A Case of Ulcerative Colitis Following Acute Hepatitis Induced by Epstein-Barr Virus Infection / 대한소화기학회지

Epstein-Barr virus (EBV) infection varies in its clinical manifestations and severity. EBV can be a causative agent of hepatitis and may have a role in the pathogenesis of chronic autoimmune diseases including inflammatory bowel disease. A 24-year-old woman was admitted to our hospital, presenting with fever and elevated liver enzymes. She was diagnosed with acute hepatitis and EBV infection according to serologic tests and liver biopsy. Within two months, she was re-admitted to our hospital, presenting with hematochezia and lower abdominal pain. She was diagnosed with ulcerative colitis. In situ hybridization for EBV was positive in initial liver biopsy and colon biopsy. Here we report an unusual case of acute EBV hepatitis followed at a short interval by ulcerative colitis.

Combination transarterial chemoembolization and radiofrequency ablation therapy for early hepatocellular carcinoma

BACKGROUND/AIMS: We compared the recurrence of hepatocellular carcinoma (HCC) and the survival of patients who received radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) with patients treated with TACE or RFA alone. METHODS: This study included 201 patients with HCC, who were consecutively enrolled at Seoul St. Mary's Hospital between December 2004 and February 2010. Inclusion criteria were a single HCC < or = 5.0 cm or up to three HCCs < or = 3.0 cm. We used a propensity score model to compare HCC patients (n = 87) who received RFA after TACE (TACE + RFA) with those who received TACE (n = 71) or RFA alone (n = 43). RESULTS: The median follow-up period was 33.3 months (range, 6.8 to 80.9). The TACE + RFA group showed significantly lower local recurrence than the RFA or TACE groups (hazard ratio [HR], 0.309; 95% confidence interval [CI], 0.130 to 0.736; p = 0.008; and HR, 0.352; 95% CI, 0.158 to 0.787; p = 0.011, respectively). The overall survival was significantly better in the TACE + RFA group compared to the RFA group (HR, 0.422; 95% CI, 0.185 to 0.964; p = 0.041). However, the survival benefit was not different between the TACE + RFA and TACE groups (p = 0.124). Subgroup analysis showed that among patients with a tumor size < 3 cm, the TACE + RFA group had significantly better long-term survival than those in the TACE or RFA groups (p = 0.017, p = 0.004, respectively). CONCLUSIONS: TACE + RFA combination treatment showed favorable local recurrence and better overall survival rates in early-stage HCC patients. Patients with tumors < 3 cm are likely to benefit more from TACE + RFA combination treatment. Additional studies are needed for the selection of suitable HCC patients for TACE + RFA treatment.

Association Between Non-erosive Reflux Disease and High Risk of Obstructive Sleep Apnea in Korean Population

BACKGROUND/AIMS: Obstructive sleep apnea is becoming more important in gastroesophageal reflux disease (GERD) patients. This study investigated the prevalence of high risk for obstructive sleep apnea in GERD patients in comparison with that in healthy controls using the Berlin Questionnaire. We also investigated the risk factors for obstructive sleep apnea in GERD patients. METHODS: We enrolled 1,007 subjects: 776 healthy controls, 115 individuals with erosive reflux disease, and 116 with non-erosive reflux disease. GERD was diagnosed and classified using endoscopy and a reflux questionnaire. The Berlin Questionnaire was used to evaluate obstructive sleep apnea. RESULTS: More patients in the GERD group (28.2%) had higher risk for obstructive sleep apnea than healthy controls (20.4%, P = 0.036). More patients with non-erosive disease (32.8%) had higher risk for obstructive sleep apnea (OSA) than patients with erosive disease (20.9%) and controls (20.4%, P = 0.010). On multivariate analysis, non-erosive disease was a high risk factor for obstructive sleep apnea (odds ratio [OR], 1.82; P = 0.011). Age > or = 55 years (OR, 1.83; P or = 25 kg/m2) (OR, 2.76; P or = 55, and a high BMI are associated with high risk for OSA.

