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1.  Endoscopic submucosal dissection for an atypical small verrucous carcinoma: a case report 
Background
Esophageal verrucous carcinoma is a rare variant of esophageal squamous cell carcinoma. In most cases, verrucous carcinoma presents as an exophytic, slow-growing mass with an extensive superficial growth pattern. Symptoms often include an insidious onset of dysphagia resulting in weight loss. In a patient presenting with super early-stage verrucous carcinoma, we were able to eliminate the aberration using endoscopic submucosal dissection.
Case presentation
An asymptomatic 68-year-old Asian man was found to have an abnormality in his esophagus. The abnormality was discovered, by chance, in a barium study for a health checkup. Esophagogastroduodenoscopy revealed a 1-centimeter polypoid lesion covered with squamous epithelium. Biopsies showed squamous high-grade intraepithelial neoplasia. An endoscopic submucosal dissection was performed and the histopathological findings showed a well-differentiated squamous cell carcinoma with hyperkeratosis with a church spire configuration. These features are consistent with the growth pattern of verrucous carcinoma.
Conclusions
Verrucous carcinoma can manifest as a small mass with nonclinical symptoms and endoscopic submucosal dissection is useful as a curative treatment. We must consider that verrucous carcinoma can manifest as appearance of a polyp that is not papillary or warty-like with and without extensive superficial growth appearance.
doi:10.1186/s13256-016-0866-y
PMCID: PMC4818443  PMID: 27036299
Verrucous carcinoma; Esophagus; Endoscopic submucosal dissection
2.  Centrilobular zonal necrosis as a hallmark of a distinctive subtype of autoimmune hepatitis 
Background and aim
Centrilobular zonal necrosis (CZN) is a known histological variant of autoimmune hepatitis (AIH). However, the significance of CZN is yet to be fully elucidated. This study aimed to determine whether CZN is a hallmark of a distinctive subtype of AIH.
Methods
Histological changes in the centrilobular zones of liver biopsies from 113 AIH patients were assessed by a single pathologist and classified into three categories: typical zonal necrosis defined as CZN (15 patients); other necroinflammatory change (NIC; 24 patients); and absence of necrosis (non-NIC; 74 patients). The clinicopathological features and immunogenetic background of CZN patients were then assessed.
Results
The clinicopathological features of AIH with CZN were distinct from other types of AIH, including a higher frequency of acute onset, lower frequency of antinuclear antibodies, lower antinuclear antibody titers, lower serum immunoglobulin G levels, lower grade interface hepatitis, less prominent lymphoplasmacytic infiltration, and lower AIH score. Increased and decreased frequencies of HLA-DR9 and HLA-DR4, respectively, were identified as immunogenetic features of AIH with CZN. Conversely, the clinicopathological characteristics of AIH with NIC were similar to those of non-NIC AIH, including the majority of the AIH patients. The therapeutic outcomes of AIH with CZN were excellent when precise diagnoses were made without delay.
Conclusion
The clinicopathological features and immunogenetic background of AIH with CZN differed from AIH without CZN. CZN may be a hallmark of a distinct subtype of AIH.
doi:10.1097/MEG.0000000000000545
PMCID: PMC4777223  PMID: 26657454
antinuclear antibody; autoimmune hepatitis; centrilobular zonal necrosis; HLA-DR antigen
3.  High level of serum cholesteryl ester transfer protein in active hepatitis C virus infection 
World Journal of Hepatology  2016;8(5):291-300.
AIM: To determine the significance of cholesteryl ester transfer protein (CETP) in lipoprotein abnormalities in chronic hepatitis C virus (HCV) infection.
METHODS: We evaluated the significance of the serum concentration of CETP in 110 Japanese patients with chronic HCV infection. Fifty-five patients had active HCV infection, and HCV eradication had been achieved in 55. The role of CETP in serum lipoprotein abnormalities, specifically, in triglyceride (TG) concentrations in the four major classes of lipoproteins, was investigated using Pearson correlations in conjunction with multiple regression analysis and compared them between those with active HCV infection and those in whom eradication had been achieved.
