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Background: To evaluate missing data methods applied to laboratory test results used for confounding adjustment, utilizing data from 10 MID-NET®-collaborative hospitals. Methods: Using two scenarios, five methods dealing with missing laboratory test results were applied, including three missing data methods (single regression imputation (SRI), multiple imputation (MI), and inverse probability weighted (IPW) method). We compared the point estimates of adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) between the five methods. Hospital variability in missing data was considered using the hospital-specific approach and overall approach. Confounding adjustment methods were propensity score (PS) weighting, PS matching, and regression adjustment. Results: In Scenario 1, the risk of diabetes due to second-generation antipsychotics was compared with that due to first-generation antipsychotics. The aHR adjusted by PS weighting using SRI, MI, and IPW by the hospital-specific-approach was 0.61 [95%CI, 0.39–0.96], 0.63 [95%CI, 0.42–0.93], and 0.76 [95%CI, 0.46–1.25], respectively. In Scenario 2, the risk of liver injuries due to rosuvastatin was compared with that due to atorvastatin. Although PS matching largely contributed to differences in aHRs between methods, PS weighting provided no substantial difference in point estimates of aHRs between SRI and MI, similar to Scenario 1. The results of SRI and MI in both scenarios showed no considerable changes, even upon changing the approaches considering hospital variations. Conclusions: SRI and MI provide similar point estimates of aHR. Two approaches considering hospital variations did not markedly affect the results. Adjustment by PS matching should be used carefully. [ABSTRACT FROM AUTHOR]

Summary: Immune-related sclerosing cholangitis (irSC) is relatively rare and its clinical characteristics are not well known. In this study, we aimed to summarize the clinical features of irSC. Clinical data were collected retrospectively from 1,393 patients with advanced malignancy treated with immune-checkpoint inhibitors (ICIs) between August 2014 and October 2021. We analyzed patients with immune-related adverse events of liver injury (liver-irAEs) and compared irSC and non-irSC groups. Sixty-seven patients (4.8%) had a liver-irAE (≥ grade 3) during the follow-up period (median, 262 days). Among these, irSC was observed in eight patients (11.9%). All patients in the irSC group were treated with anti-PD-1/PD-L1 antibodies. Compared with the non-irSC group, the irSC group showed mainly non-hepatocellular liver injury (87.5 % vs 50.8 %, P = 0.065), and had elevated serum inflammatory markers (e.g., CRP and NLR) and biliary enzymes (e.g., GGTP and ALP) at the onset of liver-irAEs. Furthermore, most patients with irSC had abdominal pain. In the non-irSC group, the liver injury of 23 patients improved only with the discontinuation of ICIs, and 22 patients improved with medication including prednisolone (PSL). Conversely, almost all patients (n=7) in the irSC group were treated with PSL, but only two patients experienced an improvement in liver injury. We found that irSC is characterized by a non-hepatocellular type of liver injury with abdominal pain and a high inflammatory response and is refractory to treatment. Further examination by imaging is recommended to detect intractable irSC in cases with these characteristics. [ABSTRACT FROM AUTHOR]

The current study aimed to identify the crude drugs associated with drug-induced liver injury (DILI) in 148 Kampo medicines prescribed throughout Japan using the Japanese Adverse Drug Event Report (JADER) database, a large-scale spontaneous reporting system in Japan. First, we tabulated the number of DILI reports from the report-based dataset and the background information from the patient-based dataset. Thereafter, we combined the 126 crude drugs into 104 crude drug groups to examine multicollinearity. Finally, the reporting odds ratios (RORs), 95% confidence intervals, p values for Fisher's exact test, and number of reports were calculated for each crude group to identify those associated with DILI. Notably, the number of adverse event reports for DILI (63,955) exceeded that for interstitial lung disease (51,347), the most common adverse event. In total, 78 crude drug groups (90 crude drugs) were reported to have an ROR > 1, a p < 0.05, and ≥10 reported cases. Our results highlight DILI as an essential issue, given that it was among the most frequently reported adverse drug reactions. We were able to clearly identify the crude drugs associated with DILI, which could help manage adverse drug reactions attributed to Kampo medicines and crude drugs. [ABSTRACT FROM AUTHOR]

