[Acute fatty liver of pregnancy and mitochondrial fatty acid oxidation. Consequences for the offspring]. / Stéatose hépatique aiguë gravidique et bêta-oxydation mitochondriale des acides gras : conséquences pour l'enfant.

Acute fatty liver of pregnancy (AFLP) is a rare liver disease unique to pregnancy that can lead to acute liver failure. The prognosis, initially often fatal for both mother and child, has been improved by prompt delivery. The diagnosis should be highly suspected if the mother presents epigastric pain, nausea and/or vomiting, or polyuria-polydipsia in the third trimester of pregnancy. AFLP has been found associated with a genetic deficiency of fatty acid beta-oxidation, which may cause sudden death in infancy. Consequently, the mother and her newborn should undergo screening for this deficiency.

[Prophylaxis of mother-to-infant transmission of hepatitis B virus]. / Prévention de la transmission materno-infantile du virus de l'hépatite B.

Hepatitis B virus (HBV) infection is a worldwide health problem and mother-to-infant (or vertical) transmission is the main source of chronic infection in Asian countries. Administration of HBV vaccine to the infant at birth, with or without concurrent specific immunoglobulin, efficiently prevents such transmission (efficacy>90%). In France, testing Ag HBs is mandatory during pregnancy in all pregnant women. Infants born to Ag HBs-positive mothers should receive the first injection of vaccine and one injection of specific immunoglobulins at birth. Vaccination should thereafter be completed according to a three-injection protocol (at 1 and 6 months) or a four-injection protocol in case of prematurity. Failure of immunoprophylaxis can be observed when the viral load is very high in the mother during pregnancy (HBV-DNA levels>200,000 IU/mL). In such women, antiviral therapy with analogs (lamivudine, telbivudine, or tenofovir) during the third trimester of pregnancy and 1 month post-partum, in association with accurate immunoprophylaxis, may prevent vertical transmission. The optimal cut-off value of maternal viral load for antiviral therapy in late pregnancy and post-partum to prevent vertical transmission is still under debate.

[Management of obstetric cholestasis in France: A national survey of obstetrical practice]. / Prise en charge de la cholestase intrahépatique gravidique en France : enquête nationale des pratiques auprès des gynécologues-obstétriciens.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is the most commonly encountered pregnancy-specific liver disease. This condition, with no proven maternal morbidity, has been associated with an increased risk of prematurity and intrauterine fetal death. There is, to date, no scientific obstetrical guideline for clinical practice in France. The objective of our study was to precise, in this situation, how French obstetricians manage patients suffering from ICP. METHODS: We carried out, during 2010, a national descriptive practice survey of ICP management in France in association with the "Collège national des gynécologues-obstétriciens français". An inquiry form with 27 multiple-choice questions was sent to all obstetricians and gynecologist officiating in a maternity hospital recorded by the French Ministry of Health. The participants answered questions regarding diagnosis, perinatal management and treatment of ICP. Only the first answer received from each maternity hospital was analyzed. RESULTS: Of the 575 maternity hospitals, 275 (41.6%) responded after one mail recovery. Among them, almost half used a standardized management protocol for ICP. In most of the cases, perinatal management was performed by obstetricians alone (73%), and in only 20% of the cases in collaboration with the specialist in hepatology. Induction of labor at 37-38 weeks was the most common policy for the majority of respondents (92.4%). CONCLUSION: This is the first French national survey for ICP management. This study demonstrated that ICP is, in most of the cases, managed by the obstetrician alone, and that fetal risks warrants an active management with induction of labor in late pregnancy.

ABCB4 gene mutations and single-nucleotide polymorphisms in women with intrahepatic cholestasis of pregnancy.

AIM: To evaluate the nature and frequency of ATP-binding cassette subfamily B member 4 (ABCB4) gene variants in a series of French patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: In this prospective study, the entire ABCB4 gene coding sequence was analysed by DNA sequencing in 50 unrelated women with ICP defined by pruritus and raised serum alanine aminotransferase activity or bile acid concentration, with recovery after delivery. Genomic variants detected in patients with ICP were sought in 107 control pregnant women. Patients with ICP and controls were of Caucasian origin. RESULTS: Eight genomic variants were observed. One nonsense mutation (p.Arg144Stop) and two missense mutations (p.Ser320Phe and p.Thr775Met) were revealed each in one heterozygous patient. A third missense mutation (p.Arg590Gln) was detected in three heterozygous patients and in two homozygous patients also homozygous for a particular haplotype of three single-nucleotide polymorphisms (c.175C>T, c.504T>C, c.711A>T). The chromosomal frequency of the p.Arg590Gln variant was significantly different between the ICP and control group (7.0% vs 0.5%; p = 0.0017; OR 16.03, 95% CI 1.94 to 132.16). An association was also found between allele T of the c.504T>C silent nucleotide polymorphism and ICP (68.0% vs 53.7%; p = 0.017; OR 1.83, 95% CI 1.08 to 3.11). The chromosomal frequency of the p.Arg652Gly variant did not differ between the ICP and control group (p = 0.40). CONCLUSIONS: This study shows that 16% of Caucasian patients with ICP bear ABCB4 gene mutations, and confirms the significant involvement of this gene in the pathogenesis of this complex disorder.