RESULTS: The serum CETP levels of patients with active HCV infection were significantly higher than those of patients in whom HCV eradication was achieved (mean ± SD, 2.84 ± 0.69 μg/mL vs 2.40 ± 1.00 μg/mL, P = 0.008). In multiple regression analysis, HCV infection status (active or eradicated) was an independent factor significantly associated with the serum CETP level. TG concentrations in low-density lipoprotein (mean ± SD, 36.25 ± 15.28 μg/mL vs 28.14 ± 9.94 μg/mL, P = 0.001) and high-density lipoprotein (HDL) (mean ± SD, 25.9 ± 7.34 μg/mL vs 17.17 ± 4.82 μg/mL, P < 0.001) were significantly higher in patients with active HCV infection than in those in whom HCV eradication was achieved. The CETP level was strongly correlated with HDL-TG in patients with active HCV infection (R = 0.557, P < 0.001), whereas CETP was not correlated with HDL-TG in patients in whom HCV eradication was achieved (R = -0.079, P = 0.56).
CONCLUSION: Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.
doi:10.4254/wjh.v8.i5.291
PMCID: PMC4757652  PMID: 26925203
Hepatitis C virus; Cholesteryl ester transfer protein; High-density lipoprotein triglyceride; Case control study; Lipoprotein metabolism
4.  Chronic hepatitis C virus infection and lipoprotein metabolism 
World Journal of Gastroenterology : WJG  2015;21(36):10299-10313.
Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic liver disease, including hepatocellular carcinoma, worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion, and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle, which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article, we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then, we review the outline of the processes of HCV assembly, secretion, and entry into hepatocytes, focusing on the association with lipoproteins. Finally, we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.
doi:10.3748/wjg.v21.i36.10299
PMCID: PMC4579877  PMID: 26420957
Hepatitis C virus; Apolipoprotein; Lipo-viral particle; Dyslipoproteinemia; Lipoprotein
5.  Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions 
Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.
doi:10.3390/ijms160920576
PMCID: PMC4613219  PMID: 26334270
chronic hepatitis C (CHC); hepatitis C virus (HCV); lipoprotein; triglyceride (TG); very-low-density lipoprotein (VLDL); VLDL sub-fractions
6.  Influencing factors on serum 25-hydroxyvitamin D3 levels in Japanese chronic hepatitis C patients 
BMC Infectious Diseases  2015;15:344.
Background
Serum 25-hydroxyvitamin D3 levels are generally lower in chronic hepatitis C patients than in healthy individuals. The purpose of this study is to clarify the factors which affect serum 25-hydroxyvitamin D3 levels using data obtained from Japanese chronic hepatitis C patients.
Methods
The subjects were 619 chronic hepatitis C patients. Serum 25-hydroxyvitamin D3 levels were measured by using double-antibody radioimmunoassay between April 2009 and August 2014. Serum 25-hydroxyvitamin D3 levels of 20 ng/mL or less were classified as vitamin D deficiency, and those with serum 25-hydroxyvitamin D3 levels of 30 ng/mL or more as vitamin D sufficiency. The relationship between patient-related factors and serum 25-hydroxyvitamin D3 levels was analyzed.
Results
The cohort consisted of 305 females and 314 males, aged between 18 and 89 years (median, 63 years). The median serum 25-hydroxyvitamin D3 level was 21 ng/mL (range, 6–61 ng/mL). On the other hand, the median serum 25-hydroxyvitamin D3 level in the healthy subjects was 25 ng/mL (range, 7–52), being significantly higher than that those in 80 chronic hepatitis C patients matched for age, gender, and season (p = 1.16 × 10−8). In multivariate analysis, independent contributors to serum 25-hydroxyvitamin D3 deficiency were as follows: female gender (p = 2.03 × 10−4, odds ratio = 2.290, 95 % confidence interval = 1.479–3.545), older age (p = 4.30 × 10−4, odds ratio = 1.038, 95 % confidence interval = 1.017–1.060), cold season (p = 0.015, odds ratio = 1.586, 95 % confidence interval = 1.095–2.297), and low hemoglobin level (p = 0.037, odds ratio = 1.165, 95 % confidence interval = 1.009–1.345). By contrast, independent contributors to serum 25-hydroxyvitamin D3 sufficiency were male gender (p = 0.001, odds ratio = 3.400, 95 % confidence interval = 1.635–7.069), warm season (p = 0.014, odds ratio = 1.765, 95 % confidence interval = 1.117–2.789) and serum albumin (p = 0.016, OR = 2.247, 95 % CI = 1.163–4.342).
