A synchronous hepatocellular carcinoma and renal cell carcinoma treated with radio-frequency ablation.

Radio-frequency ablation (RFA) is a curative treatment for hepatocellular carcinoma (HCC). Percutaneous RFA has been shown to be beneficial for patients with small renal cell carcinoma (RCC) lacking indications for resection. We experienced the case of a 53-year-old male who had conditions that suggested HCC, RCC, and alcoholic liver cirrhosis. Abdominal contrast-enhanced computed tomography (CT) and magnetic resonance image showed liver cirrhosis with 2.8 cm ill-defined mass in segment 2 of the liver and 1.9 cm hypervascular mass in the left kidney. These findings were compatible with the double primary cancers of HCC and RCC. Transarterial chemoembolization (TACE) was performed to treat the HCC. After the TACE, a focal lipiodol uptake defect was noticed on a follow up CT images and loco-regional treatment was recommended. Therefore, we performed RFAs to treat HCC and RCC. There was no evidence of recurrence in the follow up image after 1 month.

Alcoholic fatty liver disease elevates estimated coronary heart disease risk to levels comparable with those of nonalcoholic fatty liver disease in the Korean population: a cross-sectional study.

BACKGROUND/AIMS: A close relationship has been established between nonalcoholic fatty liver disease (NAFLD) and an elevated risk of coronary heart disease (CHD), but little is known about the association between alcoholic fatty liver disease (AFLD) and CHD risk. The aim of this study was to determine whether AFLD is associated with elevated CHD risk. METHODS: We retrospectively enrolled 10,710 subjects out of 11,469 individuals who visited the Konkuk University Health Care Center for a routine health checkup in 2010. AFLD was diagnosed made when the usual amount of alcohol consumption exceeded 210 g/week in males and 140 g/week in females for the previous 2 years and when hepatic steatosis was detected by liver ultrasonography. The 10-year risk for CHD was estimated using the Framingham Risk Score. RESULTS: Hepatic steatosis was diagnosed in 4,142 of the 10,710 individuals (38.7%); the remainder (i.e., n=6,568) became the control group. The 4,142 individuals with hepatic steatosis were divided into two groups: NAFLD (n=2,953) and AFLD (n=1,189). The risk of CHD was higher in AFLD (6.72±0.12) than in the control group (5.50±0.04, P<0.001), and comparable to that in NAFLD (7.32±0.07, P=0.02). CONCLUSIONS: Individuals with AFLD have an elevated 10-year risk of CHD that is comparable to those with NAFLD. Therefore, AFLD should be considered a significant risk for future CHD, and preventive measures should be considered earlier.

Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal.

BACKGROUND/AIMS: A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal. METHODS: The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis. RESULTS: Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD. CONCLUSIONS: Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.

Efficacy and safety of tenofovir-based rescue therapy for chronic hepatitis B patients with previous nucleo(s/t)ide treatment failure.

BACKGROUND/AIMS: We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies. METHODS: Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored. RESULTS: Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log10 IU/mL to 2.0 log10 IU/mL and to 1.6 log10 IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (≤20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed. CONCLUSIONS: TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients' adherence to medication is related to viral rebound.

Lamivudine plus adefovir combination therapy for lamivudine resistance in hepatitis-B-related hepatocellular carcinoma patients.

BACKGROUND/AIMS: Lamivudine (LAM) plus adefovir (ADV) combination therapy has been accepted as one of the best treatments for LAM-resistant chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of this combination therapy in hepatocellular carcinoma (HCC) patients. METHODS: The medical records of CHB patients who developed LAM resistance and were treated with LAM plus ADV combination therapy for more than 6 months were reviewed. Their virological response (VR; undetectable HBV DNA) and biochemical response (BR; alanine aminotransferase normalization) were evaluated, and the findings of HCC and non-HCC patients were compared. RESULTS: The data from 104 patients (19 with HCC and 85 without HCC) were analyzed. The VR rates did not differ significantly between the HCC and non-HCC groups: 33.3% vs. 55.6% at 12 months (P=0.119), 58.3% vs. 67.2% at 24 months (P=0.742), 50% vs. 69.8% at 36 months (P=0.280), and 66.7% vs. 71.0% at 48 months (P=1.000). The BR rates also did not differ significantly between the groups: 55.6% vs. 84.0% at 12 months (P=0.021), 58.3% vs. 83.8% at 24 months (P=0.057), 70.0% vs. 77.8% at 36 months (P=0.687), and 66.7% vs. 80.6% at 48 months (P=0.591). CONCLUSIONS: The efficacy of LAM plus ADV combination therapy is comparable in HCC and non-HCC patients.

