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Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO2) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO2 was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO2 (β = -0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.

Background Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. This study aimed to investigate the associations between SAF and MACE risk in patients with HF who underwent CR. Methods This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. Major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2017. Results Patients’ mean age was 68.1 years, and 61% were male. Patients were divided into two groups according to the median SAF levels (High and Low SAF groups). Patients in the High SAF group were significantly older, had a higher prevalence of chronic kidney disease, and more frequently had history of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a mean follow-up period of 590 days, 18 patients had all-cause mortality and 36 were hospitalized for HF. Kaplan–Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P Conclusion SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who underwent CR.

Background: The frailty state consists of not only physical but also psycho-emotional problems, such as cognitive dysfunction and depression as well as social problems. However, few reports have examined the relationship between frailty and anxiety levels in elderly patients undergoing cardiac rehabilitation (CR). Methods: We analyzed 255 patients (mean age: 74.9 ± 5.8 years, 67% male) who participated in early phase II CR at Juntendo University Hospital. At the beginning of CR, patients carried out self-assessments based on the Kihon Checklist (KCL) and the State Trait Anxiety Inventory Form (STAI). Patients were divided into three groups: frailty group (n = 99, 39%), pre-frailty group (n = 81, 32%), and non-frailty group (n = 75, 29%) according to the KCL. We assessed results from the KCL scores and its relationship with anxiety levels. Results: Among the three groups, there were no significant differences in age, underlying illnesses, or the prevalence of coronary risk factors. Depressive mood domains of the KCL were significantly higher in the frailty and pre-frailty groups than in the non-frailty groups (3.0 ± 1.5 vs. 1.4 ± 1.2 vs. 0.4 ± 0.6; P < 0.01). The state anxiety level was significantly higher in the frailty group than in the non-frailty group (41.6 ± 0.9 vs. 34.9 ± 1.0; P < 0.01). The trait anxiety levels were significantly higher in the frailty group and pre-frailty group than in the non-frailty group (45.5 ± 0.9 vs. 39.2 ± 1.0 vs. 35.1 ± 1.1; P < 0.01). State anxiety and trait anxiety also showed a significantly positive correlations with the KCL scores (r = 0.32 vs. 0.41, P < 0.01). Conclusions: Frailty scores were positively correlated not only with physical function but also with depression mood and anxiety levels in elderly patients undergoing early phase II CR. These results suggest that assessment of depressive mood and anxiety is also important in elderly patients undergoing early phase II CR. Cardiol Res. 2020;11(6):405-411 doi: https://doi.org/10.14740/cr1165

Objective The aim of this study was to examine whether preoperative phase angle (PhA) measured by bioelectrical impedance analysis was associated with a hospital-acquired functional decline in older patients undergoing cardiovascular surgery. Methods This was an observational study of prospectively collected data of 114 patients (>65 y of age) with cardiovascular disease who underwent elective cardiovascular surgery between September 2019 and August 2020. Patients were classified into tertiles based on PhA levels. Factors associated with the occurrence of hospital-acquired functional decline (postoperative recovery to preoperative physical function was not possible) were analyzed using univariate and multivariate analyses. Results Patients in the low PhA group were significantly older than those in the middle and high PhA groups; were predominantly women; had higher New York Heart Association cardiovascular and EuroSCORE severity scores; and had significantly lower levels of body mass index, Geriatric Nutritional Risk Index, hemoglobin, and albumin. There was a significant correlation between PhA and nutrition and physical function. The incidence of hospital-acquired functional decline occurred in 26.3% of all patients, with a significantly higher incidence in patients in the low PhA group. Multivariate analysis showed that PhA was extracted as a factor for the hospital-acquired functional decline in all the models. Conclusions PhA was associated with hospital-acquired functional decline in older patients undergoing cardiovascular surgery. PhA is likely to be a comprehensive indicator of physical health that indicates nutritional status, physical function, and geriatric syndrome (frailty/sarcopenia), and is an important predictor of hospital-acquired functional decline in this group of older patients.

Background: The Japanese Ministry of Health, Labour and Welfare reported that the overall constipation complaint rates among men and women are 2.5% and 4.6%, respectively. To evaluate the impact of constipation on patients with cardiovascular diseases, we investigated the association between constipation and frailty components in patients undergoing cardiac rehabilitation (CR). Methods: We enrolled 102 consecutive patients undergoing late phase II CR (mean age: 62.7 ± 13.4 years; 68 (67%) were men). We investigated clinical characteristics, observed defecation status and evaluated frailty components assessed by the Kihon checklist. According to the Clinical Guidelines for Chronic Constipation, the subjects were divided into constipation and non-constipation groups. Results: Constipation was noted in 33 patients (32%). Interestingly, the constipation complaint rate was only 15%. Age was significantly higher in the constipation group than in the non-constipation group; however, no differences in sex, underlying diseases and prevalence rates of coronary risk factors were observed between the two groups. Body mass index, hemoglobin level, albumin level and estimated glomerular filtration rate were significantly lower in the constipation group than in the non-constipation group. The prevalence of frailty was significantly higher in the constipation group than in the non-constipation group. Physical ability, seclusion and depression scores were significantly higher in the constipation group than the non-constipation group. Conclusions: Constipation was associated with physical function and depression score as components of frailty in patients undergoing CR. Cardiol Res. 2021;12(3):169-176 doi: https://doi.org/10.14740/cr1246

Background Peak oxygen uptake (peak VO2) and heart rate reserve (HRR) are independent prognostic markers of cardiovascular disease. However, the impact of peak VO2 and HRR on long‐term prognosis after off‐pump coronary artery bypass grafting (OP‐CABG) remains unclear. Hypothesis To determine the prognostic impact of peak VO2 and HRR in patients after OP‐CABG. Results We enrolled 327 patients (mean age, 65.1 ± 9.3 years; male, 80%) who underwent OP‐CABG and participated in early phase II cardiac rehabilitation. All participants underwent cardiopulmonary exercise testing (CPET) at the beginning of such rehabilitation. Overall, 48 (14.6%) patients died during the median follow‐up period of 103 months. The non‐survivor had significantly lower levels of peak VO2 (10.6 ± 0.5 vs. 13.7 ± 0.2 ml/kg/min, p

Background Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD. Methods We enrolled 319 consecutive CVD patients aged ≥40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF). Results The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P P P = 0.02). Conclusion High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM.

