[Incidental ultrasound finding of a 3 cm liver nodule in a 45-year-old woman taking hormonal substitution after hysterectomy performed for cervix carcinoma]. / Découverte fortuite d'un nodule hépatique de 3cm à l'échographie chez une femme de 45 ans (sous traitement substitutif hormonal après hystérectomie pour cancer du col de l'utérus).

Incidental liver nodules are more and more frequently encountered because of increasing sensitivity of recent imaging techniques. The identification of biliary cyst or hemangioma is usually easy. In other cases, the etiological diagnosis relies on careful radiological analysis of the pattern of the arterial phase enhancement following contrast medium injection. When there is no early arterial enhancement, a liver biopsy is usually indicated to establish the diagnosis. A strong arterial contrast enhancement pattern is indicative of hepatocellular tumor, benign or malignant. In this situation, it is crucial to establish if there is underlying liver fibrosis. In case of cirrhosis, the diagnosis of hepatocellular carcinoma is the most probable. If the non tumorous liver is normal, focal nodular hyperplasia and hepatocellular adenoma should be differentiated. The distinction between these two tumors is important because only hepatic adenoma carries a significant risk of complications (bleeding or hepatocellular carcinoma) leading to surgical resection of lesions that do not regress after steroid withdrawal. Contrast enhanced MRI and contrast ultrasound are most useful tools for the diagnosis of nodular regenerative hyperplasia but liver biopsy can be necessary in atypical forms. In recent years, the understanding of molecular mechanisms associated with adenoma occurrence allowed for the proposal of a new classification already of practical interest in the management of patients.

Non-invasive assessment of hepatic iron stores by MRI.

BACKGROUND: MRI has been proposed for non-invasive detection and quantification of liver iron content, but has not been validated as a reproducible and sensitive method, especially in patients with mild iron overload. We aimed to assess the accuracy of a simple, rapid, and easy to implement MRI procedure to detect and quantify hepatic iron stores. METHODS: Of 191 patients recruited, 17 were excluded and 174 studied, 139 in a study group and 35 in a validation group. All patients underwent both percutaneous liver biopsy with biochemical assessment of hepatic iron concentration (B-HIC) and MRI of the liver with various gradient-recalled-echo (GRE) sequences obtained with a 1.5 T magnet. Correlation between liver to muscle (L/M) signal intensity ratio and liver iron concentration was calculated. An algorithm to calculate magnetic resonance hepatic iron concentration (MR-HIC) was developed with data from the study group and then applied to the validation group. FINDINGS: A highly T2-weighted GRE sequence was most sensitive, with 89% sensitivity and 80% specificity in the validation group, with an L/M ratio below 0.88. This threshold allowed us to detect all clinically relevant liver iron overload greater than 60 micromol/g (normal value <36 micromol/g). With other sequences, an L/M ratio less than 1 was highly specific (>87%) for raised hepatic iron concentration. With respect to B-HIC range analysed (3-375 micromol/g), mean difference and 95% CI between B-HIC and MR-HIC were quite similar for study and validation groups (0.8 micromol/g [-6.3 to 7.9] and -2.1 micromol/g [-12.9 to 8.9], respectively). INTERPRETATION: MRI is a rapid, non-invasive, and cost effective technique that could limit use of liver biopsy to assess liver iron content. Our MR-HIC algorithm is designed to be used on various magnetic resonance machines.

Randomized controlled trial for hepatocellular carcinoma with portal vein thrombosis: intra-arterial iodine-131-iodized oil versus medical support.

UNLABELLED: Portal vein thrombosis is a poor prognostic factor in patients with hepatocellular carcinoma (HCC) and a contraindication for chemoembolization. Intra-arterial injection of 131I-iodized oil which does not modify arterial flow, is feasible in this condition. The aim of this prospective randomized controlled trial was to compare the efficacy of treatment with radiolabeled oil (treated group) versus medical support (control group) in patients with stage I or II HCC (classification of Okuda) with portal vein thrombosis. METHODS: Twenty-seven HCC patients (26 males, 1 female), aged 53-79 yr, with portal vein thrombosis were randomly assigned to Lipiocis group (n = 14) or Control group (n = 13). Additional injections of radiolabeled oil were given 2, 5, 8 and 12 mo after initial therapy. Medical support treatment consisted of: tamoxifen (n = 5), 5 FU intravenously (n = 1), NSAIDs or corticosteroids (n = 5). Efficacy was evaluated according to survival rate (Kaplan-Meier method; log rank test), AFP serum values (measured at 2, 5, 8 and 12 mo) and angiography. RESULTS: The two groups were comparable (Child's classification, Okuda's classification, liver function tests, location of the thrombus). Tolerance was excellent in the Treated group. The actuarial survival curves were significantly different (p < 0.01) between the two groups, the survival rates (Cl 95%) at 3, 6 and 9 mo being 71% (48%-95%), 48% (12%-55%), 7% (1%-31%) for the Treated group; and 10% (1%-33%), 0% and 0% for the Control group. CONCLUSION: Intra-arterial hepatic injection of 131I-labeled iodized oil is a safe and effective palliative treatment of HCC with portal vein thrombosis.

Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients.

The aim of the present study was to describe histologic features of the liver in insulin resistance-associated hepatic iron overload (IR-HIO), defined as the association of metabolic disorders and hepatic iron overload. We included 139 patients in the study on the basis of one or more metabolic disorders and liver iron overload unrelated to usual causes. Liver biopsy specimens were reviewed, and histologic data were compared with those of a previously published, well-defined population with genetic hemochromatosis. Iron overload was characterized by a mixed pattern with iron deposits in hepatocytes and sinusoidal cells. Steatosis was present in 59.7% of patients with inflammation in 32.4% of cases. Periportal fibrosis was found in 67.4% of patients. These patients were older, had higher sinusoidal iron scores, and had a higher prevalence of steatosis and inflammation than patients without fibrosis. Iron overload in IR-HIO was histologically different from that in genetic hemochromatosis.

In patients with cirrhosis, serum albumin determination should be carried out by immunonephelometry rather than by protein electrophoresis.

OBJECTIVE: Serum albumin is a key parameter for prognosis in cirrhosis. We compared levels of serum albumin determined by both protein electrophoresis and immunonephelometry, with special reference to the Child-Pugh classification. DESIGN AND METHODS: One hundred and thirty-one patients, including 39 with cirrhosis, were included prospectively during 2 months. The aetiology of cirrhosis was mainly alcoholism (67%) and hepatitis C virus (HCV) (18%). Serum albumin was determined simultaneously by electrophoresis (Hydrasys SEBIA following protein determination by the biuret reaction) and by immunonephelometry (BECKMAN Nephelometer). Values were compared by non-parametric tests. RESULTS: For the whole population, electrophoretic and immunonephelometric values correlated (p = 0.85; P < 0.0001), but electrophoresis significantly overestimated serum albumin by a median 1.6 g/l (P < 0.0001) with a large spread in values (range, -3.9 to 12.7). Median overestimation in cirrhosis was 2.6 g/l (P < 0.0001; range, -2.0 to 10.2) and 1.0 g/l (P < 0.0001; range, -3.9 to 12.7) in patients without cirrhosis (difference, P < 0.02). For 6/39 (15.4%) patients with cirrhosis, this overestimation led to an underestimation in the Child-Pugh classification. CONCLUSION: In our experience, electrophoresis can lead to serum albumin values which are significantly different compared to those obtained by immunonephelometry. This discrepancy may lead to an incorrect Child-Pugh classification. Therefore, in the follow-up of cirrhotic patients, serum albumin should be determined by immunonephelometry.

Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis: a randomized trial. French-Speaking Club for the Study of Portal Hypertension.

OBJECTIVE: Beta-blockers have been shown to reduce portal pressure in patients with cirrhosis and limit the development of portosystemic shunts in portal hypertensive animals. Thus, a randomized double-blind trial was conducted to evaluate propranolol in the prevention of the development of large oesophageal varices in patients with cirrhosis without varices or with small varices. METHODS: One hundred and two patients received long-acting propranolol (160 mg/day) and 104 patients received a placebo. At inclusion, there was no significant difference between the two groups in terms of clinical characteristics or biochemical tests. At 2 years, the size of varices was estimated on video recordings. RESULTS: One-third of the patients were lost to follow-up, and 95%/97% of the remaining patients were compliant in the propranolol and placebo groups, respectively. At 2 years, the proportion of patients with large varices was 31% in the propranolol group and 14% in the placebo group (P< 0.05). Three and four patients bled in the propranolol and placebo groups, respectively, and nine and ten died, respectively. CONCLUSION: This trial suggests that propranolol administration cannot be recommended for the prevention of the development of large oesophageal varices in patients with cirrhosis; thus other studies are needed in selected subgroups of patients.

