Recombinant Interferon-Beta-1alpha Plus Ribavirin for the Treatment of Chronic HCV Infection: A Prospective, Randomized, Comparative Pilot Study

BACKGROUND/AIMS: Interferon beta (IFN-beta) has been shown to have antiviral activity, and thus could be useful in treating viral infections. Therefore, we compared the efficacy and safety of recombinant IFN-beta(IFN-beta-1a) plus oral ribavirin versus interferon alpha (IFN-alpha) plus ribavirin therapy for the treatment of chronic hepatitis C (HCV). METHODS: Twenty treatment-naive patients were randomized into two equal-sized treatment groups. Both IFN-beta-1a (44microgram) and IFN-alpha (3 MIU) were given subcutaneously three times a week, while ribavirin was given orally at 1,000-1,200 mg/day. Patients were treated for 24 weeks and followed for an additional 24 weeks. RESULTS: After 24 weeks of treatment, six (60%) and four patients (40%) in the IFN-beta-1a group and IFN-alpha groups, respectively, achieved viral clearance. The sustained virological response (SVR) at the end of the observation period was similar in both groups (40%). However, the baseline viral load was significantly higher (p=0.034) in the IFN-beta-1a group than in the IFN-alpha group, and there were more HCV genotype 1 patients in the IFN-beta-1a group (eight versus seven). The IFN-beta-1a group was associated with similar adverse events in terms of frequency and severity. CONCLUSIONS: The SVR rate and safety profile were similar for the combination of IFN-beta-1a and ribavirin and that of IFN-alpha and ribavirin.

A case of hepatitis A and E coinfection in an autoimmune hepatitis patient / 대한내과학회지

In Korea, the number of Hepatitis A virus (HAV) infections has suddenly increased and has become the most common cause of acute viral hepatitis during recent years. A 36-year-old female was diagnosed with acute fulminant hepatitis caused by HAV. Her clinical symptoms and AST/ALT recovered after supportive treatment; however, a re-elevation of AST/ALT was observed. Weperformed another viral marker study, autoimmune marker study and liver biopsy to rule out another hepatic insult. As a result, anti- HEV IgM, an anti-nuclear antibody and anti-smooth muscle antibody were positive and liver histology showed chronic hepatitis. In conclusion, we report a case of hepatitis A and E coinfection in an autoimmune hepatitis patient.

A Case of Esophageal and Gastric Foreign Bodies Induced by Cyanoacrylate Ingestion / 대한소화기내시경학회지

Foreign bodies of the upper gastrointestinal tract are found in all age groups, and the foreign bodies can be ingested incidentally or intentionally. They are usually common in children, but they have also been discovered in adults with esophageal disease, artificial teeth, mental retardation, in patients seeking secondary gains and in alcoholics. The types of foreign bodies vary for different social and cultural conditions, and can include coins, corks, toys, fish bones, toothbrushes, needles, nails and pens. Foreign bodies of the upper gastrointestinal tract are usually passed into the intestinal tract spontaneously, but sometimes intervention is required. We report a case of an 80-year-old man with a past medical history of depressive disorder that had ingested adhesives. The adhesives present in the esophagus were removed by the use of therapeutic endoscopy. However, the adhesives in the stomach were too large to remove by the use of an endoscopic procedure, and gastrotomy was performed.

Non-invasive assessment of liver fibrosis by measuring the liver stiffness and biochemical markers in chronic hepatitis B patients / 대한내과학회지

