Iodipamide hepatotoxicity in the rat.

Iodipamide meglumine (Cholografin) has been implicated in several cases of liver injury in patients. The present study was designed to assess the hepatotoxic potential of this drug in rats. Iodipamide administered intraperitoneally or intravenously caused a characteristic type of necrosis which began in the midzonal area and spread to the centrilobular region. Only rats weighing 400 g or more developed necrosis when the dose administered was 2 mmol/kg. Rats weighing 200 g failed to develop liver necrosis even when given 3 mmol/kg. Selenium deficiency and pretreatment with 3-methylcholanthrene protected against liver necrosis due to iodipamide. Phenobarbital pretreatment provided little or no protection. Kidney tubular necrosis was also observed but occurred in young rats and in selenium-deficient rats which developed no liver necrosis. These results indicate that iodipamide is a hepatotoxin in rats. There are a number of factors, age being the most striking, that modify its hepatotoxicity.     

Sucralfate therapy in NSAID bleeding gastropathy.

BACKGROUND AND AIMS: A randomized, double-blind, placebo-controlled, multicenter study was conducted to assess the efficacy of 2 g sucralfate suspension in treating gastric mucosal lesions caused by long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Only patients given NSAIDs continuously for at least 2 months with positive fecal occult blood (FOB) and endoscopically confirmed mild to moderate mucosal lesions (Lanza scale, grades 2-4) were included. After 1-week run-in phase, patients were stratified into 2 groups according to gastropathy-related symptoms during the preceding 7 days (symptomatic vs. asymptomatic) and randomized to 2 g (10 mL) of sucralfate suspension or placebo twice a day over a 6-week period. NSAIDs were given according to each patient's dosage schedule and always after meals. RESULTS: Twenty-five patients received sucralfate and 25 received placebo. At the end of the study, 68% (17/25) of patients given sucralfate had no lesions (Lanza grade 0) on endoscopy compared with 35% (8/23) in controls (P = 0.042). The Lanza grades in patients given sucralfate were significantly improved compared with the placebo patients (P = 0.022). CONCLUSIONS: In this target population selected according to positive FOB test and endoscopic evidence of mucosal injury, chronic administration of sucralfate significantly decreased NSAID-induced gastric erosions.     

Propafenone hepatotoxicity: report of two new cases

Two patients developed acute cholestatic hepatitis during treatment with propafenone. Viral infections, alcohol abuse, hepatotoxicity by other drugs, and biliary obstruction were excluded as causes. In one patient, liver biopsy showed changes consistent with a drug-associated injury. Another patient had autoimmune antibodies (ANA) in the serum. Following propafenone withdrawal, the clinical and biochemical profiles of both patients improved. Hepatic toxicity from the antiarrhythmic drug propafenone is highly uncommon. Moreover, the drug produces hepatocellular injury by an unknown mechanism. Most of the seven cases reported here had acute cholestatic hepatitis after a latency period of two to four weeks.     

Heparin-induced hepatotoxicity.

Heparin-induced hepatotoxicity is well described in the literature, but rarely recognized clinically. Two cases were recently encountered. In the first case, elevated aminotransferase levels occurred after four days of heparin therapy. In the second case, enzyme levels increased after only 8 h of heparin treatment. To the authors' knowledge, this short time interval between the administration of heparin and liver enzyme elevations has not been described. The objective of this report is to increase the clinical awareness of this interesting and under-recognized biochemical observation.     

Predicting NSAID related ulcers--assessment of clinical and pathological risk factors and importance of differences in NSAID.

Although ulcers are often associated with non-steroidal anti-inflammatory drugs (NSAIDs) little is known about the feasibility of predicting their development in patients taking NSAIDs. In addition, the ulcerogenic potentials of the newer NSAIDs, taken on long term basis, have not been compared with those of more established preparations. The aim of this study was to identify the clinical and pathological characteristics of patients at a higher risk of NSAID induced ulcers, measure the ulcerogenic potential of a variety of NSAIDs, and test the effect of these potentials on the predictability of ulceration. Altogether 190 long term NSAID users were studied. The presence of abdominal complaints, previous history of ulcers, arthritis related physical disability, anaemia, gastritis, and Helicobacter pylori status were all assessed as possible risk factors. NSAIDs were classified into established drugs (group I), and newer agents (group II). Group I included naproxen, indomethacin, diclofenac, ketoprofen, piroxicam, and flurbiprofen. Group II included fenbufen, nabumetone, ibuprofen, etodolac, azapropazone, and tiaprofenic acid. Of 63 ulcers identified in the study group, 51 (81%) were seen in group I NSAID patients (51 of 132, 39%) compared with 12 ulcers in group II (12 of 58, 21%), p < 0.02; estimated relative risk (ERR): 2.41). In group I, 25 ulcers were found in 38 patients with abdominal pain (25 of 38, 66%, p < 0.01, ERR: 5.03); 18 in 25 (72%) patients with a previous history of ulcers (p < 0.001, ERR: 5.77), 26 in 44 (59%) patients with debilitating arthritis (p < 0.001, ERR 3.64), and 35 in 73 (48%) patients with H pylori associated gastritis (p < 0.01, ERR: 2.48). The presence of these factors in group II patients did not influence the risk of ulceration. Group I NSAIDs were more likely to be associated with chemical gastritis and to intensify H pylori related damage. Although silent ulcers are not uncommon in patients taking NSAIDs, recognition of the risk factors might helps predict a significant number (up to 81%), especially in those receiving group I NSAIDs.     