Interferon and ursodeoxycholic acid combined therapy in chronic viral C hepatitis: controlled randomized trial in 203 patients.

AIMS: This prospective randomized trial was carried out in order to determine whether the long-term administration of ursodeoxycholic acid after discontinuation of interferon had any beneficial effect on the clinical course of hepatitis C virus infection. METHODS: Enrolled in the study were 203 patients with chronic active hepatitis C. They were all given: interferon alpha-2a (3 MU subcutaneously thrice a week) and ursodeoxycholic acid (10 mg/kg/day) for 9 months. At month 9, biochemical responders only were randomized into ursodeoxycholic acid treatment or placebo for 12 additional months (double blind study). RESULTS: At the end of interferon therapy, 71 patients (37%) were virological responders and 107 (56%) patients were biochemical responders and were randomized: 54 into the ursodeoxycholic acid group and 53 into the placebo group. Sustained response was evaluated 12 months after withdrawal of interferon. Sustained biochemical and virological responses were, respectively, 30% and 22% in the ursodeoxycholic acid group and 46% and 32% in the placebo group, which did not significantly differ. Histological evolution of fibrosis and necrotic inflammatory activity were similar in the two groups. CONCLUSION: Continuation of ursodeoxycholic acid therapy after withdrawal of interferon in patients with end-of-treatment response did not result in any significant improvement either in the maintenance of response to interferon or in liver histology.

Superparamagnetic iron oxide: clinical time-response study.

Superparamagnetic iron oxide (AMI 25) is a promising new contrast agent for imaging the reticuloendothelial-system. Iron oxide crystals possess a large magnetic susceptibility and enhance proton relaxation rates, especially transverse relaxation (T2). In order to guide the clinical utilization of this contrast media we analyzed 4 patients with malignant lesions of the liver before and after slow intravenous administration (20 mumol Fe/kg) of AMI 25. We performed two magnetic resonance (MR) sequences at different times using a 0.35 T magnet. MR signal-to-noise ratio (SNR) of the reticuloendothelial system (particularly the liver SNR) decrease promptly. The maximum decrease in SNR (67-72% for the liver, 46-65% for the spleen, 23-41% for the bone marrow) is observed 3 h after injection (P less than 0.01). However, except the peak of contrast enhancement in T1-weighted sequences of splenic tissue, the curve describes a plateau within 30 min and 6 h, allowing a delay between injection and imaging. T2-weighted sequences give a greater contrast-to-noise ratio (CNR) by adding the spontaneous tumor contrast to the effect yielded by AMI 25. These results suggest that images must be acquired between 1 and 6 h after intravenous administration of superparamagnetic iron oxide.

[Importance of liver puncture biopsy and endoscopic retrograde cholangiography in patients with chronic anicteric unexplained cholestasis. A retrospective study in 79 patients]. / Intérêt de la ponction-biopsie hépatique et de la cholangiographie rétrograde endoscopique chez les malades ayant une cholestase chronique anictérique inexpliquée. Etude rétrospective chez 79 malades.

AIM: To determine the diagnostic value of systematic liver needle biopsy and endoscopic retrograde cholangiography in patients with unexplained chronic anicteric cholestasis. METHODS: Seventy nine patients presented with anicteric cholestasis for over 6 months as defined by: a concomitant increase in at least 2 of 3 cholestatic enzymes (GGT, alkaline phosphatase, 5'nucleotidase); a low cytolytic ratio (ALT/AP (xN/xN) < or = 5); and negative test results (normal ultrasound scan; no antimitochondrial antibodies, viral, drug-induced, or toxic hepatitis, or known ulcerative cholitis). Based on liver biopsy and endoscopic retrograde cholangiography, 5 groups were determined; group A: normal liver biopsy and endoscopic retrograde cholangiography; group B: primary sclerosing cholangitis with histological biliary lesions; group C: primary sclerosing cholangitis with normal histology; group D: histologic biliary lesions alone; group E: other (aspecific histologic lesions, isolated anomalies of intrahepatic bile ducts on endoscopic retrograde cholangiography). RESULTS: Diagnosis of cholestasis was fortuitous in 43% of cases. Group A: 5 patients had normal liver biopsy and endoscopic retrograde cholangiography; group B (10 patients): 5 with destructive cholangitis, 5 with degenerative cholangitis, associated with portal fibrosis in 90%; group C: none of the patients had primary sclerosing cholangitis with normal histology; group D: 39 patients {idiopathic ductopenia (1), Caroli's disease (1), benign recurrent cholestasis (1), regenerative nodular hyperplasia (4), destructive cholangitis without ductopenia (7), degenerative cholangitis (15), ductular proliferation (10)}; group E: 24 patients with aspecific histologic lesions, and one patient with isolated anomalies of the intrahepatic bile ducts on endoscopic retrograde cholangiography. CONCLUSIONS: In the present population: a) 13% presented with intense cholangitis and primary sclerosing cholangitis on endoscopic retrograde cholangiography; b) 49% presented with various histologic biliary lesions without primary sclerosing cholangitis. We conclude that in chronic anicteric cholestasis of unexplained origin, first choice work-up should include liver biopsy, and endoscopic retrograde cholangiography should only be performed when intense histologic cholangitis is observed.

