Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration

Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration
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DOI:
10.1002/lt.21568
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发表时间:
2008-10-01
影响因子:
4.6
通讯作者:
Rela, Mohamed
Rela, Mohamed
中科院分区:
医学2区
文献类型:
--
作者:
Quaglia, Alberto;Portmann, Bernard C.;Rela, Mohamed

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辅助性肝移植(ALT)允许对急性肝功能衰竭(ALF)患者的肝脏再生进行一系列评估。1994年至2004年,49名ALF患者[32名成人(中位年龄23岁,范围16-40岁)和17名儿童(中位年龄12岁,范围1-15岁)]在国王学院医院接受ALT治疗。血清阴性肝衰竭24例,对乙酰氨基酚中毒15例,乙肝病毒感染4例,药物性肝衰竭3例,自身免疫性肝炎2例,蘑菇中毒1例。9名没有ALT后自然肝组织学检查的患者被排除在审查之外。所有扑热息痛、乙肝病毒和药物相关的患者都有弥漫性损伤。12名血清阴性患者和1名自身免疫性肝炎患者有地图样损伤。9例醋氨酚诱导的ALF患者,9例血清阴性患者,2例药源性ALF患者,3例乙肝患者,1例自身免疫性患者恢复至接近正常的自然肝脏,无明显瘢痕形成。肝切除时弥漫性坏死区肝细胞增殖率为27.4%(3.1%~69.4%),ALT后8d肝细胞增殖率急剧下降,为ALT后最小的月和年。总而言之,在ALF患者中,肝损伤弥漫性模式--主要是扑热息痛毒性--的ALT患者,移植后几天内肝细胞就会在天然肝脏中发生增殖。如果损伤是MAP样的(大多数是血清阴性的ALF),再生似乎涉及到可变的肝细胞增殖和潜在的导管状肝细胞生成,但由于样本的差异,顺序评估很困难。在ALT时肝细胞完全丧失的情况下,组织学恢复的可能性似乎很小。
Auxiliary liver transplantation (ALT) permits the serial assessment of regeneration in livers of patients with acute liver failure (ALF). Forty-nine ALF patients [32 adults (median age, 23 years; range, 16-40 years) and 17 children (median age, 12 years; range, 1-15 years)] underwent ALT between 1994 and 2004 at King's College Hospital. Twenty-four patients had seronegative liver failure, 15 had acetaminophen toxicity, 4 had hepatitis B virus (HBV) infection, 3 had drug-induced liver failure, 2 had autoimmune hepatitis, and 1 had mushroom poisoning. Nine patients without post-ALT native liver histology were excluded from review. All acetaminophen-induced, HBV, and drug-related patients had diffuse injury. Twelve seronegative patients and the autoimmune hepatitis patient had a map-like injury. On follow-up, 9 acetaminophen-induced patients, 9 seronegative patients, 2 drug-induced ALF patients, 3 HBV patients, and the autoimmune patient recovered to a near-normal native liver with inconsequential scarring. The hepatocyte proliferative rate in diffuse necrosis was 27.4% (range, 3.1%-69.4%) at hepatectomy and sharply decreased after 8 days post-ALT, being minimal months and years after ALT. In conclusion, in patients undergoing ALT for ALF with a diffuse pattern of liver injury-mainly acetaminophen toxicity-hepatocyte proliferation occurs in the native liver within a few days of transplantation. If the injury is map-like (most cases of seronegative ALF), regeneration seems to involve variable hepatocellular proliferation and potential ductular hepatopoiesis, but sequential assessment is difficult because of sampling variation. The likelihood of histological recovery appears to be minimal in livers with total hepatocyte loss at the time of ALT.