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Factors influencing the progression of liver disease and the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection are poorly understood. Inherited variations of drug-metabolizing enzyme (DME) activities may affect liver damage and cancer risk by modifying individual susceptibility to endogenous or exogenous toxic compounds. We investigated the association of liver disease severity with common alleles of microsomal epoxide hydrolase (mEH), an enzyme involved in the metabolism of highly reactive epoxide intermediates. Three polymorphisms (Tyr113His, His139Arg, and -613C/T) were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphisms (RFLPs) in 394 patients at different stages of disease, including 92 asymptomatic carriers, 109 patients with chronic hepatitis, 100 patients with cirrhosis, and 93 patients with HCC. Reference allele frequencies were obtained from 99 healthy blood donors. Allele distributions between categories were compared using the chi(2) test; odds ratios (ORs) and 95% CI were calculated to express relative risks. Allele frequencies among 99 healthy controls were as follows: 15.1% for 113His/His, 4.0% for 139Arg/Arg, and 46.5% for -613C/T. mEH 113His/His homozygotes were overrepresented in advanced stages of disease, in particular among HCC patients (27.9%; P =.03; OR, 2.2; 95% CI, 1.0-4.6). Differences were more pronounced among men and between extreme patient categories. When mEH genotypes were combined to express a metabolic phenotype, very slow metabolizers were highly prevalent among cirrhotic and HCC patients (18% vs. 3.3% in carriers; P <.001). In conclusion, mEH gene polymorphisms were significantly associated with HCV-related liver disease severity and HCC risk. Men were at higher risk than women; this might be explained by hormonal regulation of gene expression or by differential exposure to environmental toxins.

Introduction: Interstitial laser photocoagulation (ILP) is a recent interventional procedure performed under US or CT guidance which is capable of inducing thermal necrosis in solid tumors. We have used this technique for about 2 years to treat primary and secondary liver cancers., Materials and Methods: Thirty-five patients, 20 of them with liver metastases and 15 with HCC, have been examined: 59 lesions in all, ranging in diameter 10 to 65 mm. Forty-nine lesions have been followed-up for at least 2 months and 25 for at least 6 months. The treatment was performed positioning one to six (18-21 G) modified Chiba needles in the lesions to be treated, according to their sizes, under US or CT guidance. The optical fibers (400-800 mu) were then inserted and the Laser was fired to administer 1,000 Joule/session, with 5-10 W power range. The US and CT patterns of the ILP-treated lesions are reported., Results: Dynamic CT examinations 2 months after treatment showed complete tumor destruction in 77.5% of the lesions. The best results were obtained in the lesions < 3 cm phi; in particular, 32/38 lesions (84.2%) < 3 cm and with at least 2 months' follow-up exhibited complete necrosis, as did 6 of 11 lesions (54.6%) over 3 cm phi. When residual tumor tissue was demonstrated, further ILP sessions were useless. We observed only few complications which resolved spontaneously in all cases., Conclusions: At present, ILP remains an experimental procedure: further studies on larger series of patients and comparison with the results of other interventional procedures are needed to confirm its efficacy in treating primary and secondary liver cancers.

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.

Total serum cholesterol levels have been studied in 100 patients with histological diagnoses of chronic hepatitis B and 100 wit chronic Hepatitis C, all without cirrhosis, and two age- and sex-matched control groups (B and C). Mean serum cholesterol levels of the groups were compared also in relation to sex, liver function, duration of the disease, alcohol intake, mass index, liver enzymes, presence of liver steatosis and severity of the liver disease on the basis of the histological activity index. The percentages of patients with serum cholesterol level < 150 mg/dl and > 240 mg/dl were also calculated. The mean serum cholesterol level was significantly lower in hepatitis C: 176 md/dl vs 194 mg/dl of hepatitis B (p = 0.004) and 198 of control C (p = 0.000). Twenty eight hepatitis C patients had serum cholesterol < 150 mg/dl vs 10 with hepatitis B (p = 0.001). In multivariate regression analysis, only the type of virus infection was independent related to serum cholesterol level (p = 0.0063).

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.

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.

A total of 84 patients with hepatocellular carcinoma and cirrhosis were analyzed retrospectively to investigate prognostic factors. All patients received transarterial oily chemoembolization as the only anticancer therapy. The follow-up range was 1 to 39 mo (median, 9.5 mo). The overall actuarial survival rates at 12, 24 and 30 mo were 62%, 31% and 24%, respectively. According to univariate analysis, variables significantly associated with survival were age, Child-Pugh grade, total serum bilirubin, Okuda stage, tumor size, degree of labeling of the tumor with Lipiodol, gelatin foam use, changes with treatment in tumor size and changes with treatment in alpha-fetoprotein concentration. Two multivariate analyses were performed. When pretreatment and treatment variables were considered, parameters with independent prognostic value were age, Child-Pugh grade, total serum bilirubin, tumor size and degree of Lipiodol labeling of the tumor. When follow-up variables were also considered, we (a) confirmed the prognostic significance of all these parameters (age, Child-Pugh grade, total serum bilirubin, tumor size) and (b) found the independent prognostic value of the change in tumor size (or change in alpha-fetoprotein concentration). Both models yielded different risk coefficients for each class of each variable. Two simple prognostic indexes, based on these coefficients, are proposed: an "initial" index (including pretreatment and treatment variables) and a "follow-up" index (also including follow-up variables). According to the two indexes, the patients were classified into three groups with different prognoses: good (93% and 100% actuarial survival at 1 yr for the initial and follow-up indexes, respectively), intermediate (65% and 53%, respectively) and poor (27% for both indexes).

Twenty-two patients with insulin-dependent diabetes mellitus and renal involvement were submitted to renal biopsy. Mean age was 42 years; 10 were males, 12 females. The mean interval between clinical manifestation of nephropathy and biopsy was about 2 years. At the time of biopsy, 4 groups were distinguished according to clinical conditions, depending on the presence or absence of nephrotic syndrome and renal failure. Renal lesions were semiquantitatively evaluated, a separate score being considered for glomerular and vascular lesions. Immunofluorescence most frequently showed a pattern of faint linear IgG deposits along glomerular basement membranes. Severity of histological lesions and pattern of urinary abnormalities were not correlated with the duration of diabetes or the patients' age. Both glomerular and vascular lesions were correlated with the presence of renal failure, while no relationship with the pattern of urinary abnormalities was found. Fourteen patients were followed for more than one year after biopsy: 5 had normal renal function, 4 were in chronic renal insufficiency and 5 in end-stage renal failure (3 were in dialysis, 2 died). There was no correlation between the 3 above-mentioned types of evolution and glomerular histological findings. Nevertheless a higher score of vascular impairment at biopsy was observed among patients who subsequently were found to have a more unfavorable prognosis. Therefore renal biopsy, by providing information on the degree of renal vascular damage, may have some value in predicting the clinical course of diabetic nephropathy.