-
[show abstract]
[hide abstract]
ABSTRACT: Since the introduction of lamivudine to treat chronic hepatitis B (CHB), the prevalence of lamivudine resistance is increasing among orthotopic liver transplant (OLT) candidates in Korea.
The purpose of this study was to evaluate the effect of pre-OLT lamivudine-resistance on the post-OLT prognosis of recipients.
Consecutive OLT recipient at a single tertiary care center (n = 8) between September 1999 and August 2009 were tested preoperatively for genotypic lamivudine resistance. We compared overall survival as well as incidences of graft failure, recurrent hepatitis, and hepatocellular carcinoma (HCC) between patients with (n = 35) versus without (n = 46) lamivudine-resistance.
Mortality occurred in 2 resistant and 3 nonresistant individuals. The occurrences of graft failure, recurrent hepatitis, and HCC were 1, 2, and 2 cases, respectively, in the resistance group versus 2, 2, and 2 cases, respectively, in the nonresistance cohort. Univariate analysis showed no significant difference in survival, graft failure, HCC occurrence, and recurrent hepatitis.
Our results indicated that pre-OLT lamivudine-resistance did not significantly affect the post-OLT prognosis. Thus, lamivudine-resistance may not be a barrier when considering OLT in patients with underlying CHB as a therapeutic modality, if it is treated with appropriate antiviral agents.
Transplantation Proceedings 01/2013; 45(1):231-5. · 1.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hepatitis B virus (HBV) recurrence following orthotopic liver transplantation (OLT) is generally preventable by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM). However, HBV recurrence sometimes develops despite prophylaxis. This study assessed posttransplant outcomes and identified predictors of HBV recurrence. We analyzed the outcomes of 209 consecutive patients positive for hepatitis B surface antigen who underwent OLT, who received either combination prophylaxis with HBIG and LAM (89.0%) or HBIG monoprophylaxis (11.0%). The median follow-up was 36.8 months (range, 1.0-84.4). Posttransplant HBV recurrence occurred in 22 patients (10.5%), including 13 patients with drug-resistant mutations. HBV recurrence was observed in six patients after hepatocellular carcinoma (HCC) recurrence. Independent predictors of HBV recurrence were recurrent HCC (p < 0.001), LAM therapy >1.5 years (p = 0.001) and high HBV DNA titers (> or =10(5) copies/mL) at OLT (p = 0.036). In conclusion, high viremia at OLT and prolonged exposure to LAM should be further stressed as main predictors of HBV recurrence.
American Journal of Transplantation 07/2010; 10(7):1649-59. · 6.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Acute hepatitis A (AHA) is one of the most common infectious diseases; it is usually a self-limiting disease affecting the liver. Although extrahepatic manifestations are not common, some cases have been reported associated with acute renal failure. We reviewed the clinical features of patients with AHA complicated by acute renal failure (ARF group) and compared them with patients with noncomplicated AHA (non-ARF group). The medical records of 208 consecutive patients with AHA who were diagnosed between January 2003 and October 2008 were reviewed. We identified 15 patients (7.2%) with ARF associated with AHA. There were no differences between the ARF and non-ARF group with regard to gender and age. The peak value of alanine aminotransferase (ALT) (median: 6060 IU/L vs 1792 IU/L, P < 0.001), prothrombin time (PT) (International normalized ratio, median 1.72 vs 1.10, P < 0.001), and total bilirubin level (median: 9.6 mg/dL vs 6.3 mg/dL, P = 0.04) were significantly higher in the ARF than in the non-ARF group. Twelve patients (80%) recovered completely with haemodialysis (seven patients, 46.7%) or only conservative management (five patients, 33.3%), while one patient underwent liver transplantation because of fulminant hepatic failure, and two patients died because of fulminant hepatic failure. There were no deaths among patients with noncomplicated AHA in the non-ARF group. Five patients underwent kidney biopsy; two patients were diagnosed with acute tubular necrosis, two patients with acute interstitial nephritis with IgA nephropathy and one patient with acute tubulointerstitial nephritis. All patients in the ARF group had microscopic haematuria and proteinuria (100%vs 31.1%, P < 0.001). Urine sodium levels were more than 10 mEq/L in 10 patients. The findings of high urinary sodium concentrations, microscopic haematuria and proteinuria did not support the diagnosis of hepatorenal syndrome (HRS). Patients with AHA with ARF had higher ALT levels, more prolonged PTs, and higher total bilirubin levels. The prognosis for these patients was poorer than for those without ARF. However, the patients with ARF and nonfulminant AHA had recovered with proper treatment and should not be confused with patients that have HRS.