Conclusions
Serum 25-hydroxyvitamin D3 levels in chronic hepatitis C Japanese patients were influenced by gender, age, hemoglobin level, albumin and the season of measurement.
doi:10.1186/s12879-015-1020-y
PMCID: PMC4543479  PMID: 26286329
Chronic hepatitis C; Vitamin D; 25-hydroxyvitamin D3
7.  Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C 
AIM: To evaluate interferon-λ3 (IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin (Peg-IFNα/RBV) therapy for genotype 2 (G2) chronic hepatitis C.
METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus (HCV) were treated with response-guided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response (RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype (TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV sub-genotype 2a or 2b.
RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response (SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate (96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5% (P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups (80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR (OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.
CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.
doi:10.3748/wjg.v21.i13.3904
PMCID: PMC4385537  PMID: 25852275
Hepatitis C virus genotype 2; Interferon-λ3 single nucleotide polymorphism; Pegylated-interferon plus ribavirin response-guided therapy; Rapid virologic response; Sustained virologic response
8.  Serum cytokeratin 18 fragment level as a noninvasive biomarker for non-alcoholic fatty liver disease 
Background and Aim: We evaluated the usefulness of serum cytokeratin 18 fragment (CK18-F) as a noninvasive biomarker in differentiating nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver (NAFL) since the prognosis of the 2 diseases differ. Methods: 116 Japanese patients with nonalcoholic fatty liver disease (NAFLD) proven by liver biopsy were studied. Histological findings were classified according to the NAFLD activity score (NAS) proposed by the Nonalcoholic Steatohepatitis Clinical Research Network. The correlation between histological findings and serum CK18-F levels was investigated. Results: Serum CK18-F levels showed a positive correlation with histologic steatosis (ρ = 0.271, P = 0.0033), inflammation (ρ = 0.353, P = 0.0005), ballooning (ρ = 0.372, P = 0.0001), and the total NAS (ρ = 0.474, P = 2.68 × 10-7). The serum CK18-F level was significantly lower for NAFL (NAS ≤ 2) than for borderline NASH (NAS of 3-4) or definite NASH (NAS ≥ 5) (P = 0.0294, P = 1.163 × 10-5, respectively). The serum CK18-F level was significantly higher for definite NASH than for borderline NASH (P = 0.0002). The area under the receiver operating characteristic curve of serum CK18-F to predict the presence of NAFL and definite NASH was 0.762 and 0.757, respectively. The optimal cut-off point of serum CK18-F for NAFL and definite NASH was 230 and 270 U/L, respectively. The sensitivity, specificity, positive predict value, and negative predict value of serum CK18-F for NAFL were 0.89, 0.65, 0.34, and 0.97, and those for definite NASH were 0.64, 0.76, 0.72, and 0.67, respectively. Accuracies of diagnosis for both NAFL and definite NASH were 0.70. Conclusions: Serum CK18-F could be a clinically useful biomarker to discriminate between NAFL and NASH.
PMCID: PMC4276188  PMID: 25550930
Nonalcoholic fatty liver disease (NAFLD); serum cytokeratin 18 fragment (CK18-F); nonalcoholic fatty liver disease activity score (NAS); nonalcoholic fatty liver (NAFL); definite nonalcoholic steatohepatitis (NASH)
9.  Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients 
We evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b) patients. This multicenter study involved 150 Asian treatment-naïve patients infected with HCV G1b who received 12 weeks of telaprevir in combination with 24 weeks of peginterferon-α-2b and ribavirin. The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis. Virological response was analyzed on an intent-to-treat basis. Cessation of the therapy due to adverse effects occurred in only 2 patients, who discontinued the trial at 10 weeks and at 2 weeks due to cerebral infarction and renal impairment, respectively. Among the 150 patients in whom the final virological response was determined, only genotype TT in rs8099917 was identified as a pretreatment predictor (P = 7.38 × 10−4). Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10−5). However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.
