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Biomedical subjects

J C Trinchet

Publications and source records attributed to J C Trinchet.

At least 37 records · Page 2Linked to original sources

Intra-arterial chemoembolization in patients with hepatocellular carcinoma.

Hepatocellular carcinoma occurs almost exclusively in patients with cirrhosis, at least in the West. In most of these patients, potential curative treatments, such as resection or percutaneous alcohol injection, are usually contra-indicated. Transarterial chemoembolization may induce tumor necrosis. In order to avoid massive necrosis of the non tumoral liver, two major contra-indications have been identified: inadequate portal flow and liver failure. The influence of chemoembolization on survival was thought to be high on the basis of non randomized trials. However, no beneficial effects on survival were observed in three randomized trials. In these trials, the beneficial effect on tumor necrosis was counterbalanced by frequent deleterious effects on liver function. Moreover, progressive liver atrophy may follow repeated procedures. As there is no alternative treatment for most of these patients and chemoembolization can still be beneficial in selected cases, efforts have been made to improve patient selection and method to improve the results. Good liver function, a normal portal flow, and a well limited hypervascularized tumor are necessary conditions for treatment, which may even be curative when used in association with percutaneous alcohol injection. Moreover, arterial embolization can be performed without chemotherapy, and the procedure should not be repeated in the short term.

Carcinoma, Hepatocellular↗

[Adult multi-nuclear cell hepatitis. A study in 17 patients].

OBJECTIVES: Giant-cell hepatitis is rare in adults and its significance has not been clarified. We report the clinical and histological characteristics and outcome in a group of adult patients with giant-cell hepatitis. METHODS: Seventeen patients with giant-cell hepatitis, hospitalized in our unit between 1976 and 1992, were studied retrospectively. Giant-cell hepatitis was defined as at least two hepatocytes with four or more nuclei per cell on liver biopsy. Clinical and biochemical parameters, liver histology, and the serological profile of HAV, HBV, HCV, HIV, HSV, EBV, CMV, and paramyxovirus were evaluated. Paramyxovirus immunochemistry was performed in 6 liver biopsies. RESULTS: There were 11 females and 6 males, an average of 48 years old (range: 29-80). Four patients had a well-defined etiology: acute hepatitis B infection with a favorable outcome in 2 cases, clometacine induced-hepatitis resulting in death from liver failure in one case, and chronic hepatitis B and C in one patient with AIDS. Among the 13 patients in which the etiology could not be determined, histologically defined acute hepatitis was observed in 8 and chronic hepatitis in 5. Nine patients were treated with immunosuppressive drugs. One patient was lost to follow-up. Eight patients responded to treatment, but 5 patients progressed to cirrhosis between 5 months and 7 years. Two of the 4 patients with unexplained liver disease who did not receive any treatment died of liver failure. CONCLUSION: In patient with acute or chronic hepatitis without an identified cause (with or without autoimmune abnormalities), the presence of giant-cell hepatitis seems to have a similar evolution as active autoimmune hepatitis. The poor prognosis of these patients suggests that early immunosuppressive treatment is justified.

Adult↗

[Autoimmune hepatitis induced by fibrates].

AIM: Long term treatment by fibrates could induce chronic hepatitis associated with auto-antibodies. The aim of this study was to assess the features of this hepatitis. METHODS: Baseline clinical and biological features, and liver biopsy in 5 patients with fibrate-induced chronic hepatitis were studied, as well as their outcome. RESULTS: At enrollment, patients (4 men, mean age 65 years) had highly (n = 3) or mildly (n = 2) increased serum aminotransferase activity, hypergammaglobulinemia and high titers of anti-nuclear antibodies (with homogenous fluorescence in 3 cases). Liver biopsies demonstrated a lympho-plasmocytic infiltrate in all cases. Hepatocellular necrosis was multilobular in 2 cases, and mild to moderate, located in lobular and periportal areas in 3 cases. Cirrhosis was found at presentation in 3 cases and developed within a few months in the 2 other patients. After discontinuation of fibrates, aminotransferase activity normalized within 6 weeks either spontaneously (n = 3) or under immunosuppressive treatment (n = 2). Immunosuppression was rapidly withdrawn in 2 patients (< 18 months) without relapse, while one patient was treated for 4 years because of relapse after early withdrawal. A second liver biopsy performed 6 months after discontinuation of fibrates in an untreated-patient showed no inflammation or necrosis. CONCLUSION: These observations suggest that fibrates could trigger chronic liver disease resembling type I auto-immune chronic hepatitis, which resolves after drug withdrawal.

Aged↗

Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer.

