Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

Weng, Honglei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tailing

doi:10.3389/fphys.2015.00178

Cited by 45 publications

(64 citation statements)

References 95 publications

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“…This pathophysiological process activates liver progenitor cells in order to encourage regeneration. The final clinical outcome of ACLF depends on the balance between progenitor cell‐mediated regeneration and the loss of liver parenchyma and function within a relatively short‐time period . Those who recovered from this fulminant insult presumably have a relatively greater number of functional hepatic progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

Long‐term outcomes of patients with hepatitis B virus‐related acute on chronic liver failure: An observational cohort study

Lin

Zhang

et al. 2019

Liver International

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Background and Aims The long‐term outcomes of patients with hepatitis B virus‐related acute on chronic liver failure (HBV‐ACLF) remain unclear. The main aim of the study was to compare the 5‐year survival rate and incidence rate of hepatocellular carcinoma (HCC) between patients with HBV‐ACLF and HBV‐cirrhosis. Methods Clinical data of patients with ACLF, compensated cirrhosis and decompensated cirrhosis who survived more than 3 months after diagnosis were collected. The survival rate and cumulative incidence of HCC were compared. The Cox regression was used to evaluate risk factors for outcomes. Results A total of 814 patients were included in the analysis, including 122 (14.99%) patients with ACLF, 450 (55.28%) patients with compensated cirrhosis and 242 (29.73%) patients with decompensated cirrhosis. The 5‐year survival rate of patients with ACLF (97.2%) was higher than patients with decompensated cirrhosis (86.0%), but was lower than patients with compensated cirrhosis (99.1%). The 5‐year HCC incidence rate was the highest in the decompensated cirrhosis group (14.6%, P < 0.05), while no statistical differences were found between patients with ACLF (3.5%) and compensated cirrhosis (9.5%). The episode of ACLF did not increase the risk of HCC and the overall survival when compared with patients with cirrhosis. In ACLF subgroup analysis, the age, rather than the presence of cirrhosis, was independently associated with both mortality and incidence of HCC. Conclusions ACLF patients who survived the first 3 months had a better long‐term prognosis than decompensated cirrhosis, while the HCC risk was comparable to compensated cirrhosis. HCC surveillance is strongly recommended for these patients.

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Section: Discussionmentioning

confidence: 99%

Long‐term outcomes of patients with hepatitis B virus‐related acute on chronic liver failure: An observational cohort study

Lin

Zhang

et al. 2019

Liver International

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“…45 In a study of hepatocyte proliferation rate after ALF treated by auxiliary liver transplantation by Quaglia et al, 46 hepatocyte proliferation (as assessed immunohistochemically by the cell proliferation marker Ki67) peaked in the first few days to 1 week at the time of the auxiliary liver transplant, dropping to low levels by the second week. Minimal hepatocyte proliferation was evident months to years later.…”

Section: Nonzonal Necrosismentioning

confidence: 98%

The Pathology of Acute Liver Failure

Lefkowitch

2016

Advances in Anatomic Pathology

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Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells. This paper reviews the liver pathology in ALF, including forms of zonal necrosis and their etiologies.

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“…Some FHF cases however recover spontaneously 42 . LPC have been frequently detected in liver tissues from patients with FHF 43 , but their significance in recovery was not assessed until recently 43 . There is also evidence that many of the hepatocyte nodules observed in patients with micro-nodular cirrhosis are derived from cholangiocytes, providing a new angle of research for liver cell biologists 44 .…”

Section: Possible Origins Of Lpcmentioning

confidence: 99%

Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease

2015

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Evidence from human histopathology and experimental studies with rodents and zebrafish has shown that hepatocytes and cholangiocytes may function as facultative stem cells for each other in conditions of impaired regeneration. The interpretation of the findings derived from these studies has generated considerable discussion and some controversies. This review examines the evidence obtained from the different experimental models and considers implications that these studies may have for human liver disease. Few topics of liver tissue biology have attracted as much attention as the existence of liver-specific tissue stem cells. Routine liver histology reveals two types of epithelial cells, hepatocytes and cholangiocytes (also known as biliary epithelial cells). Endothelial cells line the hepatic capillaries (sinusoids), with macrophages (Kupffer cells) interspersed along the sinusoid lumen. Stellate cells exist under the sinusoids and in close proximity to hepatocytes. None of these cells appears to have functions of a fully committed tissue specific stem cell, analogous to the cells of the intestinal crypts, the basal layer of the epidermis, bone marrow stem cells, etc. Hepatocytes and cholangiocytes can be easily identified based on their morphology and cell-specific biomarkers. Hepatocytes and cholangiocytes, however, often have mutually mixed expression of biomarkers in pathologic conditions. In patients with fulminant hepatic failure (FHF), there is rampant proliferation of cholangiocytes organized in ductular structures (“ductular reaction”1, 2). Many of these cholangiocytes (known as ductular hepatocytes) express biomarkers associated with hepatocytes, (HNF4, albumin, HEPPAR3, etc.). They are seen surrounding cells ranging in size from small to typical hepatocytes, and with a gradient of expression of cholangiocyte-associated biomarkers (e.g. EpCAM) decreasing from the periphery to the center (Regenerative Clusters: see Figure 1). It is not clear in FHF whether cholangiocytes give rise to hepatocytes or vice versa. Most cells in liver tissues from patients with FHF, however, are typical cholangiocytes, so it is likely that these are the source of hepatocytes detected in the (more rarely seen) regenerative clusters. The term “progenitor” cells (used in tissue biology to describe the immediate progeny of stem cells) is most often used to collectively cover these proliferating cells with mixed hepatobiliary biomarkers in rats, mice, humans and fish. This may be inappropriate because it implies that such cells are generated by tissue-specific stem cells, even though such stem cells are not identifiable in the liver. Though the term “progenitor cells” does not fulfill criteria used in other tissues, it does imply a transition from one type of cell differentiation to another. Thus, the term has persisted in hepatic biology, even though it is not entirely appropriate. However, in most of the scenarios below, hepatocytes and cholangiocytes appear to function as “facultative stem cells” for each other. Thus the ter...

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Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

Cited by 45 publications

References 95 publications

Long‐term outcomes of patients with hepatitis B virus‐related acute on chronic liver failure: An observational cohort study

Long‐term outcomes of patients with hepatitis B virus‐related acute on chronic liver failure: An observational cohort study

The Pathology of Acute Liver Failure

Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease

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