The aim of this study is to ascertain whether the TLL1 variant at rs17047200 is associated with the development of HCC after achieving sustained virological response (SVR) by interferon (IFN)-free therapy for chronic hepatitis C (CHC). A total of 1029 Japanese CHC patients with the following inclusion criteria were enrolled: (i) achieved SVR by IFN-free therapy, (ii) followed up at least 1 year from the end of treatment (EOT) (median 104 weeks), (iii) no history of hepatocellular carcinoma (HCC) by 1 year from the EOT. Nineteen patients developed HCC (HCC group) and 1010 did not (non-HCC group). The proportion of rs17047200 AT/TT was significantly higher in the HCC group than the non-HCC group (47.4% vs. 20.1%, P = 0.008). Multivariate analysis showed that higher levels of α-fetoprotein, FIB-4 and rs17047200 AT/TT were independent risk factors for developing HCC (HR = 3.22, P = 0.021 for α-fetoprotein > 4.6 ng/ml; HR = 3.89, P = 0.036 for FIB-4 > 2.67; HR = 2.80, P = 0.026 for rs17047200 AT/TT). Cumulative incidence of HCC was significantly higher in patients with rs17047200 AT/TT than in those with AA (P = 0.006). Comparing clinical characteristics according to the TLL1 genotypes, patients with rs17047200 AT/TT had significantly lower platelet counts and higher levels of FIB-4 than those with AA (P = 0.011 and 0.032, respectively). The TLL1 variant was independently associated with HCC development after HCV eradication by IFN-free regimen. It might be involved in hepatic fibrogenesis and thereby carcinogenesis.

This study aimed to assess the association between the serum glycobiomarker Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) for liver fibrosis and outcomes and carcinogenesis of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients with advanced fibrosis. Serum WFA+-M2BP levels were measured in 128 consecutive CHC patients including 49 with HCC histopathologically diagnosed with advanced fibrosis (44 with fibrosis stage F3 and 84 with fibrosis stage F4) in our hospital. The median WFA+-M2BP level was significantly higher in F4 than in F3 patients (6.9 vs. 2.3 cutoff index [COI], respectively; p

Aim This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy. Methods Overall, 530 Japanese patients who were infected with hepatitis C virus genotype 1 received SOF/LDV therapy for 12 weeks, and resistance-associated variants (RAVs) in the hepatitis C virus non-structural protein (NS)5A and NS5B regions were assessed at baseline and virological relapse by direct sequencing. Results Sustained virological response (SVR) rates did not significantly differ between patients with and without NS5A Y93H/N (94.2% [113/120] vs. 97.7% [345/353]), but the SVR rate was significantly lower in patients with prior DCV/ASV therapy compared to those without (69.2% [18/26] vs. 98.4% [496/504], P

Background Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. Purpose The purpose of this study was to investigate the prognostic value of SAF levels in patients with HF who underwent CR. Methods This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. The major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2018. Results Patients' mean age was 68.1 years, and 61% were males. Patients were divided into two groups according to the median SAF levels (high and low SAF groups). Patients in the high SAF group were significantly older, had a higher prevalence of chronic kidney disease, and histories of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a median follow-up period of 623 days, 25 patients experienced all-cause mortality and 34 were hospitalized for HF. Kaplan–Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P Figure 1 Conclusion SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who undergo CR.

The present study explored the treatment outcome of daclatasvir (DCV) and asunaprevir (ASV) therapy combining oral direct-acting antiviral agents (DAAs) for chronic hepatitis C (HCV) including liver cirrhosis according to resistance-associated variants (RAVs) in NS3/NS5A region. Overall, 641 patients enrolled in Japan with HCV-1b received DCV and ASV for 24 weeks. Baseline drug-resistant mutations L31F/I/M/V, Q54H, P58S, A92K, and Y93H in the HCV NS5A region and V36A, T54A/S, Q80K/L/R, R155K/T/Q, A156S/V/T, and D168A/E/H/T/V in the HCV NS3/4A region were assessed by direct sequencing. Overall, 86.9 % (543/625) of patients had SVR12, which was significantly higher in NS5A 93Y (wild) (88.3 %) compared with NS5A 93H at baseline (48.0 %), indicating the SVR12 rate was significantly lower in patients with 93H mutations. Additionally, 66.7 % (18/27) of patients with prior triple therapy including simeprevir (SMV) failure had virological failure. The virological failure rate of DCV/ASV therapy after SMV failure was significantly higher in those with preexisting NS3/4A 168 substitutions compared with without substitutions at baseline [84.2 % (16/19) vs. 28.6 % (2/7), p = 0.014]. The number of patients with multiple RAVs or deletions in NS5A increased from 0 to 85 % in failed patients. Alanine aminotransferase elevation was a frequent adverse event causing discontinuation of DCV/ASV therapy, although 87.5 % (14/16) patients achieved SVR12, subsequently. History of SMV therapy and pre-existing NS5A Y93H were associated with virological failure of DCV/ASV therapy, resulting in the emergence of multiple RAVs. Patients with RAVs at baseline should be assessed to optimize future DAA therapies.