Background: Several studies have suggested that the known biomarkers and the diagnostic scales are unreliable for the diagnosis of Kampo‐induced liver injury (KMILI). Diagnostic Biomarkers: The lymphocyte transformation test (LTT) for Kampo medicines is likely to give false positive results, while the normal level of the basophil activation test (BAT) for diagnosing Kampo liver injury remains uncertain. Diagnostic Scale: Due to the lack of reliable biomarkers, diagnostic scales have been developed; however, the Digestive Disease Week [DDW])‐Japan criteria, which is widely used in Japan, has extremely low specificity for diagnosing KMILI. Conclusion: The diagnosis of KMILI remains challenging, and we eagerly await the development of reliable biomarkers for KMILI. [ABSTRACT FROM AUTHOR]

Aim: Previous reports suggest that the null genotype (*0/*0) of glutathione S‐transferase (GST) M1 and/or GSTT1 could be risk factors for drug‐induced liver injury (DILI). However, multi‐institutional pharmacogenetic research with various suspected drugs has rarely been performed in Japan. Therefore, the aim of this study was to investigate the role of GSTM1 and GSTT1 null genotype in the occurrence of DILI in Japanese patients. Methods: Blood samples of 270 DILI patients from 23 hospitals throughout Japan collected between 2010 and 2018 were subjected to genotyping of null genotypes of GSTM1 and GSTT1 using the SmartAmp‐2 method. We also collected information on DILI types, time to onset of DILI, pharmacological classification of suspected drugs and Digestive Disease Week‐Japan score, as well as genotypes of GSTM1 and GSTT1 in each patient with DILI. Results: The distribution of a combination of null genotypes of GSTM1 and GSTT1 in Japanese patients with DILI was significantly different from that reported in the general Japanese population. Notably, the incidence of the GSTM1 null genotype in patients with DILI was significantly higher than that of the control population. A significant relationship between the frequency of GSTM1 and GSTT1 null genotypes and pharmacological classification of suspected drugs, clinical laboratory data for liver function, time to onset of DILI, and Digestive Disease Week‐Japan scores was not observed. Conclusions: The GSTM1 null genotype was associated with an increased incidence of DILI in Japanese patients. [ABSTRACT FROM AUTHOR]

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) or drug‐induced liver injury (DILI) are severe drug‐induced reactions, known as idiosyncratic drug reactions. It is believed that immune response can lead to these severe adverse drug reactions. Our previous analysis of the Japanese Spontaneous Drug Reaction database suggested that the onset of SJS/TEN and DILI was strongly associated with infection. Hence, we conducted a matched, nested case‐control study to elucidate the association between concurrent infection and the onset of SJS/TEN or liver injury in patients prescribed antipyretic analgesics. We extracted 4 112 055 patients who were prescribed antipyretic analgesics between January 2014 and December 2015. Amongst them, 553 (0.01%) were diagnosed with SJS/TEN and 12 606 (0.3%) with liver injury. In a matched, nested case‐control study, 131 and 2847 cases matched for SJS/TEN or liver injury, respectively. For each case, 3 controls were randomly matched with the case for age at index date and sex. In the conditional logistic regression analysis, there was a significant association between the combination of infection and antipyretic analgesics and the onset of SJS/TEN or liver injury (SJS/TEN: adjusted OR, 5.59; 95%CI, 2.01‐15.51; liver injury: adjusted OR, 2.79; 95%CI, 2.24‐3.46). Although it was not possible to distinguish whether the associations were caused by the infection or were a direct consequence of the antibiotic agents, our findings may help to increase awareness of the possibility of the increased onset of idiosyncratic drug reactions (SJS/TEN and liver injury) in antipyretic analgesic users because of infections. [ABSTRACT FROM AUTHOR]

