Non-invasive diagnosis of severe alcoholic hepatitis: Usefulness of cross-sectional imaging.

PURPOSE: To describe the computed tomography (CT) and magnetic resonance imaging (MRI) features of severe acute alcoholic hepatitis (SAAH) and estimate the capabilities of CT and MRI in differentiating SAAH from alcoholic cirrhosis and non-alcoholic steato-hepatitis (NASH) cirrhosis. MATERIALS AND METHODS: Fifty patients with pathologically proven SAAH (SAAH group) who underwent CT or MRI examinations up to 30 days before or 15 days after liver biopsy between January 2008 and June 2018 were retrospectively included. There were 31 men and 29 women with a mean age of 52±9 (SD) years (range: 33-67 years). Imaging features of the SAAH group were compared to those obtained in two control groups including 62 patients with alcoholic cirrhosis without acute alcoholic hepatitis (control group 1) and 19 patients with NASH cirrhosis (control group 2) by two independent radiologists blinded to the final diagnosis. Univariate analyses were performed to compare imaging characteristics between the three groups, followed by diagnostic performance analysis for the diagnosis of SAAH of the main CT features. RESULTS: Heterogeneous steatosis was significantly more frequent in SAAH group than in the control groups (41/50; 82% vs. 7/62; 10% and 1/19; 5% in control groups 1 and 2, respectively for reader 1 and 34/50; 68% vs. 8/62; 13% and 1/19; 5% in control groups 1 and 2, respectively for reader 2; both P=0.01). Transient perfusion disorders were more frequent in SAAH group than in the control groups (35/50; 70% vs. 12/62; 21% and 5/19; 26% in control groups 1 and 2, respectively for reader 1 and 39/50; 78% vs. 14/62; 23% and 13/19; 6% in control groups 1 and 2, respectively for reader 2; both P=0.01). The combination of these two findings yielded 100% specificity (45/45; 95% CI: 92-100) for readers 1 and 2 for the diagnosis of SAAH vs. alcoholic cirrhosis and NASH cirrhosis. CONCLUSION: The imaging features of SAAH are specific and mainly associate transient heterogeneous steatosis and liver perfusion disorders. CT/MRI may be useful to differentiate SAAH from alcoholic cirrhosis and NASH cirrhosis.

Management of liver failure in general intensive care unit.

OBJECTIVE: To produce French guidelines on Management of Liver failure in general Intensive Care Unit (ICU). DESIGN: A consensus committee of 23 experts from the French Society of Anesthesiology and Critical Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Association for the Study of the Liver (Association française pour l'étude du foie, AFEF) was convened. A formal conflict-of-interest (COI) policy was developed at the start of the process and enforced throughout. The entire guideline process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of the quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Some recommendations were ungraded. METHODS: Two fields were defined: acute liver failure (ALF) and cirrhotic patients in general ICU. The panel focused on three questions with respect to ALF: (1) Which etiological examinations should be performed to reduce morbidity and mortality? (2) Which specific treatments should be initiated rapidly to reduce morbidity and mortality? (3) Which symptomatic treatment should be initiated rapidly to reduce morbidity and mortality? Seven questions concerning cirrhotic patients were addressed: (1) Which criteria should be used to guide ICU admission of cirrhotic patients in order to improve their prognosis? (2) Which specific management of kidney injury should be implemented to reduce morbidity and mortality in cirrhotic ICU patients? (3) Which specific measures to manage sepsis in order to reduce morbidity and mortality in cirrhotic ICU patients? (4) In which circumstances, human serum albumin should be administered to reduce morbidity and mortality in cirrhotic ICU patients? (5) How should digestive haemorrhage be treated in order to reduce morbidity and mortality in cirrhotic ICU patients? (6) How should haemostasis be managed in order to reduce morbidity and mortality in cirrhotic ICU patients? And (7) When should advice be obtained from an expert centre in order to reduce morbidity and mortality in cirrhotic ICU patients? Population, intervention, comparison and outcome (PICO) issues were reviewed and updated as required, and evidence profiles were generated. An analysis of the literature and recommendations was then performed in accordance with the GRADE® methodology. RESULTS: The SFAR/AFEF Guidelines panel produced 18 statements on liver failure in general ICU. After two rounds of debate and various amendments, a strong agreement was reached on 100% of the recommendations: six had a high level of evidence (Grade 1 ±), seven had a low level of evidence (Grade 2 ±) and six were expert judgments. Finally, no recommendation was provided with respect to one question. CONCLUSIONS: Substantial agreement exists among experts regarding numerous strong recommendations on the optimum care of patients with liver failure in general ICU.

