Significance of megamitochondria in alcoholic liver disease

Chedid, Antonio; Mendenhall, Charles L.; Tosch, Thomas J.; Chen, T.; Rabin, Lionel; Garcia-Pont, P.; Goldberg, Stephen J.; Kiernan, Thomas; Seeff, Leonard B.; Sorrell, Michael F.; Tamburro, Carlo H.; Weesner, Robert E.; Zetterman, Rowen K.

doi:10.1016/0016-5085(86)90253-2

Cited by 121 publications

(70 citation statements)

References 16 publications

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“…The zonal distribution of these structures has not previously been examined closely, and the function of these structures within the hepatocytes remains undetermined in NASH. Unlike previous findings in alcohol-related liver disease, 4 our results show that there is no difference in the abundance of the MMC between low-stage NASH (fibrosis stages 1 and 2) and high-stage NASH (fibrosis stages 3 and 4). These structures seem to be randomly distributed among zones, regardless of the fibrosis stage of NASH (Fig.…”

Section: Discussioncontrasting

confidence: 99%

“…The explanation for these discrepancies is not certain, although a possibility is that we did not differentiate the various shapes of the megamitochondria in the present study. Our results also differed from the work of Chedid et al, 4 in which more megamitochondria were found in milder forms of alcoholic steatohepatitis. However, Chedid et al suggested that this represented an adaptive role of the megamitochondria in an early and more benign disease stage.…”

Section: Discussioncontrasting

confidence: 99%

“…Although once described as "para"-crystalline, optical diffraction studies by Sternlieb and Berger 2 demonstrated that the crystalline inclusions are true crystals, although their composition remains uncertain. Similar abnormalities have been described in Wilson disease, 3 alcoholic steatohepatitis (where they were believed to be markers of early or less severe alcoholrelated injury), 4 and more recently in nonalcoholic fatty liver, where their presence has been correlated indirectly with oxidative stress and their absence noted when cirrhosis develops. 5,6 We previously estimated that megamitochondria with crystalline inclusions (MMC) are seen in 5% to 15% of hepatocytes in nonalcoholic steatohepatitis (NASH) patients and in 5% to 10% of the mitochondria within an afflicted cell.…”

supporting

confidence: 63%

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The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis

et al. 2004

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Megamitochondria with crystalline inclusions (MMC) have been previously described in nonalcoholic fatty liver; however, their distribution within hepatic zones is unknown. We sought to determine this distribution from the core liver biopsy specimens of 31 patients: 8 males and 23 females, age range 21 to 72 years. Twenty-nine showed evidence of nonalcoholic steatohepatitis (NASH) on biopsy with steatosis, inflammation, varying degree of fibrosis, ballooned hepatocytes, and Mallory hyaline, and two patients had cryptogenic cirrhosis thought to represent "burned out" NASH. Identified by transmission electron microscopy, the abundance of MMC was compared between low-stage (fibrosis stages 1 and 2) and high-stage (fibrosis stages 3 and 4) groups and between zones with or without difference in fibrosis stage. Regardless of stage, the MMC were distributed equally in all zones and were abundant similarly in low-and high-stage groups. This abundance did not correlate with the degree of oxidative stress (4-hydroxynonenal staining) or with the abundance of ballooned hepatocytes. Consistent with age as a risk factor for more severe disease, the median age for the low-stage group was significantly lower than that of the high-stage group (P ‫؍‬ .003). In conclusion, in NASH, the MMC seem to be distributed randomly among zones and without variation in abundance, regardless of the fibrosis stage. The exact function of these structures remains to be defined. In this study, their presence did not seem to correlate with the light microscopic injury pattern represented by ballooned hepatocytes or degree of oxidative stress defined by immunostaining for 4-hydroxynonenal. (HEPATOLOGY

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

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confidence: 63%

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The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis

et al. 2004

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“…16,18,19 We found that patients who died during hospitalization, presented with more deranged laboratory parameters and more advanced liver disease in form of ascites and higher grade of hepatic encephalopathy.…”

Section: Discussionmentioning

confidence: 81%

“…Furthermore, the individual components of the MELD score have been described as individual predictors of mortality from alcoholic hepatitis in various studies. 16,17 The most recent approach is based on Lille model to identify persons at high risk of death. Patients above the ideal cutoff of 0.45 showed a marked decrease in 6-month survival and this cutoff was able to identify approximately 75% of the observed deaths.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the Model for End-stage Liver Disease (MELD) Score in Predicting Prognosis of Patients with Alcoholic Hepatitis

Goyal¹,

Dixit²,

Jain³

et al. 2014

Journal of Clinical and Experimental Hepatology

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Background: Traditionally, Maddrey discriminant function (DF) score has been used for stratifying the prognosis of alcoholic hepatitis. Recently, the Model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator. Another new prognostic approach, Lille model has been also suggested to accurately identify patients at high risk of death. Therefore, this prospective study was aimed to compare MELD, DF, Child-Turcotte-Pugh (CTP) scores and Lille model for predicting the short-term mortality in Indian patients with alcoholic hepatitis. Methods: We calculated the DF, CTP, MELD and Lille scores in patients hospitalized with alcoholic hepatitis & evaluated if the scores predicted in-hospital mortality. Results: A total of 104 patients were enrolled and thirty-two (30.7%) patients died during the hospitalization (2-30 days). Admission DF score (OR 1.1, P < 0.04), CTP (OR 2, P < 0.05) MELD score (OR 2.2, P < 0.005) and first week MELD score (OR 1.1, P < 0.05) were independently associated with in-hospital mortality. The area under the receiver-operating curve (AUROC) for the admission and day 7 MELD score was significantly higher than CTP score and was comparable to DF score and Lille model ( . The MELD score >14 at admission and >12 at day 7 had high sensitivity and specificity in predicting short-term mortality (96%, 89% and 95%, 98% respectively). The cutoff of 0.45 for the Lille model was able to identify 79% of the observed deaths, whereas DF score $32 for DF were able to identify 85%. Conclusion: MELD score, as a predictive model for assessment of short-term mortality in alcoholic hepatitis is better than CTP and comparable to DF and Lille model. ( J CLIN EXP HEPATOL 2014;4:19-24)

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Death due to alcoholic complications in a young woman with a severe eating disorder: A case report

Catterson

Pryor

Burke

et al. 1997

Int. J. Eat. Disord.

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Significance of megamitochondria in alcoholic liver disease

Cited by 121 publications

References 16 publications

The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis

The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis

Assessment of the Model for End-stage Liver Disease (MELD) Score in Predicting Prognosis of Patients with Alcoholic Hepatitis

Death due to alcoholic complications in a young woman with a severe eating disorder: A case report

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