amoxicillin-potassium-clavulanate-combination and Cholestasis

Drug-induced liver injury includes a spectrum of pathologies, some related to the mode of injury, some to the cell type primarily damaged. Among these, drug-induced bile duct injury is characterized by the destruction of the biliary epithelium following exposure to a drug. Most of the drugs associated with bile duct injury cause immune-mediated lesions to the epithelium of interlobular ducts. These share common histopathological features with primary biliary cholangitis, such as inflammation and necrosis at the expense of cholangiocytes and, if the insult persists, bile duct loss and biliary cirrhosis. Some drugs selectively target larger ducts. Such injury is often dose-dependent and thought to be the result of intrinsic drug toxicity. The histological changes resemble those seen in primary sclerosing cholangitis. This overview focuses on the clinical and pathological features of bile duct injury associated with drug treatment and on the immunological and biochemical effects that drugs exert on the biliary epithelium. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Topics: Amoxicillin-Potassium Clavulanate Combination; Bile Acids and Salts; Bile Ducts; Biomarkers; Biotransformation; Carbamazepine; Chemical and Drug Induced Liver Injury; Cholagogues and Choleretics; Cholangitis, Sclerosing; Cholestasis; Epithelial Cells; Humans; Liver

There is a growing body of evidence that amoxicillin-clavulanic acid may induce severe adverse effects in patients.. A medline search of case reports and reviews on amoxicillin-clavulanic acid induced adverse effects was performed. The criteria of a consensus conference on the reporting of drug-induced liver disease were applied.. Amoxicillin-clavulanic acid has been associated with drug-induced cholestatic hepatitis in 208 reported patients. In 153 evaluable patients there were 106 males and 47 females with a mean age of 60 years (1-90). Liver associated co-morbidity and co-medication does not play a major part in the development of disease. In most instances respiratory tract infection and sinusitis were treated by amoxicillin-clavulanic acid with a mean treatment duration of 13.9 days and a reaction time until first onset of jaundice of 25.2 days average. Infection and cholestasis from other reason were ruled out in most patients. Liver injury was classified according to laboratory parameters to be hepatocellular in 35 patients, cholestatic in 24 patients and mixed in 83 patients. Normalization of liver enzymes was observed 11.5 weeks after onset of drug administration (average); three of 153 patients did not survive the adverse event.. Amoxicillin-clavulanic acid which is marketed for treatment of respiratory infections and sinusitis/otitis may in some cases induce severe adverse effects and death in patients of different age, especially if they are on multidrug regimens. In consideration of this fact many authors recommend to reflect carefully, whether amoxicillin-clavulanic acid is necessary in treatment of patients with localized or uncomplicated infections. If amoxicillin-clavulanic acid is prescribed, transaminase, alkaline phosphatase and bilirubin tests should be obtained within the first two weeks and after four to five weeks after beginning of treatment to recognize early enough undesired hepatic side effects.

Topics: Adolescent; Adult; Age Distribution; Americas; Amoxicillin-Potassium Clavulanate Combination; Asia; Australia; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cholestasis; Comorbidity; Europe; Female; Humans; Infant; Liver Diseases; Liver Failure; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Sex Distribution

Amoxicillin/clavulanic acid is a widely used antibiotic. Hepatic dysfunction is a rare adverse reaction associated with this combination antibiotic. We report the case of a 40-yr-old woman with a somewhat unusual presentation of amoxicillin/clavulanate-related cholestatic hepatotoxicity and multiple duodenal erosions whose diagnosis was delayed until inadvertent rechallenge with the antibiotic combination. The relevant literature is also reviewed and discussed. The diagnosis may be missed because the onset of signs/symptoms may occur several weeks after the cessation of therapy. The hepatic dysfunction, which may be severe and is more prevalent in elderly patients, is usually reversible, although chronic liver disease and deaths have been reported. Immunological hypersensitivity is considered to be the most likely mechanism resulting in liver injury. Amoxicillin/clavulanate should be used with caution in patients with underlying liver disease and in the elderly.

