Fasting hyperglycaemia following trans-catheter arterial chemo-embolization for hepatocellular carcinoma in cirrhosis.

BACKGROUND AND AIMS: Following a hyperosmolar diabetic coma in a cirrhotic patient with hepatocellular carcinoma undergoing transcatheter arterial chemo-embolization, we assessed the prevalence, severity, causes and prognostic impact of impaired glucose metabolism following transcatheter arterial chemo-embolization. METHODS: Plasma glucose, pancreatic and thyroid hormones, cortisol, growth hormone, ACTH and TSH concentrations were determined before and after transcatheter arterial chemo-embolization in 98 patients (70 with a normal fasting glucose, 7 with mild fasting hyperglycaemia and 21 diabetics) undergoing 226 transcatheter arterial chemo-embolization procedures. Child status, body temperature, serum ALT and amylase levels, tumour size, gelfoam embolization and disease aetiology were recorded. Liver function was assessed before and after transcatheter arterial chemo-embolization by measuring monoethylglycinexylidide formation after i.v. lidocaine. RESULTS: A significant rise in glucose levels (p < 0.0001) was observed in 30/98 patients. Hyperglycaemia was more frequent in diabetics (67%) and patients with mild fasting hyperglycaemia (71%). Glucose concentrations doubled in 12 patients; 4 required long-term insulin. Fever, a previously altered carbohydrate metabolism and raised ALT levels were prognostic factors for hyperglycaemia (p < 0.01). Plasma C-peptide, glucose/insulin and glucose/C-peptide ratios, were increased after transcatheter arterial chemo-embolization (p < 0.05). Transcatheter arterial chemo-embolization was followed by a reduction in the monoethylglycinexylidide formation capacity (p < 0.05), particularly in hyperglycaemia patients (p < 0.02). CONCLUSIONS: Transcatheter arterial chemo-embolization is frequently followed by a derangement in glucose metabolism which is potentially severe, associated with preceding glucose imbalance, fever and a transient deterioration in liver function.

Activation of cytotoxic and natural killer T-cell system in patients with hepatocellular carcinoma and cirrhosis.

The immune response in liver cirrhosis and hepatocellular carcinoma is receiving renewed attention in consideration of the possible treatment with biological response modifiers. The aim of this study was to evaluate whether cirrhosis and hepatocellular carcinoma induce any modification in peripheral lymphocyte subsets. Lymphocytes were evaluated (number/percentage) in 61 patients with hepatocellular carcinoma, 35 with cirrhosis and 24 healthy controls. Using flow cytometry, 10 lymphocyte subpopulations were assayed, plus the CD4/CD8 ratio. Results demonstrated no change in the number of lymphocytes; cirrhosis and hepatocellular carcinoma patients had significantly more HLA-DR+ (p = 0.001) and CD3+/HLA-DR+ (activated T) (p = 0.002) and fewer CD3+ (mature T) (p = 0.02) cell than controls; hepatocellular carcinoma patients had significantly more CD3+/CD56+/CD16- (cytotoxic non-MHC restricted T cells) and CD25+ (IL-2 receptor positive cells). If the percentages of all cells with cytotoxic-T activity were pooled, a significant increase (p = 0.03) was seen in hepatocellular carcinoma patients. In conclusion, in contrast to previous data, hepatocellular carcinoma patients reveal an increased number of cytotoxic non-MHC restricted T cells.

Unresectable hepatocellular carcinoma in cirrhosis: survival, prognostic factors, and unexpected side effects after transcatheter arterial chemoembolization.

To evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma, the prognostic factors, and the side effects, 72 patients undergoing 170 chemoembolizations with lipiodol-mediated injection of adriamycin were investigated. The 1-, 2-, and 3-year survivals are 83, 61, and 56%, respectively. Significant prognostic factors for survival (by Mantael-Haenszel) are Child-Pugh and Okuda status (p = 0.00001 and p = 0.01 respectively), number of TACE courses (p = 0.002) and of courses completed with embolization (p = 0.05), stabilization or reduction of alpha-fetoprotein (p = 0.003), and concurrent tamoxifen treatment (p = 0.04). Side effects included fever, pain, increased serum amylase and transaminase levels, and one liver abscess with death of liver failure. In addition, mild hyperglycemia was observed in 19% of patients and severe in 8% (with one hyperosmolar diabetic coma), in the absence of pancreatic damage. In conclusion, transcatheter arterial chemoembolization is useful in patients with unresectable hepatocellular carcinoma. Prognostic factors are Child-Pugh and Okuda status, number of TACE courses and of embolizations, changes of alpha-fetoprotein levels, and association with tamoxifen treatment. The development of mild to severe changes of glucose metabolism suggests that glucose tolerance should be evaluated before and glycemia strictly monitored after each TACE course.