Highlights • Intraperitoneal free air can be induced by pneumothorax and pneumomediastinum. • This is the massive intraperitoneal free air by pneumothorax and pneumomediastinum. • Air dissects its way downwards along the esophagus and aorta into the retroperitoneal tissues. • Deterioration of traumatic pneumothorax and/or occurrence of pneumomediastinum after mechanically ventilation is the most considerable reason of the PP in the present case., Introduction Pneumoperitoneum (PP), or air within the abdominal cavity, is frequently a harbinger of serious abdominal pathology and often represents visceral perforation. We herein report a case of combined massive intraperitoneal free air, pneumothorax and pneumomediastinum but emergency laparotomy was negative. Presentation of case A sixty-seven-year-old man was found unconscious on a road after being hit by a car. On arrival, he showed swelling of the head and flail chest. Computed tomography (CT) demonstrated cerebral contusion, multiple bilateral rib fractures, minute subcutaneous emphysema and a left hemothorax. As his consciousness and respiratory function deteriorated, tracheal intubation with mechanical ventilation with positive end-expiratory pressure was executed on the second day. On the third day, the CT scan revealed the new appearance of pneumomediastinum and massive free air in his intraperitoneal space. Emergency laparotomy was negative. Discussion The ‘air leak’ phenomenon, in which an alveolar air cell ruptures into the perivascular and peribronchial interstitial tissues, is a well-recognized consequence of positive end-expiratory pressure therapy. Accordingly, the deterioration of traumatic pneumothorax and/or the occurrence of pneumomediastinum after mechanical ventilation was the most likely cause of the PP in the present case. However, it remains possible that a minute unrecognized diaphragmatic injury caused the massive PP in the present case. Conclusion We herein described a case of PP that occurred after mechanical ventilation in a patient with multiple injuries, but which did not originate from perforation of the gastrointestinal tract. It is most likely that the PP had an intrathoracic cause.

The patient was a 60-year-old male fell whose head and left chest hit the ground after falling from a height of 2 m. He complained of the left shoulder and chest pain after regaining consciousness. On arrival, he showed left bloody otorrhea, left chest tenderness, and a limited range of motion due to the left shoulder pain. Emergency chest roentgenography revealed multiple left rib fractures, left clavicular fracture with decreased radiolucency in the left lung field, suggesting lung contusion. When the patient was being transported for computed tomography, he suddenly displayed ventricular tachycardia with pulse and subsequently became VF storm, which required percutaneous cardiopulmonary support. The coronary angiogram showed complete obstruction of the branch of the anterior descending artery. Coronary angioplasty resulted in recanalization; however, massive hemorrhage from the left ear was recognized. Computed tomography revealed traumatic subarachnoid hemorrhage and left massive hemothorax requiring thoracostomy. Massive hemorrhage from the left ear and left thoracic cavity continued after the patient was transported to the coronary care unit. He underwent massive transfusion; however, he died on the same day.

AIM The Kihon Checklist is a useful screening tool for assessing frailty in older individuals. However, the clinical significance of the Kihon Checklist in cardiac rehabilitation patients remains unclear. The present study aimed to evaluate the relationship between the Kihon Checklist and the clinical parameters in patients who participated in cardiac rehabilitation. METHODS We enrolled 845 consecutive patients (584 men, mean age 71 years) who participated in cardiac rehabilitation at Juntendo University Hospital, Tokyo, Japan, between November 2015 and October 2017. The patients were divided into non-frailty (n = 287), pre-frailty (n = 270) and frailty (n = 288) groups according to their Kihon Checklist scores. Cardiopulmonary exercise testing was carried out in 302 patients. RESULTS The frailty group was older and had a higher prevalence of history of heart failure than the non-frailty group, although left ventricular ejection fraction did not differ significantly between groups. Nutritional index, trunk and limb muscle mass, lean body weight, and grip strength were significantly lower in the frailty and pre-frailty groups than those in the non-frailty group. In the cardiopulmonary exercise test, a stepwise significant decrease in peak oxygen uptake was observed across the three groups (non-frailty 17.2 ± 3.6, pre-frailty 16.0 ± 3.4, frailty 14.4 ± 3.5 mL/kg/min, P

Recently, we identified a novel liver fibrosis glycobiomarker, Wisteria floribunda agglutinin (WFA)-reactive colony stimulating factor 1 receptor (WFA(+) -CSF1R), using a glycoproteomics-based strategy. The aim of this study was to assess the value of measuring WFA(+) -CSF1R levels for the prognosis of carcinogenesis and outcome in liver cirrhosis (LC) patients with hepatitis C virus (HCV). WFA(+) -CSF1R and Total-CSF1R levels were measured in serum samples from 214 consecutive HCV-infected patients to evaluate their impact on carcinogenesis and the survival of LC patients. Serum WFA(+) -CSF1R levels were significantly higher in LC patients than chronic hepatitis (CH) patients (p < 0.001). The AUC of WFA(+) -CSF1R for predicting overall survival, calculated by time-dependent ROC analysis, was 0.691 and the HR (per 1-SD increase) was 1.80 (95% CI, 1.23-2.62, p < 0.001). Furthermore, the survival rate of LC patients with high WFA(+) -CSF1R levels (≥ 310 ng/ml) was significantly worse than those with lower levels (p < 0.01). The AUC of WFA(+) /total-CSF1R percentage (WFA(+) -CSF1R%) for predicting the cumulative carcinogenesis rate was 0.760, with an HR of 1.66 (95% CI 1.26-2.20, p < 0.001). In fact, the carcinogenesis rate was significantly higher in LC patients with a high WFA(+) -CSF1R% (≥ 35%, p = 0.006). Assessing serum levels of WFA(+) -CSF1R has diagnostic value for predicting carcinogenesis and the survival of LC patients.