Virological Response and Muscular Adverse Events during Long-Term Clevudine Therapy in Chronic Hepatitis B Patients.

BACKGROUND: Recently, several reports issued clevudine induced myopathy in the long term use. OBJECTIVES: The aim of this study was to investigate antiviral effects and adverse events of clevudine monotherapy in patients with chronic hepatitis B (CHB). PATIENTS AND METHODS: The subjects were 110 treatment-naïve CHB patients. They were treated with 30 mg clevudine/day for more than six months. Virological and biochemical tests, including that for serum creatine kinase (CK), were monitored at baseline and at 3-month intervals during treatment period. RESULTS: In HBeAg-positive patients, the cumulative rates of virological response were 74.0 %, 68.5 %, and 67.3 % after one, two, and three years of clevudine treatment, respectively. Cumulative rates of HBeAg loss or seroconversion were 17.8 %, 30 %, and 31.5 % after one, two and, three years of clevudine treatment, respectively. In HBeAg-negative patients, the cumulative rates of virological response were 97.3 %, 100 %, and 94.6 %, respectively. Virological breakthrough occurred in 27 patients. The rtM204I mutation in HBV polymerase was predominantly detected. Muscular adverse events were observed in 15 patients. All patients with myopathy recovered after the cessation of clevudine monotherapy. Fluctuations in CK level during the clevudine treatment period were frequently observed irrespective of development of myopathy. Multiple episodes of CK elevation were significantly related to the development of myopathy. CONCLUSIONS: Long-term clevudine monotherapy is effective for suppression of serum HBV DNA level and normalization of serum alanine amino transaminase levels, but associated with occurrence of rtM204I mutation. Clevudine-induced muscular adverse events are not uncommon, although they are totally reversible after cessation of the treatment. Muscular adverse events and serum CK level should be carefully monitored during long-term treatment with clevudine.

Predictive value of Refit Model for End-Stage Liver Disease, Refit Model for End-Stage Liver Disease-Na, and pre-existing scoring system for 3-month mortality in Korean patients with cirrhosis.

BACKGROUND AND AIM: The Model for End-Stage Liver Disease (MELD) has been widely used for predicting short-term mortality in patients with cirrhosis in the U.S. A modification of the MELD score was published in 2011. This was validated for Korean patients with cirrhosis. METHODS: The medical records of patients with cirrhosis who were admitted to Konkuk University Hospital from 2006 to 2010 were retrospectively reviewed. The predictive value for 3-month mortality was compared between the Refit MELD, Refit MELD-Na, MELD, MELD-Na, and Child-Pugh score. The comparison was performed by calculating the area under the receiver operating curve (AUROC). RESULTS: A total of 882 patients were enrolled and 77 (8.7%) died within 3 months. The most common etiology was alcohol (45.4%) followed by hepatitis B (34.2%). The AUROCs of the Refit MELD, Refit MELD-Na, MELD, MELD-Na, and Child-Pugh score were 0.842, 0.817, 0.844, 0.848, and 0.831, respectively. The Refit MELD-Na showed a lower value than MELD-Na (P = 0.0005), MELD (P = 0.0190), and the Refit MELD (P = 0.0174). When the patients with hepatitis B, C, and alcoholic cirrhosis were analyzed, the AUROCs were 0.960, 0.920, 0.953, 0.951, 0.896, 0.959, 0.956, 0.947, 0.956, 0.943, and 0.746, 0.707, 0.752, 0.747, 0.755. CONCLUSIONS: The improvement in predictive value for 3-month mortality was not definite. The Refit MELD-Na especially showed the lowest value. This result may have been due to differences in underlying etiology of cirrhosis between Korea and the U.S. Thus, a larger prospective study is warranted.

Value of the APASL severity score in patients with acute variceal bleeding: a single center experience.

