Young Kul Jung

Fanconi's Syndrome Associated with Prolonged Adefovir Dipivoxil Therapy in a Hepatitis B Virus Patient.

Adefovir dipivoxil (ADV) is commonly used as an antiviral agent in the treatment of chronic hepatitis B or human immunodeficiency virus infection. Nephrotoxicity has been shown to occur at daily dosages of 60-120 mg. Fanconis syndrome is a generalized dysfunction of the renal proximal tubular cells, which is usually accompanied by complications. Here we report a case of Fanconis syndrome in a chronic hepatitis B patient who had been treated with a prolonged regimen of ADV at 10 mg/day. A 47-year-old man complained of severe back and chest-wall pain. He had chronic hepatitis B and had been treated with ADV at a daily dose of 10 mg for 38 months. He was hospitalized because of severe bone pain, and laboratory and radiologic findings suggested a diagnosis of Fanconis syndrome with osteomalacia. After discontinuation of the ADV, he recovered and was discharged from hospital. His laboratory findings had normalized within 2 weeks. This case indicates that Fanconis syndrome can be acquired by a chronic hepatitis B patient taking ADV at a conventional dosage of 10 mg/day. Therefore, patients treated with long-term ADV should be checked regularly for the occurrence of ADV-induced Fanconis syndrome.

A nationwide seroepidemiology of hepatitis C virus infection in South Korea

The aim of this study was to reveal nationwide seroprevalence of HCV infection in South Korea by a large‐scale survey.

Change in Serum Hepatitis B Surface Antigen Level and Its Clinical Significance in Treatment-naïve, Hepatitis B e Antigen-positive Patients Receiving Entecavir

Background/Aim We investigated changes in hepatitis B surface antigen (HBsAg) level and its correlation with clinical outcomes in treatment-naive chronic hepatitis B (CHB) patients undergoing entecavir therapy. Patients and Methods Among 51 hepatitis B e antigen (HBeAg)-positive treatment-naive CHB patients receiving entecavir for more than 1 year, 28 were enrolled. HBsAg levels were measured at baseline, 6 months, and 12 months after treatment using the Architect HBsAg QT assay (Abbott, dynamic; range: 0.05 to 125,000 IU/mL). Serum alanine aminotransferase, HBeAg, anti-HBe, and hepatitis B virus (HBV) DNA (Cobas Taqman: low detection limit 1.84 log10 copies/mL) were measured at baseline and every 3 months. The HBsAg response was defined as an HBsAg level that decreased more than 1 log10 IU/mL from baseline level at 12 months after entecavir treatment. Results Twenty-eight patients were treated for a median period of 21 months (range: 18 to 24 mo). Serum HBsAg level showed a mean of 4.0, 3.7, and 3.6 log10 IU/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P<0.001). Serum HBV DNA level showed a mean of 8.1, 3.1, and 2.4 log10 copies/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P<0.001). The decline in HBsAg level was significantly correlated with that of the HBV DNA level at 12 months from baseline (γ=0.391, P=0.044). Five patients showed an HBsAg response, and cumulative incidence of HBeAg loss at 1 year after entecavir treatment was 80% versus 30% in patients with an HBsAg response and those without, respectively (P=0.034). Conclusions Monitoring changes in quantitative HBsAg level could be a useful parameter for assessing the response to entecavir therapy in HBeAg-positive treatment-naive CHB patients.

Epidemiology and clinical features of acute hepatitis A: from the domestic perspective

Acute viral hepatitis A has recently become a major public health problem in Korea, and the incidence of symptomatic hepatitis A is growing rapidly. With improvements in socioeconomic conditions and environmental hygiene, the chances of exposure to hepatitis A virus (HAV) during childhood have decreased and, in turn, the proportion of young adults with positive anti-HAV has significantly decreased. This has led to the incidence of symptomatic acute hepatitis A increasing since the late 1990s. The incidence of serious complications including fulminant hepatic failure and acute kidney injury has also showed an increasing trend. Variation of the genotype of virus isolated from recent hepatitis A patients suggests an inflow of the hepatitis virus from other countries. In this review article, we present the situation and epidemiology of hepatitis A in Korea, and recommend further investigation and policies for vaccination on a national level.

