Relevance of 3D Cholangiography and Transient Elastography to Assess Cystic Fibrosis-Associated Liver Disease?

Background. Cystic fibrosis-associated liver disease (CFLD) is a major cause of death. The objective of our retrospective study was to describe the relevance of magnetic resonance imaging (MRI) and liver stiffness measurement (LSM) for CFLD evaluation. Methods. All cystic fibrosis adult patients evaluated by MRI and LSM were included. MR signs of portal hypertension (PHT), dysmorphia, or cholangitis were collected and LSM expressed in kPa and Metavir. Results. Of 25 patients, 52% had abnormal MRI. Median LSM was 5.7 kPa (3.4-9.9). Three patients had F2 score and one had F3 score. In patients with PHT, LSM was 7.85 kPa (3.7-9.9) compared to 5 (3.4-7.5) in others, p = 0.02. In patients with abnormal liver function tests, 50% had increased LSM (≥F2), whereas 94% with normal tests had normal LSM (p = 0.04). Seven patients had abnormal MRI despite normal ultrasonography. Conclusions. MRI and LSM provide useful information on CFLD and may help to screen patients with PHT.

One-week triple therapy using omeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori in patients with non-ulcer dyspepsia: influence of dosage of omeprazole and clarithromycin.

BACKGROUND: Triple therapy based upon omeprazole, amoxycillin and clarithromycin for 7 days is the reference treatment used in France for the eradication of Helicobacter pylori. However, optimal dosages of omeprazole and clarithromycin have not been determined. AIMS: To compare four eradication regimens using this treatment in patients with non-ulcer dyspepsia. METHODS: Two hundred and seventy-four patients with symptoms of dyspepsia, normal upper GI endoscopy and a positive urease test were included in the study. A 13C-urea breath test (UBT) was obtained before and 6 weeks after treatment. Patients were randomized to one of the following 7-day regimens: 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O20AC500) or 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O20AC1000) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O40AC500) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O40AC1000). Compliance was assessed by returned tablet counts. Eradication was defined as conversion from positive 13C-UBT at entry to negative 13C-UBT 6 weeks after cessation of therapy. RESULTS: Two hundred and fifty-eight patients were included in the intention-to-treat (ITT) analysis. From the least to the most effective regimen, eradication rates were: O20AC1000: 60.0% (95% CI: 47.6-72.4), O20AC500: 64.1% (52.3-75.8), O40AC1000: 64.2% (52.7-75.7), O40AC500: 74.6% (64.2-85.0) (N.S.). Overall compliance was good in 92% of patients. The most frequent adverse events were diarrhoea and taste impairment, occurring mainly in the high-dose clarithromycin groups. CONCLUSIONS: Eradication rates obtained in this study were lower than those expected on the basis of previously reported studies. This study supports the use of a double dose of omeprazole, although the difference between groups was non-significant, but provides no argument in favour of a high dose of clarithromycin.

Chronic hepatitis C with normal or abnormal aminotransferase levels: is it the same entity?

OBJECTIVE: The features of hepatitis C virus (HCV) infection with persistently normal serum alanine aminotransferase (ALT) activity levels are not well defined. This study evaluated the characteristics of HCV infection according to the presence or absence of elevated ALT. METHODS: Demographic data, liver histology and HCV genotype were studied in a group of 80 HCV-RNA-positive subjects with persistently normal ALT (PNALT) (group 1), and compared with a second group of 455 HCV-RNA-positive patients with elevated ALT (group 2). The annual progression of liver fibrosis was also calculated. RESULTS: A higher proportion of women was found in group 1:64% vs 42% in group 2 (P< 0.0002). The HCV genotype 1 was less frequent in group 1:49% vs 60% in group 2 and genotype 2 was more frequent: 16% in group 1 vs 4% in group 2 (P< 0.002). Cirrhosis was less frequent in group 1 (4% vs 13% in group 2 (P< 0.0001)). Normal liver was more frequent in group 1:9% vs 1% in group 2 (P< 0.0001). The Knodell score was significantly different between the two groups: 3.2 +/- 0.27 vs 7.15 +/- 0.22 (P< 0.0001). The progression of liver fibrosis was lower in group 1: 0.053 +/- 0.14 units/year vs 0.13 +/- 0.24 in group 2 (P < 0.007). CONCLUSION: HCV infection with PNALT is associated with less severe histological liver disease and a lower fibrosis progression rate. This suggests that the natural history of HCV infection in these patients is different from that in patients with abnormal ALT.