Liver fibrosis staging with contrast-enhanced ultrasonography: prospective multicenter study compared with METAVIR scoring.

We prospectively assessed contrast-enhanced sonography for evaluating the degree of liver fibrosis as diagnosed via biopsy in 99 patients. The transit time of microbubbles between the portal and hepatic veins was calculated from the difference between the arrival time of the microbubbles in each vein. Liver biopsy was obtained for each patient within 6 months of the contrast-enhanced sonography. Histological fibrosis was categorized into two classes: (1) no or moderate fibrosis (F0, F1, and F2 according to the METAVIR staging) or (2) severe fibrosis (F3 and F4). At a cutoff of 13 s for the transit time, the diagnosis of severe fibrosis was made with a specificity of 78.57%, a sensitivity of 78.95%, a positive predictive value of 78.33%, a negative predictive value of 83.33%, and a performance accuracy of 78.79%. Therefore, contrast-enhanced ultrasound can help with differentiation between moderate and severe fibrosis.

[How to confirm acute fatty liver of pregnancy in case of emergency]. / Comment confirmer le diagnostic de stéatose hépatique aiguë gravidique en urgence?

Acute fatty liver of pregnancy (AFLP) is a rare disease of which prognosis could be adverse if diagnosis is delayed. Certain diagnosis is sometimes made complex because of undercurrent symptoms with pre-eclampsia or hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome. Several reports announce an increase of incidence and illustrate cases confirmed by non-invasive methods. They permit early diagnosis and improve morbidity and mortality. Reviewing seven of the most important series of AFLP, we demonstrate how to use ultrasonography or computed tomography scan to confirm AFLP. However, liver biopsy should be realised after delivery in case of uncertain diagnosis.

Hepatitis B virus reactivation after a resolutive acute hepatitis leading to a diagnosis of T cell lymphoma.

A case of hepatitis B virus reactivation leading to the diagnosis of a T cell lymphoma is reported. A 66-year-old woman with a past history (10 years before) of spontaneously recovered acute hepatitis B (with disappearance of serum hepatitis B surface antigen and appearance of anti-HBs), has been referred for hepatologic consultation for acute hepatitis. The patient was found positive again for hepatitis B surface antigen as well HBeAg and hepatitis B virus DNA. No other cause of liver disease was identified and a diagnosis of spontaneous hepatitis B virus reactivation was made. Five months later a peripheral T cell lymphoma was diagnosed. This unusual case confirms that natural immunity is not protective against hepatitis B virus reactivation and shows that such hepatitis B virus reactivation may precede the usual clinical manifestations of a peripheral T cell lymphoma.

Evaluation and improvement of a reliable diagnosis of cirrhosis by blood tests.

OBJECTIVE: To evaluate the rates of reliable diagnosis of cirrhosis by two usual blood tests. METHODS: Reliable diagnosis was mainly evaluated by comparing rates of positive (PPV) and negative (NPV) predictive values with FibroTest and FibroMeters, as either standard test or specifically designed for cirrhosis, in 1056 patients with chronic hepatitis C. RESULTS: Using the diagnostic limits provided by fibrosis stage scales, the PPV for cirrhosis was: standard FibroMeters: 68.5% versus FibroTest: 37.1%. Using 95% PPV, the cirrhosis detection rate was: specific FibroMeter: 26.1% versus FibroTest: 2.0% (P<10(-3)). The cirrhosis detection rate increased from 26 to 65% by performing liver biopsy in 8% of patients with indeterminate results on specific FibroMeter between 95% NPV and PPV. On the other hand, specific FibroMeter provided three intervals of 95% reliable diagnosis with no biopsy: less than or equal to 95% NPV: no cirrhosis (threshold: diagnosis); significant fibrosis; and greater than or equal to 95% PPV: cirrhosis. CONCLUSION: The detection rate and PPV for cirrhosis using fibrosis scales were fair for standard FibroMeter and poor for FibroTest. Around one-fourth of cases of cirrhosis are detected by the 95% PPV of specific FibroMeter, and around two-thirds by performing an additional liver biopsy in only 8% of patients. Finally, specific FibroMeter can avoid liver biopsy by classifying patients into three categories: no cirrhosis; significant fibrosis; and cirrhosis.