Long-term outcome of chronic hepatitis C in a population-based cohort and impact of antiviral therapy: a propensity-adjusted analysis.

This population-based study aimed to assess the determinants of the outcome of chronic hepatitis C with analysis of the impact of antiviral therapy with or without sustained virological response (SVR) on cirrhosis decompensation, hepatocellular carcinoma, liver-related and non-liver-related mortality. A total of 1159 HCV-positive patients newly detected between 1994 and 2001 were included. For each outcome, the prognostic effect of patients' baseline characteristics was estimated by time-dependent Cox models using age as the time-scale and adjusting for treatment received during follow-up. The impact of antiviral therapy was assessed by using a propensity score in a sample including 184 patients treated in the first 24 months following diagnosis who were matched to 184 untreated patients. At the end of a 59-month median follow-up, 100 cases of compensated disease, 58 liver cancer and 163 deaths (55 liver related) were recorded. The 5-year rates of decompensated cirrhosis, hepatocellular carcinoma, liver-related and non-liver-related death were 4.4%, 2.7%, 5.0% and 8.9%, respectively. Multivariate analyses identified two variables with pejorative influence: alcohol consumption (RR = 4.29 for CD; RR = 5.76 for HCC; RR = 6.69 for liver-related death; P < 0.0001); HCV diagnosis unrelated to systematic screening (RR = 2.25 for CD; RR = 3.05 for HCC; RR = 4.31 for liver-related death, P < 0.03). In the matched subset, no significant benefit of antiviral therapy was observed. Nevertheless, among the 144 patients who achieved SVR, no death was observed. This population-based study showed substantial rates of decompensated cirrhosis, hepatocellular carcinoma and non-liver-related mortality. Alcohol consumption and absence of systematic screening were significant determinants of poor outcome, whereas treatment did not have significant influence.

Personalized management of patients with inoperable alveolar echinococcosis undergoing treatment with albendazole: usefulness of positron-emission-tomography combined with serological and computed tomography follow-up.

The present study aimed to identify a sub-group of inoperable alveolar echinococcosis (AE) patients undergoing long-term treatment with benzimidazole (BZM) who presented with an evolution suggestive of a parasitocidal effect. An evolution compatible with parasite death was observed in five patients.

[Hepatopulmonary syndrome]. / Le syndrome hépatopulmonaire.

Hepatopulmonary syndrome is characterized by the presence of portal hypertension with or without cirrhosis, an increased alveolar-arterial oxygen partial pressure difference greater than or equal to 15 mm Hg, and dilated pulmonary capillaries. Hepatopulmonary syndrome is found in up to 20% of patients with cirrhosis and should be considered in any patient who develops dyspnea or hypoxemia. Contrast echocardiography is enough to make the diagnosis of hepatopulmonary syndrome. The exact pathophysiology of hepatopulmonary syndrome remains unknown but nitric oxide is an important factor underlying hepatopulmonary syndrome. Hypoxemia progressively deteriorates and worsens the prognosis of cirrhotic patients. Hypoxemic patients must be controlled regularly to optimise the timing of liver transplantation. Indeed, a preoperative PaO(2) of less than or equal to 50 mm Hg alone or in combination with an isotopic shunt fraction greater than or equal to 20% are the strongest predictors of postoperative mortality. There are currently no effective medical therapies for hepatopulmonary syndrome but garlic powder and iloprost inhalation demonstrate clinical improvements in the pre- and in the post-transplant period.

