Publications (38) View all
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Article: Disease progression in chronic hepatitis C patients with normal alanine aminotransferase levels.
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ABSTRACT: AIM: To investigate whether the disease progression of chronic hepatitis C patients with normal alanine aminotransferase (ALT) levels differs by ALT levels. METHODS: A total of 232 chronic hepatitis C patients with normal ALT (< 40 IU/L) were analyzed. The patients were divided into "high-normal" and "low-normal"ALT groups after determining the best predictive cutoff level associated with disease progression for each gender. The incidence of disease progression, as defined by the occurrence of an increase of ≥ 2 points in the Child-Pugh score, spontaneous bacterial peritonitis, bleeding gastric or esophageal varices, hepatic encephalopathy, the development of hepatocellular carcinoma, or death related to liver disease, were compared between the two groups. RESULTS: Baseline serum ALT levels were associated with disease progression for both genders. The best predictive cutoff baseline serum ALT level for disease progression was 26 IU/L in males and 23 IU/L in females. The mean annual disease progression rate was 1.2% and 3.9% for male patients with baseline ALT levels ≤ 25 IU/L (low-normal) and > 26 IU/L (high-normal), respectively (P = 0.043), and it was 1.4% and 4.8% for female patients with baseline ALT levels ≤ 22 IU/L (low-normal) and > 23 IU/L (high-normal), respectively (P = 0.023). ALT levels fluctuated during the follow-up period. During the follow-up, more patients with "high-normal" ALT levels at baseline experienced ALT elevation (> 41 IU/L) than did patients with "low-normal" ALT levels at baseline (47.7% vs 27.9%, P = 0.002). The 5 year cumulative incidence of disease progression was significantly lower in patients with persistently "low-normal" ALT levels than "high-normal" ALT levels or those who exhibited an ALT elevation > 41 U/L during the follow-up period (0%, 8.3% and 34.3%, P < 0.001). CONCLUSION: A "high normal" ALT level in chronic hepatitis C patients was associated with disease progression, suggesting that the currently accepted normal threshold of serum ALT should be lowered.World Journal of Gastroenterology 04/2013; 19(14):2256-2261. · 2.47 Impact Factor -
Article: Steatosis Among Living Liver Donors Without Evidence of Fatty Liver on Ultrasonography: Potential Implications for Preoperative Liver Biopsy.
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ABSTRACT: BACKGROUND: The degree of steatosis is an important factor that determines the graft function in the recipient and the recovery of the remnant liver in the living donor. To date, there is no consensus regarding how to assess steatosis among potential living liver donors. We evaluate the prevalence and risk factors for steatosis in living liver donors with normal serum aminotransferase levels and without fatty liver on ultrasonography (US-negative). METHODS: The degree of steatosis was assessed for a total of 492 US-negative living liver donors with normal aminotransferase levels (age 30.1±9.9; male 301 [61.2%]). Total steatosis was defined by adding the degree of macrosteatosis and microsteatosis. RESULTS: No liver donor had a severe degree (≥60%) of macrosteatosis or microsteatosis. A moderate degree (30-59%) of macrosteatosis and microsteatosis was seen in 4 (0.8%) and 26 (5.3%) subjects, respectively. Severe and moderate degrees of total steatosis were seen in 3 (0.6%) and 53 (10.8%) subjects, respectively. Body mass index and serum triglyceride levels were independent factors associated with the moderate or greater degree of total steatosis. CONCLUSIONS: Noninvasive preoperative assessment for liver steatosis (US-negative with normal aminotransferase level) was sufficient to exclude severe macrosteatosis or microsteatosis and moderate macrosteatosis but not sufficient to exclude moderate microsteatosis or total steatosis in living liver donors.Transplantation 03/2013; · 4.00 Impact Factor -
Article: Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures.