[Hepatitis B and pregnancy]. / Hépatite virale B et Grossesse.

In pregnant women, hepatitis B virus (HBV) infection presents the risk of mother-to-child (vertical) transmission. The contaminated newborn most often remains a chronic carrier. Mother-to-child transmission can be avoided by serovaccination of the newborn. Screening for HBs antigen is essential in all pregnant women; in France, it is mandatory at the 6-month prenatal examination. All infants born to mothers who are carriers of HBs antigen must receive a serovaccination against this virus, by intramuscular injection of vaccine and of hepatitis B immune globulin (H-BIG, 100 or 200 IU), in two different sites, in the first hours after birth. Vaccination then continues, according to the recommended protocol. Although the combination of vaccination and H-BIG is very effective in preventing chronic carriage in children (efficacy >90 %), some children may nonetheless be contaminated, especially when the viral load is very high during pregnancy. These women with very high viral loads may receive lamivudine treatment at the end of pregnancy to diminish viral load and thus the risk of chronic carriage in the child; however the role of this drug in this situation is not yet clearly defined. The efficacy of the serovaccination must be confirmed in all children by a serologic examination (HBs antigen and anti-HBs antibodies) at some time after the last vaccination. Children carrying the HBs antigen must be seen by a pediatrician who has experience with viral hepatitis. When HBs antigen is found in a woman during pregnancy, a specialist should be consulted and the family should undergo complete serologic testing (HBs antigen, anti-HBc and anti-HBs antibodies).

[Portal hypertension and pregnancy]. / Grossesse et hypertension portale.

Pregnancy in patients with portal hypertension is rare but worrying for the clinician. Although the effects of portal hypertension during pregnancy have not been fully elucidated, there is an evident increase in morbidity, especially associated with cirrhosis, which justifies the idea of at-risk pregnancy and requires management by a multidisciplinary team. The prevention and treatment of gastrointestinal haemorrhage is quite similar to that in nonpregnant patients. Investigation and management of portal hypertension before and at the beginning of pregnancy can reduce the risks of foetal loss, restricted intra-uterine growth, premature birth and maternal mortality, which are closely related to gastrointestinal haemorrhage. The risks related to the underlying disease, such as liver failure with cirrhosis and thromboembolic risk with vascular diseases associated with thrombophilia must be taken into consideration. Generally, vaginal delivery with early analgesics for the mother assisted by an extraction device should be preferred to caesarean section, which must be reserved for obstetrical indications.

[Intrahepatic cholestasis of pregnancy]. / La cholestase intrahépatique gravidique.

Intrahepatic cholestasis of pregnancy is the most common liver disorder unique to pregnancy in women without hypertension. The cause of intrahepatic cholestasis of pregnancy is still under discussion but genetic and hormonal factors are predominant. The main symptom is skin pruritus, associated with increase in serum transaminase activities and bile acid concentrations. Intrahepatic cholestasis of pregnancy carries a risk for the pregnancy because of preterm delivery and sudden intrauterine fetal death. Ursodeoxycholic acid (usually 1000mg per day or 15mg/kg per day) is currently the most effective pharmacologic treatment. Ursodeoxycholic acid reduces pruritus, transaminases and bile acid levels and probably prematurity without adverse effects. Obstetric management is still under debate. The majority of authors recommend active management with elective delivery usually before or at 38 weeks of gestation according the severity of cholestasis. Prospective controlled studies are required to confirm the benefit of ursodeoxycholic acid treatment on fetal outcome and to clarify the obstetrical management near term.

[Interferon-alpha and ribavirin treatment in a patient with hepatitis C virus-associated cutaneous periarteritis nodosa]. / Périartérite noueuse cutanée associée à une infection par le virus de l'hépatite C, régressive après une bithérapie antivirale.

BACKGROUND: Hepatitis C virus (HCV) frequently causes leucocytoclastic vasculitis as a result of type II or III cryoglobulinemia. HCV-associated vasculitis without cryoglobulinemia is less common. PATIENTS AND METHODS: A 33-year-old woman consulted for infiltrative necrotic purpura of the lower limbs, responsible for leg ulcers measuring less than 1 cm. Histopathological examination revealed vasculitis affecting the hypodermic arterioles and caused by periarteritis nodosa. No extracutaneous involvement was observed. The patient had presented asymptomatic untreated HVC infection (genotype 3) for two years. Antiviral treatment resulted in elimination of the patient's viremia and no relapse of skin lesions was observed two years after the end of treatment. COMMENTS: This patient presented vasculitis due to cutaneous nodular periarteritis associated with HVC without cryoglobulinemia. Hepatic impairment was mild and did not require any antiviral treatment. No further skin involvement was seen after treatment with colchicine and because the patient's viral genotype was favorable, we decided to initiate antiviral therapy. This therapeutic approach should be considered by dermatologists, but it is nevertheless important to assess the risk of interferon-induced aggravation of vasculitis.