Review article: the utility of reagent strips in the diagnosis of infected ascites in cirrhotic patients.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) can be diagnosed via leucocyte esterase reagent strips, although diagnostic performances vary. AIM: To perform critical review of literature on the use of reagent strips in SBP. METHODS: Nineteen studies were analysed (Medline search), comparing reagent strips in cirrhotic ascites vs. cytobacteriological methods. Diagnostic grades (G) were: GO = 0 leucocytes/mm3; G1 = 15; G2 = 70; G3 = 125; G4 = 500 for Multistix, GO = 0; G1 = 25; G2 = 75; G3 = 500 for Nephur, Combur, UriScan, and GO = 0; G1 = 25; G2 = 75; G3 = 250; G4 = 500 for Aution. RESULTS: Medians per study were: 75 patients (range: 31-1041), 136 ascites (47-2123), 17 SBP (5-117). For Multistix (12 studies), the sensitivities fell within the ranges 64.7-100% (G > or = 1), 45.7-83% (G > or = 2) and 45.3-89% (G > or = 3). For Nephur (n = 2), Combur (n = 6), UriScan (n = 1), sensitivities ranged 80.4-100% (G > or = 1), 63-100% (G > or = 2) and 67.7-97% (G > or = 3). For Aution (n = 3), sensitivities ranged 93-96% (G > or = 2) and 89% (G > or = 3). Nephur, Combur, UriScan displayed higher sensitivities than Multistix. However, in larger studies, sensitivities dramatically fell at 45.3% for Multistix (G > or = 3) if ascites polymorphonuclear count <1000/mm3 and 22.2% for bacterascites or 16.7-25% for asymptomatic patients. CONCLUSION: Use of reagent strips for the diagnosis of SBP cannot be recommended, in view of low sensitivity and a high risk of false negatives, especially in patients with SBP and low polymorphonuclear count.

[Hepar lobatum carcinomatusum: a rare cause of portal hypertension complicating hepatic metastases in breast cancer]. / L'hepar lobatum carcinomatosum: une cause rare d'hypertension portale compliquant les métastases hépatiques d'un carcinome mammaire.

SUMMARY: Hepar lobatum carcinomatosum is an acquired liver dysmorphy associated with liver metastases of carcinoma, usually breast carcinoma. It may cause portal hypertension. The pathogenesis of this condition appears to be related to multifocal occlusion of intrahepatic branches of the portal vein by neoplasic thrombi and desmoplastic changes. The prognosis is poor despite apparent tumor regression on imaging. We report a case of variceal bleeding revealing a hepar lobatum carcinomatosum. Magnetic resonance imaging supported this diagnosis which was suspected in the clinical context.

Coeliac disease in chronic hepatitis C: a French multicentre prospective study.

BACKGROUND: A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship. AIM: To conduct a French multicentre prospective study to assess the prevalence of CD in hepatitis C virus (HCV)-infected patients. METHODS: Between June 2003 and November 2005, 624 consecutive HCV-positive out-patients were tested for antiendomysial IgA antibodies (AEA), antigliadin IgA and IgG antibodies (AGA). Patients with positive AEA or IgA AGA and positive IgG AGA in a context of a high suspicion of CD were asked to undergo gastroscopy with duodenal biopsies. RESULTS: Isolated IgA AEA, IgA AGA and IgG AGA were 0.16%, 5.7% and 4.4%, respectively. Gastroscopy was required for 39 patients, 31 were performed (eight refusals), but only 25 duodenal biopsies were performed as six patients had cirrhosis. CD was never detected. CONCLUSIONS: The prevalence of CD in HCV-positive patients was 0% (95% confidence interval: 0-0.59%), but there is a low prevalence of CD in the whole French population.

Interferon for interferon naive patients with chronic hepatitis C.

BACKGROUND: A previous meta-analysis of interferon therapy in naive patients with chronic hepatitis C has documented its efficacy in achieving virologic clearance, and improving liver biochemistry and histology; however, since its publication additional trials have been reported. OBJECTIVES: To evaluate the response to interferon in interferon naive patients with chronic hepatitis C. The effect of treatment dose and duration, and the response in patients with cirrhosis and those with normal aminotransferases was also investigated. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Cochrane Library Issue 1, 1999), MEDLINE (January 1966 to December 1999), and reference lists were searched, and pharmaceutical companies were contacted for unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo, no treatment, or different regimens of interferon were selected. Abstracts were excluded. DATA COLLECTION AND ANALYSIS: The primary outcome measure was sustained disappearance of serum HCV RNA (virologic sustained response (SR)). Biochemical and end of treatment responses, liver histology, and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS: Fifty-four trials enrolling 6545 patients were included. Compared with no treatment, interferon 3 MU thrice weekly for 12 months increased the probability of a virologic SR (Peto odds ratio (OR) 4.60; 95% confidence interval (CI) 1.53 to 13.85). At this dosage and duration of therapy, the rate of virologic SR was 17% (95% CI 10 to 28%) in interferon-treated patients versus 3% (95% CI 1 to 10%) in controls. A dose of 6 MU was more effective than 3 MU thrice weekly (OR for 12 months treatment, 2.21; 95% CI 1.10 to 4.45), as were durations of 12 months or greater versus six months (OR 1.87; 95% CI 1.30 to 2.67). Adverse events were more common with higher doses and prolonged durations of treatment. Compared with no therapy, interferon increased the probability of histologic improvement (OR 9.22; 95% CI 5.69 to 14.94). The response to interferon in cirrhotic patients (virologic SR, 17%; 95% CI 11 to 26%) was similar to that in non-cirrhotic patients. However, interferon was no more effective than control in patients with normal aminotransferases. REVIEWER'S CONCLUSIONS: Interferon is effective in achieving viral clearance and improving liver biochemistry and histology in interferon naive patients with chronic hepatitis C. Higher doses and prolonged durations are more effective, but associated with more frequent adverse events. Interferon is associated with similar benefits in patients with cirrhosis, but the efficacy in patients with normal aminotransferases is unproven.

