Necrosis Index Research Articles

Does Hepatocellular Injury in Sepsis Involve Apoptosis?

Apoptosis (A0) is a process by which cells typically undergo a form of nonnecrotic cellular suicide. A0normally allows the host to selectively delete cells from a given tissue site without producing bystander injury associated with necrosis. However, inappropriate induction of A0has been associated with a variety of acute as well as chronic pathological states and may contribute to the therapeutic nonresponsiveness frequently encountered in the septic animal/patient's organ function. In this respect, while A0has been demonstrated in a variety of immune cell tissues of septic animals it is unclear if it is present in the septic liver. Therefore, it was the aim of our study to determine if A0is evident in hepatocytes of polymicrobial septic animals. To assess this, C3H/HeN male mice were subjected to polymicrobial sepsis (cecal ligation and puncture) or sham–CLP (Sham). Hepatocytes were then harvested at 4 h (early hyperdynamic phase) or 24 h (late hypodynamic state) later, and indices of A0were assessed [cell cycle analysis of Annexin V/propidium iodide (PI) staining for flow cytometric analysis, DNA extracted, and cell death ELISA]. Plasma glutamic pyruvic transaminase (GPT) was also colorimetrically assessed as well as total viable cell yield as an index of hepatocellular necrosis. The results indicate that indices of hepatocellular A0, as determined by cell cycle analysis and cell death ELISA, were markedly increased in polymicrobial septic mice at 24 h. However, while an increase in DNA fragmentation/degradation could be consistently detected, the pattern was typically faint. Similarly, although there was an increase in Annexin V staining it was not dissociated from that of PI (necrotic index). Alternatively, necrosis (as evidenced by increased GPT levels at both 4 and 24 h) preceded the induction of all the indices of A0. Taken together, these data suggest a role for both necrosis and apoptosis in the evolution of hepatocellular injury encountered in the polymicrobial septic animal/patient which may represent a unique pattern of cell death under such conditions.

Correlation of Posterior Echo Patterns and Histopathologic Features in Invasive Ductal Carcinoma of Breast

Traditionally posterior shadowing is regarded as a malignant criterion in the evaluation of breast mass by sonogram. But on the basis of our clinical experiences of breast sonogram, we often met a breast mass without posterior shadowing later confirmed breast carcinoma through pathologic examination. For the focus of what character of pathologic breast tissue influence the posterior shadowing in breast sonogram, we analyzed retrospectively the sonographic findings of 26 histologically proven invasive ductal carcinomas. Even though invasive ductal carcinoma is the only one of the many breast cancers, it represents the greater part of breast malignancy. The posterior echo pattern was compared with various histologic characteristics, such as the amount of connective tissue, degree of elastosis, necrosis, gross circumscription, accompanying inflammation, histologic differentiation, and mitotic index. Nine breast masses (35%) demonstrated posterior echo shadowing, while 17 masses (65%) showed enhancement. The tumors with posterior echo shadowing had more abundant connective tissue, increased elastosis, and poorly demarcated margin (p

Effects and metabolism of fumarate in the perfused rat heart. A 13C mass isotopomer study.

The cardioprotective effects of fumarate have been linked to its metabolism to succinate through both oxidative and reductive pathways. To date, the relative contribution of these pathways is a subject of controversy. To address this question, we designed a protocol with 13C substrates and took advantage of 13C isotopomer analysis by gas chromatography-mass spectrometry. Rat hearts were perfused with 11 mM glucose, 1 mM lactate, 0.2 mM pyruvate, 0.2 mM [1-13C]octanoate, and 0.04 or 0.4 mM [U-13C4]fumarate. On reoxygenation after 40 min of severe hypoxia, hearts perfused with 0.4 mM fumarate showed a better recovery of contractile function and released less lactate dehydrogenase (an index of cellular necrosis) than those perfused with 0.04 mM fumarate. The 13C data showed that, in hypoxic hearts, fumarate conversion to succinate occurred only through reduction, although it accounted for only 16% of total succinate release. Most of the succinate was formed through the oxidation of alpha-ketoglutarate or its precursors (50 +/- 5%) and by another yet-unidentified pathway (34 +/- 4%). These data show that, in a model of hypoxia-reoxygenation, the cardioprotective effects of fumarate were associated with its predominant metabolism to succinate through the reductive pathway.