BACKGROUND: Acute variceal bleeding is a severe complication in patients with cirrhosis. The Asian Pacific Association for Study of the Liver (APASL) severity score was proposed in 2011. This score is used for evaluating the severity of acute variceal bleeding. However, as this score is largely based on expert opinion, it requires validation. AIM: To determine the value of the APASL severity score. METHODS: We retrospectively reviewed the medical records of patients treated for acute variceal bleeding at Konkuk University Hospital from 2006 to 2011. The APASL severity score, Child-Pugh score, and Model for End-Stage Liver Disease (MELD) score were calculated, and predictive values for treatment failure, rebleeding, and in-hospital mortality were compared by the area under the receiver operating curve (AUROC). RESULTS: A total of 136 patients were enrolled, and all patients were treated by endoscopic variceal ligation (EVL) and terlipressin combination therapy. Most patients were male (n = 123, 90.4 %), and the most common etiology was alcohol (n = 91, 66.9 %). Thirteen treatment failures, eight rebleedings, and seven in-hospital mortalities occurred. The AUROCs of the APASL severity score, Child-Pugh score, and MELD score were 0.760, 0.681, and 0.607 for treatment failure; 0.660, 0.714, and 0.677 for rebleeding; and 0.872, 0.847, and 0.735 for in-hospital mortality. A significant difference was only observed between the APASL severity score and MELD score for treatment failure (p = 0.0259). CONCLUSION: APASL severity score was a useful method for predicting treatment failure. However, the predictive value for rebleeding and in-hospital mortality were not satisfactory.

Clonal evolution of hepatitis B virus polymerase gene mutations during lamivudine-adefovir combination treatment.

AIM: To identify hepatitis B virus polymerase gene mutations during antiviral therapy using lamivudine-adefovir sequential monotherapy followed by lamivudine-adefovir combination therapy. METHODS: The patient cohort included four adult chronic hepatitis B patients who had undergone sequential monotherapy, first with lamivudine (LMV) and then, after developing viral breakthrough, with adefovir (ADV) therapy. All of the patients had non-response or viral breakthrough after LMV-ADV sequential monotherapy, which resulted in the switching of their antiviral regimen to LMV-ADV combination therapy. Eleven serum samples from the four patients who showed non-response to rescue LMV-ADV combination therapy were collected sequentially at a time before the antiviral treatment and then during the LMV monotherapy, ADV monotherapy, and LMV-ADV combination therapy. For the genotypic analysis, the whole 1310-bp polymerase gene region was amplified, cloned and sequenced. RESULTS: All patients had been previously treated with 100 mg of LMV once daily for a 15- to 26-mo period. The emergence of resistance mutations to LMV, such as rtM204V/I and/or rtL180M, were found in all patients. Their antiviral regimens were switched to ADV monotherapy as the second line treatment. All patients had viral breakthrough or non-response after the LMV-ADV sequential monotherapy. ADV-resistant mutations were detected after 13 to 19 mo of LMV-ADV sequential monotherapy. The rtA181V/T mutations were predominantly identified during the ADV treatment in the LMV-resistant patients. Twenty-seven of 38 clones were combined with an amino acid change at rt181; three clones had mutations in rt236 and one clone had a combined mutation. The rtA181V/T mutations were not suppressed by the LMV-ADV combination therapy. Thirty-nine of 64 clones showed an rtA181V/T mutation and six clones showed combined mutations in rt181 and rt236. Mutations in rt204 re-emerged during the combination treatment. The rt181 and rt204 mutations did not co-exist in one clone. CONCLUSION: Add-on lamivudine therapy with adefovir for adefovir resistance may not suppress the pre-existing adefovir-resistant mutation that develops during lamivudine-adefovir sequential monotherapy.

Long-term impact of entecavir monotherapy in chronic hepatitis B patients with a partial virologic response to entecavir therapy.