The prognosis for patients with primary liver cancer (PLC) often depends on tumor recurrence and the development of extrahepatic metastases, particularly after liver transplantation. We have developed a sensitive test to detect both spontaneous circulation of tumor cells and the spread of liver cells due to chemoembolization and alcoholization. Reverse-transcription polymerase chain reaction was used to search for cells expressing alpha-fetoprotein (AFP) messenger RNA in the peripheral blood of 84 patients with PLC and 102 controls (55 patients with chronic hepatitis and/or cirrhosis, 10 patients with benign liver tumors or liver metastases from intestinal cancers, and 37 healthy individuals). By spiking the blood of healthy volunteers with HepG2 cells, we assessed the sensitivity limit: one HepG2 cell mixed with 10(7) leukocytes. All 102 controls tested negative. In contrast, 28 patients (33.3%) with PLC tested positive. Positivity for the test was significantly associated with portal thrombosis, tumor size, intravascular tumor emboli, serum AFP level, and extrahepatic metastases. Patients were followed up for a mean period of 39 +/- 51 weeks: the probability of developing extrahepatic metastases was significantly higher in positive than in negative patients. Eighteen negative patients with PLC were tested before, 1 hour after, and 24 hours after locoregional therapy: 9 tested positive either 1 or 24 hours after alcoholization or chemoembolization. In conclusion, we have developed a highly specific and sensitive test to detect circulating tumor cells in patients with PLC. This test is likely to be clinically useful in evaluating the risk of developing extrahepatic metastases and the possibility of iatrogenic spreading of liver-derived, possibly tumorous, cells.

Female↗

Predictive value of serum sex hormone binding globulin for the occurrence of hepatocellular carcinoma in male patients with cirrhosis.

BACKGROUND/AIMS: The incidence of hepatocellular carcinoma is higher in males, presumably due to the influence of sex steroids. Therefore, to further assess the role of sex steroids in the occurrence of hepatocellular carcinoma, this study investigated the predictive value of different sex hormones and their binding protein. METHODS: Among 101 male patients with cirrhosis included in a prospective screening study, 29 developed hepatocellular carcinoma. We assessed the predictive value of 17 clinico-biological and 4 serum hormonal variables collected at enrollment, by the log-rank test and the Cox model. RESULTS: Age (p = 0.003), bilirubin (p = 0.04), sex-hormone-binding-globulin (p = 0.006) and albumin (p = 0.08) were predictive using the log-rank test, while estradiol and total and free testosterone were not. The Cox model showed age (p = 0.0003; relative risk = 7.52), sex-hormone-binding globulin (p = 0.001, relative risk = 3.37) and albumin (p = 0.02, relative risk = 2.94) as the most predictive parameters. CONCLUSION: We conclude that high serum sex-hormone-binding-globulin levels have an independent predictive value for the occurrence of hepatocellular carcinoma. Serum sex-hormone-binding-globulin could be used to define patients at high risk for hepatocellular carcinoma and could hypothetically play a role in hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

Needle biopsy of hepatocellular carcinoma: assessment of prognostic contribution of histologic parameters including proliferating cell nuclear antigen labeling and correlations with clinical outcomes. Group d'Etude et de Traitement du Carcinoma Hépatocellulaire.

BACKGROUND: Although many studies concerning the prognostic factors of resected hepatocellular carcinoma have been performed, the prognostic information provided by needle biopsy of these tumors has not yet been extensively studied. METHODS: One hundred twenty-four white patients with histologically-confirmed hepatocellular carcinoma were entered into a prospective study from 1990 to 1992 with followed-up through October 1994. Most of the patients had cirrhosis (79%). Patients were classified according to Okuda's staging: Stage I (50%), Stage II (47%), and Stage III (3%). The one-year survival rate was estimated at 58% in Okuda's Stage I, and 15% in Stages II and III. Edmondson's grading, mitotic index, and proliferating cell nuclear antigen labeling index were studied on each biopsy. Univariate and multivariate analyses were performed to determine the prognostic significance of the different parameters. RESULTS: According to Edmondson's critera, 13 of the hepatocellular carcinomas were Grade I, 63 Grade II, 42 Grade III, and 6 Grade IV. There was a significant correlation between Edmondson's grade, mitotic index, and proliferating cell nuclear antigen labeling index (P < 0.01). Univariate analysis showed both the histologic grade (P < 0.001) and mitotic index (P < 0.05) correlated with survival. Cox's model indicated that Edmondson's grading yields additional prognostic information for Okuda's staging (P < 0.001). The one-year survival rate for Okuda's Stage I was 76% for Edmondson's Grades I + II versus 23% for Grades III + IV. CONCLUSIONS: Edmondson's grading appears to be an important prognostic parameter for patients with hepatocellular carcinoma, and could help stratify patients for clinical trials.

Adult↗

Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis.