New collateral flow increasing early after coronary occlusion prevented myocardial necrosis in dogs.

Increases in regional myocardial blood flow (Qm) developing soon after myocardial infarction may minimize myocardial necrosis. To test this hypothesis, Qm in the area surrounding an acutely occluded coronary artery was determined successively over 4 weeks in 11 dogs. Non-radioactive colored microspheres were injected into the left atrium 5 s (Qm at this time is referred to as Q1), 3 h (Q2), 12 h (Q3), and 4 weeks (Q4) after occlusion of the coronary artery. After termination of the experiment, the heart was removed, and Qm and three indices of myocardial necrosis i.e., myocardial creatine kinase activity (CK), infarct size determined by triphenyl tetrazolium chloride stain (TTC), and myocardial fibrosis visualized by Azan-Mallory stain, were determined. Each Qm was expressed as a percentage of normal: Qm (% of normal) = [Q/Qc] ischemic area/[Q'/Qc']non-ischemic area x 100, where Qc indicates Qm determined before coronary occlusion. In the ischemic area of the left ventricle, Q1, Q2, Q3, and Q4 were 25 +/- 3%, 30 +/- 3%, 31 +/- 3%, and 42 +/- 3% of normal, respectively, in the inner layer, and 31 +/- 3%, 52 +/- 4%, 52 +/- 4%, and 77 +/- 6% of normal, respectively, in the outer layers. During the 4-week period, the increase of Qm in the outer layer was greater than that in the inner layer. The inner layer showed a small increase of flow from Q3 to Q4 (9 +/- 2%), but in the outer layer there were greater flow increases from Q1 to Q2 (21 +/- 3%) and from Q3 to Q4 (24 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum hyaluronan as a marker of liver fibrosis in chronic viral hepatitis C: effect of α-interferon therapy

Background/Aims: It has been suggested that increases in serum hyaluronan levels might be a marker of fibrosis in chronic viral hepatitis C. Patients receiving α-interferon therapy are an excellent model to determine the relationship between serum hyaluronan and liver fibrosis, since results suggest that α-interferon could reduce liver fibrosis. Methods: We studied the relationship between serum hyaluronan and histopathological indices of liver fibrosis, inflammation and necrosis, before and after α-interferon therapy (3 MU, three times weekly for 6 months), and the effect of treatment on serum hyaluronan and on histological liver fibrosis, in 52 patients. Hyaluronan levels were measured using a radiometric assay and the liver histopathological indices were scored according to the Knodell system. Results: The serum hyaluronan level correlated with the extent of liver fibrosis both before and after α-interferon therapy ( p<0.0001), but not with the histopathological indices of liver inflammation or necrosis. Parallel changes in serum hyaluronan and liver fibrosis occurred: serum hyaluronan levels feel significantly in patients in whom fibrosis improved ( p<0.01, n=11), increased significantly in patients in whom fibrosis worsened ( p<0.05, n=10), and did not change significantly in patients in whom fibrosis was unmodified ( n=31). Furthermore, fibrosis improved only when the antiviral effect of α-interferon was reflected by persistent normalization of serum alanine amino-transferase, although there was no correlation between serum hyaluronan levels and alanine amino-transferase activities. Conclusion: Serum hyaluronan thus appears to be a non-invasive index of liver fibrosis.

Anti-neutrophil serum attenuates dextran sulfate sodium-induced colonic damage in the rat.

The role of neutrophils in experimental colonic damage induced by dextran sulfate sodium is uncertain. We test the hypothesis that neutrophils are of pathogenic significance and anti-neutrophil serum will attenuate the colonic damage induced by oral dextran sulfate sodium in rats. Rabbit anti-rat neutrophil serum (anti-neutrophil serum) or control rabbit serum was administered to, and circulating neutrophil count was monitored in, rats before and during feeding of dextran sulfate sodium or regular rat diet for 2 weeks. Histologic features of mucosal damage were evaluated in hematoxylin and eosin-stained proximal and distal colonic sections by a blinded observer. Oral dextran sulfate sodium induces weight loss, diarrhea, peripheral neutrophilia, and colonic damage. Anti-neutrophil serum induced neutropenia and significantly attenuated the weight loss, the neutrophil infiltration in the colon, and the mucosal necrosis and pathologic index in the distal colon. The data showing that anti-neutrophil serum attenuates distal colonic mucosal injury induced by dextran sulfate sodium support the hypothesis that neutrophils play a pathogenic role in this model of colonic mucosal damage.