Fine-needle biopsy in focal liver lesions: the usefulness of a screening programme and the role of cytology and microhistology.

We evaluated the diagnostic usefulness of 244 ultrasound-guided fine-needle biopsies (FNB) in 226 patients with suspected liver malignancies. A malignancy was detected in 166 cases (73%) -145 hepatocellular carcinomas (HCC), 21 metastases; benign lesions were aspirated in 60 cases (27%). The sensitivity of FNB was 93%, with 100% specificity. In the FNB false-negative cirrhotic nodules, a final diagnosis of HCC was reached on repeating the biopsy 1-8 months later. When both cytological and microhistological examinations were performed, the positive correlation between the two techniques was 80%, with a slightly higher sensitivity for microhistology (93%). The malignancies diagnosed were potentially resectable in 26% of cases. We experienced 1 acute complication of FNB and 1 case of needle tract tumour seeding. These results confirm that FNB is useful in diagnosing malignant liver tumours. We believe that US-guided FNB is the first-choice invasive technique for assessing focal benign lesions and malignant tumors in the liver.

[Ultrasound guided fine-needle aspiration biopsy in the diagnosis of hepatocellular carcinoma]. / Ultrahangvezérelt vékonytü aspirációs biopszia (FNAB) a hepatocellularis carcinoma diagnózisában.

This retrospective study was undertaken to evaluate the diagnostic usefulness of 244 sonographically guided fine- needle aspiration biopsy in 226 patients with ultrasonographically suspected hepatic malignant lesions. A final diagnosis of malignancy was established in 166 cases (73%) (145 hepatocellular carcinoma, 21 metastasis); benign lesions were aspirated in 60 cases (27%). The diagnostic sensitivity of this technique was 93%, with 100% specificity. When both cytology and microhistology were obtained, the positive correlation of the two techniques was 80% In the series of 244 fine-needle aspiration biopsy the authors had only one acute complication. They report one case of needle tract tumor seeding after biopsy. These results confirm the usefulness of sonographically guided fine-needle aspiration biopsy in diagnosing malignant hepatic tumors. The procedure is simple, safe, free of important side effects. The authors believe that ultrasound guided fine-needle aspiration biopsy represents the first choice of invasive technique in the assessment of hepatic focal benign lesions and malignant tumours.

Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis.

BACKGROUND/AIMS: Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation. METHODS: We evaluated the degree of hepatic inflammation and steatosis, serum ferritin, transferrin saturation and iron levels, tissue iron concentrations and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-related hepatitis (42 + 11). We also considered six patients with both alcohol abuse and hepatitis C virus, four males with chronic alcoholic liver disease and four males with genetic hemochromatosis, giving a total of 67. All diagnoses were histologically confirmed. Patients with cirrhosis were excluded. RESULTS: Our data show that: 1. Steatosis is more frequent in hepatitis C virus and hepatitis C virus+alcohol abuse patients; 2. In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.01 and 0.05); transferrin saturation is higher (p < 0.05) in hepatitis C virus-positive than in hepatitis B virus-positive patients only when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r = 0.833 and r = 0.695, respectively, p = 0.00001); tissue iron is significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.05); 4. In patients with chronic hepatitis, serum ferritin is a better marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have higher malondialdehyde levels and activation of turnover of glutathione, probably in response to free-radical-mediated liver damage. Females have lower liver iron levels but similar trends. CONCLUSIONS: These findings suggest that hepatitis C virus-related liver damage is characterized by increased iron storage (possibly induced by the virus) which elicits a free-radical-mediated peroxidation, with consequent steatosis and activation of glutathione turnover.

[Local transcatheter arterial chemoembolization in the palliative treatment of inoperable hepatocellular carcinoma]. / Transzkatéteres helyi arteriális kemoembolizáció az inoperábilis hepatocellularis carcinomás betegek palliatív kezelésében.

