Eun Suk Jung

Comparison of the methods for tumor response assessment in patients with hepatocellular carcinoma undergoing transarterial chemoembolization

BACKGROUND & AIMS Recently, new methods, including the concept of viable enhancing tumor such as EASL and mRECIST, have been proposed for substitution of the conventional WHO and RECIST criteria in hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Herein, we evaluated the differences of four methods and compared the association of these methods with the prognosis of HCC patients undergoing TACE. METHODS We retrospectively reviewed 114 consecutive newly diagnosed HCC patients who underwent TACE as initial treatment. We evaluated the intermethod agreement (κ values) between the methods and compared their association with the prognosis of HCC patients. RESULTS The κ values for EASL vs. WHO, EASL vs. RECIST, mRECIST vs. WHO, and mRECIST vs. RECIST were low, of 0.102, 0.088, 0.112, and 0.122, respectively. However, good correlations were observed for WHO vs. RECIST and EASL vs. mRECIST (κ=0.883, κ=0.759, respectively p<0.001). The median OS was 32.3 months. Hazard ratios (HR) for survival in responders compared with non-responders were 0.21 (95% CI; 0.12-0.37, p<0.001) for EASL and 0.27 (95% CI; 0.15-0.48, p<0.001) for mRECIST. The mean survival of responders was significantly longer than that of non-responders in both EASL (40.8 vs. 16.9 months, p<0.001) and mRECIST (41.1 vs. 20.7 months, p<0.001). In multivariate analysis, EASL response (HR 0.21, 95% CI 0.11-0.40, p<0.001) and mRECIST response (HR; 0.31, 95% CI, 0.17-0.59, p<0.001) were independently associated with survival. CONCLUSIONS The response assessment by EASL and mRECIST could reliably predict the survival of HCC patients undergoing TACE and could be applicable in practice in preference to the conventional WHO and RECIST criteria.

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.

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.

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.

Comparison of the efficacies of lamivudine versus entecavir in patients with hepatitis B virus-related decompensated cirrhosis

Suppression of hepatitis B virus (HBV) DNA is more potent, and occurrence of resistant strain is rare with entecavir than lamivudine, but whether these merits result in a more favourable outcome in HBV‐related decompensated cirrhosis patients is unclear.

Usefulness of Non-invasive Markers for Predicting Significant Fibrosis in Patients with Chronic Liver Disease

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as ≥F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, α2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, α2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

Usefulness of non‐invasive markers for predicting liver cirrhosis in patients with chronic hepatitis B

Background and Aim:  Recently, various non‐invasive blood markers and indices have been studied to overcome the limitations of liver biopsy, such as its invasiveness and sampling errors. However, the majority of these studies have focused on patients with chronic hepatitis C. Accordingly, this study was performed to evaluate the significances of various non‐invasive serum markers in terms of predicting the presence of liver cirrhosis in chronic hepatitis B.

The relationship between hepatitis B virus infection and the incidence of pancreatic cancer: a retrospective case-control study

BACKGROUND/AIMS An association between past history of hepatitis B virus (HBV) infection and pancreatic cancer (PC) has recently been reported. We investigated whether HBV and hepatitis C virus (HCV) infections are associated with the development of PC in Korea. METHODS We retrospectively recruited patients with PC and sex- and, age-matched control patients with stomach cancer (SC) during the previous 5 years. Serum HBsAg and anti-HCV were examined, and data on smoking, alcohol intake, diabetes, and the history of chronic pancreatitis (CP) were collected. RESULTS A total of 506 PC and 1008 SC were enrolled, with respectively 58.1% and 97.3% of these cases being confirmed histologically. The mean age and sex ratio (male:female) were 63.5 years and 1.5:1 in the PC patients and 63.9 years and 1.5:1 in the SC patients respectively (P>0.05). The odds ratios (95% confidence interval, 95% CI) in univariate analysis were 0.90 (0.52-1.56; P=0.70) for HBsAg, 1.87 (0.87-4.01; P=0.11) for anti-HCV, 2.66 (2.04-3.48; P<0.001) for the presence of diabetes, 2.30 (1.83-2.90; P<0.001) for smoking, 1.14 (0.89-1.46; P=0.31) for alcohol intake, and 4.40 (1.66-11.66; P=0.003) for the history of CP. Independent risk factors for PC were presence of diabetes (OR, 2.67; 95% CI, 2.00-3.56; P<0.001), smoking (OR, 2.49; 95% CI, 1.93-3.21; P<0.001) and history of CP (OR, 4.60; 95% CI, 1.56-13.53; P=0.006). CONCLUSIONS There was no significant association between seropositivity for HBsAg or anti-HCV and PC. Further studies are warranted to clarify the association between HBV infection and PC in regions where HBV is endemic.

