Impact of prior lamivudine use on the antiviral efficacy and development of resistance to entecavir in chronic hepatitis B patients

BACKGROUND/AIMS: To determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naive chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance. METHODS: We retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naive patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance. RESULTS: Genotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naive group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance. CONCLUSIONS: ETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.

Vancomycin Pharmacokinetics in Oliguric Patients Undergoing Continuous Venovenous Hemodialysis and Continuous Venovenous Hemodiafiltration / 대한신장학회지

PURPOSE: Critically ill patients receiving continuous renal replacement therapy are susceptible to infection with methicillin-resistant bacteria, which require treatment with vancomycin. However, there are limited reports regarding vancomycin pharmacokinetics in the continuous venovenous hemodialysis (CVVHD) and continuous venovenous hemodiafiltration (CVVHDF). We performed this study to investigate the pharmacokinetics of vancomycin in oliguric patients receiving CVVHD and CVVHDF. METHODS: Data at steady-state obtained as part of our routine drug monitoring of vancomycin therapy in critically ill adult oliguric patients undergoing CVVHD or CVVHDF, retrospectively. Data were available for 35 cases of 23 patients assessed for 2 years. We analyzed the pharmacokinetic parameters of these cases. RESULTS: 8 cases on CVVHD and 27 cases on CVVHDF were available. The mean intensity of CVVHD was 17.7+/-4.9 mL/hour/kg and that of CVVHDF was 32.1+/-3.9 mL/hour/kg (p=0.000). The mean clearance of vancomycin was 16.4+/-3.8 mL/min in the CVVHD group and 21.6+/-5.1 mL/min in the CVVHDF group (P=0.007). The elimination of vancomycin correlated with the intensity of CVVHD and CVVHDF (CVVHD; r2=0.745, p=0.012, CVVHDF; r2=0.452, p=0.000). CONCLUSION: CVVHD and CVVHDF are effective for vancomycin elimination and there is a strong dependency of the vancomycin removal on the intensity of continuous renal replacement therapy. Strategies for individualization of vancomycin therapy in patients receiving CVVHD and CVVHDF are proposed.

A Case of Acute Renal Failure Complicated by the Poisoning of Amanita virgineoides / 대한신장학회지

Mushroom poisonings are potentially fatal. Most fatalities are due to the amatoxin that causes fulminant hepatic failure and acute renal failure. We report a patient who developed acute renal failure after ingesting Amanita virgineoides, which required renal replacement therapy, despite recovery of liver injury. A kidney biopsy showed acute tubular necrosis. The patient was recovered with the supportive care and temporary hemodialysis.

Factors associated with liver stiffness in chronic liver disease / 대한간학회지

BACKGROUND/AIMS: Transient elastography is a new noninvasive tool for measuring liver stiffness that accurately predicts significant fibrosis and cirrhosis. However, several studies have indicated that liver stiffness can be significantly influenced by major changes in aminotransferase in patients with chronic viral hepatitis. The aim of this study was to determine the factors influencing liver stiffness in patients with chronic liver disease. METHODS: We studied 158 patients with chronic liver disease who underwent transient elastography and liver biopsy sampling. Histologic findings on fibrosis and necroinflammatory activity in the biopsy specimens were evaluated according to the Korean Society of Pathologists Scoring System. Routine biochemical tests were performed according to standard methods. RESULTS: Liver stiffness was strongly correlated with liver fibrosis stage (Spearman coefficient=0.636, P<0.001), lobular activity (Spearman coefficient=0.359, P<0.001), and portoperiportal activity grade (Spearman coefficient=0.448, P<0.001). Liver stiffness was significantly associated with serum levels of total bilirubin (P=0.025), direct bilirubin (P=0.049), gamma-glutamyl transpeptidase (P=0.014), platelet count (P=0.004), albumin (P<0.001), and international normalized ratio (P<0.001). Multivariate analysis showed that fibrosis stage (B 3.50, P=0.009) and lobular activity grade (B 3.25, P=0.047) were independently associated with liver stiffness. CONCLUSIONS: Liver stiffness as measured by transient elastography is associated with the grade of necroinflammatory activity and the stage of fibrosis, irrespective of serum ALT levels.

Comparison of radiofrequency ablation and transarterial chemoembolization for the treatment of a single hepatocellular carcinoma smaller than 4 cm / 대한간학회지

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is an established curative therapeutic modality for unresectable hepatocellular carcinoma (HCC), and transarterial chemoembolization (TACE) has been used as a palliative treatment for inoperable HCC. It is still unknown whether RFA and TACE are equally effective for improving the survival of patients with unresectable HCC that is amenable to either treatment. The aim of this retrospective study was to compare the clinical impacts of two treatments, and analyze the prognostic factors for recurrence and survival. METHODS: Ninety-three patients with a single HCC smaller than 4 cm who showed complete responses (complete ablation or complete lipiodol tagging) after treatment with RFA (n=43) or TACE (n=50) between January 2002 and February 2009 were investigated. Univariate and multivariate analyses were performed for 13 potential prognostic factors using the Cox proportional-hazards model. RESULTS: The time-to-recurrence rates at 1, 2, and 3 years after treatment were 32.9%, 44.3%, and 55.4%, respectively, for the RFA group, and 42%, 68.3%, 71.7% for the TACE group. The probability of survival at 1, 2, and 3 years was 97.7%, 77.4%, and 63.1%, respectively, for the RFA group, and 95.9%, 76.1%, and 60.2% for the TACE group. The time-to-recurrence and overall survival rates did not differ significantly between the two treatment groups. A multivariate Cox proportional-hazards model revealed that a tumor size larger than 3 cm and lower serum albumin levels were independent risk factors for recurrence, and that being male, being seropositive for hepatitis B surface antigen, and having a higher serum albumin level were independent favorable prognostic factors for survival. CONCLUSIONS: TACE and RFA exhibited similar therapeutic effects in terms of recurrence and survival for patients with a single HCC smaller than 4 cm, if they could exhibited complete responses.

Direct Medical Costs of Type 2 Diabetic Patients in the Tertiary Hospital / 당뇨병

BACKGROUND: Type 2 diabetes mellitus is a common, chronic and costly disease. Its prevalence is rapidly increasing worldwide. Diabetes has big economic burden mainly because of its chronic complications. We analyzed the annual direct medical costs of type 2 diabetic patients, including the costs associated with its complications in Korea retrospectively. METHODS: We enrolled 531 type 2 diabetic patients who had been treated in the 3 Tertiary Hospital in 2005. Clinical characteristics, duration of diabetes, modality of glycemic control, and presence of microvascular and macrovascular complications were assessed by the review of medical records. The annual direct medical costs were assessed using the hospital electronic database and included insurance covered and uncovered medical costs. RESULTS: The annual direct medical costs of type 2 diabetic patients without any complications was 1,184,563 won (95% CI for mean: 973,006~1,396,121 won). Compared to diabetic patients without complications, annual total medical costs increased 4.7-fold, 10.7-fold, and 8.8-fold in patients with microvascular complications, macrovascular complications and both complications, respectively. Hospitalization costs largely increased by 78.7-fold and 61.0-fold in patients with macrovascular complications and both complications, respectively. Major complications to increase medical costs were kidney transplantation (23.1-fold), dialysis (21.0-fold), PTCA or CABG (12.4-fold), and leg amputation (11.8-fold). The total medical costs dramatically increased according to the stage of diabetic retinopathy and nephropathy. CONCLUSION: Diabetic complications have a substantial impact on the direct medical costs of type 2 diabetic patients. The prevention of diabetic complications will benefit the patients as well as the overall healthcare expenditures.