Journal of Viral Hepatitis 10/2009; 17(9):611-7. · 4.09 Impact Factor
-
Jeong-Hoon Lee,
Donghee Kim, Hwa Jung Kim,
Chang-Hoon Lee,
Jong In Yang,
Won Kim,
Yoon Jun Kim,
Jung-Hwan Yoon,
Sang-Heon Cho,
Myung-Whun Sung,
Hyo-Suk Lee
[show abstract]
[hide abstract]
ABSTRACT: To optimize management of nonalcoholic fatty liver disease (NAFLD), a simple screening tool is necessary. In this study, we aimed to devise a simple index of NAFLD.
A cross-sectional study with 10,724 health check-up subjects (5362 cases with NAFLD versus age- and sex-matched controls) was conducted. Study subjects were randomly assigned to a derivation cohort or a validation cohort.
Multivariate analysis indicated that high serum alanine aminotransferase (ALT) to serum aspartate aminotransferase (AST) ratio, high body mass index (BMI), and diabetes mellitus were independent risk factors of NAFLD (all P<0.001). Using these variables, a formula was derived by a logistic regression model: hepatic steatosis index (HSI)= 8 x(ALT/AST ratio)+BMI (+2, if female; +2, if diabetes mellitus). HSI had an area under receiver-operating curve of 0.812 (95% confidence interval, 0.801-0.824). At values of <30.0 or >36.0, HSI ruled out NAFLD with a sensitivity of 93.1%, or detected NAFLD with a specificity of 92.4%, respectively. Of 2692 subjects with HSI <30.0 or >36.0 in the derivation cohort, 2305 (85.6%) were correctly classified. HSI was validated in the subsequent validation cohort.
HSI is a simple, efficient screening tool for NAFLD that may be utilized for selecting individuals for liver ultrasonography and for determining the need for lifestyle modifications.
Digestive and Liver Disease 09/2009; 42(7):503-8. · 3.05 Impact Factor
-
Y J Kim,
H Y Kim,
J S Kim,
J-H Lee,
J-H Yoon,
C Y Kim,
B L Park,
H S Cheong,
J S Bae,
S Kim,
H D Shin,
H-S Lee
[show abstract]
[hide abstract]
ABSTRACT: Previous studies showed that several genetic polymorphisms might influence the clinical outcome of chronic hepatitis B virus (HBV) infection, including HBV clearance or development of hepatocellular carcinoma (HCC). The aim of this study was to determine whether polymorphisms of the transforming growth factor-alpha (TGF-alpha) gene are associated with clinical outcome of HBV infection. A total of 1096 Korean subjects having either present or past evidence of HBV infection were prospectively enrolled between January 2001 and August 2003. Among 16 genetic variants in TGFA gene, nine variants were genotyped using TaqMan assay and the genetic association with HBV clearance and HCC occurrence was analysed. Statistical analyses revealed that TGFA+103461T>C, TGFA+106151C>G and TGFA-ht2 were marginally associated with clearance of HBV infection. However, only TGFA-ht2 retained significance after multiple correction (OR = 0.39, P(corr) = 0.007 in recessive model). Although no variants were significant after multiple correction, TGFA+88344G>A and TGFA+103461T>C were weakly associated in recessive model in the analysis of HCC occurrence. In addition, Cox relative hazards model also revealed that TGFA+88344G>A was associated with onset age of HCC occurrence in subjects (RH = 1.46, P(corr) = 0.04). TGF-alpha polymorphisms might be an important factor in immunity, progression of inflammatory process and carcinogenesis, which explains the variable outcome of HBV infection at least in part. Further biological evidence is warranted in the future to support these suggestive associations.