Since ancient times, Corbicula extract has been believed in Japan to have hepatoprotective effects, but it remains unclear whether these claims are true, and if so, which component is responsible for hepatoprotection. In this study, we showed that Corbicula extract exerted a protective effect against liver damage. Recent work identified acorbine (β-alanyl-ornithyl-ornithine), a novel tripeptide containing non-proteinogenic amino acids, in the extract of Corbicula japonica. Synthesized acorbine cured alcohol-induced liver damage in mice. In addition, acorbine purified from Corbicula extract exerted a protective effect against alcohol-induced hepatotoxicity in a culture liver model derived from mouse ES/iPS cells. Thus, acorbine is one of the components of Corbicula extract that protects hepatocytes against ethanol-induced death. Image 1 • Corbicula extract has hepatoprotective effect in ethanol-induced liver injury in mice. • Acorbine, isolated from Corbicula extract, has hepatoprotective effect in mice. • Synthesized acorbine has hepatoprotective effect in a murine ES/iPS cell-derived liver tissue. [ABSTRACT FROM AUTHOR]

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Objectives. Traditional Japanese Kampo medicines have been integrated into the Japanese national health-care system. In Japan, the Ministry of Health, Labor, and Welfare's website discloses adverse drug-event data that have been obtained from medical personnel reports investigated by the Pharmaceutical and Medical Devices Agency. Using these data, we investigated adverse events associated with ethical Kampo formulations. Methods. Reports of adverse events associated with ethical Kampo formulations from the domestic adverse-event data were obtained from July 30, 2003, to March 31, 2018. Adverse events were then categorized, and the relationships between categories of adverse events and crude drugs were analyzed. Results. There were 4,232 reported adverse events associated with ethical Kampo formulations. The numbers of events by category were as follows: events related to liver injury, 1,193; lung injury, 1,177; pseudoaldosteronism, 889; mesenteric phlebosclerosis, 223; drug eruption, 185; and others, 565. Among events related to both liver injury and lung injury, approximately 70% were suspected to be induced by Kampo formulations containing Scutellariae Radix. The pseudoaldosteronism-related events, which are induced by Glycyrrhizae Radix, included several events related to muscle injury, heart failure, and arrhythmia. Events related to mesenteric phlebosclerosis, believed to be induced by long-term use of Kampo formulas containing Gardeniae Fructus, increased remarkably during the study period. Among the events related to drug eruption, approximately 35% were suspected to be induced by Kampo formulations containing Ephedrae Herba. Conclusion. Kampo medicines may cause various adverse events. The present results provide valuable information regarding adverse events associated with Kampo medicines from the viewpoint of patient safety. [ABSTRACT FROM AUTHOR]

Aim: In order to know the present status of drug‐induced liver injury (DILI) in Japan, we present the data of prospectively collected DILI cases between 2010 and 2018 from 27 hospitals. Methods: Drug‐induced liver injury cases diagnosed by DILI experts from 27 hospitals all over Japan have been prospectively collected since 2010. Alanine aminotransferase level ≥150 U/L and/or alkaline phosphatase ≥2× upper limit of normal were inclusion criteria. Results: In total, data of 307 cases (125 male and 182 female individuals) aged between 17 and 86 years old were collected. The types of liver injury were as follows: 64% hepatocellular type, 20% mixed type, and 16% cholestatic type. A drug‐induced lymphocyte stimulation test was carried out in 59% of cases, and was positive in 48% and semipositive in 3% of cases. Eosinophilia ≥6% was observed in 27% of cases. Fifty‐three percent of DILI cases occurred within 30 days and 79% of DILI cases occurred within 90 days after starting drug administration. By the diagnostic scale of the Digestive Disease Week (DDW)‐Japan 2004 workshop, 93.8% of cases were diagnosed as "highly probable", and 5.9% as "possible". Conclusions: Japanese DILI patients are somewhat different from those of Europe and North America. The diagnostic scale of the DDW‐Japan 2004 workshop has been used in Japan. However, there are many issues to improve the causality assessment of DILI that we must investigate in the future. It is critical to elucidate the mechanisms of drug metabolism and the pathophysiology of liver injury by various drugs to prevent DILI. [ABSTRACT FROM AUTHOR]