Oleuropein prevents the progression of steatohepatitis to hepatic fibrosis induced by a high-fat diet in mice

Nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte injury and inflammatory cell infiltration, which has been linked to peripheral insulin resistance and increased levels of triglycerides in the liver. The purposes of this study were to establish a mouse model of NASH by feeding mice a 60% high-fat diet (HFD) and to demonstrate the anti-fibrotic effects of oleuropein, which has been shown to have anti-oxidant and anti-inflammatory properties, in this HFD-induced mouse model of NASH. C57BL/6 mice were divided into three groups: a regular diet group (Chow), a HFD group and an oleuropein-supplemented HFD group (OSD), which was fed a 0.05% OSD for 6 months. The effects of oleuropein in this model were evaluated using biochemical, histological and molecular markers. The expression levels of alpha-smooth muscle actin (alpha-SMA)and collagen type I in the HFD and OSD groups were evaluated using real-time PCR and western blotting. The body weight, biochemical marker levels, nonalcoholic fatty liver disease activity score, homeostasis model of assessment-insulin resistance (HOMA-IR) and leptin levels observed in the HFD group at 9 and 12 months were higher than those observed in the Chow group. The HOMA-IR and leptin levels in the OSD group were decreased compared with the HFD group. In addition, alpha-SMA and collagen type I expression were decreased by oleuropein treatment. We established a NASH model induced by HFD and demonstrated that this model exhibits the histopathological features of NASH progressing to fibrosis. Our results suggest that oleuropein may be pharmacologically useful in preventing the progression of steatohepatitis and fibrosis and may be a promising agent for the treatment of NASH in humans.

Serum IP-10 Levels Correlate with the Severity of Liver Histopathology in Patients Infected with Genotype-1 HCV

BACKGROUND/AIMS: Interferon-gamma-inducible protein 10 (IP-10) plays important roles in the pathogenesis of hepatitis C virus (HCV) infection. We investigated the association between serum IP-10 levels and liver pathology in patients with chronic HCV infection. METHODS: The serum IP-10 concentration was assessed in 85 patients with chronic HCV infection using a solid phase sandwich enzyme-linked immunosorbent assay, and a liver biopsy specimen was obtained. The pathology was scored using the Knodell histologic activity index (HAI). RESULTS: Of the 85 patients, 58 had genotype 1 HCV infection, 21 had genotype non-1, and 6 were undetermined. The serum IP-10 levels did not differ between patients infected with genotype 1 and genotype non-1 (p=0.472). In patients with genotype 1 infection, the total HAI score and the stage of fibrosis were highly correlated with the serum IP-10 level (r=0.555, r=0.578, p<0.001). Furthermore, the serum IP-10 concentrations of patients with severe fibrosis (stages 3, 4) were higher than those of patients with mild fibrosis (stages 0 to 2; 214.4 vs. 72.3 pg/mL, p=0.002) among patients with genotype 1 infection. However, in patients without genotype 1 infection, the histopathology was not associated with the serum IP-10 level. A multivariate analysis showed that serum IP-10 was an independent predictor of fibrosis (stages 3, 4) in patients with genotype 1 infection (odds ratio, 1.034; 95% confidence interval, 1.006 to 1.064; p=0.018). CONCLUSIONS: Serum IP-10 concentration was significantly correlated with the severity of liver histology in genotype 1 HCV infection.

Application of Helical Tomotherapy for Two Cases of Advanced Hepatocellular Carcinoma

The role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) has been limited to date, because the liver has a low tolerance to radiation. However, reconstructing tumors and surrounding organs via a three-dimensional conformal planning system can avoid excess radiotherapy exposure to the rest of the liver and adjacent organs. Recently, the concept of "adaptive radiotherapy," such as with helical tomotherapy, has been introduced for treating HCC. Helical tomotherapy obtains an image from the computed tomography component, which allows targeted regions to be visualized prior to, during, and immediately after each treatment and delivers intensity-modulated radiation therapy. We report two patients with advanced HCC who underwent tomotherapy treatment. One was a patient afflicted with advanced HCC and a portal vein tumor thrombus, which was treated with tomotherapy combined with transarterial chemolipiodolization. The other was a patient afflicted with multiple pulmonary metastases treated with tomotherapy followed by systemic chemotherapy.