Relationship between gastric mucosal changes and hemodynamic patterns in alcoholic cirrhosis. A prospective study.

Most gastric mucosal changes in cirrhosis are thought to be related to vasculopathy. The aim of this study was to determine whether there was a relationship between gastric mucosal changes and hemodynamic in cirrhosis. Thirty patients with alcoholic cirrhosis were divided into four groups: no congestive gastropathy (n = 6), mild congestive gastropathy type 1 (discrete mosaic pattern) (n = 9), mild congestive gastropathy type 2 (obvious mosaic pattern) (n = 9), and severe congestive gastropathy (n = 6). The four groups did not significantly differ with respect to clinical and biochemical data, degree of hepatic dysfunction, or endoscopic signs of portal hypertension. A hyperdynamic circulatory syndrome was observed in most patients, but tended to be more pronounced in patients with severe congestive gastropathy and mild congestive gastropathy type 2 as compared to patients with normal mucosa, or mild congestive gastropathy type 1. Systemic vascular resistance was found to be significantly lower in high-grade patients (mild congestive gastropathy type 2 + severe congestive gastropathy, n = 15) as compared with low-grade patients (no congestive gastropathy + mild congestive gastropathy type 1, n = 15) (736 +/- 267 vs 1,046 +/- 403 dyne.s.cm-5, P = 0.02). Neither splanchnic hemodynamics as assessed by the degree of portal hypertension (hepatic venous pressure gradient) and superior mesenteric artery vascular resistance (Doppler measurement of the pulsatility index) catecholamines or glucagon serum levels differed significantly between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Epidemiology of hepatitis C virus infection in 1,304 HCV positive patients: variations according to the origin of transmission and year of diagnosis]. / Epidémiologie de l'infection virale C chez 1,304 sujets VHC positif. Variations en fonction du mode de contamination et de l'année du diagnostic.

UNLABELLED: The evolution of epidemiological data on hepatitis C virus infection is poorly documented and thus the impact of screening is difficult to evaluate. AIM: To study epidemiological variations based on the origin of transmission and the year of diagnosis of hepatitis C virus infection. METHODS: The files of all 1304 patients seen in the hepatology unit of the Rennes University Hospital were analyzed (retrospectively before and prospectively after October 1995) in relation to epidemiological features. RESULTS: Despite widespread screening which is the source of 60% of the diagnoses, the total number of new cases of hepatitis C infection per year has not increased. Compared to patients diagnosed in the first years following the discovery of the virus, patients recently identified were younger (42 +/- 14 years) and frequently drug addicts (40%). Aminotransaminases were normal in 20% of cases. The frequency of cirrhosis has declined (17%). There has been a decrease in the proportion of patients who undergo liver biopsy (50%) and treatment with interferon (one third of patients). CONCLUSIONS: The impact of screening on the number of newly treated patients seems to be lower than previously predicted.

[Association of sarcoidosis and primary biliary cirrhosis: review of the literature apropos of a new case]. / Association sarcoïdose et cirrhose biliaire primitive: revue de la littérature à propose d'un nouveau cas.