Influence of human immunodeficiency virus infection on hepatitis delta virus superinfection in chronic HBsAg carriers.

It is generally agreed that hepatitis B virus (HBV) replication is reduced by hepatitis delta virus infection (HDV) and augmented by human immunodeficiency virus (HIV) infection. However, the precise nature of the interactions between HBV, HDV and HIV is controversial. The aim of this study was to evaluate the impact of HIV infection on HBV and HDV replication, and on histological scores during delta virus superinfection in HDV-positive, chronic carriers of hepatitis B surface antigen (HBsAg). We studied 38 men and six women, 15 of whom were HIV-positive and all of whom had at least one marker of HDV infection. Serum hepatitis B e antigen (HBeAg), HBV DNA, HDV RNA, anti-delta antigen antibodies (anti-HD) IgM, anti-HD IgG and hepatitis delta antigen (HDAg) were tested for in the serum and liver, respectively; anti-hepatitis C virus (HCV) antibodies were detected using a second-generation recombinant immunoblot assay. Histological specimens were scored blindly according to Knodell's classification for periportal and intralobular necrosis, portal inflammation and fibrosis. HBV DNA was detected more frequently in the HIV-positive patients than in those who were HIV-negative (25 vs 0%; P = 0.01), while markers of HDV replication (serum anti-HD IgM, serum HDV RNA and liver HDAg) were as frequent in the HIV-positive patients (69%, 40% and 50%, respectively) as in those who were HIV-negative (75%, 52% and 30%, respectively; P > 0.05). By contrast, 31% of the HIV-positive patients were serum HDAg-positive compared to only 6% of the HIV-negative patients (P = 0.001). HDV antigenaemia and anti-HD antibodies usually fluctuated in the HIV-positive patients during follow-up. The mean Knodell score was similar in the HIV-positive (11.5 +/- 3.2) and HIV-negative (10.7 +/- 2) subgroups, as was the mean semi-quantitative index of hepatic necrosis, inflammation and fibrosis. Our results provide evidence that in HDV-positive patients: (1) HIV infection counters the inhibitory effect of HDV superinfection on HBV replication; (2) serum anti-HD IgM. HDV RNA and liver HDAg are not more frequent in HIV-positive than in HIV-negative patients, suggesting that HIV infection has no effect on HDV replication (although the significance of the increased frequency of HD antigenaemia remains unclear); (3) the histological severity of liver disease is not influenced by HIV status.

Interferon-α2b therapy reduces liver fibrosis in chronic non-a, non-b hepatitis: A quantitative histological evaluation

The aim of this study was to evaluate the effect of interferon-α on liver fibrosis with an established quantitative histochemical method for determining collagen as a marker. 59 patients (31 men, 28 women; 47 ± 14 yr) with chronic non-A, non-B hepatitis (92% with hepatitis C virus antibody) received subcutaneous injections of 3 or 1 MU recombinant interferon-α2b or placebo thrice weekly for 24 wk. Needle-biopsy sections taken before and after interferon treatment were examined for histological evaluation and collagen quantitation. Values were compared with results obtained by means of morphometrical analysis of liver collagen and Knodell scoring histological index. The index of periportal and/or bridging necrosis was the only component of Knodell's histological score significantly decreased (p < 0.05) in patients treated with 3 MU interferon compared with placebo-treated controls. The fibrosis score was not significantly changed. In contrast, liver total collagen variations measured colorimetrically and morphometrically were significantly decreased in patients treated with 3 MU and 1 MU compared with the increase observed in the placebo-treated controls (p < 0.05). From these results, we conclude that a 6-mo course of 3 MU or 1 MU interferon-α2b causes slight but nonetheless significant regression of liver fibrosis as assessed on the basis of quantitative estimation of liver collagen, irrespective of other response criteria, whereas progression of liver fibrosis can be observed in the absence of treatment. (HEPATOLOGY 1993;18:1344–1349.)