[Asymptomatic pneumothorax diagnosis on pre-biopsy sonogram of the liver]. / Découverte d'un pneumothorax lors d'une échographie de repérage avant ponction biopsie hépatique.

Liver biopsy is an invasive procedure which is widely used for the management of liver diseases. An asymptomatic pneumothorax was detected on sonography prior to biopsy for chronic hepatitis C. The complications from biopsy, potentially severe, are decreased by ultrasound guidance. Currently, ultrasound guidance is recommended at the time of liver biopsy.

[An anicteric cholectasis and nephrotic syndrome: AL amyloïdosis in a 51 years-old man]. / Une cholestase anictérique associée à un syndrome néphrotique chez un homme de 51 ans: découverte d'une amylose AL.

Amyloidosis is a multiple-organ disease for which the diagnosis is often confusing and thereby delayed. Here, we present an archetypal case illustrating such difficulties. A 51 years-old man presented a mixed dyslipemia in November 2002, in June 2004 he has finally been diagnosed with a primary AL-amyloidosis. Within these two years, the arising of a non-icteric cholestasis and a nephrotic syndrome have triggered the search for a disease related to a multiple-organ protein deposition. Confirmation of the AL-amyloidosis was obtained through an histological examination, including direct immuno-fluorescence. Amyloidosis is a life threatening disease that need to be diagnosed at an early stage, in order to maximise the therapeutic expectations. The average survival after the diagnosis of AL-amyloidosis is 5% at 10 years. Often, treatments are initiated late in the course of the disease, at a time when organ lesion are constituted, severely affecting the prognosis.

Improvement of a CIDP associated with hepatitis C virus infection using antiviral therapy.

A 57-year-old man with chronic inflammatory demyelinating polyneuropathy associated with hepatitis C virus infection was treated successfully with the combination of peginterferon-alpha-2b and ribavirin. Viral eradication was confirmed during the 4th week of treatment and was followed 3 weeks later by neurologic improvement. The patient resumed normal activity 1 year after the therapy was completed.

Carbohydrate-deficient transferrin (CDT) determination by nephelometry using a commercial kit. Analytical and diagnostic aspects.

Carbohydrate-deficient transferrin (CDT) has been proposed as the most efficient marker of alcohol abuse. Absolute and relative concentrations of CDT were measured with a commercial assay (%CDTTIA from AXIS-Shield, Oslo, Norway) using rate nephelometry for transferrin determination. One hundred eighty-eight alcoholic patients (154 males, 34 females) and 132 control patients (113 males, 19 females) were included in the study. Within-run and day-to-day imprecision were 3.15% and 9.77%, respectively. The calibration curve was stable for more than 4 months with a shift below 5%. The commercial assay lacked sensitivity (Se = 0.48), but was highly specific (Sp = 0.98). Lowering the cut-off from 6% to 4.6% raised the sensitivity of the %CDTTIA test to 0.76 with a specificity of 0.90. We conclude that this adaptation to the Array Protein System (Beckman-Coulter) is suitable for routine use and offers precise results. It, however, requires an adaptation of the cut-off value for patients and of the target value for kit controls.

Serum amylase and lipase activities in normal pregnancy: a prospective case-control study.

OBJECTIVE: The diagnosis of acute pancreatitis during pregnancy is usually based on the association of upper abdominal pain, nausea or vomiting, and elevated serum amylase or lipase activities. The changes in these enzymatic activities have not been clearly established during normal pregnancy. The aim of this study was therefore to evaluate serum amylase and lipase activities in healthy pregnant women. METHODS: Serum amylase and lipase activities were measured in 103 pregnant women (first trimester, n = 34; second trimester, n = 36; third trimester, n = 33) and in 103 nonpregnant women matched for age and not receiving oral contraception. RESULTS: Serum amylase activity was similar in pregnant women and nonpregnant women during all trimesters of pregnancy. Serum lipase activity was significantly lower during the first trimester of pregnancy compared to nonpregnant women (48.6+/-27.6 vs 59.2+/-29.3 IU/L, p < 0.05) and compared to the third trimester (48.6+/-27.6 vs 76.3+/-35.8 IU/L, p < 0.001). Serum lipase activity was not statistically different between pregnant and nonpregnant women during the second and third trimesters. CONCLUSION: An increase in serum amylase and lipase activities during pregnancy should be taken into account, as in nonpregnant women.