We report a case of sarcoidosis associated with primary biliary cirrhosis in a 56-year old woman, with a 5 years' follow up. Sarcoidosis was ascertained by chest X ray, gallium scintigraphy, broncho-alveolar washing and liver biopsy (intralobular epithelioid granulomas). The diagnosis of primary biliary cirrhosis was based on IgM level increase (4 g/l), AMA positivity (1/1000) and liver biopsy assessment (non suppurative chronic cholangitis). Such an association is rare (12 detailed cases in literature), brings out pathophysiological questions and points to an additional mechanism of cholestasis in patients with sarcoidosis.

[The diagnosis of hemochromatosis in the era of the gene]. / Le diagnostic de l'hémochromatose à l'heure du gène.

The discovery of the hemochromatosis gene has deeply changed and simplified the diagnosis of the disease. In a given individual, establishing the diagnosis relies, from now on, on a simple blood sample showing the couple: elevated transferrin saturation and homozygous C282Y mutation (= C282Y +/+). Liver biopsy should only be performed when iron overload is massive in order to detect cirrhosis (or bridging fibrosis), i.e. in a prognostic view. Practically, liver biopsy is confined to the following two situations: when the C282Y +/+ patient exhibits hepatomegaly and/or an increase in serum transaminases and/or a serum ferritin level above 1,000 micrograms/L; whenever, despite a strong bio-clinical suspicion of iron overload, genetic testing does not show the expected homozygosity for C282Y. At the family level, evaluating the risk for hemochromatosis is now "instantaneous" thanks to genetic testing. One must, however, keep in mind in interpreting the data of the family members that: clinical expression of the homozygous status is not constant; heterozygosity for C282Y does not per se lead to significant iron overload, but may constitute a co-factor exacerbating (or increasing the risk of) other hepatic or non hepatic diseases. Heterozygosity exposes also to the risk of homozygosity among the offspring; this knowledge of C282Y status must be balanced by the negative impact from the standpoint of possible societal genetic discrimination.

[Quantification of iron overload]. / Quantification de la surcharge en fer.

Iron overload involves primarily hepatocytes in case of digestive hyperabsorption (hemochromatosis and dyserythropoiesis) and macrophages in case of transfusional excess. Serum iron and transferrin saturation are poorly correlated with the degree of iron overload. Serum ferritin is a better reflect of iron stores but numerous clinical conditions, unrelated to variations of iron load, can increase the serum level. Biochemical determination of liver iron overload is the gold standard of iron quantification and well correlated to the level of iron burden appreciated by the amount of iron removed by venesection, but its determination necessitates a liver biopsy and is dependant of sampling error in case of heterogeneous iron deposits (cirrhosis). The sensitivity of computed tomography is insufficient, beeing unable to detect iron overload below 5 times the normal liver iron load, especially in case of associated steatosis. Magnetic resonance imaging is a valuable tool when using T2 weighted gradient echo sequences on 1.5 Tesla magnet and permits non invasive iron overload quantification.

[Metabolic cirrhosis (hemochromatosis, Wilson's disease, erythropoietic protoporphyria)]. / Cirrhoses métaboliques (hémochromatose, maladie de Wilson, protoporphyrie érythropoïétique).

The possibility of a metabolic chronic liver disease must always be borne in mind since in certain cases treatment can prevent the lesions from getting worse. The clinical and biochemical context should suggest either (1) genetic haemochromatosis when faced with high serum iron and ferritin levels and elevated transferrin saturation or with a suggestive clinical context (melanoderma, diabetes, hypogonadism, arthropathy, myocardiopathy); or (2) Wilson's disease in young subjects, especially in the presence of neurological and ocular signs or of haemolytic anaemia; or (3) porphyria in case of cutaneous manifestations caused by exposure to sun light. Hence the importance of full clinical examination in patients with chronic liver disease.

[Non surgical treatment of hepatocellular carcinoma]. / Traitement non chirurgical du carcinome hépatocellulaire.

During the last past years, the curative and preventive treatment of hepatocellular carcinoma (HCC) has improved. The regular follow-up of patients with chronic liver disease using ultrasound examination and serum alpha-fetoprotein determination, leads to diagnose hepatocellular carcinoma at an early stage, when curative treatment could be quite efficient. Besides surgery which has been the only hope of cure for a few patients, efficient medical procedures--ie chemoembolization, in situ radiotherapy and alcohol injection--are emerging. The place of these different therapeutic procedures is to be defined. In addition, the prevalence of hepatocellular carcinoma should decrease due to the improvement of preventive policy--ie vaccination against hepatitis B infection and familial screening for genetic hemochromatosis.