Serum cystatin C level is a good prognostic marker in patients with cirrhotic ascites and normal serum creatinine levels

Background/Aims: Serum creatinine (Cr) is not a reliable marker for early detection of renal dysfunction in patients with cirrhotic ascites. Several reports have suggested that cystatin C (CysC) is more sensitive than Cr for detecting reduced renal function in these patients. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and a normal serum Cr level.

Evolution of hepatitis B virus mutation during entecavir rescue therapy in patients with antiviral resistance to lamivudine and adefovir

BACKGROUND The efficacy of entecavir (ETV) monotherapy in treatment-experienced patients with chronic hepatitis B (CHB) is debatable. METHODS A total of 22 hepatitis B e antigen (HBeAg)-positive CHB patients who had shown viral breakthrough or suboptimal response with lamivudine (3TC) and adefovir disoproxil (ADV) therapy were treated with 1.0 mg of ETV. Clinical and virological parameters were monitored every 3 months. Restriction fragment mass polymorphism assays were used to detect antiviral resistance. RESULTS During 3TC and ADV therapy, 11 patients had rtM204V/I mutations, 2 had rtA181V/T or rtN236T, 7 had both and 2 had no 3TC- or ADV-related mutations. After switching to ETV monotherapy, the median change in serum hepatitis B virus (HBV) DNA level was -2.1 log(10) copies/ml. Virological response (HBV DNA<300 copies/ml) was achieved in 1 of 18 patients with pre-existing rt204 mutations, whereas it was achieved in all 4 patients without pre-existing rt204 mutations regardless of the presence of rt181 or rt236 mutations. Changes in mutational patterns during ETV therapy showed that rt204 mutations persisted or re-emerged. Relative abundances of rtM204V/I mutations in total viral populations gradually increased under ETV rescue, whereas those with rtA181V/T and rtN236T mutations decreased. ETV resistance mutations (rtL180M+rtT184I/L[rtS202G]+rtM204V) were detected in five patients with pre-existing rt204 mutations. CONCLUSIONS ETV monotherapy resulted in a limited virological response in patients who had previously failed 3TC and ADV rescue therapy. The limited efficacy might be associated with residual or reselected rtM204V/I mutations leading to ETV resistance. Combination treatment including potent antiviral agents should be recommended for patients with pre-existing rtM204V/I mutations.

Role of interleukin 28b-related gene polymorphisms in chronic hepatitis c and the response to antiviral therapy in koreans

Background: Genetic variations in interleukin 28B (IL28B) have been strongly associated with a sustained virological response (SVR) in European and African-American patients. Genetic variation of IL28B was investigated in healthy controls and chronic hepatitis C (CHC) patients, and the treatment response in the CHC patients was analyzed according to IL28B polymorphism in the Korean population. Methods: IL28B polymorphisms (rs12979860 and rs8099917) were studied in 200 healthy controls and in 167 CHC patients who were treated with peginterferon-&agr; and ribavirin. Results: The prevalence of rs12979860 in healthy controls is as follows: the CC-genotype was 88.5%, the CT-genotype was 11.5%, and the TT-genotype was not found. The prevalence of rs8099917 in healthy controls is as follows: the TT-genotype was 89.5%, the TG-genotype was 10.5%, and the GG-genotype was not found. The CC-genotype of rs12979860 and the TT-genotype of rs8099917 were found to be closely related (linkage disequilibrium; D′=1.0, &khgr; 2=0.9082). In 106 CHC patients treated with peginterferon and ribavirin, the SVR was 67.2% (n=58) for 1b, 91.6% (n=47) for 2a. In hepatitis C virus (HCV) genotype 1b with respect to rs12979860, the SVR in CC-genotype was 72.9% and that in CT-genotype was 40.0%. On investigating predictive factors for SVR, pretreatment low-HCV RNA levels, HCV genotype non-1, early virological response, and also the IL28B CC-genotype for rs12979860 were good indicators of an SVR. Conclusions: In Korea, genetic variation of IL28B is different from that in western countries in view of high prevalence of rs12979860 CC-genotype. It seems likely that a high SVR in Korean patients with genotype 1 CHC patients is due to the genetic polymorphism in IL28B.

