Phytotherapeutic compound YHK exerts an inhibitory effect on early stage of experimentally-induced neoplastic liver lesions.

The aim of this study was to investigate the effects of the herbal compound YHK on hepatocarcinogenesis induced by diethylntrosamine (DEN) in Sprague Dawley rats. Rats were randomly divided into 3 groups and followed up for 15 weeks. Groups 1 was given standard food and represented the healthy control. Liver preneoplastic foci were induced using the DEN method in groups 2 and 3 (20 rats each). However, group 3 was concomitantly given 50mg/kg/day of YHK. For quantitative assessment of liver preneoplastic foci, the placental form of glutathione-S-transferase (GST-P) positive foci were measured using immunohistochemical staining and image analysis. Treatment using DEN caused a significant decrease in body weight and increase in liver weight compared to the control group while concomitant supplementation with YHK prevented body weight loss and liver weight increase. As compared to DENonly treated rats, the group given YHK showed a significant decrease in the number, size and volume of GSTP- positive foci. Moreover, co-administration of YHK significantly reduced the incidence, number, size and volume of hepatocellular carcinoma. Anti-inflammatory, anti-fibrotic as well as antioxidative properties of this compound are mechanisms which are likely to be advocated for to explain its protective effect. It is concluded that herbal compound YHK by preventing hepatocarcinogenesis in DEN-induced liver preneoplastic lesions in rats has the potential to a large clinical application as a functional food.

Preventive strategy for Candida gut translocation during ischemia-reperfusion injury supervening on protein-calorie malnutrition.

OBJECTIVE: The aim of the present study was to test the hypothesis that protein-calorie malnutrition aggravates the gut translocation of Candida albicans triggered by mesenteric ischemia-reperfusion (IR) injury in an experimental model while testing a natural product containing the antifungal anethole/polygodial mixture (Kolorex). METHODS: MFI strain white mice (n = 90) were randomly allocated to a 4-week dietary regimen: (1) standard pellet diet containing 25% casein; (2) low-protein (2.5%) casein diet; (3) as group 2 plus oral supplementation with 20 microL of a 5% solution of Kolorex during the last 4 days. Twenty rats from each of these groups (termed 1a, 2a and 3a) were orally inoculated with Candida suspension 6 h prior to mesenteric IR injury. Animals of each group but without Candida inoculation (termed 1b, 2b and 3b) served as control. A colon permeability study was carried out as well. Rats were killed prior to the IR injury and 3 h afterwards. Control rats were killed at the same time. RESULTS: Over 60% of the mesenteric lymph nodes and 30% of kidney samples were positive for C. albicans in the low-protein-fed rats after IR injury. Kolorex significantly decreased that rate of positivity and also significantly reduced the concentration of C. albicans per gram of each positive tissue sample examined. Protein-calorie malnourished animals showed a statistically significant increase in colon permeability and this phenomenon further increased after IR injury. The groups of rats treated with Kolorex compound showed a partial, although significant, improvement of this parameter. CONCLUSIONS: These results suggest that Kolorex might exert a competitive effect against with C. albicans colonization. The present study represents the first experimental in vivo investigation of the anethole/polygodial-containing compound under the specific conditions of calorie-protein malnutrition and the results have potential clinical interest.

Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect.

OBJECTIVE: The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. METHODS: Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. RESULTS: Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. CONCLUSIONS: Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization.

Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

Are alanine aminotransferase, hepatitis B virus DNA or IgM antibody to hepatitis B core antigen serum levels predictors of histological grading in chronic hepatitis B?

Paired sera and liver biopsies from 105 patients with chronic hepatitis B virus infection (34 HBeAg positive and 71 anti-HBe positive) were studied to investigate the relation between the degree of histological activity and alanine aminotransferase (ALT), hepatitis B virus DNA (HBV-DNA) or IgM antibody to hepatitis B core antigen (IgM anti-HBc) levels. ALT levels were significantly higher in patients with piecemeal necrosis (155 +/- 124 vs 75 +/- 42, p = 0.0017), but there were no differences in the ALT values of patients with or without intralobular necrosis. ALT values were within normal range in 29% of 31 patients without versus 15% of 65 with piecemeal necrosis (p = 0.19). Serum HBV-DNA levels were not related to the grade of lobular or portal/periportal activity in HBeAg-positive patients. Anti-HBe-positive subjects with piecemeal necrosis had higher HBV-DNA levels (34 +/- 93 vs 4 +/- 6, p = 0.01). IgM anti-HBc indexes were significantly higher in patients with intralobular necrosis (0.635 +/- 0.600 vs 0.356 +/- 0.367, p = 0.0005) or piecemeal necrosis (0.671 +/- 0.633 vs 0.321 +/- 0.219, p = 0.0002). In summary, since serum IgM anti-HBc-IMx indexes can reflect the grade of histological activity, the quantitative assessment of this antibody could be useful for non-invasive monitoring of hepatocellular damage in chronic hepatitis B.

