Development of bronchiolitis obliterans organizing pneumonia during standard treatment of hepatitis C with Peg-IFNα2b

No abstract available.

Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated with Systemic Chemotherapy or Immunosuppressive Therapy

BACKGROUND/AIMS: According to the results of several studies, the outcome of hepatitis C virus (HCV) reactivation is not as severe as the outcome of hepatitis B virus reactivation. The aim of this study was to evaluate the effect of pharmacological immunosuppression on HCV reactivation. METHODS: The medical records of patients who underwent systemic chemotherapy, corticosteroid therapy, or other immunosuppressive therapies between January 2008 and March 2015 were reviewed. Subsequently, 202 patients who were seropositive for the anti-HCV antibody were enrolled. Exclusion criteria were: unavailability of data on HCV RNA levels, a history of treatment for chronic hepatitis C, and the presence of liver diseases other than a chronic HCV infection. RESULTS: Among the 120 patients enrolled in this study, hepatitis was present in 46 patients (38%). None of the patients were diagnosed with severe hepatitis. Enhanced replication of HCV was noted in nine (27%) of the 33 patients who had data available on both basal and follow-up HCV RNA loads. Reappearance of the HCV RNA from an undetectable state did not occur after treatment. The cumulative rate of enhanced HCV replication was 23% at 1 year and 30% at 2 years. CONCLUSIONS: Although enhanced HCV replication is relatively common in HCV-infected patients treated with chemotherapy or immunosuppressive therapy, it does not lead to serious sequelae.

A Case of Sarcomatoid Cholangiocarcinoma Which Developed at the Site Previously Treated by Transarterial Chemoembolization

Intrahepatic sarcomatoid carcinoma is a rare tumor with poor prognosis due to its highly invasive and metastatic nature and difficulty for early detection. The most common form of intrahepatic sarcomatoid carcinoma is the sarcomatoid hepatocellular carcinoma, the development of which is usually associated with previous treatment for hepatocellular carcinoma. In contrast, sarcomatoid cholangiocarcinoma is extremely rare and results from spontaneous sarcomatoid transformation during the development of tumor. Here, we report a case of sarcomatoid cholangiocarcinoma, in a 58-year-old male, which developed at the site of previous treatment for hepatocellular carcinoma. A 9 × 7 cm sized tumor which had not been detected in the computed tomography exam 3 months before diagnosis was newly observed. The tumor rapidly progressed and the patient died only 31 days after the diagnosis.

A Case of Severe Chronic Active Epstein-Barr Virus Infection with Aplastic Anemia and Hepatitis / 대한소화기학회지

Epstein-Barr virus (EBV) causes various acute and chronic diseases. Chronic active EBV infection (CAEBV) is characterized by infectious mononucleosis-like symptoms that persist for more than 6 months with high viral loads in peripheral blood and/or an unusual pattern of anti-EBV antibodies. Severe CAEBV is associated with poor prognosis with severe symptoms, an extremely high EBV-related antibody titer, and hematologic complications that often include hemophagocytic lymphohistiocytosis. However, CAEBV which led to the development of aplastic anemia (AA) has not been reported yet. A 73-year-old woman was admitted to our hospital with intermittent fever, general weakness and elevated liver enzymes. In the serologic test, EBV-related antibody titer was elevated, and real-time quantitative-PCR in peripheral blood showed viral loads exceeding 10(4) copies/microg DNA. Liver biopsy showed characteristic histopathological changes of EBV hepatitis and in situ hybridization with EBV-encoded RNA-1 was positive for EBV. Pancytopenia was detected in peripheral blood, and the bone marrow aspiration biopsy showed hypocellularity with replacement by adipocytes. AA progressed and the patient was treated with prednisolone but deceased 8 months after the diagnosis due to multiple organ failure and opportunistic infection. Herein, we report a rare case of severe CAEBV in an adult patient accompanied by AA and persistent hepatitis.