BACKGROUND: Transient elastography (FibroScan(R)) is a rapid and non-invasive method to measure liver stiffness and this allow the assessment of liver fibrosis. The aim of this study was to assess the diagnostic accuracy of measuring the liver stiffness in addition to measuring the other biochemical markers such as the aspartate transaminase to platelet ratio index [APRI] and the AST/ALT ratio. METHODS: We enrolled 228 HBsAg positive patients whose liver stiffness was measured by FibroScan(R) between March 2005 and September 2005. Liver biopsy examinations were performed in 34 patients. The fibrosis (F) was staged on a 0-4 scale according to the Ludwig classification. RESULTS: According to the clinical diagnosis, the median values of liver stiffness were 7.0+/-2.7 kPa for inactive carriers (n=29), 8.3+/-5.3 kPa for chronic hepatitis patients (n=106), 15.9+/-8.3 kPa for compensated cirrhosis patients (n=63), 31.8+/-20.3 kPa for decompensated cirrhosis patients (n=26), and 45.1+/-34.5 kPa for HCC patients (n=4). The degree of liver stiffness was significantly different between the different disease groups (p or =2; 0.92, 0.73, and 0.56, respectively, for F> or =3; and 0.97, 0.79, and 0.55, respectively, for F=4. FibroScan(R) offered the best diagnostic performance both for significant fibrosis (F> or =2) and severe fibrosis-cirrhosis (F3-F4). CONCLUSIONS: FibroScan(R) is a reliable, rapid non-invasive method to diagnose the severity of chronic liver disease and to predict fibrosis in patients with chronic hepatitis B, in addition to using the APRI and AST/ALT ratio.

Long-term therapeutic effects of partial splenic embolization on secondary hypersplenism / 대한내과학회지

BACKGROUND: Liver cirrhosis causes secondary hypersplenism and thrombocytopenia is clinically troublesome. Splenectomy (SPL) was thought to be the curative management for correcting thrombocytopenia. However, decompensated liver function prevents any surgical approach due to high morbidity and mortality. Hence, partial splenic embolization (PSE) has been introduced, which is a less invasive procedure. The purpose of this study was to assess the long-term therapeutic effects of PSE and to compare them with those of SPL. METHODS: This study was performed retrospectively in patients who underwent PSE or SPL from Jan. 1999 to Dec. 2003. The patients either had symptoms of bleeding or they needed to correct their thrombocytopenia for further treatment of associated diseases. The therapeutic effects were evaluated, and the complications were assessed. RESULTS: Forty and 35 patients were enrolled in the PSE and SPL groups, respectively. WBC, platelet and hemoglobin counts were all significantly increased at the 2 year follow-up in both groups. Child-Pugh score significantly decreased in the PSE group from 6.5 before treatment to 5.5 after treatment (p=0.004). Minor complications were easily controlled with supportive care, and major complications very rarely occurred in both groups. CONCLUSIONS: PSE and SPL both proved to be effective measures with few serious complications for treating pancytopenia in patients with liver cirrhosis. Considering the improved liver function (the prothrombin time) and the Child-Pugh score after PSE, it may be more reasonable to initially recommend PSE for the patients with liver cirrhosis and secondary hypersplenism.

Clinical Features and Treatment Outcome of Advanced Hepatocellular Carcinoma with Inferior Vena Caval Invasion or Atrial Tumor Thrombus / 대한간학회지

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) with an extension to the inferior vena cava (IVC) or right atrium is uncommon, and its prognosis remains unclear due to the few case reports. In order to elucidate the natural history and treatment outcome, this study investigated advanced HCC patients with an IVC invasion or atrial tumor thrombus. METHODS: Between November 1987 and June 2004, a total of 41 patients were diagnosed as having HCC with IVC or right atrial involvement using the new imaging techniques including a two-dimensional echocardiography. Those patients were stratified into the untreated 'control group' (n=17) and 'treated group' (n=24). The clinical features, treatment outcome and prognosis including patient survival were analyzed. RESULTS: The mean age of the total patients was 55 years (male:female, 33:8). The most common cause of HCC was a hepatitis B virus infection (85.4%), followed by a hepatitis C virus infection (7.4%). According to the Child-Pugh classification, 24 patients were Child-Pugh class A (58.5%), 15 were Child-Pugh class B (36.6%), and 2 were Child-Pugh class C (4.9%). Lung metastases were identified in 10 patients (24.5%). The treatment modalities of the treated group included 11 systemic chemotherapy regimens (5-FU and cisplatin), 10 transarterial chemotherapy regimens, 2 chemoradiation procedures and 1 hepatic resection. The overall survival was 3.0 months (range, 1-29 months). The 6 month survival rate was 23.5% (4/17) in the control group and 29.2% (7/24) in the treated group. The 12 months survival rate was 0% (0/17) and 25.0% (6/24), respectively. Independent prognostic factor affecting the survival was whether or not any treatment had been carried out. CONCLUSIONS: Although the prognosis of advanced HCC with IVC invasion or a right atrial tumor thrombi is poor, treatment might improve the survival rate.