Topics: Acute Disease; Adult; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Therapy, Combination; Female; Humans; Recurrence; Sinusitis

Drug-induced liver injury (DILI) is a frequent cause of liver injury and acute liver failure. We aimed to review all hospitalized DILI cases in a tertiary Egyptian center from January 2015 through January 2016. Cases with elevated alanine aminotransferase more than 3-fold and/or alkaline phosphatase more than 2-fold the upper limit of normal value were prospectively recruited and followed for one year. Drug history, liver biopsy whenever feasible and application of Roussel Uclaf Causality Assessment Method (RUCAM) were the diagnostic prerequisites after exclusion of other etiologies of acute liver injury. In order of frequency, the incriminated drugs were: Diclofenac (31 cases, 41.3%), amoxicillin-clavulanate (14 cases, 18.7%), halothane toxicity (8 cases, 10.7%), ibuprofen (4 cases, 5.3%), Khat (3 cases, 4%), tramadol (3 cases, 4%), Sofosbuvir with ribavirin (2 cases, 2.7%), and acetylsalicylic acid (2 cases, 2.7%) with one offending drug in 93.3% of cases. Forty-four cases (58.7%) were males; while 56 cases (74.7%) had HCV related chronic liver disease. Thirty-two cases (42.7%) presented with pattern of hepatocellular injury, while 23 cases (30.7%) were with cholestasis, and 20 cases (20.7%) with a mixed hepatocellular/cholestatic injury. One case received a transplant (0.75%), 7 cases died (9.3%), 23 cases (30.6%) developed liver decompensation (hepatic encephalopathy and ascites), and 44 cases completely resolved (58.7%). In conclusion, Diclofenac is the commonest offender in DILI occurrence in an Egyptian cohort. Age and prothrombin concentration were the only predictors of unfavorable outcomes of DILI.

Topics: Adult; Alanine Transaminase; Alkaline Phosphatase; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Cholestasis; Cyclooxygenase Inhibitors; Diclofenac; Egypt; Female; Hepatic Encephalopathy; Humans; Liver; Liver Failure, Acute; Male; Middle Aged; Prognosis; Prospective Studies; Tertiary Care Centers

Amoxicillin-clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs.. Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials.. One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI.. AC-DILI causes a moderately severe, mixed hepatocellular-cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation.

Topics: Age Factors; Alanine Transaminase; Alkaline Phosphatase; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Bilirubin; Black or African American; Chemical and Drug Induced Liver Injury; Cholestasis; Cohort Studies; Ethnicity; Female; Hispanic or Latino; Humans; Jaundice; Jaundice, Obstructive; Liver; Male; Middle Aged; Prospective Studies; Registries; Sex Distribution; Time Factors; United States; White People

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Cholestasis; Humans; Liver Function Tests; Male; Middle Aged; Recurrence

Topics: Acute Disease; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Cholestasis; Humans; Male

Topics: Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Biopsy; Cholestasis; Female; Humans; Liver; Pneumonia

Topics: Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Therapy, Combination; Humans; Terminology as Topic

Topics: Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Therapy, Combination; Humans; Male; Middle Aged

Toxic hepatitis secondary to amoxycillin-clavulanic acid is an infrequent clinical picture. Most of the cases are reported to have a benign course. We report two cases of severe hepatic failure following amoxycillin-clavulanic acid use. One of the cases had cholestatic features primarily, and the other had hepatocellular injury prominently. The first case had also findings of trombotic trombositic purpura and had a fatal course.

Topics: Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Jaundice; Male

Hepatotoxity associated with amoxicillin/clavulanic acid is usually a self-limited disease with complete recovery. We report a rapidly progressing liver disease with ductopenia and portal fibrosis in a 3-year-old boy treated with Augmentin.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bile Duct Diseases; Bile Ducts, Intrahepatic; Child, Preschool; Cholestasis; Drug Eruptions; Drug Therapy, Combination; Humans; Jaundice; Liver; Liver Cirrhosis; Male

A 55-year-old man was admitted because of cholestatic jaundice. Extrahepatic obstruction and viral causes were excluded. A diagnosis of liver damage due to the combination preparation amoxicillin and clavulanic acid (Augmentin) was made. The patient had an uneventful recovery. It is pointed out that in case of cholestatic jaundice drug-induced cholestasis should be suspected early in the course. History taking is an important tool. If a suspected drug is found other causes of the disease can be excluded with simple tests.