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ABSTRACT: To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients after multiple failures. A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue (NA) treatments were included. Study subjects were treated with TDF alone (n = 13) or in combination with lamivudine (LAM, n = 12) or entecavir (ETV, n = 4) for ≥ 6 mo. Complete virologic response (CVR) was defined as an achievement of serum hepatitis B virus (HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment. Safety assessment was based on serum creatinine and phosphorus level. Eleven patients had histories of LAM and adefovir dipivoxil (ADV) treatment and 18 patients were exposed to LAM, ADV, and ETV. Twenty-seven patients (93.1%) were hepatitis B e antigen (HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL. The median treatment duration was 16 mo (range 7 to 29 mo). All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it. Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV. One patient had a resistance to both ADV and ETV. The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%, respectively. Although one patient failed to achieve CVR, serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL, achieving near CVR. No patients in this study showed viral breakthrough or primary non-response during the follow-up period. The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%, 12%, and 27% at 6, 12, and 18 mo of treatment, respectively. Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations. History of prior exposure to specific antiviral agents did not make a difference to treatment outcome. Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV. No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed. There were no other adverse events related to TDF therapy observed in the study subjects. TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.World Journal of Gastroenterology 12/2012; 18(47):6996-7002. · 2.47 Impact Factor -
Article: Pre-S Mutation Is a Significant Risk Factor for Hepatocellular Carcinoma Development: A Long-Term Retrospective Cohort Study.
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ABSTRACT: BACKGROUND: Several cross-sectional studies have shown an association between pre-S mutation and hepatocellular carcinoma (HCC). AIMS: We aim to verify whether pre-S mutation represents a risk for HCC development in a longitudinal way. METHODS: A total of 195 patients with chronic HBV infection [age: 43.7 ± 10.8 years, males: 141 (72.3 %), genotype C: 195 (100 %), hepatitis B e antigen (HBeAg) positive: 109 (55.9 %), cirrhosis: 79 (40.5 %), and pre-S mutation positive: 44 (22.6 %)] were followed up for a median of 7.2 years (range 1.0-7.8 years). RESULTS: HCC developed in 24 patients during follow-up. The 1-, 3-, and 5-year cumulative incidences of HCC were 0.5, 4.9, and 10.4 %, respectively. Patients with pre-S mutation had significantly higher 5-year cumulative incidences of HCC than those without (26.5 vs. 5.7 %, p < 0.001) and showed higher hazard ratio for HCC [3.04 (95 % CI 1.24-7.42), p = 0.015, adjusted for age, gender, HBeAg, cirrhosis and baseline HBV DNA level]. Notably, in patients aged ≥50 years, the 5-year cumulative incidences of HCC in patients with pre-S mutation were considerably high (58.3 %), compared to those without (16.1 %, p < 0.001). CONCLUSIONS: Patients with pre-S mutations had higher incidence of HCC during follow-up, especially in aged patients. Patients with pre-S mutations, especially older ones, may require careful attention to HCC development.Digestive Diseases and Sciences 09/2012; · 2.12 Impact Factor -
Article: Screening for Extrahepatic Metastases by Additional Staging Modalities is Required for Hepatocellular Carcinoma Patients Beyond Modified UICC Stage T1.
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ABSTRACT: Background/Aims: Accurate staging of hepatocellular carcinoma (HCC) is critical for guiding optimal treatment, and the presence of extrahepatic metastases (EHM) can seriously affect the optimal choice of treatment in the sorafenib era. However, there is limited data about when and how to screen EHM for newly diagnosed HCC patients, especially for patients without symptoms or signs of EHM. Methodology: We analyzed 314 newly diagnosed HCC patients who had no symptoms or signs of EHM and who had undergone additional modalities. Results: EHM was found in 50 of 314 patients (15.9%). Fifteen of 50 EHM (30%) were missed by conventional modalities but revealed by additional modalities. The frequency of EHM were 0% (0/26), 7.6% (10/131), 25.0% (30/120) and 27.0% (10/37) for the modified UICC stages T1, T2, T3 and T4, respectively (p<0.001). The proportions of EHM detected by additional modalities were 50% (5/10 EHM), 33% (10/30 EHM) and 0% (0/10 EHM) for modified UICC stages T2, T3 and T4, respectively. Conclusions: Application of additional staging modalities resulted in change of HCC stage in a significant proportion of HCC patients beyond modified UICC stage T1 by revealing EHM that had not been detected by conventional modalities.Hepato-gastroenterology 08/2012; 60(122). · 0.66 Impact Factor