Background: In Japan, fatalities among patients who experienced an acute reaction following self-administration of novel psychoactive substances (NPS) have been more frequently reported since June 2014.Objective: This survey aimed to document and analyze trends in NPS consumption in emergency patients.Methods: We conducted a multicenter retrospective survey of patients who were transported to emergency facilities after consuming NPS-containing products between January 2013 and December 2014. Letters requesting participation were sent to 467 emergency facilities, and questionnaires were mailed to facilities that agreed to participate.Results: We surveyed 589 patients from 85 (18.2%) facilities. Most patients were male (89.6%) and young (median age, 30 years), and inhaled (88%) NPS contained in herbal products (80.5%). Harmful behavior was observed at the scene of acute reaction, including violence (6.9%), traffic accidents (4.9%), and self-injury or suicidal attempts (1.1%). Other than neuropsychiatric and physical symptoms, many patients also had physical complications such as rhabdomyolysis (17.5%), liver injury (12.4%), acute kidney injury (9%), and physical injury (1.9%). Of the 256 patients (43.5%) admitted to hospitals, 35 (5.9%) were hospitalized for seven or more days. Most patients (93.2%) completely recovered, although a few (1.4%) died. However, synthetic cannabinoids and synthetic cathinones were only detected in the blood of five patients.Conclusion: Consumption of NPS-containing products have been associated with harmful behaviors such as violence and traffic accidents, physical complications (e.g., rhabdomyolysis, liver injury), death, or physical and neuropsychiatric symptoms. Compared to a previous survey (2006-2012), the present survey revealed more severe toxicity. [ABSTRACT FROM AUTHOR]

Aim To examine the prevalence and characteristics of hepatitis A virus ( HAV) and hepatitis E virus ( HEV) infections in the northern part of Honshu, Japan, during the last decade. Methods Using the registration system of a prospective cohort study for acute liver injury ( ALI) in Iwate and three neighboring prefectures, we examined the prevalence of sporadic acute hepatitis ( AH) with HAV ( AH-A) and HEV ( AH-E) and the distribution of viral genotypes in 487 patients diagnosed with ALI between 2004 and 2013. Results Among all 487 patients, 135 (28%) had ALI with viral infection. In the cases with viral ALI, the prevalence of hepatitis B virus-related AH was highest (55.6%). AH-E was seen in 23 patients (17.0%) and its prevalence was higher than that of AH-A (10 patients, 7.4%). There were no appreciable differences in the prevalence of AH-A and AH-E between 2004-2008 and 2009-2013. However, subgenotype IIIA HAV homologous to Korean strains has recently emerged, and the number of AH-E cases seems to be increasing. HEV genotype 3 was predominant throughout the observation period, but HEV genotype 4 was found in three patients after 2010. The transmission routes of HAV and HEV infections were unknown in approximately 60% of the patients. Conclusion In the northern part of Honshu, Japan, HEV has been more frequently implicated in the development of AH than HAV, and HEV genotype 4 has been recently increasing. To provide an effective prophylactic management for HAV and HEV infections, further clarification of the transmission routes is needed. [ABSTRACT FROM AUTHOR]

Background and Aims: Serum levels of ferritin and heme oxygenase (HO)-1 are both markers of macrophage activation. We evaluated simple markers for predicting the prognosis of severe acute liver injury in which macrophage activation plays an important role. Methods: Subjects comprised 114 patients with acute liver injury, admitted to the liver unit of Nagasaki Medical Center between January 2001 and September 2010. Subjects included 11 patients with fulminant hepatic failure (FHF), 82 patients with ordinary acute hepatitis (AH), and 21 patients with severe-form AH (AHS). We determined serum levels of ferritin, HO-1 and other biochemical makers, and analyzed relationships between clinical outcomes of patients and each of these parameters alone and in combination. Results: Median serum ferritin levels were significantly higher in FHF (25 900 ng/mL) and AHS (3060 ng/mL) than in AH (700 ng/mL; P < 0.01 each). Median HO-1 levels were also significantly higher in FHF (123 ng/mL) and AHS (51 ng/mL) than in AH (19 ng/mL; P < 0.01 each). Similarly, median ferritin/alanine aminotransferase (F/A) ratio was significantly higher in FHF (6.7) than in AHS (1.6, P < 0.05) or AH (0.5, P < 0.01). Among the 11 FHF patients, three recovered, seven died and one underwent liver transplantation. The ability of F/A ratio to distinguish non-survivors from survivors was analyzed using receiver operating characteristics curves. A cut-off level of 3.12 provided high sensitivity (87.5%) and specificity (81.2%). Conclusion: These results suggest that F/A ratio offer a quick and simple marker for predicting the prognosis of acute liver injury. [ABSTRACT FROM AUTHOR]