Topics: Amoxicillin-Potassium Clavulanate Combination; Cholestasis; Humans; Male; Middle Aged; Sinusitis; Treatment Outcome

We described a patient with history of chronic hepatitis B in whom cholestatic hepatitis occurred after amoxicillin/clavulanic acid (Augmentin) therapy, which to our knowledge is the first case reported in Asia. An atypical serology profile of hepatitis B virus (HBV) markers, demonstrated by negative hepatitis B surface antigen (HBsAg) associated with transient positivity of hepatitis B e antigen (HBeAg) and HBV DNA, was noted during the development of cholestasis.

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cholestasis; Clavulanic Acids; DNA, Viral; Drug Therapy, Combination; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Humans; Male

In four patients, two men and two women aged 73, 68, 84 and 72 years respectively, reversible cholestatic liver injury was seen 28-35 days after the start of treatment with amoxycillin-clavulanic acid (Augmentin). This rare complication of amoxycillin-clavulanic acid treatment is characterized by a relatively long latent period before the onset of symptoms or biochemical abnormalities, which makes early recognition difficult. The mechanism responsible for this idiosyncratic cholestasis is unknown.

Topics: Aged; Aged, 80 and over; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cholestasis; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Male

Topics: Adult; Adverse Drug Reaction Reporting Systems; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Australia; Cholestasis; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Male

A case of cholestatic jaundice following treatment with Augmentin is reported. The awareness of hepatotoxicity due to drug should help to avoid unnecessary invasive procedures in the evaluation of this reversible condition.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cholestasis; Clavulanic Acids; Drug Therapy, Combination; Humans; Male; Middle Aged; Pancreatitis

Topics: Adverse Drug Reaction Reporting Systems; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Clavulanic Acids; Drug Therapy, Combination; Female; Floxacillin; Humans; Middle Aged

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Clavulanic Acids; Drug Therapy, Combination; Humans; Male

To report a case of death due to Augmentin-induced cholestatic hepatitis and discuss a possible drug interaction between Augmentin and oestrogenic steroids.. An 81-year-old man, on oestrogen therapy for prostatic malignancy, presented with obstructive jaundice one week after completing a four-week course of Augmentin for recurrent urinary tract infection. Liver biopsy showed features of a drug-induced cholestatic hepatitis with bile duct injury. His clinical course was marked by progressive deterioration with increasing jaundice and the development of hepatic encephalopathy. A course of prednisolone did not result in any improvement and he died nine weeks after the onset of jaundice.. The cholestatic hepatitis induced by Augmentin is usually reversible but may be progressive, leading to death. The concurrent administration of ethinyloestradiol, a potentially cholestatic agent, may have altered the susceptibility and/or course of the reaction in this patient.

Topics: Aged; Aged, 80 and over; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Clavulanic Acids; Drug Interactions; Estradiol Congeners; Humans; Male; Prostatic Neoplasms; Urinary Tract Infections

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Chemical and Drug Induced Liver Injury; Cholestasis; Clavulanic Acids; Drug Therapy, Combination; Humans

Amoxicillin-clavulanate potassium, a semisynthetic penicillin-beta-lactamase inhibitor combination drug, is a widely used oral antibiotic. Since the marketing of this drug in 1984, more than nine million prescriptions have been dispensed. Several cases of jaundice and hepatic dysfunction have been observed and reported to the Food and Drug Administration and the pharmaceutical company (Beecham Laboratories). A review of 18 of these cases revealed a predominantly cholestatic syndrome in 7 cases, a mixed hepatocellular-cholestatic picture in 6 cases, a hepatocellular pattern in 4, and in 1 case the injury could not be clearly defined. No fatalities were observed, and all cases had reversal of hepatic dysfunction upon cessation of the drug. Fever was present in 2 patients and eosinophilia in 6 of 10 patients tested, suggesting a hypersensitivity phenomenon contributing to hepatic dysfunction in some of the cases. A percutaneous liver biopsy had been performed in 7 of 18 patients and four of these were reviewed by the authors. Prominent centrizonal cholestasis was seen in all four biopsies. Additionally, 1 patient had periportal and another had midzonal cholestasis. Although infrequent, recognition of an often benign cholestatic syndrome associated with amoxicillin-clavulanate potassium will help avoid unnecessary, invasive, and expensive diagnostic studies and also ameliorate symptoms upon withdrawal of the drug.

Topics: Adult; Aged; Aged, 80 and over; Alanine Transaminase; Alkaline Phosphatase; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Aspartate Aminotransferases; Cholestasis; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Liver; Male; Middle Aged; Prognosis