Differences in the patterns and outcomes of enhanced viral replication between hepatitis C virus and hepatitis B virus in patients with hepatocellular carcinoma during transarterial chemolipiodolization / 대한간학회지

BACKGROUND/AIMS: Enhanced replication of hepatitis C virus (HCV) is well described in the setting of moderate to severe immunosuppression. The aims of this retrospective study were to determine the incidence of enhanced HCV replication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemolipiodolization (TACL) and to identify the factors associated with enhanced replication of HCV. The clinical pattern of enhanced HCV replication was compared with hepatitis B virus (HBV) reactivation during TACL. METHODS: This study enrolled 49 anti-HCV-seropositive patients who were diagnosed with HCC between January 2005 and December 2010 and who underwent TACL using epirubicin and/or cisplatin with consecutive HCV RNA copies checked. For comparison, 46 hepatitis B surface antigen1-positive patients with HCC who were treated with TACL were also enrolled. The frequency, associated factors, and clinical outcomes of enhanced HCV replication were analyzed and compared with those of HBV reactivation during TACL. RESULTS: Enhanced replication of HCV occurred in 13 (26.5%) of the 49 anti-HCV-seropositive patients during TACL. Of these 13 patients, 4 developed hepatitis, but none of the subjects developed decompensation due to the hepatitis. No significant clinical factors for enhanced HCV replication during TACL were found. Compared with HBV reactivation, the frequency of hepatitis attributed to enhanced HCV replication was significantly lower than that for HBV reactivation (8.2% vs. 23.9%, P=0.036). CONCLUSIONS: TACL can enhance HCV replication; however, the likelihood of hepatitis and decompensation stemming from enhanced HCV replication was lower than that for HBV reactivation in patients undergoing TACL.

Suppression of hepatic tumor growth and metastasis by metronomic therapy in a rat model of hepatocellular carcinoma

Although continuous low-dose (metronomic [MET]) therapy exerts anti-cancer efficacy in various cancer models, the effect of long-term MET therapy for hepatocellular carcinoma (HCC) remains unknown. This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 wk. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve wk of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear antigen-positive cells and decreased hypoxia-inducible factor-1alpha levels and microvessel density. Lung metastases were detected in 100%, 80%, and 42.9% in the control, MTD, and MET groups, respectively. MET therapy significantly decreased expression of TIMP-1, MMP-2 and -9. For mediators of pro-MMP-2 activation, MET therapy induced significant suppression in the TIMP-2 and MMP-14 level. The survival in the MET group was significantly prolonged compared to the control and MTD groups. Long-term MET scheduling suppresses tumor growth and metastasis via its potent anti-angiogenic properties and a decrease in MMPs and TIMPs activities. These results provide a rationale for long-term MET dosing in future clinical trials of HCC treatment.

Hepatic Failure Caused by Reactivation of YMDD Mutants Occurring during Preemptive Lamivudine Therapy

Reactivation of hepatitis B virus (HBV) replication is a frequent phenomenon in patients receiving immunosuppressants or chemotherapy. It was recently reported that regional therapy, such as transarterial chemotherapy (TAC) or radiotherapy, can also induce HBV reactivation in patients with hepatocellular carcinoma (HCC), and this can be prevented by preemptive lamivudine treatment. We report an unusual case of fatal hepatitis caused by reactivation of the tyrosine-methionine-aspartate-aspartate (YMDD) lamivudine-resistant strain in a 51-year-old male patient with HCC who was receiving preemptive lamivudine therapy. This patient received combined helical tomotherapy and TAC for the treatment of HCC with pulmonary metastasis. HBV reactivation and hepatitis exacerbation occurred after 2 months of therapy, but preemptive antiviral therapy was continued. Laboratory tests showed that the serum HBV DNA level had increased by more than 10,000-fold and a severe elevation of the aminotransferase level to 1,060 U/L. Although adefovir was added to lamivudine immediately after detecting the YMDD mutants, the patient eventually died of hepatic failure. Our experience suggests that for preemptive therapy, the use of potent antiviral drugs with a low risk of drug resistance as well as close viral monitoring are important for chronic HBV carriers undergoing intensive anticancer therapy.