Recurrence of Multiple Focal Nodular Hyperplasia in a Young Male Patient / 대한소화기학회지

Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor that is usually found in women. Diagnosis of FNH mainly depends on imaging studies such as color Doppler flow imaging, computed tomography, and magnetic resonance imaging. It is characterized by the presence of stellate central scar and is nowadays incidentally diagnosed with increasing frequency due to advances in radiologic imaging technique. FNH typically presents as a single lesion in 70% of cases and generally does not progress to malignancy or recur after resection. Herein, we report a case of a young male patient with recurrent multiple FNH who underwent surgical resection for presumed hepatic adenoma on computed tomography.

Frequency of Killer Cell Immunoglobulin-like Receptors (KIRs) in Korean Patients with Chronic HCV Infection

Natural killer (NK) cells play an important role in innate immunity, especially in the response to viral infections, such as hepatitis C virus (HCV). Killer cell immunoglobulin-like receptors (KIRs) are the primary receptors of NK cells that mediate innate immunity. KIRs are also involved in acquired immunity, because some KIRs are expressed on the surface of certain subsets of T cells. In this study, the frequency of KIR genes, HLA-C allotypes, and combinations of KIR genes with their HLA-C ligands were evaluated in two different groups of the Korean population: controls and patients with chronic HCV infection. The study population consisted of 147 Korean patients with chronic HCV infection. The frequency of KIR2DS2 in patients with chronic HCV infection was 9.5% which was significantly lower than 19.5% of the control (P < 0.01). However, there were no significant differences in the frequency of other KIR genes, HLA-C allotypes or different combinations of KIR genes with their HLA-C ligands. This study can contribute to the further prospective study with a larger scale, suggesting the assumption that KIR2DS2 might aid in HCV clearance by enhancing both the innate and acquired immune responses of people in Korea.

A Case of Citrobacter braakii Sepsis Complicated with Hepatocellular Carcinoma

Citrobacter species is a gram-negative bacilli that can cause opportunistic infections in immunocompromised hosts. Citrobacter braakii refers to the genomospecies 6 of the Citrobacter freundii complex. There are no detailed studies on infections caused by this newly identified specific genetic species in Korea. We herein report a case of a patient with hepatocellular carcinoma who, after undergoing transcatheter arterial chemoembolization, developed biloma which later progressed to C.braakii sepsis and did not respond to treatment. To our knowledge, this is the first reported case in Korea on C. braakii infection resulting in septic shock in a patient with malignancy in Korea.

Composite Large Cell Neuroendocrine Carcinoma and Adenocarcinoma of the Ampulla of Vater

Large Cell Neuroendocrine Tumors (LCNEC) in the ampulla of Vater are extremely rare. This report addresses a case of concurrent LCNEC and adenocarcinoma in the ampulla of Vater. A 60-year-old male patient experienced fever, body chills and jaundice. He had a periampullary ulcerative lesion and underwent radical pancreaticoduodenectomy. Histopathologically, the tumor consisted of an LCNEC component and an adenocarcinoma component. Simultaneous LCNEC and adenocarcinoma has been reported in a few cases. Our patient had a coexisting LCNEC and an adenocarcinoma of the ampulla of Vater. We also present a review of the literature

A case of HELLP syndrome accompanied by retinal detachment / 대한내과학회지

Weinstein et al. first described the HELLP (hemolytic anemia, elevated liver enzymes, and low platelets) syndrome in 1982. The incidence of HELLP syndrome is 0.2~0.6% in normal pregnant women and 4~12% in women with preeclampsia. This syndrome is accompanied by serious medical complications, including hepatic and renal failure, coagulopathy, hypertension, and pulmonary edema. Retinal detachment is an unusual, but well documented, complication of hypertensive disorder in pregnancy affecting 0.2~2% of patients with severe preeclampsia and 0.9% of patients with HELLP syndrome. This paper reports on a patient with HELLP syndrome accompanied by retinal detachment who recovered after controlling the blood pressure and receiving systemic steroids.