This survey aims at clarifying if there are common features of drug-induced liver injury (DILI) in local areas and in the national surveys, and the degree of dissemination of the new diagnostic criteria (JDDW scale) proposed during the Japan Digestive Disease Week (JDDW) in 2004 and Manual for Serious Side-Effects of DILI (Manual) published in April 2008. An anonymous questionnaire for DILI was conducted for 6 weeks starting on 20 October 2008. The participants were 179 medical doctors. One hundred and fifty-seven of them belonged to the Medical Association of Nakatsu City (population: 86 000 persons), which is located in northern Kyushu, and 22 physicians working in a core hospital, Nakatsu Municipal Hospital. Seventy-four percent of the responding doctors with 13 various specialties had experienced DILI cases. The three most frequent causative drugs were antibiotics, folk medicines and drugs for the circulatory system. DILI associated with folk medicines was encountered mostly after 2000. The doctors' recognition of the JDDW scale and Manual were as low as 17% and 29%, respectively. This survey revealed that the results of the national investigations conducted by the Japan Society of Hepatology (JSH) reflect the current state of DILI in local areas in which there is no hospital with Members of the Board of Councilors of the JSH. Widespread utilization of the Manual and JDDW scale by local doctors must be facilitated for early diagnosis of DILI and the prevention of severe conditions. [ABSTRACT FROM AUTHOR]

Two hundred and eighty seven Japanese cases of drug induced liver injury were assessed by the diagnostic scale of the International Consensus Meeting (ICM). They were classified to the hepatocellular (55%), mixed (24%) and cholestatic (22%) type according to the type of liver injury. Five cases were diagnosed as ‘unrelated’, since the reaction occurred more than 15 days after stopping the drug. The remaining 282 cases were classified to 69 cases of ‘highly probable’, 170 cases of ‘probable’, 39 cases of ‘possible’, and four cases of ‘unlikely’. The cases with positive drug-lymphocyte stimulation test (DLST) and with eosinophilia distributed to higher scores. Although the diagnostic scale of the ICM was found to be also useful for Japanese cases, the modification of the scale including the data of DLST and eosinophilia together with some other modifications were recommended in the view of the present status of Japan. Using the modified diagnostic scale, the 287 cases were classified to 173 cases of ‘highly probable’, 102 cases of ‘‘probable’, 11 cases of ‘possible’, and one case of ‘unlikely’. Although the modified diagnostic scale seems better than the original one, further assessment of the modified scale using many Japanese cases is needed for the further improvement of the scale. [Copyright &y& Elsevier]

Eighty-five Japanese patients with drug-induced liver injury were assessed by criteria of Consensus Meetings in Europe on causality assessment of drug-induced liver injury. Histopathological investigation was performed for all patients to confirm the diagnosis. We divided these patients into two groups by the date of disease onset. Cases before 1989 were defined as past cases, and those after 1990 as recent cases, because the clinical-pathological characteristics of drug-induced liver injury have changed due to the ability to diagnose hepatitis C virus infection since 1990. Fifty-seven patients with drug-induced liver injury were enrolled as past cases, and 28 as recent cases. For past cases, the results of assessment by the criteria of Consensus Meetings in Europe were as follows: ‘very likely’: 14 patients (25%), ‘likely’: 23 patients (40%), ‘possible’: 15 patients (26%), ‘dubious’: five patients (9%), and ‘unlikely’: none (0%). For recent cases, the results were as follows: ‘very likely’: six patients (22%), ‘likely’: 14 patients (42%), ‘possible’: six patients (22%), ‘dubious’: two patients (7%), and ‘unlikely’: none (0%). There were no differences between the past and recent cases in distribution of assessment. More than 90% of patients were assessed as ‘possible’ or more, and the remaining seven patients were assessed as ‘dubious’. No patients were assessed as ‘unlikely’. Five of seven patients assessed as ‘dubious’ had long-term cholestasis, and two had alcohol consumption. These results indicated that the criteria of Consensus Meetings in Europe were useful for diagnosing drug-induced liver injury in Japanese patients. [Copyright &y& Elsevier]