Although the shortened dental arch (SDA) concept has been known to all over the world, acceptance of the SDA concept as an oral health standard can be questionable from the patients' point of view, even if it is biologically reasonable. Furthermore, because the health insurance system covers removable partial dentures (RPDs) for all citizens in Japan, SDA patients seem to prefer to receive prosthetic treatment to replace the missing teeth. However, there were few field surveys to investigate the usage rate of RPDs in Japan. The purpose of this study was to determine the usage rate of RPDs in older Japanese subjects and to investigate the factors related to the usage of RPDs. Partially edentate participants (n = 390) were included in this study. Oral examinations were conducted to record several indices. The Cochran-Armitage trend test was used to evaluate the relationship between the number of missing teeth and the usage rate of RPDs. Chi-squared tests and logistic regression analysis were conducted to evaluate the factors related to the usage rate of RPDs. Usage of RPDs had a significantly positive association with the number of missing distal extension teeth and bilaterally missing teeth. The usage rate of RPDs increased as the number of missing distal extension teeth increased (P for trend

Aim Serum low-density lipoprotein cholesterol (LDL-C) increases during treatment of chronic hepatitis C (CHC) with interferon-free direct-acting antivirals (DAAs). We sought to compare the changes of serum lipid profiles caused by three regimens. Methods A total of 216 CHC patients were enrolled. Among 170 patients infected with hepatitis C virus (HCV) genotype 1b, 85 received daclatasvir plus asunaprevir (DCV/ASV) and 85 received sofosbuvir plus ledipasvir (SOF/LDV). Forty-six infected with HCV genotype 2 received sofosbuvir plus ribavirin (SOF/RBV). Serum total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol, and triglyceride were measured at baseline and 4, 8, 12 (for all regimens), and 24 weeks (for DCV/ASV) during treatment (4w, 8w, 12w, and 24w, respectively) and 12 and 24 weeks after treatment (p12w and p24w, respectively). Results In 69 (81.2%) patients who received DCV/ASV and achieved a sustained virologic response at 24 weeks after the end of treatment (SVR24), TC and LDL-C increased significantly from baseline to p24w. In 84 (98.8%) treated with SOF/LDV who achieved SVR24, TC and LDL-C increased significantly from baseline to 8w, and TC decreased significantly from 8w to p12w. The 45 (97.8%) who received SOF/RBV and achieved SVR24 showed no significant changes. At 12w, TC and LDL-C increased to a greater degree in patients receiving SOF/LDV than in those receiving DCV/ASV or SOF/RBV. Conclusion During treatment with DAAs, the serum lipid profile may reflect not only recovery from the disruption of lipid metabolism induced by HCV, but also the pharmacological effects of DAAs. Further investigations are needed to elucidate the effect of DAAs on serum lipid profiles.

AIM Several studies have shown that high pretreatment concentrations of serum interferon-γ-inducible protein-10 (IP-10) are correlated with non-response to pegylated interferon (PEG-IFN) plus ribavirin (RBV) for chronic hepatitis C (CHC). However, there are few reports on their effect on the Asian population. METHODS We enrolled 104 Japanese genotype 1 CHC individuals treated with PEG-IFN/RBV and 45 with PEG-IFN/RBV/telaprevir, and evaluated the impact of pretreatment serum IP-10 concentrations on their virological responses. RESULTS The pretreatment serum IP-10 concentrations were not correlated with IL28B genotype. The receiver-operator curve analysis determined the cut-off value of IP-10 for predicting a sustained virological response (SVR) as 300 pg/mL. In multivariate analysis, the IL28B favorable genotype and IP-10 concentration of less than 300 pg/mL were independent factors for predicting SVR. In a subgroup of patients with the IL28B favorable genotype, the SVR rate was higher in the patients with IP-10 of less than 300 than in those with 300 pg/mL or more, whereas no patient with the IL28B unfavorable genotype and IP-10 of 300 pg/mL or more achieved SVR. Among the patients treated with PEG-IFN/RBV/telaprevir, low pretreatment concentrations of serum IP-10 were associated with a very rapid virological response, defined as undetectable HCV RNA at week 2 after the start of therapy. CONCLUSION Pretreatment serum IP-10 concentrations are associated with treatment efficacy in PEG-IFN/RBV and with early viral kinetics of hepatitis C virus in PEG-IFN/RBV/telaprevir therapy.

Summary Inosine triphosphatase (ITPA) genetic variants are strongly associated with ribavirin (RBV)-induced anaemia during pegylated interferon (PEG-IFN) plus RBV therapy. However, the treatment efficacy of ITPA genetic variants has not been fully explored. We enrolled 309 individuals infected with hepatitis C virus genotype 1, who were treated with PEG-IFN plus RBV for 48 weeks. The ITPA SNP: rs1127354 and IL28B SNP: rs8099917 were genotyped. We examined the risk factors for severe anaemia up to week 12 after the start of treatment and treatment efficacy. The incidence of severe anaemia, ≥3 g/dL reduction or

Background and Aims Liver biopsy is the gold standard test to determine the grade of fibrosis, but there are associated problems. Because gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid is secreted partially in hepatocytes and bile, it is possible that ethoxybenzyl-magnetic resonance imaging (EOB-MRI) correlates with liver function and liver fibrosis. The aim of this study was to compare the fibrosis seen in liver biopsy samples to the signal intensity of the hepatobiliary phase measured on EOB-MRI in hepatitis C virus (HCV)-infected patients. Methods Two hundred twenty-four (estimation 149, validation 75) HCV-infected patients with histologically proven liver tissue who underwent EOB-MRI were studied. Overall, fibrosis staging was 15/24/19/46/45 for F0/F1/F2/F3/F4, respectively. A 1.5-Tesla magnetic resonance system was used, and the regions of interest of the liver were measured. Four methods were used: (i) relative enhancement: (post-enhanced signal intensity [SI] − pre-enhanced intensity)/pre-enhanced intensity; (ii) liver-to-intervertebral disk ratio (LI): post-enhanced (liver SI/interdisc SI)/pre-enhanced (liver SI/inter disc SI); (iii) liver-to-muscle ratio: post-enhanced (liver SI/muscle SI)/pre-enhanced (liver SI/muscle SI); and (iv) liver-to-spleen ratio: post-enhanced (liver SI/spleen SI)/pre-enhanced (liver SI/spleen SI). Results To discriminate F0-1 versus F2-4 or F0-2 versus F3-4 or F0-3 versus F4, LI at 25 min (LI25) had the highest area under receiver operating characteristic (0.88, 0.87, and 0.87, respectively) in these four methods and also in the validation set. Conclusion LI at 25 min seems to be a useful method to determine the staging of fibrosis as a non-invasive method in HCV-infected hepatitis or cirrhosis patients.

Aim The factors associated with hepatitis recurrence after discontinuation of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B were analyzed to predict the risk of relapse more accurately. Methods A total of 126 patients who discontinued NA therapy were recruited retrospectively. The clinical conditions of a successful discontinuation were set as alanine aminotransferase (ALT) below 30 IU/L and serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL. Results Relapse of hepatitis B were judged to occur when maximal serum ALT became higher than 79 IU/L or when maximal serum HBV DNA surpassed 5.7 log copies/mL following NA discontinuation since these values corresponded with mean values of ALT (30 IU/L) and HBV DNA (4.0 log copies/mL), respectively. At least 90% of patients with either detectable hepatitis B e antigen or serum HBV DNA higher than 3.0 log copies/mL at the time of NA discontinuation relapsed within one year. In the remaining patients, higher levels of both hepatitis B surface and core-related antigens at the time of discontinuation, as well as a shorter course of NA treatment, were significantly associated with relapse by multivariate analysis. Conclusions It appears that negative results for hepatitis B e antigen and serum HBV DNA lower than 3.0 log copies/mL are essential for successful NA discontinuation, which may be attained by a longer treatment period. Levels of hepatitis B surface and core-related antigens are also significant factors independently associated with relapse of hepatitis.

Purpose Common reasons for tooth extractions include periodontal disease, dental caries and root fracture. The purpose of this study was to investigate the association of tooth loss after prosthetic treatment, particularly incidences due to root fracture, which occur frequently and are difficult to prevent. Methods Data were collected from consecutively selected medical records of patients taken over 3 years after their initial visit to Osaka University Dental Hospital. Collected data included (1) age and gender, (2) number of teeth at the initial visit and number of extracted teeth, (3) reasons for extraction, (4) restored with or without a post and (5) abutment of removable partial dentures (RPDs). A Chi-squared test was applied among the reasons for extraction, whether the tooth was restored with a post or not and clasped or not. A logistic regression analysis was used to determine the associations of root fracture with the patient data. Results This study included 101 patients (296 extracted teeth). The reasons for extraction included periodontal disease (64.6%), caries (25.3%) and root fracture (10.1%). The percentage of root fracture was significantly higher for female than male, for restored teeth with posts than without posts and for abutment of RPDs than for non-abutment teeth. Logistic regressions showed that root fractures were significantly associated with gender and abutments. Conclusion The most frequently stated reasons for tooth extraction after prosthetic treatment were periodontal disease and dental caries, followed by root fracture. Root fractures were significantly associated with gender and abutment teeth of RPDs.

Most patients who acquire chronic hepatitis B virus (HBV) infection by perinatal transmission become inactive carriers (IC) after hepatitis B e (HBe) antigen seroconversion, whereas some patients have persistent abnormal serum transaminase levels and develop hepatocellular carcinoma (HCC) in the anti-HBe-positive phase. The aim of this study was to investigate the HCC-related mutations of HBV.Complete sequences of HBV were examined among eight IC and eight HCC patients infected with HBV genotype C before and after seroconversion.The frequency of the T1653 mutation tended to be higher among HCC patients after seroconversion (16.7% vs. 62.5%; P = 0.086). The prevalence of a basal core promoter double mutation (T1762/A1764) was high among both IC and HCC patients after seroconversion (83.3% vs. 87.5%; P = 0.825). Among the HCC patients, a pre-S deletion mutant was detected in 62.5% patients before seroconversion, and in 37.5% patients after seroconversion. The core deletion mutant was also detected in 50% of HCC patients only before seroconversion. Deletion mutants of the pre-S or core region before seroconversion were significantly associated with HCC patients (0% vs. 62.5%; P = 0.007, 0% vs. 50%; P = 0.021, respectively).Our data showed a significant association of pre-S and core deletion mutants before seroconversion with HCC development. The T1653 mutation after seroconversion was frequently found in HCC patients infected with HBV genotype C. These results suggest that mutations may be predictive factor for development of HCC.

Background. Most patients with chronic hepatitis B virus infection become carriers of inactive virus after hepatitis B e antigen seroconversion; however, a subgroup of patients have persistent abnormal transaminase levels and develop hepatocellular carcinoma after seroconversion. Methods. In an age-matched case-control study, 40 carriers of inactive virus (mean age ± standard deviation [SD], 50.9 ± 11.1 years), 40 patients with chronic hepatitis (mean age ± SD, 50.2 ± 8.9 years), and 40 patients with hepatocellular carcinoma (mean age ± SD, 50.7 ± 9.4 years) who were infected with hepatitis B virus genotype C and had test results positive for antibody to hepatitis B e antigen were analyzed. Results. The prevalence of T1653 in the box a was significantly higher among patients with hepatocellular carcinoma than among carriers of inactive virus who did not have hepatocellular carcinoma (70% vs. 25%; P< .0001) or chronic hepatitis (70% vs. 35%; P =.003). Mutations in the basic core promoter region (T1762/A1764) were frequently found in all groups, regardless of clinical status (in 77.5% of carriers of inactive virus, 77.5% of patients with chronic hepatitis, and 90% of patients with hepatocellular carcinoma). In the multivariate analysis, the presence of T1653, an alanine aminotransferase level of ≥37 U/L, and a platelet count of

To evaluate the efficacy of ethoxibenzyl-magnetic resonance imaging (EOB-MRI) as a predictor of hepatocellular carcinoma (HCC) development.Between August 2008 and 2009, we studied 142 hepatitis C virus-infected patients (male 70, female 72), excluding those with HCC or a past history, who underwent EOB-MRI in our hospital. The EOB-MRI index [liver-intervertebral disc ratio (LI)] was calculated as: (post-liver intensity/post-intervertebral disc intensity)/(pre-liver intensity/pre-intervertebral disc intensity).The median follow-up period was 3.1 years and the patients were observed until the end of the study period (31 December, 2012). In the follow-up period, HCC occurred in 21 patients. The cumulative occurrence rates were 2.1%, 9.1%, and 14.1% at 1, 2, and 3 years, respectively. Using the optimal cut-off value of LI 1.46, on univariate analysis, age, aspartate amino transferase (AST), α-fetoprotein (AFP) ≥ 10, albumin, total cholesterol, prothrombin time, platelets, and LI1.46 were identified as independent factors, but on multivariate analysis, LI1.46: risk ratio 6.05 (1.34-27.3, P = 0.019) and AFP ≥ 10: risk ratio 3.1 (1.03-9.35, P = 0.045) were identified as independent risk factors. LI and Fib-4 index have higher area under the receiver operating characteristic curves than other representative fibrosis evaluation methods, such as Forn's index and AST-to-platelet ratio index.LI is associated with the risk of HCC occurrence in hepatitis C patients. LI may be a substitute for liver biopsy when evaluating this risk and its combined use with Fib-4 is a better predictive method of HCC progression.

Aim: The aim of this study was to determine the prevalence of anti-liver/kidney microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. Methods: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/kidney microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. Results: Anti-liver/kidney microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. Conclusion: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.

症例1: 62歳の男性。1988年肝細胞癌にて,肝右葉切除。再発のため96年に部分切除。98年右眉毛部に無症候性の紅色腫瘤出現。病理組織像にて真皮中層以下に肝細胞類似の腫瘍細胞巣を認め,肝細胞癌の皮膚転移と考えた。症例2: 67歳の男性。1982年頃より慢性肝炎。98年肝腫瘍を認め,生検にて肝細胞癌と診断,腹部血管造影下に肝動脈塞栓術施行したが著効見られず,化学療法を併用。経過中に胸部左側に皮下腫瘤が出現,病理組織像にて肝細胞類似の腫瘍細胞をみとめ,肝細胞癌の皮膚転移と診断。肝臓癌皮膚転移の既報24例についてまとめた。内訳は,肝細胞癌21例,胆管癌3例で,平均年齢57.9歳,男女比7:1,部位は頭頚部が59%であった。皮膚転移から死亡までの期間は平均4ヵ月であった。

Mouthguards are effective means of protection against traumatic injury in the maxillofacial complex during sports. The thickness of the mouthguard material which is essential to provide shock absorption can also have side effects such as increase in vertical dimension and disturbance in speech.The objective of our current study was to examine the possibility of utilizing newly developed high-shock absorption silicone material (α-Gel) for fabricating mouthguards to reduce their thickness. Shock absorption was tested with the accelometer on the testing machine and on two volunteer subjects. The results indicated that α-Gel is a promising material to reduce the thickness of mouthguards without losing shock absorption.

A 70-year-old woman underwent Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) for bleeding gastric varices, which was unsuccessful. Then, she underwent Percutaneous Transhepatic Obliteration (PTO) to block the main blood supply route. On the 5th postoperative day, the white blood cell and platelet counts suddenly fell markedly, and CT showed that the splenomegaly had worsened rapidly after PTO. Since blood flow to the gastric varices was still present, Partial Splenic Embolization (PSE) was performed in an attempt to reduce portal venous blood flow. However, rebleeding from the gastric varices occurred, and so embolization with Histoacryl was performed. Although portal hypertension after PTO is a relatively common event, we report this case because no case has been reported in which massive splenomegaly with leukocytopenia developed within a short period of time.

Shunsuke Nojiri,1 Atsunori Kusakabe,1 Kei Fujiwara,1 Noboru Shinkai,1 Kentaro Matsuura,1 Etsuko Iio,1 Tomokatsu Miyaki,1 Tomoyuki Nomura,2 Satoshi Sobue,3 Hitoshi Sano,4 Izumi Hasegawa,5 Tomoyoshi Ohno,5 Yoshitsugu Takahashi,6 Etsuro Orito,7 Takashi Joh11Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, 2Inabe General Hospital, Inabe, 3Kasugai Municipal Hospital, Kasugai, 4Tajimi Prefectural Hospital, Tajimi, 5Social Chukyo Insurance Hospital, Nagoya, 6Chita Kousei Hospital, Aichi-ken, 7Nagoya Daini Red Cross Hospital, Showa-ku, JapanBackground: Sorafenib has been approved in the indication of unresectable hepatocellular carcinoma, but there are many cases in which administration of the drug is discontinued due to severe side effects. In this study, we compared the characteristics of patients who continued and discontinued sorafenib.Methods: Ninety-six patients (75 men and 21 women) were initiated on sorafenib from July 2009 through September 2011. The patient characteristics of interest included gender, age, etiology, Child-Pugh classification, treatment history and frequency, and levels of α-fetoprotein, des-gamma-carboxy prothrombin, aspartate amino acid transferase, and alanine aminotransferase. Duration of administration of sorafenib and reasons for its discontinuation were compared.Results: Median overall survival was 11.8 months. Discontinuation of sorafenib within 90 days was identified as an independent prognostic factor for overall survival on multivariate analysis (P < 0.0001). Transarterial chemoembolization performed six times or more (P = 0.013) was also identified as an independent factor contributing to discontinuation of sorafenib within 90 days in multivariate analysis. Patients who received sorafenib for ≥90 days had significantly longer overall survival than those who discontinued it (P < 0.0001).Conclusion: Prolonged treatment with sorafenib is an important factor in achieving extended overall survival. We recommend starting sorafenib before latent liver damage has occurred as a result of too many transarterial chemoembolization procedures.Keywords: sorafenib, hepatocellular continuation, discontinuation, efficacy

