BACKGROUND/AIMS: This study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection. METHODS: This retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/-2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment. RESULTS: SVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of < 800,000 IU/mL (p < 0.001), and a baseline platelet count of > 150 × 10³/µL (p < 0.001) were significant SVR predictors, regardless of the genotype. In particular, predictive accuracy for achievement of SVR was 87.3% for a baseline platelet count of > 150 × 10³/µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001). CONCLUSIONS Young age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.

BACKGROUND/AIMS: The aim of this study was to investigate parameters that predict radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to identify the clinical significance of RILD. METHODS: We retrospectively reviewed the medical records of 117 HCC patients who were treated by SBRT from March 2011 to February 2015. RILD was defined as elevated liver transaminases more than five times the upper normal limit or a worsening of Child-Pugh (CP) score by 2 within 3 months after SBRT. All patients were assessed at 1 month and every 3 months after SBRT. RESULTS: Median follow-up was 22.5 months (range, 3 to 56) after SBRT. RILD was developed in 29 of the 117 patients (24.7%). On univariate analysis, significant predictive factors of RILD were pretreatment CP score (p < 0.001) and normal liver volume (p = 0.002). Multivariate analysis showed that CP score was a significant predictor of RILD (p < 0.001). The incidence of RILD increased above a CP score of 6 remarkably. The rate of recovery from RILD decreased significantly above a CP score of 8. Survival analysis showed that CP score was an independent prognostic factor of overall survival (p = 0.001). CONCLUSIONS: CP score is a significant factor to predict RILD in patients with chronic liver disease. RILD can be tolerated by patients with a CP score ≤ 7. However, careful monitoring of liver function is needed for patients with a CP score 7 after SBRT.
Carcinoma, Hepatocellular* ; Follow-Up Studies ; Humans ; Incidence ; Liver Diseases* ; Liver* ; Medical Records ; Multivariate Analysis ; Radiosurgery ; Retrospective Studies ; Transaminases

No abstract available.

BACKGROUND/AIMS: The optimal timing for discontinuing oral antiviral therapy in patients with HBeAg-positive chronic hepatitis B (CHB) is unclear. The aim of our study was to investigate sustained remission after stopping antiviral therapy in patients with HBeAg-positive CHB. METHODS: We analyzed the medical records of 58 patients who were HBeAg-positive and had discontinued antiviral therapy. Antiviral therapy was discontinued after HBeAg seroconversion and HBV DNA negativity for 6-12 months with consolidation therapy. Virologic relapse was defined as an increase in serum HBV DNA >2,000 IU/mL. RESULTS: No difference was observed between the virologic non-relapse and virologic relapse groups in baseline HBV DNA level (p=0.441) or duration of seroconversion (p=0.070). Time-to-undetectable HBV DNA during treatment was shorter in the virologic non-relapse group (29 patients) compared to the relapse group (29 patients) (4.9+/-2.6 vs. 13.2+/-12.7 months; p<0.01). Cumulative relapse rates were 12.7 in month 3, 32.7 in month 6, 47.3 in month 12, and 52.7% in month 18. We determined by multivariate analysis that the consolidation period (> or =18 months, p=0.020) and early virologic response (HBV DNA <20 IU/mL) at six months during antiviral therapy (p=0.017) were significant predictors for sustained remission. CONCLUSIONS: A consolidation period of at least 18 months and early virological response at six months during antiviral therapy were associated with sustained remission in patients with HBeAg-positive CHB after treatment.
Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis ; Female ; Hepatitis B e Antigens/*blood ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Withholding Treatment