Fatal Neutropenic Enterocolitis during Pegylated Interferon and Ribavirin Combination Therapy for Chronic Hepatitis C Virus Infection

It is known that neutropenia caused by combination pegylated interferon plus ribavirin therapy for hepatitis C virus (HCV) infection is well tolerated and carries a negligible risk of infection. Neutropenic enterocolitis is encountered most frequently in patients with hemato-oncologic diseases who are undergoing intensive chemotherapy. However, little information exists regarding this life-threatening event in the setting of HCV therapy. We present here an unusual case of fatal neutropenic enterocolitis in a cirrhotic patient receiving combination therapy for HCV infection. This is the first report of a death from neutropenic enterocolitis associated with treatment for chronic HCV infection. The present case suggests that caution should be exercised when continuing HCV therapy in neutropenic patients with advanced fibrosis, and the decision to maintain such therapy should be balanced against the potential for serious adverse events.

Impact of adherence to peginterferon-ribavirin combination therapy in chronic hepatitis C patients on achieving a sustained virologic response / 대한간학회지

BACKGROUND/AIMS: Various predictive factors for peginterferon alpha and ribavirin therapy in chronic hepatitis C have been reported, but the effect of adherence to therapy has not been established. We investigated how adherence affects the sustained virologic response (SVR). METHODS: We analyzed 92 chronic hepatitis C patients receiving peginterferon alpha and ribavirin combination therapy. Patients were first identified as having either genotype 1 or genotype non-1 infection and then categorized into three groups according to their adherence to the treatment protocol: (1) patients who received > or =80% of the recommended dosage of both peginterferon alpha and ribavirin for > or =80% of the intended duration of therapy, (2) patients who received <60% of the recommended dosage of both peginterferon alpha and ribavirin for <60% of the intended duration of therapy, and (3) patients who were not included in either group 1 or 2. RESULTS: The rates of early virologic response, end of treatment response, and SVR differed significantly with the degree of adherence to the treatment. The SVRs of genotype 1 patients were 86.7%, 26.7%, and 66.7% in groups 1, 2, and 3, respectively (P=0.003), and those of genotype non-1 were 100%, 16.7%, and 88.9%, respectively (P<0.001). CONCLUSIONS: Adherence to therapy is a key factor in achieving an SVR. Supportive strategies to improve adherence will increase overall SVR rates.

The value of serum retinol-binding protein 4 levels for determining disease severity in patients with chronic liver disease / 대한간학회지

BACKGROUNDS/AIMS: Serum retinol-binding protein 4 (RBP4) is known to be a specific transport protein for retinol, and has recently been reported to be associated with insulin resistance. Hyaluronic acid (HA) is a well-known marker of liver fibrosis. In this study, the degree to which serum RBP4 levels can be used to predict disease severity in patients with chronic liver disease (CLD) was evaluated. METHODS: Serum levels of RBP4 and HA were measured in 573 CLD patients [235 with chronic hepatitis (CH), 230 with liver cirrhosis Child-Pugh grade (Child) A, and 108 with liver cirrhosis with Child B and C] and 40 normal controls. RESULTS: The mean age of the whole cohort was 53.1 years and the causes of CLD were hepatitis B virus (61.9%), hepatitis C virus (9.8%), alcohol (9.0%), and nonalcoholic steatohepatitis (3.8%). Serum levels of RBP4 significantly reduced and HA increased with disease condition, from none (normal controls) to advanced cirrhosis (normal control: RBP4 4.3+/-0.1 mg/dL, HA 25.3+/-28.1 ng/mL; CH: RBP4 3.6+/-0.1 mg/dL, HA 75.5+/-7.8 ng/mL; cirrhosis with Child A: RBP4 2.6+/-0.1 mg/dL, HA 184.4+/-14.5 ng/mL; and cirrhosis with Child B and C: RBP4 1.6+/-0.1 mg/dL, HA 656.5+/-86.7 ng/mL; P<0.001, respectively). Serum RBP4 level was a distinguishing factor at the early stage of CLD between CH and Child A cirrhosis (post-hoc test; P<0.001) and was correlated with histological fibrosis score (n=80, P<0.05) and several biochemical factors. Antiviral therapy (n=45, median interval 1,205 days) resulted in an improvement in serum RBP4 levels (P=0.001). CONCLUSIONS: The results of our study suggest that RBP4 is a serologic marker for disease severity in patients with CLD. It could also be useful as an early marker of CLD and of the relative success of antiviral therapy.