Background: With the growth and sophistication of laparoscopic surgery, increased attention is now being focused on safety and complications.Methods: In an attempt to address questions regarding the safety of laparoscopic surgery, a retrospective study of the time period from January 1991 to December 1995 was conducted by the Study Group of Endoscopic Surgery in Kyushu, Japan.Results: The response rate was 84.4% (152 of 180 hospitals). During the last 5 years 17,626 patients underwent endoscopic operations and 87.5% (15, 422 patients) had laparoscopic surgery while 12.5% (2,204 patients) underwent thoracoscopic surgery. In 96.6% of the hospitals a minimal open laparotomy was used. Among the various operations, a cholecystectomy was performed in the largest number of patients (13, 787). The total number of complications was 415 (2.7%), of which 156 (37.6%) were related to needle or trocar insertion. Visceral injury was found in 22 patients (0.14%): major vessel injury in 10, gastrointestinal tract injury in 11, and liver injury in one patient. Abdominal wall injury was seen in 79 patients (0.52%), bleeding in 70 (0.46%), and a hernia in 9 (0.06%). Extraperitoneal insufflation occurred in 55 patients (0.36%). There was no mortality. The complication rate significantly decreased year by year after the use of laparoscopic surgery began.Conclusions: The most common complications of laparoscopic surgery are related to needle and trocar insertion. These are preventable by placement under direct vision with verification of the intraperitoneal location of the needle and trocar. [ABSTRACT FROM AUTHOR]

Unlabelled: A 3-oxo-delta4-steroid 5beta-reductase (5beta-reductase) deficiency is difficult to diagnose because severe liver damage can result in a similar pattern of metabolite excretion. We investigated the usefulness of immunoblot analysis for diagnosis of 5beta-reductase deficiency and quantitatively analysed urinary bile acids by gas chromatography-mass spectrometry in a 5-month-old Japanese boy with severe neonatal cholestasis associated with hypertyrosinaemia. A liver sample was examined by immunoblot analysis using monoclonal antibodies against 5beta-reductase. Urinary 3-oxo-delta4 bile acids accounted for 88.3% of total bile acids, 5alpha-bile acids for 0.9%, and primary bile acids for 9.1%. Immunoblot analysis of the liver tissue showed an indistinct band of 5beta-reductase.Conclusions: These findings suggest that this patient had a secondary 5beta-reductase deficiency due to severe liver damage, even though 3-oxo-delta4 bile acids constituted more than 70% of total urinary bile acids. However, the patient may possibly have had an inherited 5beta-reductase deficiency. [ABSTRACT FROM AUTHOR]