Treatment of chronic hepatitis B (HBeAg-HBV DNA-positive) with lymphoblastoid alpha interferon with or without corticosteroids: short- and long-term follow-up.

Efficacy and safety of therapy with lymphoblastoid interferon-alpha alone or combined with deflazacort has been investigated in 38 HBsAg-HBeAg+ patients with biopsy-proven chronic hepatitis. Group I received 5 MU/m2 interferon thrice a week for 26 weeks; group II took interferon for 26 weeks simultaneously with a 6-week course of deflazacort. Follow-up was 18-72 months (median 42). After 12 months, responses were achieved in 3 (18%) out of 17 patients on interferon alone vs 5 (26%, p > 0.05) out of 19 on combined therapy. Blind histological assessment revealed no improvement in either group or in patients who responded to therapy within the first year of follow-up ("early responders"). "Delayed" responses were observed in 4 (29%) patients who took interferon alone vs 5 (36%, p > 0.05) who took the combined therapy. Serum HBV DNA levels decreased significantly during treatment and remained low up to 24 and 36 months of follow-up in both groups. One early responder developed hepatocellular carcinoma, another had exacerbation of liver disease in long-term follow-up. No non-responders developed liver failure or hepatocellular carcinoma. These results indicate that lymphoblastoid interferon-alpha inhibits HBV replication and corticosteroids have no synergistic effect in treatment of HBsAg-HBeAg+ chronic hepatitis.

HLA typing in chronic type B, D and C hepatitis.

AIMS: We aimed to test the hypothesis that susceptibility to chronic HBV, HDV and HCV infections or their pathology is influenced by host genetic factors. METHODS: The Human Leukocyte Antigens (HLA) (A, B, DR and DQ) were determined by microlymphocytotoxicity assay in patients with chronic C (n = 117), B (n = 97) or D (n = 27) hepatitis and their frequencies were compared with those of 489 healthy controls. RESULTS: No statistically significant association was found between any HLA antigen and chronic B or D hepatitis. A significantly higher frequency of HLA-B14 was observed in patients with chronic persistent or active C hepatitis (16.7% of 90 versus 5.9% of 489, chi(2) = 10.9, pc < 0.05, Relative Risk = 3.17, Etiological Fraction = 0.11). The frequency of HLA-DR5 was lower in HCV positive patients (24.8%) than in controls (45%, chi(2) = 15.1, pc < 0.005, RR = 0.4, EF = -0.37). CONCLUSIONS: No correlation could be observed between clearance of HBV or HDV and HLA phenotype. Immunogenetic factors may have a role in determining susceptibility to chronic HCV hepatitis, and in Italian patients HLA-DR5 is a protective factor.

Inflammatory pseudotumour of the liver with malignant transformation. Report of two cases.

Inflammatory pseudotumour is a rare pathologic lesion, of unknown aetiology, rarely involving the liver. Resection seems to be the treatment of choice and it is generally associated with a good prognosis. Histologically, these processes appear to be benign, nevertheless, aggressive courses or recurrences of inflammatory pseudotumour with tumor-like deaths have been reported. The cases of two patients are described who underwent hepatic lobectomy for a liver mass that was diagnosed as liver inflammatory pseudotumour at the initial histopathological assessment: albeit a malignant course followed and both the patients died cachectic. One patient, a 39-year-old man, had an unusually aggressive clinical course and recurrence of the disease with multiple hepatic masses and extension into the thorax six years later. In the other case, in a 28-year-old woman, the hepatic lesion was identified as a low-grade hepatic sarcoma only seven years after surgery.

Induction of poly(ADP-ribose) polymerase gene expression in lectin-stimulated human T lymphocytes is dependent on protein synthesis.

The poly(ADP-ribose) polymerase mRNA level in quiescent T lymphocytes was low, but was significantly higher than that in B lymphocytes or monocytes. When T lymphocytes were stimulated with phytohemagglutinin, a prompt increase in the mRNA level was observed from 4 hours after stimulation. The level of poly(ADP-ribose) polymerase mRNA reached a maximum in the late G1 phase about 1-2 days after lectin stimulation, and then decreased gradually returning to the basal level 10 days after lectin stimulation. Cycloheximide abrogated increase in poly(ADP-ribose) polymerase gene expression suggesting that a newly synthesized protein(s) was involved in poly(ADP-ribose) polymerase gene induction in lectin-stimulated T lymphocytes.