A case report of treatment with pegylated interferon alpha for lamivudine-resistant chronic hepatitis B virus infection / 대한간학회지

The wide use of lamivudine in chronic hepatitis B has produced a monotonic increase in patients with lamivudine resistance. Therefore, treating lamivudine resistance in chronic hepatitis B is a major concern in clinical practice for the treatment of hepatitis B virus (HBV). There is conflicting evidence on the outcome of pegylated interferon alpha (PEG-IFN alpha) therapy against lamivudine-resistant HBV, which is due to mutations in the YMDD motif. We experienced a patient with chronic hepatitis B who was successfully treated with PEG-IFN alpha-2a after the development of virologic and biochemical breakthrough during lamivudine therapy. Virologic breakthrough was associated with the emergence of YMDD mutants 48 months after starting lamivudine therapy. Treatment with PEG-IFN alpha-2a for 12 months resulted in an undetectable serum level of HBV DNA and the resolution of hepatitis, and the virologic response was maintained over 16 months after cessation of PEG-IFN alpha-2a.

A case of hepatic epithelioid hemangioendothelioma that caused extrahepatic metastases without intrahepatic recurrence after hepatic resection / 대한간학회지

Epithelioid hemangioendothelioma is a neoplasm of vascular origin with a low-to-intermediate malignant potential and is one of the rare sarcomas arising from the liver. Its etiology is unknown and its clinical outcome is unpredictable. There is no generally accepted therapeutic strategy because of its rarity and the variable natural course between hemangioma and angiosarcoma. We report a case of a 64-year old woman who underwent hepatic resection due to epithelioid hemangioendothelioma in the right lobe that progressed to extrahepatic metastases of the bone, pleura, and peritoneum 22 months later. However, after resection there was no primary hepatic recurrence.

Efficacy of Transarterial Chemolipiodolization with or without 3-Dimensional Conformal Radiotherapy for Huge HCC with Portal Vein Tumor Thrombosis / 대한간학회지

BACKGROUND/AIMS: The treatment efficacy for advanced hepatocellular carcinoma is poor. This study examined the efficacy and toxicity of 3-dimensional conformal radiotherapy (3D-CRT) in combination with transarterial chemolipiodolization (TACL) for a huge hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS: From March 2001 to November 2004, 49 patients with advanced HCC with PVTT (size>8 cm, modified UICC stage IVa) were enrolled in this retrospective study. Twenty two patients underwent more than 2 cycles of TACL (adriamycin 50 mg/m2, cisplatin 60 mg/m2, 5-fluorouracil 200 mg/m2 every 4-6 weeks) without 3D-CRT, while 27 patients underwent consecutive TACL with 3D-CRT (40-45 Gy for 4-5 weeks) that was started one week after the 1st TACL. The response was assessed by a computed tomography (CT) and the serum alpha-fetoprotein (AFP) level at 1-2 month intervals. RESULTS: The objective response rates in the TACL group and TACL with 3D-CRT group were 18% and 48% at 3 months (P=0.051), and 10.5% and 42% at 6 months (P=0.024) respectively. The median survival time was 13 months and 13.5 months in TACL and TACL with 3D-CRT groups, respectively (P=0.502). The treatment response was better in the TACL with 3D-CRT group but there was no significant difference in survival between the two groups. Most toxicities in the two groups were mild, not exceeding grade 1 according to the WHO criteria. CONCLUSIONS: For patients with a huge HCC with PVTT, TACL with 3D-CRT achieved some meaningful clinical benefit. Prospective controlled trials will be needed to confirm the real benefit of TACL combined with 3D-CRT.

A Risk Factor for Wound Infection after Percutaneous Endoscopic Gastrostomy: Decreased Performance Status / 대한소화기내시경학회지

BACKGROUND/AIMS: Percutaneous endoscopic gastrostomy (PEG) has been widely used for long term enteral nutrition. The most common complication is peristomal wound infection. The aim of this study is to investigate the risk factors for peristomal wound infection after PEG. METHODS: We reviewed the records of 55 patients who had undergone PEG placement at Kangnam St. Mary's hospital via the Pull-string technique. We analyzed the underlying disease, the performance status and the nutritional state of the patients to determine the risk factors for wound infection. RESULTS: Peristomal wound infection after PEG occurred in 20 (36.4%) of the 55 patients. Methicillin resistant Staphylococcus aureus (MRSA) was the most common isolated microorganism. On univariate analysis, the underlying CNS disease, non-malignant disease and a decreased performance status (ECOG 3, 4) were correlated with wound infection. On multivariate analysis, a decreased performance status was an independent risk factor for wound infection after PEG (p=0.007, OR=6.011, CI: 1.64~22.09). CONCLUSIONS: A decreased performance status was an independent risk factor for peristomal wound infection after PEG.