Duodenojejunal motility after oral and enteral nutrition in humans: a comparative study.

BACKGROUND: Small bowel motility during enteral nutrition (EN) remains poorly known. Our aim was to compare, in six healthy volunteers, the duodenojejunal motor patterns after a 750-kcal meal either ingested or infused intraduodenally at two different infusion rates: 2 kcal/min for 6 hours (6-hour EN) or 1 kcal/min for 12 hours (12-hour EN). METHODS: In each volunteer, the three manometric studies were carried out in a random order with an interval of > or = 1 week between each recording. Number of phase III (PIIIs), their characteristics, number of waves (NW), and area under the curve (AUC) were determined. RESULTS: PIIIs were interrupted by each type of nutrition in every volunteer. In five of six during 6-hour EN and in six of six during 12-hour EN, the first PIII returned before the end of EN. The mean duration of the fed pattern was similar in the three studies. During the interruption of PIIIs after oral meal, duodenojejunal motility was characterized by uninterrupted random contractions. By contrast, in four of six during the 6-hour EN and in five of six during 12-hour EN, it was organized as regular short bursts of contractions separated by motor quiescence. In all studies during the disruption of PIIIs, NW and AUC values decreased progressively with time and were higher at the jejunum level than in the duodenum (p < .001). However, at each level of recording, NW and AUC values were similar in the three types of feeding. After the return of PIIIs, the number, duration, and propagation velocity of PIIIs, NW, and AUC values were similar in the three studies. CONCLUSIONS: EN interrupts PIIIs, but, in most cases, PIIIs reappear before the end of EN. During the interruption of PIIIs, the organization of the contractions is qualitatively different from the fed pattern observed after oral feeding. For the same caloric value of the meal, the quantitative duodenojejunal motor response is not affected by the infusion rate, and the more important jejunal, rather than duodenal motor response found after an oral meal, is observed during EN. During EN, after the return of PIIIs, despite the persistence of a nutrient infusion into the duodenum, the small bowel motor patterns are not qualitatively or quantitatively different from those recorded in fasting subjects.

[Upper digestive hemorrhage in patients over 80 years of age: incidence and prognostic factors]. / Hémorragies digestives hautes du sujet âgé de plus de 80 ans: fréquence et facteurs pronostiques.

OBJECTIVES: The aim of this study was to assess the incidence and the prognosis of upper gastrointestinal hemorrhage in patients aged over 80 years. METHODS: Between January and December 1993, among 360 patients admitted for upper gastrointestinal hemorrhage, 63 were older than 80 years (18%). Data were prospectively collected in all patients. RESULTS: Before admission, 8 experienced a lipothymia and 3 a shock. The median initial hematocrit was 29%. Endoscopy was performed in 59 patients and a cause was determined in 49 (83%). The main cause of bleeding was gastric and duodenal ulcer (n = 26, 53%) and ten of them were graded Forrest < or = IIb. Endoscopy did not contribute in 10 patients and was impossible in 4 because of an hemodynamic failure. Gastrotoxic drugs intake was found in 28 patients: non steroidal anti-inflammatory drugs (n = 14) and aspirin (n = 14). Endoscopic injection therapy was performed in the 10 patients with gastric or duodenal ulcer < or = Forrest IIb and permanent hemostasis was achieved in 8 out of 10. No further bleeding was seen in 53 patients (84%), while bleeding persisted in 4 and rebleeding occurred in 6 (9.5%) (3 duodenal ulcers, 2 gastric carcinomas and 1 esophageal varices bleeding). Only one patient required emergency surgery (rebleeding duodenal ulcer). The overall mortality was 12/63 (19%):50% of the deaths were related to hemorrhagic complications and 50% to concomitant disease. Only one patient among those taking gastrotoxic drug died from bleeding. The risk factors of death from bleeding were: initial shock (P = 0.02), lipothymia before admission (P = 0.02), rebleeding (P < 0.01), persistence of bleeding (P < 10(-4)). Gastrotoxic drugs intake was associated with a favorable prognosis (P < 0.05). The prognosis was not significantly affected by an initial hematocrit < 30% or blood units transfused > or = 4. CONCLUSIONS: People older than 80 years account for a large proportion of upper gastrointestinal bleeding (18%). The more common cause is gastric or duodenal ulcer. Mortality in these patients is high (19%). An initial shock or lipothymia, rebleeding or persistence of bleeding worsens prognosis. Gastrotoxic drugs intake is frequent (44%), but is associated with a good prognosis.

