing a complete response, 20% showing a partial response) and the relapse rate was 73.3%. The overall survival (OS) rate was 55.1% at 1 year, 31.5% at 5 years, and 23.6% at 9 years. The disease-free survival (DFS) rate was 46.7% at 1 year and 30.0% at 7 years. The 5-year OS rate in relation to the regimens was 60% with the Stanford/NCOG regimen, 50% with the CAVOP regimen, and 33.3% with the m-BACOP regimen. The patients treated with the hyper-CVAD regimen had an 18.2% 2-year OS rate, and other patients with CHOP or COPBLAM-V expired early in their course. The OS rate in patients treated with conventional chemotherapy alone was 19.8%, whereas patients treated with subsequent PBSCT after chemotherapy showed 50% overall survival (p=0.25). The age at presentation influenced the outcome of the patients (p=0.01). The Stanford/NCOG regimen is an effective initial choice of therapy for lymphoblastic lymphoma patients, and is superior to the hyper-CVAD regimen in complete response rate and overall survival rate (p=0.36). Addition of PBSCT after chemotherapy may be needed for achieving optimal outcomes.
Treatment Outcome ; Time Factors ; Stem Cell Transplantation/methods ; Retrospective Studies ; Prognosis ; Middle Aged ; Male ; Lymphoma, Lymphoblastic/*mortality/*therapy ; Humans ; Female ; Disease-Free Survival ; Antineoplastic Agents/pharmacology ; Aged ; Adult ; Adolescent

A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks. Laboratory tests showed elevated levels of liver enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL); negative for hepatitis virus infection; elevated serum levels of triiodothyronine (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of thyroid stimulating hormone (TSH, <0.025 microIU/mL); and positive for thyroid stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral steroid therapy was started with 60 mg of prednisolone under the impression of AIH associated with Graves' disease. After a week of steroid therapy, the clinical manifestation showed significant improvement, with normalization of both liver and thyroid functions. Diagnosis of the liver condition of patients who present with hyperthyroidism and liver dysfunction is important, so that appropriate therapy can be promptly initiated.
Adult ; Alanine Transaminase/analysis ; Antibodies, Antinuclear/blood ; Aspartate Aminotransferases/analysis ; Bilirubin/blood ; Female ; Graves Disease/complications/*diagnosis/drug therapy ; Hepatitis, Autoimmune/complications/*diagnosis/drug therapy ; Humans ; Immunoglobulins, Thyroid-Stimulating/blood ; Liver/enzymology/metabolism/pathology ; Prednisolone/therapeutic use ; Steroids/therapeutic use ; Thyrotropin/blood

No abstract available.
Fatty Liver/*diagnosis ; Female ; Humans ; Liver Cirrhosis/*diagnosis ; Male

Background/Aims: Real-world data about the treatment outcomes of patients receiving rituximab-containing immunochemotherapy followed by rituximab maintenance are required to understand better the treatment for follicular lymphoma (FL). Methods: A cross-sectional study analyzed FL patients who were treated with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab maintenance. Results: Of 139 patients, 85 patients received R-CVP and 54 received R-CHOP. The characteristics did not differ significantly between the groups. Only grade 3 of FL was more common in R-CHOP. The complete response rate did not differ significantly between R-CHOP (50/54, 92.6%) and R-CVP (77/85, 90.6%). The number of disease relapses during rituximab maintenance did not differ significantly between the groups (p = 0.798). Therefore, the comparison of progression-free survival (PFS) showed no significant difference: the 3-year PFS rates for R-CVP and R-CHOP were 77% and 85%, respectively (p = 0.567). Although five of 56 hepatitis B virus (HBV) core antibody (anti-HBc)-positive patients experienced HBV reactivation, all cases of HBV reactivation were identified during regular monitoring for HBV DNA in blood, and were successfully managed with antiviral treatment. Conclusions The survival outcomes of FL patients on rituximab maintenance after responding to R-CVP or R-CHOP were similar. Rituximab-containing immunochemotherapy followed by rituximab maintenance can be safely used for anti-HBc-positive patients if HBV DNA titer in blood can be regularly monitored.

Background/Aims: The abscopal effect, a rare phenomenon induced by radiation, can be reinforced by immunotherapy. Although radiation therapy and immunotherapy are increasingly being utilized for the treatment of hepatocellular carcinoma (HCC), whether immunotherapy could boost the abscopal effect remains unclear. In this study, we aimed to elucidate the immunological mechanisms underlying the abscopal effect induced by the combination of irradiation and immunotherapy in a murine HCC model. Methods: A syngeneic HCC mouse model was established by transplanting murine Hepa 1–6 HCC cells into both hind legs of immunocompetent C57BL/6 mice. The tumors on the right hind legs were irradiated, and abscopal effects were observed in the non-irradiated tumors on the left hind leg with or without the coadministration of anti-programmed cell death 1 (PD-1) antibodies. Flow cytometric analyses were performed to analyze the distributions of immune cells infiltrating both irradiated and non-irradiated tumors and the tumor-draining lymph nodes (TDLNs). Results: Administration of 16 Gy in two fractions more effectively inhibited the growth of both irradiated and nonirradiated tumors with higher tumor infiltration of cytotoxic T cells than 8 Gy did in a single fraction. The higher dose also increased activated dendritic cells in TDLNs, which had higher expression of the programmed cell death ligand 1. Coadministration of anti-PD-1 antibodies significantly enhanced the abscopal effect and increased infiltration of activated cytotoxic T cells in both irradiated and non-irradiated tumors. Conclusions Our findings show that adding anti-PD-1 therapy to radiation enhanced the abscopal effect in a syngeneic murine model of HCC.

We report on a case of a 57-year-old male who underwent a curative resection for hepatocellular carcinoma (HCC) with histological confirmation of a spontaneously necrotized tumor. Initial serum AFP level was 4,778 ng/mL. A 3.7 cm hyperechoic mass in segment 6 of the liver was observed on ultrasonography and dynamic contrast-enhanced liver MRI showed a 3.7x3.1 cm sized HCC. He was scheduled to undergo curative surgical resection under the clinical diagnosis of an early stage HCC (Barcelona Clinic Liver Cancer stage A). Without treatment, the serum AFP level declined rapidly to 50 ng/mL over five weeks. He underwent curative wedge resection of segment 6 of the liver. Histology revealed complete necrosis of the mass rimmed by inflamed fibrous capsule on a background of HBV-related cirrhosis with infiltration of lymphoplasma cells. Exact pathophysiology underlying this event is unknown. Among the proposed mechanisms of spontaneous neoplastic remission of HCC, circulatory disturbance and activation of host immune response offer the most scientific explanation for the complete histologic necrosis of HCC in the resected mass seen in our patient.
Carcinoma, Hepatocellular/*diagnosis/diagnostic imaging/pathology ; Hepatitis B/complications/diagnosis ; Humans ; Liver/diagnostic imaging/pathology ; Liver Cirrhosis/etiology ; Liver Neoplasms/*diagnosis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Necrosis ; Radiography ; Remission, Spontaneous ; Ultrasonography ; alpha-Fetoproteins/analysis