BACKGROUND/AIMS: Deficiencies of 25-hydroxyvitamin D (25(OH)D) are prevalent in patients with chronic liver disease (CLD). Liver fibrosis is the main determinant of CLD prognosis. The present study was performed to evaluate the correlation between 25(OH)D levels and liver fibrosis as assessed by transient elastography (TE) in patients with compensated CLD. METHODS: Serum 25(OH)D levels and liver stiffness were determined in a total of 207 patients who were subjected to the following exclusion criteria: patients with decompensated CLD; patients who had malignancies; patients who were taking medications; and patients who were pregnant. RESULTS: The most common etiology was chronic hepatitis B (53.1%). Advanced liver fibrosis (defined by TE [≥9.5 kPa]) was present in 75 patients (36.2%). There was a significant correlation between 25(OH)D deficiency and liver stiffness. Based on the multivariate analysis, the following factors were independently associated with advanced liver fibrosis: 25(OH)D deficiency (odds ratio [OR], 3.46; p=0.004), diabetes mellitus (OR, 3.04; p=0.041), and fibrosis-4 index (OR, 2.01; p<0.001). CONCLUSIONS: Patients with compensated CLD exhibit a close correlation between vitamin D level and liver stiffness as assessed by TE. Vitamin D deficiency was independently associated with advanced liver fibrosis.
Diabetes Mellitus ; Elasticity Imaging Techniques* ; Hepatitis B, Chronic ; Humans ; Liver Cirrhosis* ; Liver Diseases* ; Liver* ; Multivariate Analysis ; Prognosis ; Vitamin D ; Vitamin D Deficiency

BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) plays a pivotal role in the management of drug-resistant chronic hepatitis B. However, it remains unclear whether TDF-nucleoside analogue combination therapy provides better outcomes than TDF monotherapy. This study aimed to compare the efficacy of TDF monotherapy with that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B. METHODS: This retrospective cohort study included 76 patients receiving TDF-based rescue therapy for more than 12 months. Suboptimal response was defined as serum HBV-DNA level of >60 IU/mL during prior rescue therapy. Multi-drug resistance was defined as the presence of two or more drug resistance-related mutations confirmed by mutation detection assay. The relationship between baseline characteristics and virologic response (HBV DNA <20 IU/mL) at 12 months were evaluated using logistic regression analysis. RESULTS: Fifty-five patients (72.4%) were suboptimal responders to prior rescue therapy, and 26 (34.2%) had multi-drug resistance. Forty-two patients (55.3%) received combination therapy with nucleoside analogues. Virologic response at 12 months was not significantly different between the TDF monotherapy group and TDF-nucleoside analogue combination therapy group (p=0.098). The serum HBV DNA level was reduced to -4.49+/-1.67 log10 IU/mL in the TDF monotherapy group and to -3.97+/-1.69 log10 IU/mL in the TDF-nucleoside analogue combination therapy group at 12 months (p=0.18). In multivariate analysis, female sex (p=0.032), low baseline HBV-DNA level (p=0.013), and TDF monotherapy (p=0.046) were predictive factors for virologic response at 12 months. CONCLUSIONS: TDF monotherapy showed similar efficacy to that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B.
Adult ; Aged ; Antiviral Agents/pharmacology/*therapeutic use ; Cohort Studies ; DNA, Viral/blood ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Hepatitis B virus/drug effects/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Nucleosides/chemistry/therapeutic use ; Retrospective Studies ; Sex Factors ; Tenofovir/*therapeutic use ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: Chronic hepatocellular damage is closely associated with hepatic fibrosis and fatal complication in most liver diseases. The aim of this study is to compare the efficacy and safety of biphenyl dimethyl dicarboxylate (DDB) and ursodeoxycholic acid (UDCA) in patients with abnormal ALT. METHODS: One-hundred thirty-five patients with elevated ALT were randomized to receive either 750 mg/day of DDB or 300 mg/day of UDCA for 24 weeks in 4 referral hospitals. Ninety-three (69%) patients had non-alcoholic steatohepatitits, 27 (20%) had alcoholic hepatitis, and 15 (11%) had chronic hepatitis. The primary end point was the rate of ALT normalization at week 24. The secondary endpoints were changes in AST, liver stiffness, and the incidence of adverse events. RESULTS: A total of 101 patients completed 24 weeks of therapy. ALT normalization at week 24 was observed in 44 (80.0%) patients in DDB group and 16 (34.8%) in UDCA group (p<0.001). Higher mean reduction of ALT levels from baseline to 24 weeks was seen in DDB group compared with UDCA group (-70.0% vs. -35.9%, p<0.001). Normalization of AST level (p=0.53) and change in the liver stiffness (p=0.703) were not significantly different between the two groups. Severe adverse drug reaction occurred in 1 patient in DDB group but the subject continued therapy during the study period. CONCLUSIONS: DDB was not inferior to UDCA for normalizing ALT level. Furthermore it was safe and well tolerated by patients with abnormal ALT.
Adolescent ; Adult ; Aged ; Alanine Transaminase/*blood ; Cholagogues and Choleretics/*therapeutic use ; Dioxoles/*therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Hepatitis, Alcoholic/*drug therapy ; Hepatitis, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*drug therapy ; Tertiary Care Centers ; Treatment Outcome ; Ursodeoxycholic Acid/*therapeutic use ; Young Adult

