Liver injury associated with drug intake during pregnancy

Kamath, Padmanabh; Kamath, Ashwin; Ullal, Sonali

doi:10.4254/wjh.v13.i7.747

Cited by 11 publications

(16 citation statements)

References 112 publications

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“…Liver injury is described under three categories, hepatocellular, cholestatic and mixed type based on the liver enzyme which are elevated at diagnosis 1. A ratio of alanine transaminase (ALT)/alkaline phosphatase (ALP) of more than or equal to five is indicative of hepatocellular injury, whereas a ratio less than or equal to two is suggestive of cholestasis.…”

Section: Investigationsmentioning

confidence: 99%

Acute liver injury in pregnancy

Murali,

Jose,

Giliyar

2024

BMJ Case Rep

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A woman in her fifth month of pregnancy presented to the outpatient department with vomiting, generalised itching and yellowish discolouration of the skin for 1 week. No history of rashes, fever, pain abdomen or altered stools. In view of four pregnancy losses previously, she was evaluated to have antiphospholipid antibody syndrome and was advised low molecular weight heparin. She was a known type-II diabetic on insulin. Prophylactic oral dydrogesterone and natural micronised progesterone were started at a local hospital 2 months prior, in view of threatened abortion. Investigations revealed grossly elevated serum bilirubin and liver enzymes. Other blood investigations were unremarkable and abdominal ultrasonography was normal. The most likely diagnosis in this case, is drug-induced liver injury due to oral progestin consumption. Causality assessment by Roussel Uclaf Causality Assessment Model was used to establish the diagnosis. High doses of progestin over a prolonged period resulted in acute hepatic toxicity causing itching, jaundice and transaminitis. Cautious use of progestins in appropriate dosage is recommended during pregnancy.

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Section: Investigationsmentioning

confidence: 99%

Acute liver injury in pregnancy

Murali,

Jose,

Giliyar

2024

BMJ Case Rep

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“…Among these factors, DILI is a major cause of acute liver failure (ALF) and one of the leading indications for liver transplantation ( Chalasani et al, 2015 ; Xu et al, 2022 ). It's reported that the annual incidence of DILI in the general population ranges between 13 and 24 cases per 100,000 inhabitants ( Sgro et al, 2002 ; Bjornsson et al, 2013 ; Shen et al, 2019 ; Kamath et al, 2021 ). DILI is a rare potential complication in pregnant women, but it can adversely affect both the mother and the fetus.…”

Section: Introductionmentioning

confidence: 99%

“…DILI is a rare potential complication in pregnant women, but it can adversely affect both the mother and the fetus. Clinical trials seldomly study drug’s hepatoxic effects in pregnant women due to ethical and safety concerns unless the drug is specifically used in pregnant women ( Kamath et al, 2021 ). It is therefore essential to establish a research model relevant to human fetal livers in order to study the drug’s hepatotoxicity in fetuses.…”

Section: Introductionmentioning

confidence: 99%

High-throughput bioengineering of homogenous and functional human-induced pluripotent stem cells-derived liver organoids via micropatterning technique

Jiang

et al. 2022

Front. Bioeng. Biotechnol.

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Human pluripotent stem cell-derived liver organoids are emerging as more human-relevant in vitro models for studying liver diseases and hepatotoxicity than traditional hepatocyte cultures and animal models. The generation of liver organoids is based on the Matrigel dome method. However, the organoids constructed by this method display significant heterogeneity in their morphology, size, and maturity. Additionally, the formed organoid is randomly encapsulated in the Matrigel dome, which is not convenient for in situ staining and imaging. Here, we demonstrate an approach to generate a novel type of liver organoids via micropatterning technique. This approach enables the reproducible and high-throughput formation of bioengineered fetal liver organoids with uniform morphology and deterministic size and location in a multiwell plate. The liver organoids constructed by this technique closely recapitulate some critical features of human liver development at the fetal stage, including fetal liver-specific gene and protein expression, glycogen storage, lipid accumulation, and protein secretion. Additionally, the organoids allow whole-mount in-situ staining and imaging. Overall, this new type of liver organoids is compatible with the pharmaceutical industry’s widely-used preclinical drug discovery tools and will facilitate liver drug screening and hepatotoxic assessment.

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“…Doxycycline, azithromycin, chloramphenicol, and rifamycins are useful in treating the disease to varying extents, with most studies supporting the use of doxycycline 2 . Doxycycline is generally contraindicated for use in pregnancy due to concerns of possible musculoskeletal and dental defects in the fetus and hepatotoxicity in the mother 3,4 . However, drugs other than doxycycline are not useful to treat all rickettsial diseases, such as anaplasmosis and ehrlichiosis, and the patient outcomes also may be comparatively inferior 5 …”

Section: Introductionmentioning

confidence: 99%

“…2 Doxycycline is generally contraindicated for use in pregnancy due to concerns of possible musculoskeletal and dental defects in the fetus and hepatotoxicity in the mother. 3,4 However, drugs other than doxycycline are not useful to treat all rickettsial diseases, such as anaplasmosis and ehrlichiosis, and the patient outcomes also may be comparatively inferior. 5 The Centers for Disease Control and Prevention recommends the use of doxycycline in pregnancy, although it does acknowledge that, based on the available evidence, a teratogenic risk cannot be completely ruled out.…”

Section: Introductionmentioning

confidence: 99%

Doxycycline use and adverse pregnancy or neonatal outcomes: A descriptive study using the United States Food and Drug Administration Adverse Event Reporting System database

Kaundinnyayana

Kamath

2022

Health Science Reports

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Background and Aims Doxycycline is recommended for use in rickettsial diseases. The available evidence regarding its safety for rickettsial infection in pregnancy is limited. Our study aimed to describe the adverse events of doxycycline when used during pregnancy for any indication, in terms of adverse maternal and/or neonatal outcomes, using the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods We used the OpenVigil software for extracting the safety reports from the United States submitted to the FAERS from 2004 to 2021. We manually reviewed reports of doxycycline use resulting in adverse pregnancy outcomes or congenital anomalies to describe the patient and safety event characteristics. Results From 2004 to 2021, 59 individual case safety reports containing preferred terms indicative of drug exposure during pregnancy or drug‐induced adverse fetal outcomes were identified in the FAERS database. Following deduplication and manual review, 20 relevant adverse event reports were obtained. Doxycycline was the suspect medication in 13/20 (65%) reports. The common adverse event terms reported were premature delivery/baby in 6 reports, spontaneous abortion in 6, intrauterine death in 2, and various congenital anomalies in the rest. Fifty percent of the safety reports contained other medications which could have potentially caused the outcome. Conclusions The number of reported events in the FAERS database of adverse pregnancy/neonatal outcomes following doxycycline use is small, similar to the numbers reported from large cohort or surveillance studies. Given the presence of concomitant medications that could have contributed to the outcome, there does not seem to be a strong signal of harm, although this needs to be confirmed by surveillance studies.

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Liver injury associated with drug intake during pregnancy

Cited by 11 publications

References 112 publications

Acute liver injury in pregnancy

Acute liver injury in pregnancy

High-throughput bioengineering of homogenous and functional human-induced pluripotent stem cells-derived liver organoids via micropatterning technique

Doxycycline use and adverse pregnancy or neonatal outcomes: A descriptive study using the United States Food and Drug Administration Adverse Event Reporting System database

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