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Liver Giant Mitochondria Revisited 412 J Clin Pathol 1992;45:412-415 Liver giant mitochondria revisited N J Robertson, C H Kendall J Clin Pathol: first published as 10.1136/jcp.45.5.412 on 1 May 1992. Downloaded from Abstract alcohol induced liver damage and the presence Aims: To examine the correlation be- of ICRBs. In a study by Chedid et al' in 1986, tween the severity of alcohol induced ICRBs were observed most frequently in liver liver damage and the presence of biopsies exhibiting mild degrees of alcohol intracytoplasmic red bodies (defined as induced damage. Junge et al2 in 1987 obtained periodic acid-Schiff diastase negative, similar results. However, in a study by globular, hyaline cytoplasmic inclusions Bruguera et al' in 1977 the frequency of larger in size than the hepatocyte ICRBs in liver biopsies from alcoholic nucleolus). To investigate the incidence patients was found to be unrelated to the of intracytoplasmic red bodies (ICRBs) nature of the histological changes present. in non-alcoholic liver disease. The significance of ICRBs with respect to Methods: Liver biopsy specimens from non-alcoholic liver disease remains equally 53 patients with alcoholic liver disease unclear. The main purposes of this study are and 50 patients with a variety of non- therefore: (1) to examine the correlation be- alcohol related liver diseases were tween the severity of alcohol induced liver examined by light microscopy for the damage and the presence of ICRBs; (2) to presence of ICRBs. For the 53 patients investigate the incidence of ICRBs in non- with alcoholic liver disease an assess- alcoholic liver disease. ment of recent alcohol consumption was Since the advent of transmission electron made indirectly from measurements of microscopy giant mitochondria have been red cell volume (MCV) and plasma identified in hepatocytes in liver biopsies y-glutamyl transferase (GGT). In addi- exhibiting both alcohol induced damage and tion, 10 liver biopsies with alcohol ICRBs.'" It has therefore followed that induced changes and ICRBs were exam- ICRBs seen in liver biopsies exhibiting alco- ined by electron microscopy for the hol induced damage have been interpreted as presence of mitochondrial aberrations being giant mitochondria, providing they are http://jcp.bmj.com/ including enlargement. periodic acid-Schiff diastase negative. There Results: ICRBs were detected in 18 of the has remained, however, some doubt as to the 53 liver biopsy specimens showing alco- exact nature of ICRBs, and a further aim of hol induced changes, and were more this study is to investigate liver biopsies con- abundant in those showing more advan- taining ICRBs ultrastructurally. ced changes. Those patients whose liver specimens contained ICRBs were found Methods on September 27, 2021 by guest. Protected copyright. to have a significantly higher mean The material consists of 103 liver biopsy plasma GGT activity and mean MCV specimens from 102 adults and one child; 53 than those individuals whose liver biopsy were from patients who either gave, or were specimens did not contain ICRBs. Two of strongly suspected of having, a recent history the 50 liver biopsy specimens showing of regular high alcohol consumption. Average non-alcohol induced changes contained daily intakes in excess of 60 g for men and ICRBs. Giant mitochondria were not 40 g for women are considered high and are detected by electron microscopy, but associated with increased morbidity and mor- this may reflect sampling. tality from a variety of diseases.5 And all 53 Conclusions: The results of this study biopsy specimens exhibited histological indicate that ICRBs are definitely as- changes consistent with an alcoholic aetiology: sociated with alcoholic liver disease and 50 liver biopsy specimens were from patients are more likely to be found in liver having a variety of non-alcohol related liver biopsy specimens showing more advan- diseases, and these included the following: ced alcohol induced damage, and when primary biliary cirrhosis (nine cases), chronic recent alcohol consumption has been active hepatitis (seven cases), chronic persis- Department of high. tent hepatitis (one case), sarcoidosis (two Histopathology, Leicester Royal cases), miliary tuberculosis (one case), Reye's Infirmary, Leicester Globular intracytoplasmic red bodies (ICRBs) syndrome (one child case), ascending cholan- LE1 SWW have long been recognised by light micro- gitis (one case), chronic pericholangitis (one N Robertson scopy in hepatocytes in liver biopsies, and C H Kendall case), chronic large bile duct obstruction (one especially in those liver biopsies from patients case), a-l-antitrypsin deficiency (one case) and Correspondence to: with Dr N J Robertson alcoholic liver disease. There is, non-specific changes (25 cases). All biopsy Accepted for publication however, conflicting evidence in the literature specimens were obtained between 1983 and 8 October 1991 as to the correlation between the severity of 1989. Liver giant mitochondria revisited 413 Table I Histological category and the presence of ICRBs in