OBJECTIVE: Partial virologic response (PVR) in chronic hepatitis B (CHB) patients during antiviral therapy is associated with an increased risk of occurrence of viral resistance and treatment failure. The aim of this study was to evaluate the clinical and virological responses of partial responders to long-term entecavir (ETV) monotherapy. MATERIAL AND METHOD: In this open-labeled prospective study, 128 treatment-naïve CHB patients treated with 0.5 mg ETV once daily for more than 12 months were monitored at baseline and at 3-month intervals during treatment. RESULTS: At baseline, the mean age of subjects was 47.0 ± 13.0 years, and the median duration of treatment was 27 months; 85 subjects (66.4%) were HBeAg-positive, and 47 patients (36.7%) had liver cirrhosis. Eighteen of 128 patients (14.0%) showed PVR to 48 weeks of ETV treatment, and 13 patients were followed up for over 24 months. Among them, 9 of 13 patients (69.2 %) achieved a complete virologic response (VR, HBV-DNA < 60 IU/mL) during prolonged ETV treatment. Four showed persistent PVR, but only one patient with poor compliance developed genetic resistance to ETV at month 27. The occurrence of PVR was independently associated with a high viral load, more than 7 log(10) IU/mL (p = 0.014). CONCLUSIONS: CHB patients with a high viral load, more than 7 log log(10) IU/mL, are related to the occurrence of PVR during ETV monotherapy. Long-term ETV monotherapy may be effective for suppressing serum HBV DNA levels in treatment- naïve CHB patients with a PVR to ETV.

Virologic response to therapy increases health-related quality of life for patients with chronic hepatitis B.

BACKGROUND & AIMS: We evaluated changes in health-related quality of life (HRQoL) in a longitudinal study of patients given antiviral therapy for chronic hepatitis B (CHB). METHODS: We analyzed changes in HRQoL reported by 2856 Korean patients with CHB who started first-line or rescue antiviral therapy from January 2007 to June 2007; the mean age of the study subjects was 43.3 years, 72% were male, 80% were positive for hepatitis B e antigen, 20% had cirrhosis, and 13% had concomitant disease. These subjects all completed the translated version of the Chronic Liver Disease Questionnaire (CLDQ) and the EuroQol-5 Dimension (EQ5D) when the study began (baseline), and at the end of a 24-week follow-up period. We analyzed changes in utility scores from baseline to 24 weeks of antiviral treatment. RESULTS: After 24 weeks of antiviral therapy, patients had significant improvements in liver function and reduced mean levels of hepatitis B virus DNA (from 6.3 to 3.9 log(10) copies/mL). Utility scores from the visual analogue scale and EQ5D improved after 24 weeks of antiviral therapy (from 0.84 ± 0.19 to 0.94 ± 0.14; P < .0001). Improved CLDQ scores were associated with virologic response (level of hepatitis B virus DNA, <4 log(10) copies/mL); scores increased from 5.21 ± 0.99 at baseline to 6.09 ± 0.72 after 24 weeks of antiviral therapy in responders, but from 5.31 ± 0.94 at baseline to 6.06 ± 0.66 in nonresponders (P = .003). CONCLUSIONS: Patients with CHB who have a virologic response to 24 weeks of antiviral therapy also have significant improvements in HRQoL, measured by EQ5D and CLDQ.

Epidemiology and prevention of hepatitis B virus infection.

Hepatitis B virus (HBV) infection has been a major global cause of morbidity and mortality. The recognition of the problem led to a worldwide effort to reduce transmission of HBV through routine infant vaccination. HBV infection is the most common cause of chronic liver diseases and hepatocellular carcinoma in Korea. After hepatitis B vaccine era, seroprevalence of hepatits B surface antigen is decreasing, particularly in children. Hepatitis B vaccine is remarkably safe and shows high immunogenicity. Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life is a highly effective method for prevention and control of hepatitis B.

Carotid intima-media thickness is increased not only in non-alcoholic fatty liver disease patients but also in alcoholic fatty liver patients.

BACKGROUND/AIMS: There are many reports of non-alcoholic fatty liver disease (NAFLD) patients with increased carotid intima-media thickness (IMT). However, there is little information about carotid IMT in alcoholic fatty liver disease (AFLD) patients. We aimed to compare the carotid IMT of NAFLD patients and AFLD patients. METHODS: The medical records of individuals who underwent carotid IMT measurement and abdominal ultrasonography between January 2006 and December 2008 at Korea University Ansan Hospital were retrospectively reviewed. The patients were divided into group A (no fatty liver without alcohol history), group B (NAFLD), group C (AFLD) and group D (no fatty liver with alcohol history). The carotid IMT results were compared across all groups. RESULTS: The mean carotid IMT was 0.55 ± 0.1 mm for group A, 0.6 ± 0.1 mm for group B, 0.59 ± 0.1 mm for group C, and 0.54 ± 0.1 mm for group D. There were significant differences between groups A and B, groups A and C, and groups C and D (p < 0.05), but there were no differences between groups B and C (p = 0.736). CONCLUSIONS: We determined that patients with fatty livers have an increased carotid IMT both in NAFLD and AFLD patients.