Isoniazid hepatotoxicity in children.

One hundred sixteen children, including 50 less than 10 years of age, received isoniazid therapy for tuberculous infection. Determinations of serum glutamic oxaloacetic transaminase concentrations at time of institution of therapy, 6 to 20 weeks later, and again at the completion of the therapeutic course, showed no evidence of hepatotoxicity. Clinical symptoms were never such that discontinuation of therapy was necessary.     

静脉应用胺碘酮致急性肝损害六例临床分析

目的分析静脉应用胺碘酮致急性肝损害的临床特点及转归。方法对我院2001年1月至2005年1月静脉应用胺碘酮后致急性肝损害6例患者应用的适应证、剂量、肝损害出现的时间及转归进行分析。结果6例患者出现急性肝损害前静脉应用胺碘酮剂量为290—3000（1322．5±973．8）mg。6例患者用药后（40±29）h肝酶开始升高，天门冬氨酸氨基转移酶（AST）峰值为199—9885（2992±3453）U／L，丙氨酸氨基转移酶（ALT）峰值为247—6750（2583±2402）U／L。停药护肝降酶治疗后（28±17）d肝酶降至正常。结论静脉应用胺碘酮可以导致急性肝损害，应及时监测肝脏功能。     

Visible small-intestinal mucosal injury in chronic NSAID users.

BACKGROUND & AIMS: Patients who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs) have an increased risk for small-intestinal mucosal ulceration and bleeding, which may present as anemia of undetermined gastrointestinal origin or protein loss. The prevalence and severity of small-intestinal lesions remains unclear. Our aim was to assess the frequency of NSAID-induced small-bowel injury among chronic NSAID users. METHODS: Ambulatory patients with various types of arthritides who took NSAIDs daily (>3 mo duration) or took either acetaminophen alone or nothing were enrolled in the study. All patients fasted overnight and underwent wireless video capsule endoscopy. Two investigators, blind to therapy, reviewed each video beginning after the pylorus. Lesions were scored as normal, red spots, small erosions, large erosions, or ulcers. An ulcer was defined as a larger lesion with apparent depth and a definite rim. RESULTS: Forty-one patients, 36 men and 5 women, ages ranging from 22 to 66 years (mean age, 49.8 y) were analyzed including 21 chronic NSAID users and 20 control patients. Small-bowel injury was seen in 71% of NSAID users compared with 10% of controls (P < .001). Injury was mild (few or no erosions, absence of large erosions/ulcers) in 10 NSAID users compared with 2 controls. Five NSAID users had major (>4 erosions or large ulcers/ulcers) damage compared with none in the control group. There were no complications or problems with the capsule endoscopy procedure. CONCLUSIONS: Endoscopically evident small-intestinal mucosal injury is very common among chronic NSAID users. The role of endoscopically evident injury in unexplained iron-deficiency anemia and hypoalbuminemia among chronic NSAID users remains undetermined.     

Possible hepatotoxicity of Doxidan.

A patient with chronic constipation developed liver injury and leukopenia following the ingestion of Doxidan, a combination drug consisting of danthron and dioctyl calcium sulfosuccinate. Evidence is presented that dioctyl calcium sulfosuccinate may have potentiated the toxicity. The liver injury was associated with deposition of IgE in the Kupffer cells. The mechanism of toxicity remains unclear.     

含丙硫异烟胺和对氨基水杨酸治疗方案发生药物性肝损伤129例临床分析

目的 了解含丙硫异烟胺(Pto)和(或)对氨基水杨酸(PAS)的抗结核治疗方案发生药物性肝损伤(DILI)情况,为及时合理治疗DILI提供依据.方法 回顾性分析2008年1月至2013年1月北京胸科医院应用含Pto和(或)PAS方案治疗的结核病患者发生DILI情况,对DILI的发生时间、年龄、性别、严重程度、临床表现及转归等方面进行分析.两组间比较采用x2检验.结果 含Pto 和(或)PAS方案的患者共1714例,治疗中发生DILI者226例,排除病毒性肝炎、酒精性肝病及不能确定抗结核药物所致DILI者97例,抗结核药物所致DILI共129例,总发生率为7.5％ (129/1714),女性DILI发生率(9.2％,59/641)高于男性(6.5％,70/1073),差异有统计学意义(x2=4.143,P＜0.05).DILI多发生于用药后1～2个月,以2～4周多见(30.2％,39/129),47.3％ (61/129)的患者发生DILI时无明显临床症状.在不同抗结核药物组合方案中,Pto+ PAS+吡嗪酰胺方案的DILI发生率最高(20.7％,19/92),且显著高于Pto+吡嗪酰胺方案(9.8％,8/82),差异有统计学意义(x2=3.927,P＜0.05).结论 应用含Pto和(或)PAS等二线抗结核药物时应警惕DILI的发生,尤其是女性及Pto+ PAS+吡嗪酰胺联合应用患者,在抗结核治疗中无明显临床表现时也应定期复查肝功能,做到早发现、早治疗DILI,避免严重DILI的发生.