The Efficacy and Safety of Telbivudine in Korean Patients with Chronic Hepatitis B / 대한간학회지

BACKGROUND AND AIMS: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. METHODS: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. RESULTS: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. CONCLUSIONS: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.

Efficacy and Long-Term Follow Up of Combination Therapy with Interferon Alpha and Ribavirin for Chronic Hepatitis C in Korea

Combination therapy with interferon alpha (IFN- alpha) and ribavirin for 24 or 48 weeks according to HCV genotype has improved the overall sustained virological response (SVR) rates to approximately 40%. The aim of this study was to investigate the long-term efficacy of combination therapy with IFN-alpha and ribavirin for chronic hepatitis C in Koreans. One hundred thirty-eight patients with chronic hepatitis C who received this combination therapy between 1995 and 2003 were analyzed retrospectively. All patients were treated with IFN-alpha 3-6 million units three times weekly in combination with 900-1200 mg/day of ribavirin for 24 weeks. The overall SVR rate was 41.3%. Patients were followed up for a median of 41 months (range, 12-105 months) after completion of therapy. In all of the SVR patients (57 patients), SVR was conserved during the follow-up period. None of the patients progressed to decompensated liver disease or hepatocellular carcinoma (HCC). However, 5 of the 81 non-SVR patients (6.2%) progressed to decompensated liver disease or HCC. In conclusion, combination therapy with IFN-alpha and ribavirin shows good long-term efficacy in patients with chronic hepatitis C in Korea, one of the highest endemic areas of hepatitis B virus (HBV) infection.

Natural History of HBeAg Negative Chronic Hepatitis B Virus Infection: A Cohort Study / 대한간학회지

BACKGROUND/AIMS: The long-term virologic and biochemical changes in patients with HBeAg negative HBV infection, especially in Asia, remain unclear. To address this issue, we conducted a 3 year- retrospective, cohort study. METHODS: A total of 157 patients with HBeAg negative HBV infection who were monitored without treatment were reviewed between January 1999 and March 2004. Those patients were followed up every 3 months with liver function tests and serologic tests. All patients were stratified into 3 groups; inactive carrier (IC), viremic carrier (VC) and chronic hepatitis (CH). Serum HBV DNA was measured by a hybridization assay (sensitivity: 1.4 x 10(5) genomes/mL, Digene Diagnostics, Silver Spring, USA). RESULTS: The median age of enrolled patients was 42.7 years (M:F=2.3:1). By single time-point observations, the 3 year-cohort prevalence of HBeAg negative CH varied from 12.7 to 35.8% (median 20.7%) HBeAg negative CH was accumulated over time (P=0.002) and transition rates among three groups after 3 years of follow-up are as follows: IC to CH, 6.0%; IC to VC, 4.1%; VC to CH, 23.2%. VC seems to be a disease state in the middle of transition from IC to CH. CONCLUSIONS: We demonstrated the dynamic changing patterns of HBeAg negative CH with time, of which the change from IC or VC to CH was dominant.