[Effect of lipid intake in meals on the duodenojejunal and sigmoid motor responses in healthy volunteers]. / Influence de la charge lipidique du repas sur les réponses motrices duodéno-jéjunale et sigmoïdienne chez le volontaire sain.

OBJECTIVES: In man, fat induces a fed motor pattern in the small bowel and stimulates colonic motility. With a pure lipid meal, these motor effects are dose-related. However, animal studies have suggested that the motor effects of fat are reduced when lipids are mixed with proteins and carbohydrates. Our aim was to study in healthy volunteers the duodeno-jejunal and sigmoid motor responses after two 750-kcal meals, one containing 28%, the other 58% lipids. METHODS: Combined duodeno-jejunal and sigmoid manometric sessions were performed in each volunteer during 3 hours after each test meal. Meal was always given 30 minutes after the occurrence of a phase III in the duodenum. The order of the two studies was randomly assigned with a minimal interval of 8 days between the two studies. The number of waves and the area under curve were calculated both on the overall and on each of the 6 successive half hours of the recording period. RESULTS: Phases III were interrupted at least for 3 hours by both types of meals in each volunteer. The overall duodeno-jejunal motor response was not different after the two meals and, in all cases, a progressive decrease of the motor parameters with time was demonstrated. A lower response in the duodeno-jejunum during the first postprandial hour and a delayed onset of the maximal motor activity were observed with the high fat meal. In the sigmoid, a motor response to food was observed in all volunteers without any quantitative difference between the low and high fat meals. CONCLUSION: A two-fold increase of the lipid fraction of a meal does not enhance the duodeno-jejunal and sigmoid motor responses to food. At variance, it reduces the first hour motor response and delays the peak of maximal activity in the duodeno-jejunum. Our data confirm that the specific motor effects of fat are modified by their combination with proteins and carbohydrates.

Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study.

This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.

Digestive manifestations in an immunocompetent adult with varicella.

A case of varicella with pancreatic pain as a first manifestation, a typical papulovesicular rash, pulmonary and hepatic and esophageal localizations occurring in an immunocompetent adult is reported. Treatment with intravenous acyclovir resulted in a prompt improvement and recovery in less than 4 days.

Detection and genotyping of the hepatitis C RNA in tear fluid from patients with chronic hepatitis C.

Tear fluid from 51 patients with chronic hepatitis C virus (HCV) infection was analyzed for the presence of the hepatitis C RNA to assess the potential role of this fluid in virus transmission. HCV sequences were amplified from sera and tear fluids by nested polymerase chain reaction using primers from the 5' non coding region of the virus genome. Positive samples were genotyped by the LiPA procedures. HCV RNA was detected in 76.5% (39/51) of the sera and in 9.8% (5/51%) of the tear fluid samples. The presence of the RNA in the tear fluid was independent of the severity of the hepatitis and of the viral load as measured by the branched DNA assay. The genotypes of the tears and serum isolates were different for two patients. For another patient, the HCV RNA was positive in the tear sample but negative in the serum sample. These findings suggest that tear fluid may transmit HCV but the source of HCV RNA in this fluid needs to be better understood.

Autoimmune hepatitis and systemic sclerosis: a new overlap syndrome?

OBJECTIVE: We report the cases of two patients with the complete CREST variant (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) of systemic sclerosis (SSc) who developed autoimmune hepatitis. RESULTS: Our findings suggest that autoimmune hepatitis can be considered to be one of the liver manifestations associated with SSc. Our data also indicate that, because liver involvement may precede skin manifestations, evaluation for SSc is appropriate when autoimmune hepatitis is noted, and that the evaluation should include clinical examination, testing for antinuclear antibodies (especially for anticentromere antibodies) and nailfold capillaroscopy. CONCLUSIONS: From a practical point of view, our two cases emphasize that suspicion of autoimmune hepatitis in SSc patients presenting with cytolytic hepatitis will help to achieve both accurate diagnosis and optimal management.