BACKGROUND/AIMS: Lamivudine is an antiviral nucleoside analogue effective for the treatment of hepatitis B virus (HBV) infection via the inhibition of DNA polymerase activity. The mutations, however, in YMDD motif, such as YVDD and YIDD, have been found to interfere with the therapeutic efficacy of lamivudine. This study was performed to identify the role of such mutant-type HBV among Korean hepatitis B patients with chronic hepatitis or cirrhosis receiving lamivudine treatment. METHODS: Serum samples were collected from four groups of patients; patients with breakthrough (group I, n = 8); patients who showed no response after the treatment (group II, n = 6); patients who showed good response (group III, n = 6); patients with chronic hepatitis B without any treatment (group IV, n = 4). Mutations were detected by PCR-cloning and automated sequencing. RESULTS: Mutations in YMDD were found in only 4 (50%) in group I and were negative in group II. No mutations could be identified in the serum samples collected before treatment and from groups III and IV. YVDD mutation was found to be associated with two additional mutations, 'L-to-M' in 528th amino acid and 'L-to-V' in 577th amino acid. CONCLUSIONS: Lamivudine resistance appeared in three different patterns: (1) breakthrough related to the mutations in YMDD motif; (2) breakthrough not related to the YMDD mutations; and (3) primary non-responder not related to the YMDD mutations.
DNA ; Fibrosis* ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis B, Chronic* ; Hepatitis* ; Hepatitis, Chronic* ; Humans ; Lamivudine

Genetic changes between codons 2209 and 2248 of NS5A of genotype 1b hepatitis C virus (HCV-1b) have been reported to be associated with the sensitivity to interferon-alpha (IFN-alpha). The present study was performed to analyze such relationship in Korean patients with chronic hepatitis C and HCV-1b (n=19), including 12 chronic hepatitis C patients treated with IFN-alpha, 3 chronic hepatitis C patients without treatment as controls, and 4 patients with hepatocellular carcinoma (HCC). Two serum samples, before and after the treatment, were analyzed for the mutations by reverse transcription-polymerase chain reaction, cloning and sequencing. The mutations were identified in 32% (6/19), including five intermediate type (1-3 mutations) and one mutant type (4 or more). In 12 patients treated with IFN-alpha, the number of amino acid substitutions in NS5A2209-2248 was not associated with outcome of the treatment.
Adult ; Aged ; Amino Acid Sequence ; Antiviral Agents/therapeutic use* ; Base Sequence ; Carcinoma, Hepatocellular/virology* ; Carcinoma, Hepatocellular/blood ; Codon ; Female ; Genotype ; Hepatitis C, Chronic/virology* ; Hepatitis C, Chronic/drug therapy* ; Hepatitis C, Chronic/blood ; Hepatitis C-Like Viruses/isolation & purification ; Hepatitis C-Like Viruses/genetics* ; Hepatitis C-Like Viruses/classification ; Human ; Interferon-alpha/therapeutic use* ; Liver Neoplasms/virology* ; Liver Neoplasms/blood ; Male ; Middle Age ; Molecular Sequence Data ; Mutation* ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction