Viral eradication reduces both liver stiffness and steatosis in patients with chronic hepatitis C virus infection who received direct-acting anti-viral therapy.

BACKGROUND: Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR). METHODS: A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24). RESULTS: Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70-4.18) kPa and 2.80 (2.40-3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7-3.4)% and 1.9 (1.3-2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24. CONCLUSION: Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).

Ability of 18-fludeoxyglucose positron emission tomography/CT to detect incidental cancer.

OBJECTIVE: To determine the prevalence and clinical features of pathologically proven incidental cancer (IC) detected by whole-body fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT, as well as the incidence of false-positive and false-negative results. METHODS: We retrospectively reviewed reports derived from (18)F-FDG PET/CT images of 3079 consecutive patients with known or suspected malignancies for 3 years. Discrete focal uptake indicating IC was identified from reports as well as pathological or clinical diagnoses, and the clinical courses were investigated. The false-positive result was defined as uptake indicating IC but not pathologically confirmed as malignant during follow-up. The false-negative result was defined as pathologically proven IC detected by another modality at initial clinical work-up or diagnosed during the follow-up period. RESULTS: We found (18)F-FDG uptake indicating IC in 6.7% of all patients, and IC was pathologically proven in 2.2% of all patients. The most common sites were the colon, lung and stomach. The median survival duration of patients with IC was 42 months. The results were false positive in 4.5% of all patients, and the results were false negative in 2.3% of all patients. CONCLUSION: (18)F-FDG PET/CT is a valuable tool for detecting IC. The rates of false-positive and false-negative results are within acceptable range. ADVANCES IN KNOWLEDGE: This is the first report to describe the survival of patients with IC, and the detailed features of false-negative results at actual clinical settings.

Correlation of serum ribavirin concentration with pretreatment renal function estimates in patients with chronic hepatitis C receiving combination antiviral therapy with peginterferon and ribavirin.

Serum ribavirin concentration is an important factor in antiviral therapy in combination with peginterferon (PEG-IFN) and ribavirin for patients with chronic hepatitis C in terms of both beneficial and adverse effects. We evaluated whether the serum ribavirin concentration can be predicted on the basis of renal function estimates. Serum creatinine and cystatin C concentrations were measured at the start of treatment in a total of 148 patients with chronic hepatitis C who underwent combination PEG-IFN and ribavirin therapy. Creatinine clearance (CrCl) and total clearance of ribavirin (CL/F) were calculated on the basis of the serum creatinine level. The glomerular filtration rate was calculated with two different formulae on the basis of the serum cystatin C level. These values were compared with serum ribavirin concentrations 4 weeks after the start of therapy. The cystatin C level increased with the progression of liver fibrosis, whereas the creatinine level was constant regardless of the degree of liver fibrosis. Significant correlation was not observed between the serum ribavirin concentration and serum creatinine level, cystatin C level, or calculated renal function estimates. However, significant correlation was found between the serum ribavirin concentration and CrCl and CL/F in patients who were given ribavirin >800 mg/day. Overall, renal function estimates do not correlate with the serum ribavirin concentration in Japanese patients with chronic hepatitis C who undergo combination PEG-IFN and ribavirin therapy. Serum creatinine-based renal function estimates might be predictive for the serum ribavirin concentration only in patients with a daily ribavirin intake of 800 mg or more.

Endoscopic management and follow up of Dieulafoy lesion in the upper gastrointestinal tract.

BACKGROUND AND STUDY AIMS: Dieulafoy's lesion is an important cause of upper gastrointestinal bleeding, and the safety and efficacy of endoscopic treatment have been widely accepted. The aim of this study was to evaluate the effectiveness of endoscopic management, including hemoclipping and injection methods, for bleeding Dieulafoy lesions in the upper gastrointestinal tract. PATIENTS AND METHODS: Between 1995 and 2003, 61 patients with bleeding Dieulafoy lesions underwent endoscopic treatment. The available hemostatic methods were hemoclipping, hypertonic saline-epinephrine injection, and pure ethanol injection. Clinical data, endoscopic features, and treatment outcome were analyzed retrospectively. RESULTS: Comorbid conditions were present in 39 patients (64 %). Active bleeding was noted in 20 patients (33 %). Hemoclipping was a selected treatment in 48 patients (79 %). Initial hemostasis was achieved in 61 patients (100 %). One patient had rebleeding 6 days after the initial procedure but was successfully treated endoscopically. The 30-day mortality was 0 %. During follow-up, for a mean of 47 months, 15 patients (25 %) died of causes unrelated to the Dieulafoy lesion. Two patients had recurrent bleeding due to non-Dieulafoy gastric ulcer, and responded to endoscopic therapy. We encountered no patients who required surgery. CONCLUSIONS: Dieulafoy lesion can be successfully managed by endoscopic treatment. The long-term outcome is acceptable.

Energy expenditure during walking with weight-bearing control (WBC) orthosis in thoracic level of paraplegic patients.

STUDY DESIGN: Comparative study of the effectiveness of walking exercise with a newly developed gait orthosis, the weight-bearing control (WBC) orthosis, for thoracic level of paraplegic patients. OBJECTIVES: To test its feasibility as a rehabilitation alternative for paraplegic patients, the energy consumption and cost during walking with WBC were calculated and compared with the values of conventional orthoses given in previous reports. SETTING: National Rehabilitation Center for the Disabled, Japan. METHODS: Four paraplegic patients with traumatic spinal cord injuries ranging from T8 to T12 participated. Experiments were conducted after 3 months of the orthotic gait training with WBC. The cardiorespiratory parameters were continuously measured at rest and during walking with a telemetric device. The steady-state value of the oxygen uptake (V(O2)), heart rate (HR), the energy consumption (J/kg/s) and energy cost (J/kg/m) were calculated. RESULTS: The average walking speed was 19.0 +/- 2.58 m/min. The steady-state value of the V(O2) and HR were 16.08 +/- 1.93 ml/kg and 147.3 +/- 10.94 b/min, respectively. The energy cost during orthotic walking tended to be better than the values of conventional orthoses, whereas the energy consumption was almost similar. CONCLUSION: WBC enables thoracic level of paraplegic patients to walk at relatively higher speed than conventional orthoses under similar energy expenditure. The special devices equipped with WBC are therefore considered to lead to improvement of the energy cost of walking. The physical intensity presumed by cardiorespiratory responses during walking with WBC is suited to promote their aerobic capacity. Therefore, it is concluded that the WBC orthosis could be an effective alternative in rehabilitation for thoracic level of paraplegic patients.

Liver dysfunction among workers handling 5-nitro-o-toluidine.

BACKGROUND: 5-Nitro-o-toluidine is an aromatic nitro amino compound. While other aromatic compounds are known to damage the human liver and are registered as toxic substances, toxicity information concerning 5-nitro-o-toluidine is lacking. AIMS: To investigate the hepatotoxicity of 5-nitro-o-toluidine. PATIENTS AND METHODS: Of 15 workers in the same factory who handled 5-nitro-o-toluidine, three were hospitalised with symptoms of acute liver dysfunction. Suspecting a link between liver dysfunction and working conditions, we correlated workplace factors with clinical findings in all 15 workers. RESULTS: Blood biochemistry tests indicated liver damage in seven of 15 study subjects. Workers who handled 5-nitro-o-toluidine and nitrosyl sulphuric acid often loosened their respiratory protective equipment shortly after 5-nitro-o-toluidine powder had been dispersed into the air of the room. No potential hepatotoxins were present except for 5-nitro-o-toluidine. Six of the affected workers had handled 5-nitro-o-toluidine 12 to 20 times; the seventh worker had handled the powder three times; and the other eight workers without liver dysfunction had handled the material once or twice. No other significant differences in background were evident between the affected and unaffected workers, such as age, sex, or protective measures. Histological findings during recovery from liver damage were similar to those of acute viral hepatitis. None of the 15 subjects has demonstrated liver damage since the factory was closed. CONCLUSIONS: A link between liver dysfunction and 5-nitro-o-toluidine exposure is suggested by greater severity of liver dysfunction associated with more episodes of handling.

Effect of the dose and duration of interferon-alpha therapy on the incidence of hepatocellular carcinoma in noncirrhotic patients with a nonsustained response to interferon for chronic hepatitis C.

OBJECTIVE: We evaluated the effect of dose and duration of treatment with interferon (IFN)-alpha on the incidence of hepatocellular carcinoma (HCC) after IFN treatment in patients with chronic hepatitis C. METHODS: A total of 291 noncirrhotic patients with chronic hepatitis C without hepatitis B virus coinfection in whom hepatitis C virus (HCV) was not eradicated by IFN-alpha therapy were retrospectively analyzed. The incidence of HCC after IFN therapy was compared according to the total dose or duration of treatment. RESULTS: Patients were followed up for 6-117 months after the end of IFN treatment. The duration of IFN treatment (< or =24 vs. >24 weeks) had no effect on the incidence of HCC. However, the incidence of HCC was significantly lower in patients who received >500 million units of IFN as a total dose than in patients who received < or =500 million units of IFN (p = 0.0480), and the total dose of IFN (>500 million units) was an independent factor affecting the incidence of HCC (p = 0.0405). In addition, when focusing on patients whose histology was F2 or F3 before IFN treatment, the suppressive effect of the total dose of IFN (>500 million units) was emphasized (p = 0.0049 in generalized Wilcoxon test and p = 0.0178 in multivariate analysis). CONCLUSIONS: Patients with chronic hepatitis C should receive more than 500 million units of IFN when IFN is used to decrease the incidence of subsequent HCC.

Bullectomy is beneficial in the pulmonary blood flow/driving pressure relationship in bullous emphysema patients.

OBJECTIVES: Few physiological studies have been on pulmonary circulation, including the relationship between pulmonary blood flow and driving pressure, and viscosity changes arising from hematocrit changes before versus after lung volume reduction Surgery or bullectomy in emphysematous patients. METHODS: We studied the relationship between pulmonary blood flow and driving pressure before and after bullectomy using a unilateral pulmonary artery occlusion test based on pulmonary blood flow fractions obtained by pulmonary blood flow scintigraphy in 7 patients with pulmonary emphysema associated with bullae. RESULTS: Among the 7 undergoing bullectomy, the pulmonary blood flow/driving pressure relationship decreased in 5 and was unchanged in 2. Of the 11 lungs treated by bullectomy, this relationship decreased in 8 lungs, but not 3 (p < 0.01). No significant difference was seen in oxygen partial pressure in arterial and mixed venous blood or hematocrit. CONCLUSION: We concluded that bullectomy shifted the pulmonary blood flow/driving pressure relationship downword in some cases with significant bullae.

Impact of diabetes mellitus on the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) have coexisting cirrhosis or chronic hepatitis, often complicated by diabetes mellitus. In the current study, the authors evaluated the impact of diabetes mellitus on the prognosis of patients with HCC. METHODS: Among 581 patients with HCC who had been diagnosed and treated between 1990 and 1999, survival was compared between those patients with and those patients without diabetes mellitus. The rate of disease recurrence after treatment also was analyzed. RESULTS: Ninety-two patients (15.8%) had diabetes mellitus. There was no significant difference with regard to patient characteristics (i.e., age, gender, or alcohol intake) or liver function between those patients with and those patients without diabetes mellitus. No differences were observed in survival between patients with diabetes mellitus and patients without it. Among the 195 patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension, the survival of the 32 patients with diabetes mellitus was significantly poorer than that of the 163 patients without diabetes mellitus (P = 0.0273), despite no apparent difference in liver function between the 2 groups. On multivariate analysis, diabetes mellitus was found to be an independent factor predicting lower survival after treatment (P = 0.0077) among patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension. No difference in the rate of recurrence was observed between the two groups in all the patients and in those patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension. CONCLUSION: The results of the current study indicated that the presence of diabetes mellitus worsens the prognosis of patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension; it appears to impact prognosis in patients with HCC when HCC is treatable, based on the size and the number of lesions. However, diabetes mellitus did not appear to affect the prognosis in the general population of patients with HCC. Based on the current study data, diabetes mellitus does not appear to modify the progression of HCC and its recurrence after treatment, but it does appear to worsen the prognosis of patients with HCC by means of a rapid decline in remnant liver function caused by repeated treatment of HCC.

Characteristics and course of small hepatocellular carcinomas in patients with hepatitis C virus types 1 and 2.

The associations between types of HCV and tumor characteristics and recurrence and survival after treatment of small HCC were investigated. Viral genotype-specific antibodies were measured in sera obtained at the time of diagnosis of HCC, in 92 patients with HCC < or = 2 cm in diameter who were treated between 1990 and 1998. The degrees of tumor differentiation and angiographically-evaluated hypervascularity were compared between patients infected with HCV type 1 and those with type 2. Survival, time to recurrence, and patterns of recurrence after initial treatment also were compared. On pathologic evaluation, 6 of 21 HCC (28.6%) in patients with HCV type 2 were well-differentiated, whereas 28 of 48 HCC (58.3%) in patients with HCV type 1 were well-differentiated (P = 0.0229). HCC in patients with HCV type 2 showed hypervascularity more frequently than HCC in patients with HCV type 1, with tumor staining evident by digital subtraction arteriography in 17 of 22 patients with HCV type 2 (77.3%) vs. 20 of 50 in patients with HCV type 1 (40.0%, P = 0.0036). Survival and overall recurrence rates were similar in patients infected with HCV type 1 and with HCV type 2 (P = 0.5537). In the analyses of patterns of recurrence, recurrences in patients infected with HCV type 2 were relatively more likely to be intrahepatic metastases (P = 0.0342), that was closely related to the differentiation of HCC. Multicentric occurrence of HCC was a more frequent type of recurrence in patients with HCV type 1 (P = 0.1619), and infection of HCV type 1 was an independent factor for multicentric occurrence in multivariate analysis (P = 0.0021). In HCC < or = 2 cm in diameter, HCV type 2 is associated with more progression of HCC than HCV type 1, whereas patients with HCV type 1 may be at higher risk for multicentric HCC occurrence after the treatment of HCC.

[A new development in interventional radiology for hepatocellular carcinoma].

In Japan, interventional radiology (IVR) treatments such as transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), and intraarterial infusion chemotherapy play an important role in the treatment of hepatocellular carcinoma because of the associated cirrhosis (impairment of liver function) and occasional multicentricity. With progress in catheters, embolic materials, and imaging equipment such as the so-called "IVR-CT", superselective TAE and precise evaluation of tumor lesions has become feasible. However, the impact of TAE on survival in patients with hepatocellular carcinoma remains to be determined because no survival benefit was seen in four of five randomized controlled trials (RCTs) in Europe and Eastern countries, in which TAE was compared with no treatment (3 trials), i.v. 5-fluorouracil (1 trial), or tamoxifen (1 trial). To resolve questions arising from these results, a fair number of trials, particularly RCTs are needed in Japan.

Effect of skin pressure by clothing on small bowel transit time.

We examined the effect of increased skin pressure from tight clothing on small bowel transit time by means of the breath hydrogen test, using milk that contained lactulose as an additional indigestible disaccharide, which is used as a test meal after overnight fasting. In this experiment, we measured the small bowel transit time from 9 healthy and non-constipated female subjects with two different skin pressures that were applied by loose-fitting experimental garment or an additional tight-fitting girdle on two consecutive days. The skin pressure of the latter condition was 8-9 mmHg higher than that of the former one on the participants' waist, abdomen and hip region. The experimental order of the two skin pressure conditions was counterbalanced. As a result, the small bowel transit time obtained with and without girdle did not differ significantly (165.0 +/- 26.0 minutes for less skin pressure condition and 173.3 +/- 26.8 minutes for more skin pressure condition, n = 9, p = 0.43). This result indicated that the skin pressure from clothing has no effect on the passage rate of food through the small intestine.

Effects of skin pressure by clothing on digestion and orocecal transit time of food.

In order to reveal the influence of clothing skin pressure on digestion of food through the gastrointestinal tract, we examined the absorption of dietary carbohydrate and orocecal transit time of a test meal by means of a breath hydrogen test on 7 healthy young women. In this experiment, we collected breath samples from the participants wearing loose-fitting experimental garment on the second day of the experiment and from the same participants but wearing an additional tight-fitting girdle on the following day for 16 hours and 9 hours, respectively. Skin pressure applied by a girdle on participant's waist, abdomen and hip region was 15.5 +/- 0.4 mmHg (mean +/- SE), 11.0 +/- 0.2 mmHg, and 13.6 +/- 0.6 mmHg, respectively, and the values were 2-3 times larger than those of the experimental garment. The hydrogen concentration vs. time curve showed that breath hydrogen levels at its peaks (15:00, 15:30, 16:00, 16:30, and 17:00 hr) on the third day of the experiment were significantly higher than those of the corresponding time on the second day (p < 0.05 at 17:00 and 15:00, p < 0.01 at 15:00, 16:00 and 16:30). Consequently, significantly pronounced breath hydrogen excretion was observed under the "pressure" clothing condition (p < 0.01). On the other hand, the transit time of the test meal for the subjects wearing a girdle did not differ significantly from that for the subjects wearing the garment of less pressure (270 +/- 18 minutes and 263 +/- 21 minutes, respectively). These results indicate that the clothing skin pressure has an inhibitory effect on the absorption of dietary carbohydrate in the small intestine, but no effect on the orocecal transit time of a meal.

[A case of aneurysm of the ductus arteriosus in the adult].

Aneurysm of the ductus arteriosus in the adults is rare. A 60-year-old male with no symptoms was admitted to our hospital. 3 D-CT scans and aortograms indicated a diagnosis of aneurysm of the ductus arteriosus. Operation was done through median sternotomy with the aid of partial cardiopulmonary bypass. The saccular aneurysm was located between the aortic isthmus and the left pulmonary artery. The aneurysm was resected and closed a patch. The post-operative course was uneventful.

Characterization of cross-links between cellulose microfibrils, and their occurrence during elongation growth in pea epicotyl.

The occurrence and chemical nature of the cross-links between cellulose microfibrils in outer epidermal cell walls in Pisum sativum cv. Alaska was investigated by rapid-freezing and deep-etching techniques coupled with chemical and enzymatic treatments. The cell wall in the elongating region of epidermal cells was characterized by the absence of the cross-links, while in the elongated region, the cell wall was characterized by the presence of cross-links. The cross-links remained in the cell wall of the elongated region after treatment with SDS electrophoresis sample buffer and treatment with 4% potassium hydroxide. After treatment with endo-1,4-beta-glucanase, which fragments xyloglucan, the cross-links were remarkably reduced from the cell wall of the elongated region. The endoglucanase treatment also reduced immunogold labeling of xyloglucan in the cell wall. The endoglucanase hydrolysate from the cell wall fraction of the elongated region gave spots of oligosaccharides in thin layer chromatography, which were identical to the spots of xyloglucan oligosaccharides produced by xyloglucanase from both the cell wall fraction and tamarind xyloglucan. These results indicate that the cross-links are made of xyloglucan. We discussed the possibility of cross-links involved in the control of mechanical properties of the cell wall.