The effect of preoperative transcatheter hepatic arterial chemoembolization in the treatment of hepatocellular carcinoma / 대한내과학회지

BACKGROUND: Transcatheter hepatic arterial chemoembolization (TACE) is used for curative or palliative treatment of hepatocellular carcinoma (HCC). However, it is neither well known how much TACE induces tumor necrosis histologically, nor whether preoperative TACE has benefit for resectable HCC. The purpose of this study is to measure the degree of tumor necrosis induced by one session of TACE and to evaluate the effect of preoperative TACE for resectable HCC. METHODS: Between January 1999 and January 2004, 20 HCC patients with one session of preoperative TACE (TACE group) and 36 HCC patients with only preoperative hepatic angiography, without TACE (angiography group) were enrolled. RESULTS: In TACE group, 12 patients had tumor necrosis of 100%, 5 patients having between 80% and 99%, and 3 patients less than 50%. The mean tumor necrosis rate of HCC less than 5 cm in diameter were 84.7%, while 90.5% in larger size (>5 cm in diameter) of HCC (p>0.05). The mean tumor necrosis rate of the recurred patients in TACE group and in angiography group was 98.75 and 17.5% (p=0.02), respectively. Disease free survival time of the recurred patients in TACE and in angiography group was 16.75 and 20.25 months, respectively (p=0.77). CONCLUSIONS: The tumor size was not related with the degree of tumor necrosis and no relevant factors could be found. Although the mean tumor necrosis was greater in TACE group than in angiography group, the disease free survival time was not different between the two groups.

Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0-->> 4.2, p=0.000) ; lactulose group (11.3-->> 5.0, p=0.000) ). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

Efficacy of Repeated Hepatic Arterial Infusion Chemotherapy in Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis / 대한간학회지

BACKGROUND/AIMS: The aim of this study is to elucidate the efficacy of repeated hepatic arterial infusion chemotherapy (HAIC) and different chemotherapeutic regimens for treating patients having advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS: From Jan. 1999 and Dec. 2003, a total of 103 patients diagnosed as having HCC with PVTT, but without extrahepatic spreading, were enrolled in this study. They were stratified into two groups. Group I (67 patients) received intraarterial cisplatin (CDDP, 80 mg/m2 for 2 hours on Day 1), Group II (36 patients) received intraarterial CDDP (60 mg/m2 for 2 hours on Day 2) and 5-fluorouracil (5-FU, 500 mg/m2 for 5 hours on Day 1-3). They were scheduled to receive at least three consecutive courses of the HAIC at 1 month intervals. RESULTS: Among the 66 patients who completed the protocol, one (2.5%) and seven (17.5%) patients of group I, and one (3.8%) and four (15.4%) of group II, exhibited complete and partial responses, respectively. The median survival period of all the patients was 6 months. Group II showed a tendency to improve the median survival compared to group I (8.5 vs 5.0 months, respectively, P=0.45). The most common adverse reaction was nausea (58.2%). However, an elevation of the total bilirubin level was more frequent in Group I than in Group II (61.3% vs 20.7%, respectively, P<0.05). CONCLUSIONS: Repeated HAIC using CDDP achieved favorable results in a few patients with HCC with PVTT, and additional 5-FU may be useful.

Usefulness of PIVKA-II for diagnosis and evaluation of recurrence of hepatocellular carcinoma / 대한내과학회지

BACKGROUND: Although alpha-fetoprotein (AFP) is most widely used tumor marker for hepatocellular carcinoma (HCC), the sensitivity is about 60~70% in advanced HCC. Furthermore, the specificity of AFP is relatively low. The aim of this study was to evaluate the usefulness of prothrombin-induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HCC, and of recurrence after curative surgical resection. METHODS: Between April 2001 and March 2004, a total of 245 patients with pathologically confirmed HCC and a total of 267 patients with non-HCC, chronic liver diseases were enrolled. RESULTS: With cutoff-value 20 ng/mL for AFP and 40 mAU/mL for PIVKA-II, the sensitivity of AFP and PIVKA-II was 48.6% (119/245) and 75.1% (184/245), respectively. The specificity of them was 81.3% (217/267) and 94.8% (253/267), respectively. When AFP and PIVKA-II were combined, the sensitivity and specificity was 83.3% (204/245) and 77.2% (206/267), respectively. For HCC