Journal of Viral Hepatitis 09/2009; 17(7):518-26. · 4.09 Impact Factor
-
J-H Lee,
J-H Yoon,
C-H Lee,
S J Myung,
B Keam,
B H Kim,
G E Chung,
W Kim, Y J Kim,
J J Jang,
H-S Lee
[show abstract]
[hide abstract]
ABSTRACT: To optimize management of chronic liver disease (CLD), a simple and noninvasive test to determine oesophageal varices (EV) and liver fibrosis is necessary. We performed a cohort study in a single tertiary care centre in order to devise a simple index reflecting EV and liver fibrosis. We derived an index reflecting EV which resulted from portal hypertension (the first part) and evaluated the index's ability to detect liver fibrosis which resulted in portal hypertension (the second part). Five hundred fifty-six patients (the first part, n = 409, mean age = 55.4 years, EV prevalence = 34.0%; the second part, n = 147, mean age = 48.8 years, cirrhosis prevalence = 12.9%) with virus-related CLD were included. P2/MS [(platelet count [10(9)/L])(2)/(monocyte fraction [%] x segmented neutrophil fraction [%])] was derived to detect EV. The area under the receiver-operating characteristic curve (AUROC) of P2/MS was 0.916 (95% confidence interval, 0.879-0.954) for detecting EV, and 0.905 (0.862-0.947) for detecting high-risk EV (grade >or= II or with red colour signs). P2/MS had AUROCs of 0.952 (0.904-0.999) and 0.873 (0.792-0.955) for histological cirrhosis (METAVIR F4) and significant fibrosis (METAVIR F2-F4), respectively, which were significantly greater than those of AST-to-platelet count ratio index (0.658, P < 0.001; 0.644, P = 0.003) and FIB-4 (0.776, P = 0.031; 0.707, P = 0.026). The predictive values of P2/MS were maintained at similar accuracy in subsequent validation sets. Our study suggests that P2/MS comprising only the complete blood count results is an efficient and noninvasive marker reflecting the presence of EV and the grade of liver fibrosis in patients with virus-related CLD. An independent external validation of P2/MS is required.
Journal of Viral Hepatitis 02/2009; 16(6):444-52. · 4.09 Impact Factor
-
H D Shin,
K S Park,
B L Park,
H S Cheong,
Y M Cho,
H K Lee,
J-Y Lee,
J-K Lee,
H T Kim,
B G Han,
J W Kim,
I Koh, Y J Kim,
B Oh,
K Kimm,
C Park
[show abstract]
[hide abstract]
ABSTRACT: Growing evidence supports the hypothesis that chronic low-grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses.
We have sequenced the gene, including all exons, exon/intron boundaries, and the -1.5 kb of the 5' flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study.
Eight polymorphisms, including four non-synonymous forms, were identified in CD14. No polymorphisms were found in association with T2DM. However, one common promoter SNP (-260T>C) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non-diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 +/- 0.81 vs. 1.46 +/- 0.80 mmol/l; P = 0.0007) and BMI (23.96 +/- 3.00 vs. 23.28 +/- 3.22 kg/m(2); P = 0.04) as compared with subjects carrying T/T genotypes.
Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism-mediated genetic propensity to non-specific inflammatory responses.
Diabetic Medicine 02/2006; 23(1):72-6. · 2.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objective: Hepatocellular carcinoma (HCC) is one of the most common cancers and is mainly caused by viral infections including hepatitis B virus (HBV). Recently, the decreased expression level of the transforming growth factor, beta receptor III (TGFBR3) gene, has been implicated in HCC and other human cancers. This study investigated whether TGFBR3 polymorphisms might be associated with HBV clearance and HCC occurrence. Methods: This study identified 27 single nucleotide polymorphisms (SNPs) in the exon, promoter, and exon-intron boundary regions of TGFBR3 by resequencing in 24 individuals. Then, 9 SNPs in the promoter and exons of the gene were genotyped from 1,065 Koreans composed of 637 chronic carriers (CC) and 428 spontaneously recovered (SR) subjects. Results: Two SNPs, rs1805113 (Phe676Phe) in exon 13 and rs1805117 in 3′-UTR (p = 0.009 and p = 0.008, respectively) were significantly associated with HBV clearance. In addition, Cox relative hazards analyses revealed that haplotype BL2_ht2 showed a significant association with the age of HCC occurrence among chronic HBV patients (relative hazard = 1.38; p = 0.007). Conclusion: Our findings suggest that TGFBR3 polymorphisms and its haplotypes might be associated with HBV clearance and age of HCC occurrence.
Digestive Diseases. 08/1970; 29(3):278-283.