A case of rhabdomyolysis during hospitalization for acute hepatitis A / 대한간학회지

A 29-year-old man was admitted to hospital with fever, myalgia, and sore throat. Initial laboratory findings were compatible with acute hepatitis; he was positive for the serologic marker for acute hepatitis A. On the 3rd day of admission, in spite of normalization of body temperature and a reduction in serum liver enzyme levels, serum levels of creatinine phosphokinase had increased up to 16,949 U/L. The patient recovered with supportive therapy and was discharged on the 12th day. We report a case of acute hepatitis A complicated by rhabdomyolysis during hospitalization.

Clinical Outcomes of Delayed Clearance of Serum HBsAg in Patients with Chronic HBV Infection

BACKGROUND: Spontaneous delayed clearance of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection is a rare event. The aim of this study was to investigate the incidence of delayed clearance of serum HBsAg in chronic HBV infection and to determine the characteristics and clinical outcomes of HBsAg delayed clearance in Korean patients. METHODS: From April 1981 to June 2003, 4,061 patients who were positive for HBsAg were evaluated retrospectively. The following assessments were undertaken in 47 patients who had spontaneous delayed clearance: liver biochemistry, viral markers, alpha-fetoprotein levels, and radiographic examinations including ultrasonography every three to six months for 6-264 months (median 87.9 months). RESULTS: Twenty-four of 47 patients were asymptomatic carriers. The others included seven patients with chronic hepatitis, seven with liver cirrhosis and nine with hepatocellular carcinoma. The estimated annual incidence of HBsAg seroclearance was 0.4%. The time span from positive HBsAg to HBsAg seroclearance in the AHC, CH, LC, and HCC was 62.9, 141, 63, and 95.3 months during follow up. Twenty-four of 24 AHC remained normal, 5 of 7 CH remained as CH and 2 patients remained normal, 1 of 7 with LC developed HCC and 6 of the LC remained as LC, and 4 of 9 HCC patients died. CONCLUSION: The clinical course following delayed clearance of HBsAg had diverse outcomes from AHC to HCC. Therefore, these patients require close follow up for the possible development of hepatocellular carcinoma following HBsAg clearance.

A Case of Hepatoid Carcinoma of the Pancreas / 대한소화기학회지

Hepatoid carcinoma is a primary extrahepatic neoplasm exhibiting features of hepatocellular carcinoma (HCC) in terms of morphology, immunohistochemistry, and behavior. In many cases, tumor cytoplasm is positive for alpha- fetoprotein (alpha-FP) with elevated serum alpha-FP level. Because not all hepatoid carcinomas are associated with alpha- FP overproduction, diagnosis should be made essentially by histological features of the tumor. We present a case of hepatoid carcinoma of the pancreas in a 21-year-old male patient. Abdominal computed tomography and magnetic resonance imaging revealed an inhomogeneously enhanced pancreatic head mass. Serum alpha-FP level was markedly elevated. He underwent pylorus-preserving Whipple's operation. The tumor showed hepatoid and neuroendocrine components simultaneously. The histopathological diagnosis was hepatoid carcinoma associated with neuroendocrine tumor of the pancreas. Seven months after the surgery, the patient is healthy without evidence of recurrence. To date, only 7 cases of hepatoid carcinoma of the pancreas have been reported in the literature, and this is the first case report in Korea.