Risk factors of acute hepatic failure associated with transcatheter arterial chemoembolization for hepatocellular carcinoma / 대한내과학회지

BACKGROUND: Transcatheter Arterial Chemoembolization (TACE) has been the most widely used treatment for advanced hepatocellular carcinoma (HCC) in Korea. However a number of complications associated with TACE have been reported in many studies. Acute hepatic failure is one of the most serious complications of TACE, because of its grave prognosis. The aim of this study was to investigate the risk factors associated with acute hepatic failure after TACE. METHODS: A total of 263 TACE procedures performed in 163 patients with HCC were included in this study. We reviewed retrospectively the complications that occurred after TACE and analysed the risk factors associated with acute hepatic failure after TACE. RESULTS: Complications included post-embolization syndrome (187 cases), temporary hepatic insufficiency (90 cases), acute hepatic failure (13 cases), hepatic arterial injury (9 cases), intrahepatic biloma (4 cases), liver infarction (2 cases), liver abscess (2 cases), tumor rupture (1 cases), gastrointestinal bleeding (14 cases), septicemia (3 cases), gall bladder infarction (2 cases), thrombocytopenia (2 cases), gastric perforation (1 cases), pneumonia (1 cases), urticaria (1 cases), sensorineural hearing loss (1 cases), femoral artery aneurysm (1 cases). According to univariate analysis, risk factors associated with acute hapatic failure after TACE were serum bilirubin and albumin, prothrombin time, dose of adriamycin, pre-TACE Child-Pugh class, tumor size, diffuse tumor type, portal vein thrombosis and TNM stage. Multivariate analysis revealed that serum bilirubin {odd ratio=3.86 (95% CI: 1.59-9.32)}, and diffuse tumor type {odd ratio=5.29 (95% CI: 1.46-23.86)} were statistically significant risk factors. CONCLUSIONS: It is recommended that above mentioned risk factors should be considered carefully before TACE to prevent the occurrence of acute hepatic failure after TACE in HCC patients.

HBV-specific CD8+ T cells for Sustained HBeAg Seroconversion after Lamivudine Therapy / 대한간학회지

BACKGROUND/AIMS: Viral suppression of the hepatitis B virus (HBV) can be induced by lamivudine, but the relapse seen in many patients after cessation of lamivudine therapy is troublesome. We thought that the host immune response is important to prevent viral relapse. We compared the frequency of HBV-specific CD8+ T cells in the peripheral blood and their expansion capacity after exposure to viral antigen between the patients showing sustained HBeAg seroconversion after use of lamivudine and those patients without sustained response. METHODS: We analyzed HBV-specific CD8+ T cells that were isolated from the blood of 14 patients with HLA-A2 who showed lamivudine induced HBeAg seroconversion (HBV DNA < 0.5 pg/mL, and the cells were negative for HBeAg) at the end of lamivudine therapy. The purified T cells were directly stained ex vivo, after they had been stimulate with synthetic peptide, using the HBV core 18-27-specific HLA tetramer (Tc 18-27) and monoclonal antibody to CD8. The HBV viral load was quantified by the Amplicor HBV Monitor assay. RESULTS: In patients with a sustained HBeAg response (the sustained group) for a duration of 15.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 49.5 (15-135). On the contrary, in patients who experienced relapse (the relapsed group) during a median of 7.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 13.5 (0-95). Especially, among patients with a viral load of HBV DNA < 1 X 10(3) copies at the end of treatment, the median number of Tc 18-27 cells out of 5 X 10(4) CD8+ T cells was 87 (45-135) in sustained group compared to 12 (6-50) in the relapsed group. All patients in the sustained group demonstrated a vigorous expansion of the core 18-27-specific CD8+ T cells after stimulation with viral peptide, in contrast to only 3 out of 8 patients in the relapsed group. CONCLUSIONS: This study demonstrates that the frequency and functional responsiveness of the circulating HBV-specific CD8+ T cells may be important for obtaining a sustained HBeAg response to lamivudine.