doi:10.1155/2014/549709
PMCID: PMC4150495  PMID: 25197269
10.  Elevation in Serum Concentration of Bone-Specific Alkaline Phosphatase without Elevation in Serum Creatinine Concentration Secondary to Adefovir Dipivoxil Therapy in Chronic Hepatitis B Virus Infection 
Of 168 patients with chronic hepatitis B virus (HBV) infection-related liver disease, 20 patients who had received 100 mg of lamivudine plus 10 mg/day of adefovir dipivoxil (ADV) (ADV group) and 124 patients who had received 0.5 mg/day of entecavir or 100 mg/day of lamivudine (non-ADV group) for >1 year were enrolled. For comparative analyses, 19 well-matched pairs were obtained from the groups by propensity scores. At the time of enrollment, serum creatinine and phosphate concentrations were similar between the ADV and non-ADV groups; however, urinary phosphate (P = 0.0424) and serum bone-specific alkaline phosphatase (BAP) (P = 0.0228) concentrations were significantly higher in the ADV group than in the non-ADV group. Serum BAP was significantly higher at the time of enrollment than before ADV administration in the ADV group (P = 0.0001), although there was no significant change in serum BAP concentration in the non-ADV group. There was a significant positive correlation between the period of ADV therapy and ΔBAP (R2 = 0.2959, P = 0.0160). Serum BAP concentration increased before increase in serum creatinine concentration and was useful for early detection of adverse events and for developing adequate measures for continuing ADV for chronic HBV infection-related liver disease.
doi:10.1155/2013/739247
PMCID: PMC3782837  PMID: 24106611
11.  Serum Lipoprotein Profiles and Response to Pegylated Interferon Plus Ribavirin Combination Therapy in Patients With Chronic HCV Genotype 1b Infection 
Hepatitis Monthly  2013;13(5):e8988.
Background
Abnormal serum lipid profiles have been noted in patients with chronic hepatitis C virus (HCV) infection. Moreover, many reports suggest that serum lipoprotein profiles are more profoundly distorted in patients with HCV G1b infection who have an unfavorable response to pegylated interferon (peg-IFN) plus ribavirin (RBV) combination therapy. However, after the discovery of single nucleotide polymorphisms near the IL28B gene (rs8099917 and rs12979860) as potent predictive factors affecting the response to peg-IFN plus RBV, lipid factors are thought to be confounding factors.
Objectives
To re-examine the significance of lipoprotein profiles on virological response to peg-IFN plus RBV combination therapy in patients with chronic HCV G1b infection, we examined cholesterol and triglyceride concentrations in each lipoprotein fraction separated by high performance liquid chromatography.
Patients and Methods
Lipoprotein profiles were examined using fasting sera from 108 patients infected with HCV G1b who had chronic hepatitis, as determined by liver biopsy. Results of lipoprotein profiles and clinical data, including IL28B genotype and amino acid substitution at aa70 of HCV G1b, were compared between patients with a sustained virological response (SVR) and non-SVR or a non-virological response (NVR) and virological responses other than NVR (non-NVR). In addition, significant predictive factors independently associated with virological response to peg-IFNα-2b plus RBV were determined by logistic regression analysis.
Results
An increased ratio of cholesterol/triglyceride in very low-density lipoprotein (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.01-9.44) along with a major genotype of rs8099917 (OR 9.09; 95% CI 2.94-33.33), were independent predictive factors for SVR. In contrast, lipid factors were not elucidated as independent predictive factors for NVR.
Conclusions
Examination of the fasting lipid profile has clinical importance in predicting the efficacy of peg-IFN-α-2b plus RBV combination therapy for patients with HCV G1b even after the discovery of the IL28 genotype as a potent predictive factor.
doi:10.5812/hepatmon.8988
PMCID: PMC3743300  PMID: 23967025
Hepatitis C; Ribavirin; Lipoproteins; Lipoproteins VLDL; Chromatography, High Pressure Liquid
12.  Alcohol, postprandial plasma glucose, and prognosis of hepatocellular carcinoma 
AIM: To identify factors associated with prognosis of hepatocellular carcinoma (HCC) after initial therapy.