Clinical and Biochemical Parameters of Nutrition to Predict Hepatic Encephalopathy in Cirrhotic Patients / 대한소화기학회지

BACKGROUND/AIMS: Protein-calorie malnutrition is a common complication in cirrhosis. Protein restriction for the treatment of hepatic encephalopathy (HE) may cause disease progression and poor prognosis. Therefore, we evaluated important clinical parameters for nutritional state in cirrhotic patients with or without HE to predict the development of HE. METHODS: Twenty-two cirrhotic patients were divided into two groups; group A-13 patients without HE and group B-9 patients with HE. Clinical and biochemical parameters, serum proteins {serum albumin, insulin-like growth factor-1 (IGF-1), transferrin, leptin, etc}, immunologic parameters and anthropometry were measured. RESULTS: Child-Pugh score and Model for End-stage Liver Disease (MELD) scale were higher in group B (p<0.01). After correction of various factors affecting nutritional assessment, especially of Child-Pugh score and MELD scale, leptin was higher in group B (p<0.05). There was no difference in anthropometric measurements. Transferrin correlated inversely with MELD scale in group A (p<0.01). IGF-1 correlated inversely with total lymphocyte count in group B (p<0.05). Leptin correlated with Child-Pugh scores, total lymphocyte count and mid-arm muscle cirumference in group A (p<0.05, p<0.05 and p<0.05, respectively), and correlated inversely with CD8 in group B (p<0.05). CONCLUSIONS: Leptin level is higher in patients with HE, and further studies for parameters of nutrition to predict HE in many cirrhotic patients will be needed.

A Case of Hemolysis in ABO-unmatched Liver Transplantation: Use of Washed Group O Red Blood Cells and Steroids / 대한소화기학회지

Liver transplantation is the only curative therapy for patients with end-stage liver disease. The high success rate and the increasing demand for the transplantation sometimes calls for ABO-compatible but nonidentical blood group orthotopic liver transplantation (OLT), which affords the opportunity to the production of antibody to red blood cells. Hemolytic anemia usually occurs 1 to 2 weeks after transplantation. Although mild in most patients, it can be life-threatening. Until now, a few cases showing hemolytic anemia due to donor ABO antibody formation after ABO-nonidentical OLT have been reported. In the reported cases of hemolytic anemia, most ABO-nonidentical OLT cases were O-to-A, but few reports are available on this subject with O-to-B ABO- nonidentical OLT. Herein, we report the experience with hemolysis after ABO-nonidentical OLT in a group O donor into a group B recipient and the successful treatment with transfusion of washed group O red blood cells and 60 mg dose of prednisolone for 3 days.

Prediction of Hepatic Fibrosis Using Serum Hyaluronic Acid in Patients with Chronic Liver Disease / 대한소화기학회지

BACKGROUND/AIMS: The extent of hepatic fibrosis is important in chronic liver disease. Liver biopsy is essential for diagnosis of fibrosis. However, biopsy is invasive and may not represent the whole liver state. Serum hyaluronic acid (HA), a major component of connective tissues, was introduced as a useful non-invasive index of hepatic fibrosis. The aim of this study was to evaluate the relationship among HA, the degree of fibrosis, several hematologic and biochemical parameters in patients with chronic liver diseases or post state liver transplantation (PSLT). METHODS: Total 102 cases were divided into 4 groups: 57 chronic hepatitis (CH), 12 cirrhosis, 21 hepatocellular carcinoma (HCC), 12 PSLT. HA was measured by enzyme-linked binding protein assay and evaluated in relation the degree of fibrosis, several hematologic and biochemical parameters. RESULTS: Among four groups, HCC showed the highest HA and HA of HCC significantly higher than that of CH. The degree of fibrosis were correlated with HA. HA was correlated with age, platelet count and albumin but, not with ALT and PT. There is no significant relation between HA and the presence of acute rejection in liver transplantation. CONCLUSIONS: In chronic liver diseases, HA is a useful non-invasive index of hepatic fibrosis and disease severity.

Suppression of Tumor Formation and Induction of Natural Killer Cell Activity in BALB/c Nude Mice by Human B7-1 (CD80) Gene Transfer Subcutaneously Injected with Human Hepatocellular Carcinoma Cells (Huh-7) / 대한간학회지

BACKGROUND/AIMS: Immunogene therapy is extensively studied for a therapeutic modality of various cancers. This study was conducted to investigate the efficacy of immunogene therapy using the T-cell costimulatory molecule and human B7-1 (CD80, hB7-1) in an in vivo human hepatocellular carcinoma (HCC) model. METHODS: The stable HCC cell line expressing hB7-1 gene was established using retroviral vector (Huh-7/hB7-1). Of fourteen BALB/c nude mice, 7 were subcutaneously injected with 2 X 10(6) Huh-7/hB7-1 cells, while the other 7 were injected with 2 X 10(6) Huh-7/mock cells as a control group. After the injection, the mice were observed weekly for three months for subcutaneous tumor formation. Assay for natural killer (NK) cell cytotoxicity and serum IFN-gamma was performed at 1 and 2 weeks after inoculation. RESULTS: In BALB/c nude mice inoculated with Huh-7/hB7-1 cells, no tumor growth was observed. BALB/c nude mice inoculated with Huh-7/hB7-1 cells showed significantly increased NK cell activities of splenocytes compared with those with Huh-7/mock cells. Serum IFN-gamma was not measurable at 1 week, but significantly increased at 2 weeks after inoculation to the level of 470 pg/ml in BALB/c nude mice with Huh-7/mock cells and 521 pg/ml in BALB/c nude mice with Huh-7/hB7-1. CONCLUSIONS: Our results demonstrate the in vivo anti-tumor immunity and NK cell activation by transfer of hB7-1 gene into human HCC in xenogeneic BALB/c nude mice model. This approach may provide a tool for the development of immunogene therapies against human malignant tumors.

Electron Microscopic Mesenchymal Response in Chronic Viral Hepatitis / 대한간학회지

BACKGROUND/AIMS: This study was designed to clarify the fine structures of the hepatocytes and mesencymal tissues in chronic hepatitis according to severity. METHOD: For the purpose of elucidating the ultrastructural characteristics of mesenchymal tissues, liver biopsy specimens were studied by light and electron microscopy in 20 patients with chronic hepatitis. RESULTS: 1) Hepatocytes in mesenchymal tissues were thought to be in the stage of regenerated or degenerated process. 2) Regenerating nodules were surrounded by a basement membrane-like materials in the space of Disse. 3) In the widened Disse space the deposition of collagen fiber bundles and increased numbers of hepatic stellate cells in necrotic area were observed. 4) In necrotic areas, hepatic mesenchymal cell response including an increase of collagen fibers and fibroblast, angiogenesis, and a proliferation of bile ductules were also observed. CONCLUSIONS: These observations suggest that the fibrosis in severe chronic hepatitis was accompanied by the mesenchymal response including the proliferation of hepatic stellate cells, fibroblasts, capillarization of Disse space, and mesenchymal proliferation. Finally, this fibrosis observed electron microscopically may be a cause of functional hepatic failure.

PCNA Expression and Electron Microscopic Study of Acinus-Forming Hepatocytes in Chronic Hepatits B

BACKGROUND: One of the major morphologic characteristics of hepatitis B is a hepatocellular regeneration which is induced by massive hepatocyte necrosis and associated with proliferative activity of hepatocytes. The purpose of this study is to document the proliferative activity of hepatocytes in various types of hepatitis B by immunohistochemical staining for proliferative cell nuclear antigen-labelling index (PCNA-LI) and electron microscopy. METHODS: We studied 83 patients with hepatitis B; 11 cases of acute viral hepatitis, 24 cases of mild chronic hepatitis, 34 cases of severe chronic hepatitis with early cirrhosis and 14 cases of severe chronic hepatitis. The PCNA was tested by immunohistochemical staining using anti-PCNA antibody. Furthermore we evaluated the ultrastructure of acinus-forming hepatocytes (AFH) by electron microscopy. RESULTS: The expression rate and labelling index of PCNA were 27.3% and 5.3 +/- 0.9% in acute viral hepatitis, 62.5% and 22.9 +/- 31.7% in mild chronic hepatits, and then 47.1% and 14.1 +/- 24.2% in severe chronic hepatitis with early cirrhosis, respectively (Figure 1). By contrast, no detectable PCNA expression was noted in AFH. Electron microscopic findings showed that hepatocytes forming a rosette underwent marked degenerative changes with sinusoidal capillarization and increased fine strands of collagen fiber in portal area. CONCLUSION: The proliferative acitivity of hepatitis B was significantly decreased in severe chronic hepatitis containing AFH. This result suggested that differences in proliferative activity was associated with hepatic cell necrosis and AFH.