Re-Endoscopic Mucosal Resection for a Residual or Locally Recurrent Gastric Lesion after Endoscopic Mucosal Resection / 대한소화기내시경학회지

BACKGROUND/AIMS: Re-endoscopic mucosal resection of a residual or locally recurrent gastric lesion after endoscopic mucosal resection (EMR) is often difficult due to submucosal fibrosis. The aim of this study was to investigate the factors related to the local recurrence of gastric lesions and the results of re-EMR. METHODS: We retrospectively reviewed 245 patients with adenoma or early gastric cancer (EGC) treated by EMR. The factors related to local recurrence after EMR were analyzed. Ten patients with local recurrences after complete resection were treated with re-EMR and analyzed. RESULTS: The mean size of the re-EMR lesions was 15.1 mm (5~30 mm). Seven patients were treated with endoscopic submucosal dissection (ESD) and three were treated with conventional EMR. En bloc resection was performed in eight patients (80%) and complete resection was performed in nine patients (90%). Bleeding was a complication of re-EMR in five patients (50%). There was no recurrent lesion after re-EMR in nine patients over a mean follow-up duration of 14.7 months. The local recurrence rate was significantly higher when the tumor was resected piecemeal (p<0.001). CONCLUSIONS: Local recurrences occurred more frequently when the tumors were resected piecemeal. Re-EMR was a possible tool for the treatment of residual or locally recurrent lesions in 90% of the patients. Re-EMR may be the treatment of choice for a locally recurrent lesion after EMR according to the indication.

A Case of Acute Injury in the Stomach and Duodenum after Cyberknife Therapy / 대한소화기내시경학회지

Therapeutic radiation therapy has developed new technologies that use a high dose of radiation with three- dimensional targeting for a few days instead of conventional radiation therapy that uses small doses of radiation for a longer period of time. A Cyberknife is an image- guided robotic system for stereotactic radiosurgery. The Cyberknife was first developed for the treatment of intracranial lesions, and recently has been used for tumors in the chest and abdomen. A Cyberknife can use a high dose of radiation for treatment of a hepatocellular carcinoma and can be employed to minimize radiation injury around the tumor. However, in a large tumor, the therapeutic efficacy is reduced and injury can occur around the organs. We report a case of acute injury in the stomach and duodenum after Cyberknife treatment of a hepatocellular carcinoma near the hepatic portal area.

Endoscopic Argon Plasma Laser Trimming of Biliary Self Expanding Metallic Stent / 대한소화기내시경학회지

A self-expanding metal stent is an effective treatment for biliary stenosis, improving obstructive jaundice and maintaining the long term patency of the bile duct. The complications of the metal stent are a perforation, distal migration, restenosis and duodenal mucosa injury from the contralateral wall impaction or trauma. However, the metal stent is a relatively permanent device and its removal is technically challenging. We report a case of protrusion of biliary stents into the duodenal lumen of a distal common bile duct cancer patients that was managed successfully by endoscopic argon plasma laser trimming.

Macrophage Activation Syndrome in Juvenile Rheumatoid Arthritis Successfully Treated with Cyclosporine A: A Case Report

Macrophage activation syndrome (MAS) is one of the serious complications of juvenile rheumatoid arthritis (JRA) and recently, cyclosporine A has been found to be effective in patients with corticosteroid-resistant MAS. A 29-yr-old male was admitted with high fever and jaundice for one month. He was diagnosed as juvenile arthritis 16 yr ago. Physical and laboratory results showed hepatosplenomegaly, high fever, pancytopenia and impaired liver and renal function tests, elevated triglyceride and serum ferritin levels. Bone marrow biopsy showed hyperplasia of histiocytes with active hemophagocytosis. He was diagnosed as MAS associated with juvenile rheumatoid arthritis and managed with high-dose corticosteroids initially, but clinical symptoms and laboratory findings did not improve immediately. Finally, he completely recovered after treatment with cyclosporine A (3 mg/kg/day).