Interferon-α2b therapy reduces liver fibrosis in chronic non-A, non-B hepatitis: A quantitative histological evaluation

The aim of this study was to evaluate the effect of interferon-alpha on liver fibrosis with an established quantitative histochemical method for determining collagen as a marker. 59 patients (31 men, 28 women; 47 +/- 14 yr) with chronic non-A, non-B hepatitis (92% with hepatitis C virus antibody) received subcutaneous injections of 3 or 1 MU recombinant interferon-alpha 2b or placebo thrice weekly for 24 wk. Needle-biopsy sections taken before and after interferon treatment were examined for histological evaluation and collagen quantitation. Values were compared with results obtained by means of morphometrical analysis of liver collagen and Knodell scoring histological index. The index of periportal and/or bridging necrosis was the only component of Knodell's histological score significantly decreased (p < 0.05) in patients treated with 3 MU interferon compared with placebo-treated controls. The fibrosis score was not significantly changed. In contrast, liver total collagen variations measured colorimetrically and morphometrically were significantly decreased in patients treated with 3 MU and 1 MU compared with the increase observed in the placebo-treated controls (p < 0.05). From these results, we conclude that a 6-mo course of 3 MU or 1 MU interferon-alpha 2b causes slight but nonetheless significant regression of liver fibrosis as assessed on the basis of quantitative estimation of liver collagen, irrespective of other response criteria, whereas progression of liver fibrosis can be observed in the absence of treatment.

Comparison of magnetic resonance imaging studies with enzymatic indexes of myocardial necrosis for quantification of myocardial infarct size

To evaluate the potential of gadolinium-diethylene triamine pentaacetic acid (DTPA)-enhanced magnetic resonance imaging (MRI) in the quantification of infarct size in patients with a first acute myocardial infarction, 24 patients with a first acute myocardial infarction were studied by electrocardiographic gated MRI at a mean of 4.3 days after the acute event Multislice, singlephase, T1-weighted, spin-echo MRI in the true short-Axis plane was performed 20 minutes after intravenous injection of gadolinium-DTPA (0.15 mmol/kg of body weight). Circumscript myocardial regions of increased signal intensity on gadolinium-DTPA-enhanced images were considered to be infarcted. Infarct size (in g) was determined using Simpson's rule, and was compared with that based on cumulative release of alphahydroxybutyrate dehydrogenase activity in plasma and with peak creatine kinase-MB level in plasma. Infarct size quantified with MRI correlated well with “enzymatic” infarct size (in g equivalents) (y = 0.99x + 0.71; r = 0.93; p = 0.0001) and peak creatine kinase-MB levels (r = 0.72; p = 0.002). It is concluded that gadolinium-DTPA-enhanced MRI enables accurate quantification of infarct size in patients with a first acute myocardial infarction.

Enzymatic determinations in acute rejection after liver transplantation: preliminary report on necrosis index

The catalytic activities of some mitochondrial and cytoplasmic enzymes were measured in plasma from 19 patients after orthotopic liver transplantation, in order to detect and monitor the evolution of hepatocellular damage and to predict liver rejection. The enzymatic activities determined were: mitochondrial isoenzyme of aspartate aminotransferase, glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltranspeptidase and alkaline phosphatase. The results of all enzymatic activities were normalized by expressing them as multiples of the upper limit of the relevant reference range and then the necrosis index (NI) has been calculated. The proposed NI consists of percent ratio of the normalized mitochondrial enzymatic activities over the sum of cytoplasmic and mitochondrial normalized activities. We observed that NI values higher than 30% correctly identified all but two acute rejection events which were documented by liver biopsies showing a diagnostic sensitivity of 90%, specificity of 78% and a predictive value of 90%.

Radioprotective effect of exogenous glutathione on rat parotid glands.

The prophylactic effect of glutathione (GSH) on radiation injury in rat parotid glands was investigated. GSH was administered to male Wistar rats i.p. 15 min prior to irradiation. The necrosis index (NI) of the glands was determined histologically 24 h after a single dose of 15, 30, or 60 Gy. Total amylase activity, total protein content and wet weight of the glands were measured 30, 60 and 90 days after irradiation. Administration of GSH prior to radiation minimized acute and chronic radiation injuries as a function of the GSH dose: i.e. reduction of NI and prevention of the decrease in total amylase activity, total protein content and gland weight. The intraglandular level of non-protein-bound thiols (NPSH) and GSH increased significantly after i.p. administration of GSH, whether or not the glands were irradiated. An autoradiographic study revealed that i.p.-administered 35S-GSH was actively taken up by the glandular parenchyma, especially in the acini and ducts. It was shown that elevation of the intraglandular level of NPSH after exogenous administration of GSH protected the parotid glands from radiation injury in the rat.