Significance of Anti-HCV Signal-to-Cutoff Ratio in Predicting Hepatitis C Viremia

Background/Aims Hepatitis C virus (HCV) RNA testing can be performed using qualitative or quantitative assays, and it is still unclear which is more useful as a primary test in patients positive for anti-HCV. The present study evaluated the usefulness of anti-HCV signal-to-cutoff ratio (S/CO ratio) for predicting HCV RNA results. Methods Patients on whom a qualitative HCV RNA test was performed due to a positive anti-HCV enzyme immunoassay were enrolled. Patients were divided into viremia and no-viremia groups according to HCV RNA results. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of anti-HCV S/CO for a diagnosis of viremia. Results In total, 487 patients were enrolled. HCV RNA was positive in 301 subjects (61.8%). Age, serum ALT level, and anti-HCV S/CO ratio were significantly different between the viremia and no-viremia groups. By ROC curve analysis, anti-HCV S/CO ratio (area, 0.989; 95% confidence interval, 0.981 to 0.998) accurately predicted the presence of viremia, with a cutoff value of 10.9 (sensitivity, 94.4%; specificity, 97.3%). Conclusions Anti-HCV S/CO ratio was found to be highly accurate at predicting HCV viremia. The anti-HCV S/CO ratio can be used to determine whether a quantitative or qualitative HCV RNA test should be used to confirm HCV viremia in patients with a positive anti-HCV by the following criteria: if the anti-HCV S/CO ratio is <10.9, a qualitative HCV RNA test can be used, and if the anti-HCV S/CO ratio is ≥10.9 a quantitative HCV RNA test can be performed.

Comparison of clevudine and entecavir for treatment-naive patients with chronic hepatitis B virus infection: two-year follow-up data.

Background/Aim Clevudine and entecavir are highly potent antiviral agents being used in treatment of chronic hepatitis B. However, no data comparing clinical efficacy and safety of these 2 drugs over a long-term period is available. The aims of this study are to compare virologic, biochemical, and serologic response rates of clevudine and entecavir, as well as treatment failure rates up to 2 years. Methods Data of patients who started clevudine (n=86) or entecavir (n=159) as a primary treatment for chronic hepatitis B at Korea University Ansan or Guro Hospital between January 2007 and June 2008 were analyzed. Results Treatment responses were compared at 3-month intervals up to 24 months. Per protocol analysis showed no difference in virologic responses between the 2 groups at all time points, except at 18 months. When analyzed on intention-to-treat basis for virologic response at 24 months, the response rates were 45.3% in the clevudine group and 72.3% in the entecavir group, which are significantly different (P<0.001). Rates of biochemical response and HBeAg seroconversion were not significantly different between the groups at all time points. Up to 24 months, antiviral resistance developed in 18 patients (24.4%) in the clevudine group. Clevudine was discontinued owing to muscle-related problems in 10 patients (11.6%). Conclusions Although both drugs showed potent antiviral activity, entecavir showed better virologic response at 24 months, primarily owing to treatment failures in the clevudine group that were associated with development of drug resistance and muscle-related problems.