Aim: This study aims to validate Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) and confirm the feasibility of performing transplantation., Methods: We included 60 patients with acute liver injury. Demographic and clinical features were retrospectively collected, and the primary outcome was compared among 4 types: acute liver failure (ALF) with hepatic coma (n = 23), ALF without hepatic coma (n = 12), acute liver injury (n = 20), and ACLF (n = 5). Moreover, 80 transplanted patients were enrolled to compare the difficulty of transplantation between ALF (n = 8) vs non-ALF (n = 72) patients., Results: Seven patients in the ALF with hepatic coma group and 1 patient in the ACLF with hepatic coma group were transplanted. Ten patients who could not be registered for transplantation died. In univariate analysis, liver failure type (P < .0001), total bilirubin level (P = .05), and prothrombin time internationalized ratio (P < .0001) were associated with patient survival. In multivariate analysis, liver failure type was associated with patient survival (P < .0001). The respective 1-, 3-, and 5-year patient survival rates were 45.9%, 45.9%, and 45.9% for ALF patients with hepatic coma; 100.0%, 100.0%, and 100.0% for ALF patients without hepatic coma and acute liver injury; and 80.0%, 80.0%, and 80.0% for ACLF patients (P < .0001). Chronic liver disease did not affect operation time (P = .46) and bleeding volume (P = .49)., Conclusion: Patients diagnosed with ACLF via Japanese criteria presented significantly higher survival rates than ALF patients with hepatic coma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Gefitinib and erlotinib have minor differences in their chemical structures, and thus it remains unclear whether the hepatotoxicity induced by one compound is affected by the other. The case of a patient who developed erlotinib-induced liver injury and was then treated with gefitinib without hepatic toxicity or disease progression is presented.Case Presentation: A 31-year-old Japanese woman, who never smoked and who was diagnosed as having lung adenocarcinoma with carcinomatous meningitis, was treated with erlotinib. She developed erlotinib-induced liver injury after four weeks of treatment. The treatment was stopped right away, but the symptoms of meningitis re-appeared immediately. Gefitinib treatment was started and continued without recurrence of drug-induced liver injury.Conclusion: Gefitinib appears to be a potential treatment option after erlotinib-induced liver injury. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to examine the association between contrast extravasation (CE) on initial computed tomography (CT) scan and pseudoaneurysm (PSA) development in pediatric blunt splenic and/or liver injury., Methods: We conducted a multi-institutional retrospective study in cases of blunt splenic and/or hepatic injury who underwent an initial attempt of nonoperative management. A logistic regression model was used to compare PSA formation and CE on initial CT scan, and the area under the receiver operating characteristic curve (AUC) with and without CE was used to assess the predictive performance of CE for PSA formation., Results: Of 236 cases enrolled from 10 institutions, PSA formation was observed in 17 (7.2%). Multivariate analysis showed a significant association between CE on initial CT scan and increased incidence of PSA formation (odds ratio, 4.96; 95% confidence interval, 1.37-18.0). There was no statistically significant association between the grade of injury and PSA formation. The AUC improved from 0.75 (0.64-0.87) to 0.80 (0.70-0.91) with CE., Conclusion: Active CE on initial CT scan was an independent predictor of PSA formation. Selective use of follow-up CT in children who showed CE on initial CT may provide early identification of PSA formation, regardless of injury grade., Level of Evidence: Prognostic and epidemiological, level III., Competing Interests: Disclosure The authors declare no conflicts of interest or sources of funding regarding this work., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The article discusses research being done on drug-induced liver injury (DILI) between older and younger patients in Japan between January 1997 and December 2006. It references a study by H. Takikawa, Y. Murata et al., published in the 2009 issue of "Hepatology Research." The study considered the hepatoxicity of Chinese herbal medicines and dietary supplements. A comparison of the Takikawa study with a study by Tameda et al. on DILI is presented.

Objectives: To show the characteristics and therapeutic trends of renal trauma in Japan using a nationwide database., Methods: All renal trauma cases from the Diagnosis Procedure Combination database during 6 months of each year from 2006 to 2008 were included in the analysis. The following variables were considered: demographics, ambulance use, comorbid trauma, interventions, mechanism of injury and the Abbreviated Injury Scale. Patients were divided into two groups by trauma range: limited to rib, abdomen and pelvis (group A) or more extended (including supradiaphragmatic regions or lower extremities; group B). Rib fracture impact was assessed as a predictor of comorbid organ trauma. The incidences of angioembolization failure and nephrectomy were also evaluated., Results: A total of 1505 renal trauma cases (1014 and 491 in groups A and B, respectively) were identified. Comorbid trauma in the liver, spleen and lumbar/pelvic fractures were 7.4%, 5.6% and 5.1% in group A and 24.0%, 11.2% and 17.5% in group B, respectively. The rates of angioembolization (and its failure proportion), nephrectomy, transfusion and mortality were 7.9% (12.5%), 3.3%, 15.6% and 1.1% in group A, and 17.1% (11.9%), 2.6%, 28.3% and 8.1% in group B, respectively. Risks of coincident traumas in the liver, spleen and pelvic fracture were 2.23, 2.35 and 2.72 times higher if a rib fracture was observed. The incidences of renal trauma and nephrectomy (per 100 000 person-years) were estimated as 2.06 and 0.063, respectively., Conclusions: Angioembolization failure is not rare, and nephrectomy is an important last resort. Patients with comorbid rib fracture should be explored for coincident traumas., (© 2012 The Japanese Urological Association.)