The aim of this study was to identify high-risk patients for hepatocellular carcinoma (HCC). Among 151 patients with histologically proven cirrhosis hospitalized from 1987 to 1990 and prospectively followed-up until June 1994, 31 developed HCC. We assessed the predictive value of 22 variables recorded at enrollment for HCC occurrence by the log rank test and the Cox proportional hazards model. Six clinical and biological variables summarized predictive information of HCC: age > or = 50 years (P = .01), male (P = .01), large esophageal varices (EV) (P = .03), prothrombin activity < 70% (P = .04), serum alpha-fetoprotein (AFP) > or = 15 ng/L (P = .06), and anti-hepatitis C virus antibodies (P = .08). A clinicobiological predictive score identified two groups of patients at low (n = 67; 3-year cumulative incidence, 0%) and high risk for HCC (n = 84; 3-year cumulative incidence, 24%). The predictive value of this score was confirmed using an independent population of 49 patients with cirrhosis. Furthermore, liver large-cell dysplasia (LCD) had an additional predictive value in high-risk patients (P = 10(-4), which thus helped to define a subgroup at very high risk for HCC (n = 12; 3-year cumulative incidence, 72%). In Western patients with cirrhosis, a limited number of usual variables can identify a group of patients at high risk for HCC. Among these patients, liver biopsy allows for the determination a subgroup of patients at very high risk for HCC requiring intensive screening or preventive measures.

Age Factors↗

Transjugular renal biopsy in the treatment of patients with cirrhosis and renal abnormalities.

When renal lesions are suspected in patients with cirrhosis, clotting disorders often preclude percutaneous renal biopsy. This study was undertaken to determine whether transjugular renal biopsy is possible, safe, and useful in such patients. From 1987 to 1994, 70 patients with cirrhosis and clotting disorders underwent transjugular renal biopsies, providing renal tissue in 55. Of these 55 patients, 41 were Child-Pugh class B or C, 35 were alcoholic, serum creatinine levels were > or = 130 micromol/L in 46, and proteinuria was > or = 0.5 g/d in 37. Clinically significant complications of transjugular renal biopsy were persistent hematuria in 4 and perirenal hematoma in 4, requiring blood transfusions in 1 and 2 cases, respectively. There were no deaths related to renal biopsy. Renal lesions were identified as glomerular in 41 (74.5%), interstitial in 7, and end-stage in 2 and were absent in 5. Transjugular renal biopsy influenced treatment in 21 patients (38%), including 11 who were proposed for liver transplantation and 4 who had chronic liver rejection. Decisions based on results of transjugular renal biopsy were to perform liver transplantation in 8 and combined renal and liver transplantation in 5, whereas 2 were refused. In 6 other patients, the results of renal biopsy modified the medical regimen. We conclude that transjugular renal biopsy may be a useful procedure in patients with cirrhosis and clotting disorders. This technique does not entail undue risks and may influence treatment decisions, particularly in patients proposed for liver transplantation.

Adult↗

High prevalence of diabetes mellitus in patients with chronic hepatitis C. A case-control study.

OBJECTIVES AND METHODS: Extrahepatic manifestations have been reported in hepatitis C virus infection. To assess the relationship between diabetes mellitus and hepatitis C virus, we studied 152 patients with chronic hepatitis C and 152 controls hospitalized during the same period with hepatitis B virus (n = 51) or alcohol-induced (n = 101) liver diseases matched for age, sex, and the presence of cirrhosis (prevalence: 58%). Patients with jaundice, ascites, encephalopathy, prothrombin activity < 65%, or serum albumin < 35 g/L were excluded. RESULTS: Diabetes, defined by fasting serum glycemia > 1.4 g/L on at least two separate occasions or previously treated overt diabetes, was present in 38 patients with chronic hepatitis C (24%) and in 13 patients in the control group (9%, P < 0.002). In the 51 diabetic patients, irrespective of serum anti-hepatitis C virus status, 41 (81%) had non insulin dependent diabetes and 45 (88%) had cirrhosis. Family history of diabetes or obesity was observed in 2 (5%) of the diabetic patients with chronic hepatitis C and in 6 (46%) of the diabetic controls (P = 0.002). Plasma C-peptide (855 +/- 448 pmol/L versus 1,152 +/- 491 pmol/L, NS) and insulin levels (83 +/- 40 pmol/L versus 184 +/- 86 pmol/L, NS), assayed in 17 diabetic patients with chronic hepatitis C and in 9 diabetic controls, were lower in the former. The prevalence of HLA B8, DR3 or DR4 antigens, which was searched for in 77 patients with chronic hepatitis C, was not different in diabetic and non diabetic patients, and, was similar to the reference population. Serum islet-cell antibodies were found in 5 patients with chronic hepatitis C (3 with diabetes) and in 2 controls. CONCLUSION: Diabetes mellitus is more prevalent in patients with chronic hepatitis C than in patients with other liver diseases, and usually occurs in the absence of predisposing factors. These results suggest a role of hepatitis C virus infection in the pathogenesis of diabetes.

Adult↗