Efficacy and Safety of Long-term Lamivudine Therapy in the Patients with Decompensated Liver Cirrhosis Secondary to Hepatitis B / 대한간학회지

BACKGROUND/AIMS: Lamivudine use in patients with decompensated cirrhosis B has been reported to improve the hepatic function and often delay the need for liver transplantation. In the present study, we evaluated the efficacy and safety of long-term lamivudine therapy in patients with decompensated cirrhosis by comparative study using a matched, untreated cohort. METHODS: 41 patients with decompensated cirrhosis B were included for this study (31 male and 10 female; mean age, 50 years; mean observation period, 18 months). They were divided into two groups: a lamivudine treatment group and an untreated control group. 21 patients in the treatment group were treated with lamivudine 75 or 150 mg daily for at least 12 months. Biochemical and serologic markers were evaluated at two to three-month intervals for all patients. Clinical improvement was defined by a decrease in the Child-Pugh score of at least 2 points. RESULTS: During the observation period, 62% (13/21) was responders, 33% (7/21) was breakthrough, and 5% (1/21) was non-responder in the treated group. The mean Child-Pugh score was significantly improved from 8.6 to 6.0 in the treatment group, but aggravated from 8.7 to 10.0 in the control group during the follow-up. The HBeAg seroconversion rate was 31% in the treatment group (5/16) and none in the control group (0/14). Clinical improvement was observed in fifteen of 21 in the treatment group (71%) and only one of 20 in the control group (5%). According to the treatment responses, clinical improvement was observed in ten of 13 responders (77%), four of 7 breakthrough (57%), and one non-responder. CONCLUSIONS: The long-term administration of lamivudine for patients with decompensated cirrhosis B is effective and safe, although breakthrough and non-response occurred in some patients.

Increased Microfilaments in Hepatocytes and Biliary Ductular Cells in Cholestatic Liver Diseases

To assess the extent of microfilaments in cholestatic liver diseases we examined the cytoplasmic microfilaments in intrahepatic and extrahepatic cholestasis in man by electron microscopy. Study subjects were two patients with drug-induced intrahepatic cholestasis, three patients with intrahepatic cholestasis due to viral hepatitis, four patients with extrahepatic cholestasis due to stones of the common bile duct and two patients with primary biliary cirrhosis. Two biopsied specimens from patients without clinical or histological evidence of liver disease served as noncholestatic controls. The microfilaments in hepatocytes and biliary ductular cells were significantly increased in cholestasis compared with those in non-cholestatic controls. Well developed bundles of microfilaments were noted around the pericanalicular ectoplasm and seemed to be parallel to plasma membrane of the hepatocytes in cholestasis. In cholestasis, there were increased bundles of microfilaments around the periluminal region, lateral cell wall, and nucleus of biliary ductular cells. Two patterns of microfilaments bundles (fine microfilamentous network and spindle-shaped dense or clusters of microfilaments) were associated with cholestasis. The clustered form of microfilaments also seemed to be clearly associated with intracytoplasmic vacuoles containing bile salts. In conclusion, the increase of microfilaments in hepatocytes and biliary ductular cells may be the consequence of various forms of cholestasis. Further studies are needed to clarify the functional significance of increased microfilaments in cholestasis.