Cadmium fluoride (CdF) is commonly used as an insulator for ulta high speed mass telecommunications equipment, and there is a considerable risk that industrial workers will inhale CdF particles. Despite the possibility that acute exposure can cause harmful systemic effects, there are no studies to date that address the health consequences of acute CdF exposure. This study therefore aimed to determine the acute lethal dose of CdF and its effects on various target organs, including the liver and kidney. We also determined the effect of CdF on serum electrolytes and acid-base balance. The effective lethal dose was determined and dose-response study was conducted after intravenous administration of CdF in rats. The 24 h LD(50) of CdF was determined to be 3.29 mg/kg. The dose-response study used doses of 1.34, 2.67, 4.01 mg/kg CdF. Saline or sodium fluoride solution were used for controles. Severe hepatocellular injury was induced at doses greater than 2.67 mg/kg, as demonstrated by AST and ALT activities greater than 1,500 IU/l in rats injected with a dose of 4.01 mg/kg. Acute renal failure was induced at doses greater than 2.67 mg/kg. Decreased serum Ca, increased serum K and metabolic acidosis were induced at a dose of 4.01 mg/kg. Decreased serum Ca was caused by exposure to ionized F. CdF has the strongest lethal and hepatic toxicity among all Cd containing compounds.

Objective: To clarify information on and frequency of complications as well as mortality rate after radiofrequency ablation (RFA) for hepatocellular carcinoma., Methods: The results of a questionnaire obtained mainly from members of the Osaka Liver Cancer Study Group at 43 departments of 38 facilities were analyzed in order to clarify the current status of RFA, and information on and frequency of complications and death occurring after RFA., Results: Between January 1999 and May 2002, a total of 3,891 RFA therapies were performed percutaneously in 2,542 patients, laparoscopically in 23, and operatively in 49 (2,614 patients in total). Complications were observed in 207 of 2,614 patients (7.9%), and 9 (0.3%) died within 3 months after RFA. Among these 9 nonsurvivors, 3 had liver failure, 3 rapid progression and sarcomatous changes, 1 biliary injury, 1 gastrointestinal bleeding, and 1 acute myocardial infarction. The departments that treated larger numbers of patients per month had a smaller number of complications and deaths., Conclusion: It is possible that complications of RFA can be reduced by gathering experience., (Copyright 2007 S. Karger AG, Basel.)

Background: In hepatocellular carcinoma (HCC), new tumors develop in the residual liver within a few years after hepatectomy. However, the biological risk factors of multifocal occurrence of cancers remains unclear. In this study, the thymidine phosphorylase (TP) activity, which is known as an angiogenic factor, of cancerous and non-cancerous liver tissues in HCC was analyzed to determine its suitability as a biological marker of the multifocal occurrence of HCCs., Materials and Methods: Fresh tissues (tumor: HCC and adjacent liver tissue: N-HCC) from 63 patients with HCC and normal liver tissues (NL) from 6 patients without HCC were obtained. The TP activities of the tissues were analyzed by an enzyme-linked immunosorbent assay (ELISA)., Results: The mean TP activity of 63 HCCs (136 U/mg protein) was higher than that of 63 N-HCCs (81 U/mg protein) and that of 6 NLs (47 U/mg protein, p < 0.001). Multifocal occurrence of HCCs were detected in 17 patients. In these 17 patients, the mean TP activity of HCCs (145 U/mg protein) was not different from that of HCCs from the remaining 46 patients (133 U/mg protein, p = 0.272), however the mean TP activity of N-HCCs (110 U/mg protein) was significantly higher than that of N-HCCs from the remaining 46 patients (71 U/mg protein, p = 0.038). Moreover, only a high TP activity of N-HCCs was detected as a significant risk factor of multifocal occurrence of HCCs., Conclusion: Patients who have tumors with high TP activity in the non-cancerous livers may have a risk of multifocal occurrence of HCCs in the residual liver.