Clinical features of acute viral hepatitis B in Korea: a multi-center study.

BACKGROUND/AIMS: The incidence of Hepatitis B has significantly declined since the introduction of an HBV vaccination program. The aim of this study was to investigate recent clinical features of acute viral hepatitis B (AVH-B) in Korea. METHODS: A total of 2241 patients with acute viral hepatitis were enrolled and their data were collected from nine medical-centers between January 2006 and December 2009. RESULTS: One hundred nineteen (5.3%) of the 2241 were diagnosed as AVH-B. Among 78 patients with AVH-B whose data were analyzed, 50 were male, and the mean age was 38.6 years. In an initial test, mean AST, ALT and total-bilirubin levels were 1296.2 IU/L, 2109.6 IU/L and 9.3 mg/dl, respectively. Positivity frequencies for HBeAg and anti-HBe were 55.1% and 67.9%, respectively, and the mean HBV DNA level was 5.2 log10 copies/ml. The mean length of hospitalization was 11.6 days. During follow-up, AST, ALT and total bilirubin levels were normalized or near-normalized in all patients without serious complications. Sixty-three of 66 (95.4%) patients showed HBsAg loss and 37 (56.1%) patients showed HBsAg seroconversion. Only 3 patients (4.5%) showed persistent hepatitis B viremia. There was no case of death or liver transplantation. Nine patients (11.3%) had received anti-viral agents and their clinical outcomes were not significantly different from those of patients treated without antiviral agents. CONCLUSIONS: The prevalence of AVH-B among acute hepatitis patients is relatively low in Korea. AVH-B infection can be cured without complications in almost all patients, regardless of antiviral treatment.

[A case of osteomalacia related to adefovir in a patient with chronic hepatitis B].

Adefovir dipivoxil, an acyclic nucleoside analogue, has been approved for the treatment of patients with chronic hepatitis B. This agent is efficacious particularly in those who have developed lamivudine resistance. The report according to hypophosphatemia induced by low dose adefovir therapy is very rare. We report one case in which osteomalacia with hypophosphatemia developed in a patient with chronic hepatitis B on adefovir dipivoxil at a low dose, 10 mg daily. A 66-year-old man, who had been taking adefovir for more than 4 years due to lamivudine resistance, presented with muscle weakness and bone pain in both thighs. After 3 years of adefovir therapy, hypophosphatemia and elevated serum alkaline phosphatase levels had been noted. A bone scan showed multiple hot uptakes. All the image findings and clinical symptoms, such as bone pain and muscle weakness were improved after correcting the hypophosphatemia with oral phosphorous supplementation.

Virologic response at 12 months of treatment predicts sustained antiviral efficacy in patients with adefovir-treated Lamivudine-resistant chronic hepatitis B.

BACKGROUND/AIMS: The aim of our study was to define the potential role of virologic response at 12 months of treatment (VR12) in predicting subsequent virologic and clinical outcomes in adefovir (ADV)-treated lamivudine-resistant chronic hepatitis B. METHODS: Two hundred and four patients with lamivudine-resistant chronic hepatitis B virus (HBV) treated with ADV monotherapy were included. Serum HBV DNA was quantified by real-time polymerase chain reactions. VR12 was defined as a HBV DNA level of less than 4 log(10) copies/mL after 12 months of ADV treatment. RESULTS: VR12 was observed in 110 of the 204 patients (54%). The mean HBV DNA reductions from baseline after 12 months of ADV treatment were 3.8 and 1.9 log(10) copies/mL in patients with and without VR12, respectively (p<0.001). The hepatitis B "e" antigen (HBeAg) seroconversion rates in patients with and without VR12 were 32% and 14% at 12 months treatment, respectively (p=0.018), and 40% and 27% at 24 months of treatment (p=0.032). The genotypic mutation rates to ADV in patients with and without VR12 were 0% and 6% at 12 months of treatment, respectively (p=0.033), and 21% and 42% at 24 months (p=0.012). The rates of viral breakthrough in patients with and without VR12 were 0% and 7% at 12 months of treatment, respectively (p=0.072), and 9% and 25% at 24 months (p=0.006). CONCLUSIONS: Patients without VR12 may need to switch to or add on other potent antiviral drugs in their medical regimens.