Hepatocellular carcinoma is a tumor with high mortality. Adequate oncological therapy is essential to modify the poor prognosis. Transcatheter arterial chemoembolisation has been proposed as a useful and well-tolerated treatment for unresectable carcinoma. In the study 51 patients with unresectable carcinoma (mean age 61.6, range 45-81, Child-Pugh A = 34 patients, Child-B = 13, Child-C = 4; Okuda I = 33 patients, Okuda II = 18) underwent chemoembolisation. A total of 122 procedure were performed, with a median number of 2.4 (range 1-6) per patient. One and two year survivals are 91% and 74% respectively (Child-A: 100% and 82%; Child-B: 100% and 63%; Child-C 0% at 1 year). The difference among the 3 groups is statistically significant (p = 0.001). Median overall survival is 20 months, with 22, 20 and 6 month in Child-A, B and C patients respectively (p = 0.006). Commonly reported side effects and biochemical changes included: fever, pain and increased serum amylase, transaminase levels. One patient developed a liver abscess and died of liver failure. In addition, in 18 patients (35%) mild to severe changes in glucose metabolism were also observed. Mild hyperglycemia was observed in 14 patients, with severe derangement in 4 patients (8%). It is suggested that careful evaluation of glucose metabolism is advisable in patients being considered for chemoembolisation. Their results confirm the usefulness of chemoembolisation in Child-A and B patients with unresectable hepatocellular carcinoma.

Hepatocellular carcinoma in alcoholic cirrhosis: is sex hormone imbalance a pathogenetic factor?

OBJECTIVE: A sex hormone imbalance has been reported in patients with hepatocellular carcinoma (HCC). We investigated the serum levels of eight sex hormones in patients with alcohol-related and non-alcohol-related cirrhosis and HCC. METHODS: Luteinizing hormone, follicle-stimulating hormone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone and sex hormone binding globulin were assayed in 81 patients with cirrhosis (59 men, 22 women) and 97 with HCC and cirrhosis (82 men, 15 women). Hepatitis B or hepatitis C virus infection was present in 58% of patients with cirrhosis and 69% of patients with HCC. Alcohol abuse was the aetiopathogenetic factor in the remaining patients. RESULTS: In men, mean testosterone levels were at the lower limit of the normal range for both patients with HCC and for controls with cirrhosis. Mean estradiol levels were increased both in patients with HCC and in those with cirrhosis, but patients with alcohol-related HCC had higher estradiol levels (P = 0.0002). An index of sex hormone imbalance, the estradiol to testosterone ratio (ETR), was calculated. The ETR was significantly higher in patients with alcohol-related HCC (P = 0.0002). Multiple regression analysis showed that the ETR correlated best with patients' diagnosis (P < 0.05). In women, the ETR was significantly lower in patients with HCC than in controls with cirrhosis. CONCLUSIONS: Men with alcohol-related HCC are characterized by an oestrogen and androgen imbalance and have a higher ETR than patients with other types of liver damage. Since sex hormones modulate hepatocellular proliferation, our data suggest that a sex hormone imbalance plays a role in hepatocarcinogenesis in patients with alcohol-related cirrhosis.

Zinc, iron, and peroxidation in liver tissue. Cumulative effects of alcohol consumption and virus-mediated damage--a preliminary report.

In an attempt to elucidate further the mechanisms involved in alcohol-mediated liver damage and the correlation between alcohol and viruses in chronic liver lesions, we determined the levels of liver glutathione (GSH), thiobarbituric acid reactive substances (TBARS), iron (Fe), and zinc (Zn) in 31 patients with chronic viral hepatitis (CAH), 6 with alcohol-related chronic hepatitis (CALD), 6 with alcoholic cirrhosis (AC), 8 with primary biliary cirrhosis (PBC), and 10 healthy controls (C). Liver GSH was significantly lower in CALD and AC patients (p < 0.005). TBARS levels were significantly higher in CAH, CALD, and PBC patients (p < 0.001, < 0.02, and < 0.001, respectively). In CAH patients, alcohol consumption correlated inversely with GSH and directly with TBARS (p < 0.05). Patients with both CAH and alcohol abuse had a further reduction in liver GSH levels (p < 0.005). Tissue levels of Fe were significantly increased in CALD and AC patients with respect to controls and CAH patients, whereas no significant difference was observed in Zn. These data confirm that patients with chronic ethanol exposure reveal a depletion in liver GSH content clearly correlated with an increase in lipid peroxidation and Fe liver storage. On the other hand, these findings appear to suggest no significant change in Zn levels in chronic hepatitis.