Gross examination of musculoskeletal sarcomas Estimation of tumour volume and sampling for unbiased morphometry

A method for handling and gross examination of specimens from musculoskeletal sarcomas is described. The method, which can be modified to relate to modern, preoperative tumour imaging, allows an accurate estimation of tumour volume and a systematic random sampling for morphometry, which for instance permits the unbiased estimation of tumour necrosis, cellularity and mitotic index. Furthermore, sampling can be performed in such a way that stereological parameters (for the estimation of nuclear size and pleomorphism) based on 'vertical sections' can be measured. The method in no way prohibits routine sampling, for instance from specimen margins and specific areas of interest within the tumour, and with a little practice does not take much extra time.

ECG evidence of limited myocardial infarction following coronary occlusion trated by early intravenous rt-PA infuslon

Serial 12-lead surface electrocardiograms (ECGs) were analysed in 110 patients with first evolving myocardial infarction entered in a double-blind placebo-controlled trial of intravenous rt-PA within 2.5 h (mean 1.9 +/- 0.5 (SD)) of pain onset. ECG analysis was performed by two 'blinded' analysts. QRS scoring (by the modified Selvester method) was used as an index of myocardial necrosis. Patient results were analysed according to infarct location. There was no difference between the two treatment groups in ST-segment elevation or QRS score at entry or up to 24 h after symptom onset. However from 24 h, QRS score was lower in patients with anterior infarction given rt-PA than in those given placebo: 5.4 +/- 2.8 vs 7.7 +/- 4.1 (P = 0.02) at 48 h; 4.7 +/- 3.2 vs 8.0 +/- 4.0 (P = 0.01) at 4-10 days; and 4.6 +/- 3.9 vs 7.5 +/- 3.9 (P = 0.01) at 21 days. For patients with inferior infarction, rt-PA treatment also resulted in a lower QRS score although this was not significantly different from the score of the placebo group (P = 0.07). Comparison of QRS scores with ejection fraction measured from the contrast ventriculogram taken at 21 days showed a moderate correlation (r = 0.46) in patients with anterior infarction but a poor correlation in patients with inferior infarction. These ECG results indicate that in evolving anterior myocardial infarction, there is limitation of infarct size from early rt-PA infusion.

Lymphatics in Primary Cutaneous Melanoma

Using Ulex europaeus I lectin (UEA1) to demonstrate endothelial cells, we have previously shown that frequency of capillary invasion correlates closely with maximum tumor thickness in primary cutaneous melanoma. UEA1 demonstrates both vascular and lymphatic capillaries; however, only vascular capillaries possess basement membranes. In order to ascertain whether these capillaries were lymphatic or vascular, we employed a double staining technique, using UEA1 in conjunction with a monoclonal anti-type IV collagen antibody. We studied 21 primary cutaneous melanomas. Seven of the 21 included lymphatic capillaries, while 14 did not. These lymphatic capillaries were very sparse and appeared to be residual dermal lymphatics rather than a result of lymphangiogenesis. Lymphatic permeation by melanoma was not seen in any of the tumors studied. There was no apparent association among tumor thickness, level of invasion, growth phase, necrosis, regression or mitotic index, and presence of lymphatics within the melanomas. Although scanty lymphatics are present in some primary cutaneous melanomas, this study does not suggest that lymphatic permeation plays a major role in the spread of melanoma to locoregional lymph nodes.

Effect of 2,3,5‐triiodobenzoic acid on calcium level in sunflower plants and incidence of bract necrosis

Abstract Experiments were conducted with sunflower (Helianthus annuus, L.) of two inbred lines and eight cultivars grown in the field, in pots in the greenhouse or growth chamber and in nutrient solution. Water solutions of 2,3,5‐triiodobenzoic (TIBA) were sprayed over the top of the plants or added to the nutrient solution TIBA treatment resulted in induction of bract necrosis in some plants, increasing the bract necrosis index with higher TIBA concentration. TIBA had little effect on element concentration in leaves but it decreased the levels of Ca, Mg and B in bracts of plants. At a low TIBA concentration (25 μM) in the nutrient solution, young plants growing in hydroponic solution at a low Ca level, the levels of Ca and Mg of young leaves were decreased but TIBA treatment did not affect significantly the levels of these elements in roots. Since TIBA produces both bract necrosis and lower Ca content in bracts, it is suggested that bract necrosis is a physiological disorder related with lower Ca levels ...