Pulmonary Arteriovenous Malformation in Cryptogenic Liver Cirrhosis Associated with Turner's Syndrome.

Turner's syndrome is a genetic disorder of the sex chromosomes (e.g., 45,X or 45,X/46,XX) that manifests as various congenital anomalies. Despite its numerous extragonadal manifestations and frequent accompanying abnormalities in liver function tests, liver cirrhosis associated with Turner's syndrome has not been reported in Korea. Moreover, pulmonary arteriovenous malformations (PAVMs) have rarely been reported in association with liver cirrhosis, but there have been no reports of PAVMs occurring in cryptogenic liver cirrhosis associated with Turner's syndrome. We report a case of PAVM that occurred in cryptogenic liver cirrhosis associated with Turner's syndrome.

Laboratory characteristics of recent hepatitis A in Korea: ongoing epidemiological shift.

AIM: To evaluate seroprevalence of hepatitis A virus (HAV) antibody and investigate demographic, clinical, and laboratory features of recent cases in Korea. METHODS: For the evaluation of hepatitis A seroprevalence, we analyzed the data from 3127 subjects including, healthcare workers and patients who visited Konkuk University Hospital, a secondary referral center, from January to October 2009. The sera with positive IgM were excluded from seroprevalence data for total HAV antibody. We retrospectively reviewed the electronic medical records of 419 patients with HAV, who were diagnosed by the presence of serum IgM antibodies against HAV. All patients presented at Konkuk University Hospital between August 2005 and September 2008. RESULTS: Among 3127 sera tested, 1428 (45.7%) were positive for anti-HAV antibody. The seroprevalence was very low in teenagers or those in their twenties, increased in those in their thirties, and was > 90% in older patients. In children younger than 10 years, seroprevalence was increased again. Most patients with HAV hepatitis were in their twenties and thirties. The gamma-glutamyl transpeptidase increased with age and was significantly higher in patients older than 30 years. Indicators of severity, such as decreased albumin and increased bilirubin, were also more prominent in the older age group; however, the leukocyte count was higher and the frequency of leukopenia was lower in younger patients than in older adults. CONCLUSION: There has been an apparent epidemiological shift in HAV seroprevalence and a change in the peak age of HAV hepatitis. This study could provide baseline data of recent hepatitis A in Asia.

Identification and characterization of clevudine-resistant mutants of hepatitis B virus isolated from chronic hepatitis B patients.

Clevudine (CLV) is a nucleoside analog with potent antiviral activity against chronic hepatitis B virus (HBV) infection. Viral resistance to CLV in patients receiving CLV therapy has not been reported. The aim of this study was to characterize CLV-resistant HBV in patients with viral breakthrough (BT) during long-term CLV therapy. The gene encoding HBV reverse transcriptase (RT) was analyzed from chronic hepatitis B patients with viral BT during CLV therapy. Sera collected from the patients at baseline and at the time of viral BT were studied. To characterize the mutations of HBV isolated from the patients, we subjected the HBV mutants to in vitro drug susceptibility assays. Several conserved mutations were identified in the RT domain during viral BT, with M204I being the most common. In vitro phenotypic analysis showed that the mutation M204I was predominantly associated with CLV resistance, whereas L229V was a compensatory mutation for the impaired replication of the M204I mutant. A quadruple mutant (L129M, V173L, M204I, and H337N) was identified that conferred greater replicative ability and strong resistance to both CLV and lamivudine. All of the CLV-resistant clones were lamivudine resistant. They were susceptible to adefovir, entecavir, and tenofovir, except for one mutant clone. In conclusion, the mutation M204I in HBV RT plays a major role in CLV resistance and leads to viral BT during long-term CLV treatment. Several conserved mutations may have a compensatory role in replication. Drug susceptibility assays reveal that adefovir and tenofovir are the most effective compounds against CLV-resistant mutants. These data may provide additional therapeutic options for CLV-resistant patients.