The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on gastroduodenal mucosal proliferation remains somewhat controversial. Experiments in rats have shown that acute administration of NSAIDs inhibits cell proliferation in the gastric mucosa while chronic administration of NSAIDs stimulates cell proliferation in gastric fundic and duodenal mucosa but has no effect in the gastric antral mucosa. Studies in humans have demonstrated that NSAIDs stimulate cell proliferation in the gastroduodenal mucosa. The stimulatory effect may be a compensatory reaction to mucosal injury and represent one of the mechanisms of gastric and duodenal mucosal adaptation to continued NSAID exposure. NSAIDs inhibit cell proliferation in the gastric mucosa at the ulcer margin in both rats and humans. This effect may account for the epidemiologic findings of delayed ulcer healing in patients taking long-term NSAIDs therapy. Since cell proliferation and renewal in gastroduodenal mucosa is one of the major mechanisms for the maintenance of mucosal integrity and enables repair of injury and ulcer healing, the effect of NSAIDs on cell proliferation in gastroduodenal mucosa is an important clinical issue.

Aim: Peptide-based therapeutic vaccines are being developed. The aim of this study was to determine the feasibility of immunotherapy to hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) by assessing the inductivity of peptide-specific cytotoxic T lymphocyte (CTL) by dendritic cells. Methods: The inductivity of CTL was characterized in six patients with HCV-positive HCC, and compared to seven healthy volunteers and six patients with chronic HCV hepatitis (control). Results: Peptide-specific CTL was comparably induced in controls, but not induced in any patients with HCC. To characterize this, the cytokine profile and the expression of surface molecules interacting between dendritic and T cells were evaluated. Among the cytokines, production of interferon (IFN)-γ was found to be impaired and closely related to the results of CTL assays, while the expression of surface molecules showed no significant changes. Conclusions: In HCV-positive HCC patients, CTL inductivity by dendritic cells is impaired. This may be related to the impaired production of IFN-γ.

In the United Republic of Tanzania, 457 voluntary blood donors were enrolled in hepatitis B virus (HBV) serological screening; 4.8% (22/457) carried HBsAg, 13.6% (3/22) of whom were HBeAg-positive. The mean age among HBeAg-negative carriers was 31 years. HBV DNA was detectable in 81.8% (18/22), the mean level was 3.67 (+/-1.77) log copies/ml. Genotype A was determined in 90.9% (20/22) and 18/20 were classified into subgenotype Aa (Asia/Africa). The basal core promoter, precore and partial core nucleotide sequences were analyzed in the 18 strains; T1809/T1812 ("Kozak" sequence) and A/T1888 (encapsidation signal) variants were identified in 100% and 78%, respectively. The complete genome sequencing for one of the Tanzanian strains revealed no recombination. In conclusion, HBV seroprevalence is high among general population in Tanzania, and the HBV/Aa-infection is predominant. The indicated tendency to early HBeAg seroconversion and declining of the viral load should be confirmed further in case-control studies.

Background/aims In eastern Asian countries, hepatitis B virus (HBV) genotype Ba (HBV/Ba), HBV/Bj and HBV/C are prevalent. The aim was to investigate the response or resistance to lamivudine therapy among patients with different HBV genotypes. Methods Of 67 Japanese and Chinese patients with chronic hepatitis B, 18 patients with HBV/Bj, 15 with HBV/Ba and 34 with HBV/C were selected for a case–control study matched according to gender and age. All the patients were treated with lamivudine for 2 years and evaluated the response or emergence of the YMDD mutation at year 2 during the treatment. HBV genotypes were detected by the restriction fragment length polymorphism. The YMDD mutation was detected by the direct sequencing after amplification by PCR. Results At year 2 during therapy, 44.8% of the patients showed normalization of ALT and undetectable HBV DNA (favorable response), 35.8% developed the YMDD mutation. There was no significant difference of response to the therapy among the three genotype groups. The emergence of the YMDD mutation was associated with HBV/C. By the multiple logistic regression analysis, however, the significant factor of a favorable response was a higher pretreatment ALT level and negative HBeAg status and the significant factor of the emergence of the YMDD mutation was HBV/C. Conclusions Higher pretreatment ALT level, HBeAg status or HBV genotype may affect the response or resistance to lamivudine therapy.

To develop a new sensitive and inexpensive hepatitis C virus (HCV) combination test (HCV Guideline test) that enables the determination of HCV genotypes 1, 2 and 3, and simultaneous determination of HCV viral load using commercial Amplicor GT HCV MONITOR test v2.0 (microwell version).The HCV Guideline test used the PCR product generated in commercial Amplicor GT HCV Monitor test v2.0 for viral load measurement using microwell plate version of Amplicor HCV Monitor and also captured on separate plates containing capture probes and competitive oligonucleotide probes specific for HCV genotypes 1, 2 and 3, The HCV genotype was subsequently determined using the biotin-labeled PCR product and five biotin-labeled HCV-specific probes.The sensitivity of the HCV Guideline test was 0.5 KIU/mL. Specificity of the HCV Guideline test was confirmed by direct sequencing of HCV core region and molecular evolutionary analyses based on a panel of 31 samples. The comparison of the HCV Guideline test and an in-house HCV core genotyping assay using 252 samples from chronic hepatitis C patients indicated concordant results for 97.2% of samples (59.5% genotype 1, 33.7% genotype 2, 6.0% genotype 3, and 0.8% mixed genotypes). Similarly, the HCV Guideline test showed concordance with a serological test, and the serological test failed to assign any serotype in 12.7% of the samples, indicating a better sensitivity of the HCV Guideline test.Clinically, both viral load and genotypes (1, 2 and 3) have been found to be major predictors of antiviral therapy outcome regarding chronic hepatitis C based on guidelines and they are, in normal circumstances, performed as separate stand-alone assays. The HCV Guideline test is a useful method for screening large cohorts in a routine clinical setting for determining the treatment regimen and for predicting the outcome of antiviral therapy of chronic hepatitis C.

