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Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China.

Zhu Y, Li YG, Wang JB, Liu SH, Wang LF, Zhao YL, Bai YF, Wang ZX, Li JY, Xiao XH - Gut Liver (2015)

Bottom Line: Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found.Twenty-four children (34.8%) developed chronic DILI.Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury.

View Article: PubMed Central - PubMed

Affiliation: Integrative Medicine Center, 302 Military Hospital, China.

ABSTRACT

Background/aims: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited.

Methods: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied.

Results: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs. 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs. 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs. 18/39, p=0.031).

Conclusions: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.

No MeSH data available.


Related in: MedlinePlus

Examples of the most common pathological injury patterns. (A) Acute hepatitis due to herbal decoction with Ephedra sinica for respiratory infection. Biopsy shows confluent and bridging necrosis around the central vein and significant lobular inflammation. (B) Chronic hepatitis due to the combination of cephalosporin antibiotics and antipyretic analgesics for fever of unknown origin. Liver biopsy shows fibrous septa formation and moderate interface hepatitis. (C) Acute cholestasis due to azithromycin. Biopsy showed hepatocellular and canalicular cholestasis with bile plugs. (D, E) Cholestatic hepatitis due to herbal decoction with Polygonum multiflorum for vitiligo. Biopsy showed prominent canalicular cholestasis, confluent necrosis, and neutrophilic infiltration (H&E stain, ×200; for orientation, V indicates the central vein, P indicates the portal area, and arrows indicate cholestasis).
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f2-gnl-09-525: Examples of the most common pathological injury patterns. (A) Acute hepatitis due to herbal decoction with Ephedra sinica for respiratory infection. Biopsy shows confluent and bridging necrosis around the central vein and significant lobular inflammation. (B) Chronic hepatitis due to the combination of cephalosporin antibiotics and antipyretic analgesics for fever of unknown origin. Liver biopsy shows fibrous septa formation and moderate interface hepatitis. (C) Acute cholestasis due to azithromycin. Biopsy showed hepatocellular and canalicular cholestasis with bile plugs. (D, E) Cholestatic hepatitis due to herbal decoction with Polygonum multiflorum for vitiligo. Biopsy showed prominent canalicular cholestasis, confluent necrosis, and neutrophilic infiltration (H&E stain, ×200; for orientation, V indicates the central vein, P indicates the portal area, and arrows indicate cholestasis).

Mentions: Liver biopsies were performed in 59 children (85.5%) and the pathological patterns of injury in 55 children were listed in Table 1, whereas four of the cases could not be classified into any pattern because of mild histological changes. Liver cell degeneration, necrosis, and lobular inflammation were common findings, with typical confluent necrosis in 11 cases (18.6%), bridging necrosis in five cases (8.5%), and submassive necrosis in one case who did not present with clinical features of liver failure. Twenty-nine biopsies (49.2%) showed various degrees of interface hepatitis. Hepatocellular and/or canalicular cholestasis were observed in 16 cases (27.1%). Twenty-nine biopsies (49.2%) demonstrated eosinophil infiltration and none had duct sclerosis or loss. Typical examples of pathological patterns were described in Fig. 2. In 15 cases (25.4%), the liver biopsy after the normalization of liver biochemistry still showed the histologic features of chronic hepatitis, such as moderate portal inflammation, interface hepatitis, fibroplastic proliferation, and fibrous septa formation. All three cases with ALF showed the pathological characteristics of cholestatic hepatitis involving confluent and bridging necrosis, cholestasis, interface hepatitis, and fibrous septa formation, but none demonstrated submassive necrosis.


Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China.

Zhu Y, Li YG, Wang JB, Liu SH, Wang LF, Zhao YL, Bai YF, Wang ZX, Li JY, Xiao XH - Gut Liver (2015)

Examples of the most common pathological injury patterns. (A) Acute hepatitis due to herbal decoction with Ephedra sinica for respiratory infection. Biopsy shows confluent and bridging necrosis around the central vein and significant lobular inflammation. (B) Chronic hepatitis due to the combination of cephalosporin antibiotics and antipyretic analgesics for fever of unknown origin. Liver biopsy shows fibrous septa formation and moderate interface hepatitis. (C) Acute cholestasis due to azithromycin. Biopsy showed hepatocellular and canalicular cholestasis with bile plugs. (D, E) Cholestatic hepatitis due to herbal decoction with Polygonum multiflorum for vitiligo. Biopsy showed prominent canalicular cholestasis, confluent necrosis, and neutrophilic infiltration (H&E stain, ×200; for orientation, V indicates the central vein, P indicates the portal area, and arrows indicate cholestasis).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4477997&req=5

f2-gnl-09-525: Examples of the most common pathological injury patterns. (A) Acute hepatitis due to herbal decoction with Ephedra sinica for respiratory infection. Biopsy shows confluent and bridging necrosis around the central vein and significant lobular inflammation. (B) Chronic hepatitis due to the combination of cephalosporin antibiotics and antipyretic analgesics for fever of unknown origin. Liver biopsy shows fibrous septa formation and moderate interface hepatitis. (C) Acute cholestasis due to azithromycin. Biopsy showed hepatocellular and canalicular cholestasis with bile plugs. (D, E) Cholestatic hepatitis due to herbal decoction with Polygonum multiflorum for vitiligo. Biopsy showed prominent canalicular cholestasis, confluent necrosis, and neutrophilic infiltration (H&E stain, ×200; for orientation, V indicates the central vein, P indicates the portal area, and arrows indicate cholestasis).
Mentions: Liver biopsies were performed in 59 children (85.5%) and the pathological patterns of injury in 55 children were listed in Table 1, whereas four of the cases could not be classified into any pattern because of mild histological changes. Liver cell degeneration, necrosis, and lobular inflammation were common findings, with typical confluent necrosis in 11 cases (18.6%), bridging necrosis in five cases (8.5%), and submassive necrosis in one case who did not present with clinical features of liver failure. Twenty-nine biopsies (49.2%) showed various degrees of interface hepatitis. Hepatocellular and/or canalicular cholestasis were observed in 16 cases (27.1%). Twenty-nine biopsies (49.2%) demonstrated eosinophil infiltration and none had duct sclerosis or loss. Typical examples of pathological patterns were described in Fig. 2. In 15 cases (25.4%), the liver biopsy after the normalization of liver biochemistry still showed the histologic features of chronic hepatitis, such as moderate portal inflammation, interface hepatitis, fibroplastic proliferation, and fibrous septa formation. All three cases with ALF showed the pathological characteristics of cholestatic hepatitis involving confluent and bridging necrosis, cholestasis, interface hepatitis, and fibrous septa formation, but none demonstrated submassive necrosis.

Bottom Line: Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found.Twenty-four children (34.8%) developed chronic DILI.Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury.

View Article: PubMed Central - PubMed

Affiliation: Integrative Medicine Center, 302 Military Hospital, China.

ABSTRACT

Background/aims: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited.

Methods: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied.

Results: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs. 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs. 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs. 18/39, p=0.031).

Conclusions: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.

No MeSH data available.


Related in: MedlinePlus