Clinical Outcome of Pulmonary Resections in Patients with Pulmonary Metastasis of Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Although the lung is the most common site of extrahepatic spread from hepatocellular carcinoma (HCC), the role of surgery for pulmonary metastasis remains unclear. The aim of this study was to evaluate the efficacy of pulmonary resection in patients with pulmonary metastasis from HCC. METHODS: Between July 2000 and July 2004, a total of 6 patients with pulmonary metastasis from HCC underwent curative pulmonary resections. The patients were divided into two groups (Surgery group and Non-surgery group) according to the primary treatment modality of HCC. Medical records, imaging studies, and pathologic reports of the surgical specimens were reviewed. RESULTS: Three patients in the surgery group underwent pulmonary resections for a solitary metastasis after hepatectomy for HCC, and they are all still alive. One of the 3 patients developed a tumor recurrence in the chest wall after pulmonary resection. The survival time after diagnosis of HCC were 79, 122, and 54 months, respectively. The survival time after pulmonary metastatectomy were 49, 39, and 20 months in the three patients. Another 3 patients in the non-surgery group, received a pulmonary metastatectomy; they had either a complete response HCC or partial radiologic response. These 3 patients developed recurrent disease in the liver. One of 3 patients died. The survival time after diagnosis of HCC were 153, 83, 12 months. The survival time after pulmonary metastatectomy were 51, 4, 2 months. CONCLUSIONS: The surgical resections of a solitary pulmonary metastasis from HCC in highly selected patients might be an effective treatment modalities for prolonged survival.

Efficacy of Individual Prediction Model for the Early Diagnosis of Hepatocellular Carcinoma / 대한내과학회지

BACKGROUND: Screening tests for hepatocellular carcinoma (HCC) in the high risk population can detect tumors at an earlier stage and thus confer a higher chance of receiving treatment. However, the usefulness, frequency and cost-effectiveness of screening for HCC may differ in different areas, possibly reflecting differences in risk factors. Last decade, we have identified risk factors for HCC in 4339 Korean patients. The aim of this study was to investigate the efficacy and usefulness of individual prediction model for the early diagnosis of HCC. METHODS: We studied a total of 833 patients who visited Yonsei University Medical Center for regular check-up including ultrasonography and alpha-fetoprotein from January 1999 to December 2000. The patients were classified into a low risk group ( 15%) by the probability of HCC development according to individual prediction model (IPM). The patients who developed HCC during the follow-up periods were analyzed using IPM. All the detailed data of clinical parameters were obtained by our self-exploited data base system prospectively and analyzed by SAS program. RESULTS: 44 (5.3%) out of 833 patients developed HCC during mean follow-up periods of 36 months. According to IPM, 2 (0.62%) of 324 patients in the low risk group, 20 (4.84%) of 413 patients in the intermediate risk group, and 22 (22.9%) of 96 patients in the high risk group were diagnosed as HCC. In 29 of 44 HCC patients (65.9%), initial presentation of tumor size was less than 3 cm in diameter. CONCLUSION: We confirmed the reliability of established IPM for screening of HCC and this model may help screening program to be done effectively by focusing high risk groups for HCC.

A Case of Hypercalcemia Associated with Hepatic Tuberculosis / 대한내분비학회지

In this report, a 70-year-old female patient was detected with laboratory findings of hypercalcemia. The most common causes of hypercalcemia are primary hyperparathyroidism and malignant disease. Her laboratory tests did not show any evidence for neither primary hyperparathyroidism nor malignant diseases. Thus, granulomatous disease was suspected as the cause of the hypercalcemia. Liver MRI (magnetic resonance image) was performed on the subject, which suggested the presence of hepatic tuberculosis and sarcoidosis. Because the chest x-ray did not show a definite tuberculous lesion, we performed a laparoscopic liver biopsy for a final diagnosis. Findings from the biopsy specimen showed typical tuberculosis. After treatment with tuberculosis medication, hypercalcemia of the subject was resolved. Hypercalcemia is a well recognized as a possible complication of active pulmonary tuberculosis. But one should consider hepatic tuberculosis without pulmonary tuberculosis as a cause of hypercalcemia.