Primary malignant melanoma of the nasal cavity: a clinicopathologic study of nine cases.

Nine cases of primary malignant melanoma of the nasal cavity are presented. All the patients had epistaxis and nasal obstruction at admission. Gross aspect of the neoplasia showed a fungating mass located in the right nasal cavity in six cases and in the left nasal cavity in three. Eight tumors were formed by polygonal cells and one tumor by spindle cells. Melanosis of the adjacent mucosa was found in only 1 case. S-100 protein was demonstrated by indirect immunoperoxidase in all cases. The mean survival rate was 23.8 months. Prognosis was not related to the histologic pattern, cell atypia, necrosis, pigment secretion, or mitotic index. Radiotherapy seemed to have some beneficial influence on the survival but did not influence the local recurrence and metastatic spread of the disease.

Small-caliber skeletal muscle fibers do not suffer necrosis in mdx mouse dystrophy.

The prevalence of internal nuclei in muscle fibers (centronucleation), which is a reliable cumulative index of all prior muscle fiber necrosis, was measured at different ages in different muscles of mdx mice and was correlated with muscle fiber diameter. The prevalence of centronucleated fibers (as percentage of total number of fibers) rose gradually after age 20 days until it reached a peak level of 80% at age 60 days. No significant centronucleation (or necrosis) was observed in the following circumstances: in 4 different limb muscles before age 15 days, in leg muscles that were denervated by peripheral nerve section or rendered immobile by high thoracic cordotomy at 15 days, or in rotator extraocular muscles throughout the animals' life span. In these situations, muscle fiber diameter remained below approximately 20 micron. The mechanism by which small-diameter fibers are resistant to necrosis in mdx dystrophy is unknown, but a similar situation exists in hamster and Duchenne muscular dystrophy.

Diagnostic value of body surface potential mapping in old anterior non-Q myocardial infarction

Body surface potential maps (BSM) were recorded from 140 chest leads in 30 healthy control subjects (C) and in 20 patients who had had an acute non-Q wave myocardial infarction (MI) 1–82 months before the study, to identify reliable indices of necrosis. In 12 MI patients the QRS complex was within normal limits on standard 12-lead ECG (group A), and in 8 patients no pathologic Q waves were present but the R waves were small and did not normally increase from V 1 to V 4 (group B). In each subject instantaneous potential distributions throughout the QRS interval were examined. Moreover, the potential—time integrals relating to three intervals (first 40 msec, mid-third, and last third of QRS) were calculated at each lead point and displayed as integral (I) maps. For each time interval, deviation index maps (DI), indicating the standardized differences from normal values, were calculated. An area where the integral values differed at least 2 SD from normal mean was considered abnormal. In most group A patients the inspection of instantaneous potential maps did not reveal definitively abnormal patterns. In group B patients a greater variety of patterns was found and in four cases the characteristic features of the anterior Q wave MI were observed. The DI maps of the first 40 msec of QRS provided the best diagnostic accuracy: areas of negative values 2 SD lower than normal were present in all group B patients (100%), in 8 group A patients (67%), and in 4 group C subjects (13%). These findings indicate that in most patients with an old MI, abnormalities of surface potential distributions during ventricular depolarization are present, even when the 12-lead ECG does not show diagnostic Q waves.

Enzymatic studies and isoenzyme pattern of gammaglutamyl transpeptidase (GGTP) in Indian childhood cirrhosis (CC).

Histopathological studies of liver cell showing necrosis, parenchymal cell injury and microsomal cell damage are known to affect membrane bound enzymes such as gamma-glutamyl transpeptidase (GGTP), alkaline phosphatase (AP) and 5′-nucleotidase (5′-NT). The significant rise in GGTP, AP and 5′-NT indicates the damage of microsomes of parenchymal cell in Indian Childhood Cirrhosis (ICC) patients. SGPT/AP ratio may be an index for distinguishing ICC with other liver diseases. The isoenzyme pattern of GGTP in sera of control and ICC subjects have one band prominent activity. Similarly biopsy samples of control and ICC subjects show one prominent band of GGTP activity. The appearance of isoenzyme of GGTP in blood circulation is an index of microsome damage, cell necrosis and parenchymal cell injury. The isoenzyme pattern of GGTP could be a diagnostic test for ICC.