METHODS: A total of 377 HCC patients who were newly treated at Katsushika Medical Center, Japan from January 2000 to December 2009 and followed up for > 2 years, or died during follow-up, were enrolled. The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis. A similar analysis was performed in 282 patients with tumor stage T1-T3. Additionally, factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence. Finally, 214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels, and differences in their causes of death were examined.
RESULTS: On multivariate Cox proportional hazards regression analysis, the following were significantly associated with survival: underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C, hazard ratio (HR): 0.603, 95% CI: 0.417-0.874, P = 0.0079], HCC stage (T1/T2 vs T3/T4, HR: 0.447, 95% CI: 0.347-0.576, P < 0.0001), and mean postprandial plasma glucose after initial therapy (< 200 vs ≥ 200 mg/dL, HR: 0.181, 95% CI: 0.067-0.488, P = 0.0008). In T1-T3 patients, uninterrupted alcohol consumption after initial therapy (no vs yes, HR: 0.641, 95% CI: 0.469-0.877, P = 0.0055) was significant in addition to underlying liver disease stage (non-cirrhosis/Child-Pugh A vs B/C, HR: 0649, 95% CI: 0.476-0.885, P = 0.0068), HCC stage (T1 vs T2/T3, HR: 0.788, 95% CI: 0.653-0.945, P = 0.0108), and mean postprandial plasma glucose after initial therapy (< 200 mg/dL vs ≥ 200 mg/dL, HR: 0.502, 95% CI: 0.337-0.747, P = 0.0005). In patients without local recurrence, time from initial to subsequent therapy for newly emerging HCC was significantly longer in the “postprandial glucose within 200 mg/dL group” than the “postprandial glucose > 200 mg/dL group” (log-rank test, P < 0.05), whereas there was no difference in the period between the “non-alcohol group” (patients who did not drink regularly or those who could reduce their daily consumption to < 20 g) and the “continuation group” (drinkers who continued to drink > 20 g daily). Of 214 T1-T3 patients who died during the observation period, death caused by other than HCC progression was significantly more frequent in “group AL” (patients in the continuation and postprandial glucose within 200 mg/dL groups) than “group N” (patients in the non-alcohol and postprandial glucose within 200 mg/dL groups) (P = 0.0016).
CONCLUSION: This study found that abstinence from habitual alcohol consumption and intensive care for diabetes mellitus were related to improved prognosis in HCC patients.
doi:10.3748/wjg.v19.i1.78
PMCID: PMC3542757  PMID: 23326166
Hepatocellular carcinoma; Prognosis; Alcohol consumption; Diabetes mellitus; Postprandial plasma glucose level; Initial therapy; Local recurrence; Survival
13.  Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C 
AIM: To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon α plus ribavirin for chronic hepatitis C.
METHODS: Five hundred and sixty-one Japanese patients with hepatitis C virus genotype 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction. Factors influencing significant anemia (hemoglobin concentration < 10.0 g/dL at week 4 of treatment) and significant hemoglobin decline (declining concentrations > 3.0 g/dL at week 4) were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors.
RESULTS: Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline: hemoglobin decline at week 2 [P = 3.29 × 10-17, odds ratio (OR) = 7.54 (g/dL)], estimated glomerular filtration rate [P = 2.16 × 10-4, OR = 0.962 (mL/min/1.73 m2)], rs1127354 (P = 5.75 × 10-4, OR = 10.94) and baseline hemoglobin [P = 7.86 × 10-4, OR = 1.50 (g/dL)]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia.
CONCLUSION: Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.
doi:10.3748/wjg.v18.i41.5879
PMCID: PMC3491594  PMID: 23139603
Chronic hepatitis C virus infection; Ribavirin; Pegylated interferon α; Prediction model; Hemolytic anemia; Single nucleotide polymorphism

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