Background and Aim: Occult hepatitis B virus (HBV) infection in hepatitis C virus (HCV)-infected patients might enhance the severity of chronic liver disease (CLD). To elucidate the correlation between occult HBV infection and the clinical course of HCV-related CLD, we evaluated whether the fluctuation of occult HBV-DNA directly affects the serum alanine aminotransferase (ALT) level. Methods: Forty-one patients with HCV-related CLD who received regular outpatient treatment and 42 age-, sex-, and antibody to hepatitis B core antigen positivity-matched healthy volunteers were enrolled. Serum HBV-DNA was quantitatively detected using real-time detection polymerase chain reaction (RTD–PCR). Serial serum samples in three patients were measured for HBV-DNA, ALT and HCV core antigen. Results: Hepatitis B virus DNA was amplified in eight of the HCV-related CLD patients (19.5%), which was significantly higher than that of healthy volunteers (2.4%). No significant difference between the genotype 1 HCV-related CLD group and the genotype 2 group was found. Based on the analyses using serial serum samples, the elevation of HBV-DNA did not occur before the ALT flares, but occurred at the same time or after the ALT flares. Conclusions: The prevalence of occult HBV infection of HCV-related CLD is significantly higher than that of control. Occult HBV infection has no influence on ALT flares among patients with HCV-related CLD.

Lupus erythematosus panniculitis (profundus), a rare variant of chronic panniculitis, sometimes develops during the course of discoid lupus erythematosus or systemic lupus erythematosus. A 61-year-old woman had suffered from autoimmune hepatitis type I for 5 years. Prednisolone had been administered as maintenance therapy and her hepatitis had been well controlled. However, asymptomatic erythematous indurated nodules developed symmetrically in both pre-auricular regions, and skin biopsy revealed lupus erythematosus panniculitis (profundus). Increase in dosage of prednisolone resolved the skin lesion, leaving depressed atrophic scars. This is the first report of lupus erythematosus panniculitis complicating autoimmune hepatitis.

A 48-year-old woman had suffered from gradual progression of skin pigmentation since 1987 and liver dysfunction since 1994, without having been treated by specialists. In September 1996, she suffered from acute development of morning stiffness of the hands and multiple arthralgias, especially of the fingers. In November 1996, her regular physician, who suspected she had rheumatoid arthritis, referred her to the Departments of Orthopedics, Rheumatology, and Internal Medicine of our hospital. Laboratory findings revealed elevation of titers of antinuclear antibody (× 320, homogeneous pattern), anti-smooth-muscle antibody (× 320), levels of immunoglobulin G (2.58 g/L; normal, 8.70–1.70 g/L), anti-DNA antibody (16 IU/mL; normal, 0–7 IU/mL), aspartate aminotransferase (97 U/L; normal, 0–35 U/L), and alanine aminotransferase (88 U/L; normal, 0–35 U/L). Results of tests for rheumatoid factor immunoglobulin M and G, hepatitis B surface antigen, hepatitis C virus antibody, lupus erythematosus cells, lupus erythematosus test, antimitochondrial antibody, anticentromere antibody, and anti-Sjogren syndrome A and B antibodies were all negative. Other laboratory findings were within normal ranges. Autoimmune hepatitis was suspected and liver biopsy was performed. A liver biopsy specimen revealed chronic nonsuppurative destructive cholangitis with dense lymphocytic infiltration around the portal veins, piecemeal/spotty necrosis, and periductal fibrosis. On the basis of these clinicopathologic findings, autoimmune cholangitis was diagnosed. Her skin pigmentation was examined at the Department of Dermatology of our hospital. On initial examination, reticular or ‘‘rippled,’' gray–brown pigmentation was found on the nape of the neck, upper back ( Fig. 1), and the extensor aspects of both arms ( Fig. 2). There was no Raynaud's phenomenon. No sclerodactylia or proximal scleroderma was found. She had no history of pre-existing dermatoses, such as atopic dermatitis, chronic eczema, or contact dermatitis. She denied the occurrence of excessive friction of the skin. A skin biopsy specimen revealed eosinophilic homogeneous masses in the papillary dermis and upper dermis. These homogeneous masses were positive to Dylon and Congo red staining ( Fig. 3). In the liver biopsy specimen, no materials positive to Dylon or Congo red staining were found. In addition, results of electrophoresis of urinary and blood protein were normal. The patient was therefore diagnosed with macular-type primary localized cutaneous amyloidosis. Figure 1. Reticular or ‘‘rippled’' gray–brown pigmentation on the upper back Download figure to PowerPoint Figure 2. Skin pigmentation on the extensor aspects of both arms Download figure to PowerPoint Figure 3. Homogeneous masses, positive to Dylon staining, in the papillary dermis (Dylon staining; original magnification, × 300) Download figure to PowerPoint Administration of prednisolone 30 mg daily improved liver function and arthralgia. The dosage of prednisolone was gradually decreased to 10 mg daily without exacerbation. Although no progression of skin lesions has occurred, skin pigmentation has persisted as of November 1999.