Reappraisal of HBV Genotypes and Clinical Significance in Koreans Using MALDI-TOF Mass Spectrometry / 대한간학회지

BACKGROUND/AIMS: Recent studies have shown that the genotype of hepatitis B virus (HBV) may correlate with the disease natural history and treatment outcome. However, several of these studies used low sensitivity assays in a small number of patients, and this has precluded an accurate evaluation of Korean HBV genotypes. We analyzed Korean HBV genotypes in a large population by employing a new technology, restriction fragment mass polymorphism (RFMP) using MALDI-TOF mass spectrometry, in a sensitive and specific manner. METHODS: Between February 1995 and December 2003, a total of 475 patients with chronic HBV infection were enrolled. The assay is based on the mass measurement of oligonucleotides having genotypic variations of the S gene. Clinical features including the virologic status and disease progression were also evaluated. RESULTS: The median age of the total patients was 35.5 years. Out of 475 patients, there were 162 (34.1%) inactive carriers, 172 (36.2%) had chronic hepatitis, 77 (16.2%) had liver cirrhosis and 64 (13.5%) had hepatocellular carcinoma (HCC). There were 454 patients (95.6%) with genotype C, 4 patients (0.8%) with genotype A, 16 patients (3.4%) with the mixed A and C genotype [7 patients (1.4%) with AA], and 1 patient (0.2%) with B genotype. Comparing genotype A and C, genotype A patients were all inactive carriers without HCC, whereas genotype C patients included those with chronic hepatitis, liver cirrhosis and HCC. CONCLUSIONS: HBV genotype C is highly prevalent in Korea. Although it is a small percentage, genotype A also exists and it seems to take a more benign clinical course than genotype C. Further studies are necessitated to assess the relationship between HBV genotypes and the various aspects of the diseases' clinical course.

Clinical Features and Prognostic Factors of Fulminant Hepatic Failure in Koreans / 대한간학회지

BACKGROUND/AIMS: There have been scant reports on the prognostic factors of fulminant hepatic failure for selecting the patients who need liver transplantation. We investigated the clinical features and prognostic factors throughout the clinical course of the disease in Korean patients with fulminant hepatic failure. METHODS: Between 1992 and 2003, a total of 60 patients with fulminant hepatic failure were divided into the survival group and the non-survival group, and these groups were compared according to gender, age, etiology, values of the laboratory tests, grade of the encephalopathy that was obtained at the time of admission and the worst clinical status (hepatic encephalopathy). RESULTS: The mean age of the total patients was 40.9 years (M:F=31:29) and the survival rate was 28.3% (n=17). Drugs (n=25, 12 herbal medicines) and viral infection (n=24, 18 HBV infection) were most common causes. On univariate analysis, the WBC, AST, ALT, total bilirubin and HE IV stage at the time of admission were the significant factors for a poor prognosis. Total bilirubin, albumin and HE IV stage also remained as significant factors at the time of the worst clinical status. On multivariate analysis, total bilirubin (P=0.033) and ALT (P=0.042) at admission were the prognostic factors, and the progression to HE IV stage (P=0.019) or hypoalbuminemia (P=0.028) during hospitalization represented the significant factors for a poor prognosis. CONCLUSIONS: In contrast to Western countries, HBV infection and herbal medicines were major causes of fulminant hepatic failure in Korea. The total serum bilirubin level and progressive hyperbilirubinemia with HE (stage IV) during hospitalization seemed to be the most important prognostic factors, and liver transplantation should be considered before the patient reaches this status.