Prognostic value of the soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alfa. Multicenter GER-CYT 04 Group.

BACKGROUND/AIMS: High serum levels of the soluble interleukin 2 receptor (sIL-2R) have been reported in patients with chronic hepatitis C. The aims of this study were to determine the evolution of sIL-2R considered as an indicator of activation of T cells in patients with hepatitis C virus (HCV) treated with IFN-alpha and to correlate sIL-2R serum levels with parameters reflecting ongoing liver disease and with outcome of interferon treatment. METHODS: In a case-control study, we studied patients enrolled in a multicenter randomized clinical trial which had demonstrated the benefit of a reinforced regimen of interferon alpha. Each of the 26 sustained virological responders (SVR) was paired for treatment regimen with two non-responders (NR). RESULTS: Prior to treatment, higher levels of sIL-2R were found in the sera of 78 patients compared with healthy controls (3791+/-210 pg/ml versus 956+/-88 pg/ml (p<0.001)). In the 78 patients after 4 weeks of treatment, the levels of sIL-2R were higher than pretreatment levels (4308+/-206 pg/ml (p<0.01)). In the NR, levels of sIL-2R increased significantly after 4 weeks of treatment compared with pretreatment levels (p<0.01), and levels of sIL-2R at week 72 were not significantly different from those at pretreatment. Conversely, in the SVR, levels of sIL-2R at week 4 did not significantly increase compared to pretreatment values, and thereafter gradually decreased. At week 72, levels of sIL-2R were significantly lower than before treatment (p<0.001). The difference between levels of sIL-2R at week 4 and before initiation of treatment (delta s IL-2R) was smaller in the SVR than in the NR (142+/-219 pg/ml versus 704+/-107 pg/ml (p<0.02). The disappearance of HCV RNA from the serum at week 4 showed a sensitivity of 92% (95% confidence interval 86-98) and a specificity of 60% (95% confidence interval 49-71), delta sIL-2R had a sensitivity of 42% (95% confidence interval 31-53) and a specificity of 81% (95% confidence interval 79-90) for the prediction of a sustained virological response 6 months after stopping treatment. The disappearance of HCV RNA from serum at week 4 and delta sIL-2R were independent and early predictive factors for a sustained virological response 6 months after stopping treatment. CONCLUSIONS: At week 4, delta sIL-2R may be a more specific parameter than the disappearance of HCV RNA for assessing total, and hence more sustained, elimination of HCV infection 6 months after stopping treatment.

Reinforced regimen of interferon alfa-2a reduces the incidence of cirrhosis in patients with chronic hepatitis C: a multicentre randomised trial. Multicentre GER-CYT-04 Group.

BACKGROUND/AIMS: Our aim was to assess and compare the long-term effect of interferon at standard (6 months) and reinforced dose and duration regimens in chronic hepatitis C. METHODS: A multicentre institutional trial included 244 previously untreated patients with chronic hepatitis C, without cirrhosis, who were randomly allocated to either standard (3 MU thrice a week for 24 weeks; n=120) or reinforced (6 MU daily for 12 days, 6 MU thrice a week for 22 weeks, 3 MU thrice a week for 24 weeks; n=124) regimens. The main endpoint was sustained ALT response at 72 weeks (18 months); secondary end-points were virological (branched DNA and PCR) and histological responses (incidence of cirrhosis) at month 18. RESULTS: Sustained ALT response was observed in five patients (4%, 95% confidence interval 0-8%) in the standard group and in 21 patients (18%, 95% confidence interval 11-25%), from the reinforced group (p=0.002), in agreement with virological response in 21 (81%) patients. Cirrhosis at month 18 was observed in ten (10%) patients in the standard group and one (1%) in the reinforced group (p=0.004). CONCLUSIONS: The standard regimen of interferon, in chronic hepatitis C, confers a minimal sustained response rate at 18 months and may not prevent the occurrence of cirrhosis. Reinforced regimens allow sustained response to be reached in a limited number of patients and reduce the risk of cirrhosis during 18 months of follow-up.