HBsAg seroclearance in chronic hepatitis b: Implications for hepatocellular carcinoma

Goals and Background The long-term clinical course, including the development of hepatocelluar carcinoma (HCC) after hepatic B surface antigen (HBsAg) seroclearance is not established. We discovered that the incidence of HCC and the risk factors for HCC in chronic hepatitis B (CHB) patients after HBsAg seroclearance. Study During 28 years, 96 CHB patients with HBsAg seroclearance were retrospectively reviewed. These patients continued to undergo HCC surveillance. The median follow-up time from initial visit was 166.5 months (range, 7 to 321 mo). Results The mean age at the initial visit and at the time of seroclearance was 39.2±10.6 years and 46.4±9.9 years, respectively. The mean age at the time of HBsAg seroclearance was significantly lower (P=0.03) in patients with spontaneous HBsAg seroclearance than patients with treatment-associated HBsAg seroclearance. During a median of 56 months (range, 7 to 238 mo) of follow-up after HBsAg seroclearance, 6 (6.5%) patients developed HCC. The mean age at the time of developing HCC was 55.8±10.3 years. On univariate analysis, the evidence of liver cirrhosis from the time of HBsAg seroclearance and age more than 45 years at the time of HBsAg seroclearance were significant risk factors for HCC development. In multivariate analysis, the evidence of liver cirrhosis at HBsAg seroclearance was the only significant risk factor for HCC development. Conclusions HCC can develop after HBsAg seroclearance in patients with known cirrhosis. Patients who achieved HBsAg seroclearance at older age (>45) may have undiagnosed cirrhosis and hence remain at risk for HCC. HCC surveillance should be carried out for both of those patient populations.

Hepatitis B Viral Surface Mutations in Patients with Adefovir Resistant Chronic Hepatitis B with A181T/V Polymerase Mutations

The hepatitis B virus (HBV) polymerase gene has overlapping reading frames with surface genes, which allows to alter the amino acid codon of the surface genes. In adefovir (ADV) treated chronic hepatitis B patients carrying rtA181T/rtA181V mutations, overlap with surface gene mutations such as sW172stop/sL173F has been reported. However, the clinical consequences of such surface mutations have not been determined. The aim of this study was to determine the surface gene sequence in ADV-resistant patients carrying the A181T/V mutation and to describe the clinical significance. Of the 22 patients included in this study, 13 were ADV-resistant with rtA181T/V mutations (polymerase mutation group, Group P) and nine were antiviral treatment-naïve (control group, Group C). The Pre-S1 gene mutation, V60A, was detected in 11 patients (Group P=8, Group C=3). A start codon mutation in the Pre-S2 gene was found in five patients (Group P=3, Group C=2). An S gene mutation, sA184V, was found in nine patients, all of whom were in group P. Although sW172stop and sL173F mutations were detected, reduced HBsAg titer was not observed. Further study of these mutations and their clinical implications are needed.

BCLC stage B is a better designation for single large hepatocellular carcinoma than BCLC stage A

Although the Barcelona Clinic Liver Cancer (BCLC) staging system is widely used for hepatocellular carcinoma (HCC) staging, the most appropriate BCLC stage designation for single large HCC (SLHCC, single nodule > 5 cm) remains controversial. This study investigated the prognosis of patients with SLHCC.