liver biopsy specimensfrom patients with and without alcohol induced liver damage Number of ICRBs Number Specimens of positive J Clin Pathol: first published as 10.1136/jcp.45.5.412 on 1 May 1992. Downloaded from Histological category (-) (+ (+ +) (+ + +) biopsies for ICRBs Group I(n = 53) Fattychangealone 21 5 0 0 26 5 (19-2%) Patients with alcohol Fatty change with 12 5 0 1 18 6 (33 3%) induced liver damage alcoholic hepatitis or fibrosis or both Cirrhosis with or 2 3 1 3 9 7 (77-7%) without any other alcohol induced changes Group II (n = 50) Patients with non-alcohol A variety ofnon- 48 2 0 0 50 2 (4%) related liver damage alcohol related changes of various severity All the liver biopsy specimens exhibiting ICRBs throughout the biopsy specimen were alcohol induced changes were categorised for denoted (+ + +), and (+ +) denoted an subsequent data analysis according to the intermediate number of ICRBs. An absence nature and severity of the histological changes of ICRBs was registered as (-). present. The categories were defined as For 10 cases with histological evidence of follows: fatty change alone, fatty change with both alcohol induced damage and ICRBs, tiny alcoholic hepatitis or fibrosis or both, and cubes of paraffin wax embedded tissue were cirrhosis with or without any other alcohol dewaxed in xylene, post fixed in 1% osmium induced changes. tetroxide and embedded in resin. Semi-thin The quantity of alcohol consumed around sections for orientation were stained with 1% the time of liver biopsy was assessed indirectly toluidine blue, and finally ultra-thin 90 nm from measurements of red cell volume (MCV) sections were stained with saturated uranyl and plasma y-glutamyl transferase (GGT). acetate/Reynold's citrate and examined in a Both these parameters are used clinically as Jeol 100 CX transmission electron micro- markers of alcohol consumption. Using upper scope. reference limits of 98 fl for MCV and 50 IU/l for GGT, Chick et al6 observed macrocytosis in 10 and increased GGT in 15 out of 30 Results company directors admitting to a daily alcohol In sections stained with haematoxylin and intake of more than 65 g. eosin ICRBs appeared as weakly eosinophilic All liver biopsy specimens were processed rounded bodies in otherwise normal for haematoxylin and eosin, chromotrope hepatocytes and in hepatocytes containing fat http://jcp.bmj.com/ aniline blue (CAB), Martius scarlet blue vacuoles. Their identification was much enhan- (MSB), and periodic acid-Schiff (PAS) before ced, however, on staining with CAB and MSB and after diastase digestion. Intracytoplasmic where they appeared bright red, and confusion red bodies (ICRBs) were defined as well cir- with red blood cells was eliminated as MSB cumscribed, globular, hyaline, intracytoplas- stained these cells yellow. milz bodies which stained bright red with CAB In all biopsy specimens where ICRBs were and MSB, and failed to stain with PAS after identified, they occurred in a minority of on September 27, 2021 by guest. Protected copyright. diastase digestion. Only red bodies larger than hepatocytes and their acinar distribution was the hepatocyte nucleolus were recorded and, entirely random. ICRBs ranged in size between in order to avoid confusion with red blood 2 and 10 gm and their number within cells, only red bodies seen to be clearly within hepatocytes varied markedly; some hepato- the hepatocyte cytoplasm and within the same cytes contained only one while others con- focal plane as the nucleus were recorded. tained two or more. Confusion with red blood cells was minimised Table 1 relates the presence of ICRBs to the with MSB staining as red blood cells appear histological categories defined earlier. Group I yellow with this staining method. comprises 53 liver biopsy specimens from The number of ICRBs per unit area of a patients with alcohol induced liver damage, section of liver biopsy specimen was variable, and group II comprises 50 patients with a both within the same biopsy and between variety of non-alcohol related liver diseases. different biopsies. ICRBs were subjectively ICRBs were observed in 18 liver biopsy semiquantified as (+ + +), (+ +), (+)), and specimens from group I and in two from group (-), according to their relative frequency in II, the latter being from two cases of primary the biopsy specimen. When only occasional biliary cirrhosis. ICRBs were seen in five of 26 ICRBs were detected in the entire biopsy liver biopsy specimens showing fatty change specimen this was denoted (+). Numerous alone and in seven of nine showing alcoholic Table 2 Mean plasma GGT activity and mean MCV in relation to the presence and absence of ICRBs Mean plasma GGT activity Number of (IU/I) (SD) Mean MCV (fl) (SD) liver biopsy specimens ICRBs present (n = 18) 478-5 (98-2) 1059 (4 8) 18 ICRBs absent (n = 35) 225-5 (60 3) 94-0 (2 1) 35 414 Robertson, Kendall cirrhosis. Of the 18 biopsy specimens showing ted of abusing alcohol. Notwithstanding this, fatty change with alcoholic hepatitis and/or the evidence strongly suggests that ICRBs are fibrosis six contained ICRBs.
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