Interferon for acute hepatitis C.

BACKGROUND: Acute hepatitis C virus (HCV) infection progresses to chronicity in the majority of patients. In order to prevent the progression to chronic disease, several studies have assessed interferon in patients with acute hepatitis C. OBJECTIVES: The aim of this review was to assess the efficacy of interferon in acute HCV infection. SEARCH STRATEGY: We searched MEDLINE, the Cochrane Controlled Trials Register, and the abstracts of the American Association for the Study of Liver Diseases (June 2001). We also contacted pharmaceutical companies to obtain unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo or no treatment, and published as an article, abstract, or letter were selected. No language limitations were used. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The following endpoints were analysed: normalization of alanine aminotransferase (ALT) activity at the end of treatment (biochemical ETR); sustained ALT normalization at the end follow-up (biochemical SR); disappearance of serum HCV RNA by polymerase chain reaction assay at the end of treatment (virologic ETR) and at the end of follow-up (virologic SR). Histologic data and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS: Six randomised trials involving 206 patients with acute hepatitis C met the inclusion criteria. Four trials assessing interferon alfa-2b in 141 patients, all with transfusion-acquired acute hepatitis C, were included. They demonstrated no significant heterogeneity in the outcomes assessed. When compared with no treatment, interferon alfa-2b was associated with an increase in the rates of virologic ETR and SR by 45% (95% CI 31-59%, P < 0.00001) and 29% (95% CI 14-44%, P = 0.0002), respectively. The virologic ETR was 42% (95% CI: 30-56%) in the interferon alfa-2b group versus 4% (95% CI 0-13%, P < 0.00001) in the control group. At the end of follow-up, a virologic SR was seen in 32% (95% CI 21-46%) of interferon-treated patients versus only 4% (95% CI 0-13%, P = 0.00007) of controls. The tolerability of therapy, or the impact of interferon alfa-2b on hepatic histology, was not reported. Two trials assessed interferon beta in a total 65 patients. The efficacy of interferon beta could not be assessed, however, due to heterogeneity of these trials. REVIEWER'S CONCLUSIONS: Interferon alfa is effective in improving biochemical outcomes and achieving sustained virologic clearance in patients with transfusion-acquired acute hepatitis C. The effect on long-term clinical outcomes could not be assessed due to limitations in the current data.

The role of T cell subsets and cytokines in the pathogenesis of Helicobacter pylori gastritis in mice.

Gastritis due to Helicobacter pylori in mice and humans is considered a Th1-mediated disease, but the specific cell subsets and cytokines involved are still not well understood. The goal of this study was to investigate the immunopathogenesis of H. pylori-induced gastritis and delayed-type hypersensitivity (DTH) in mice. C57BL/6-Prkdc(scid) mice were infected with H. pylori and reconstituted with CD4+, CD4-depleted, CD4+CD45RB(high), or CD4+CD45RB(low) splenocytes from wild-type C57BL/6 mice or with splenocytes from C57BL/6(IFN-gamma-/-) or C57BL/6(IL-10-/-) mice. Four or eight weeks after transfer, DTH to H. pylori Ags was determined by footpad injection; gastritis and bacterial colonization were quantified; and IFN-gamma secretion by splenocytes in response to H. pylori Ag was determined. Gastritis and DTH were present in recipients of unfractionated splenocytes, CD4+ splenocytes, and CD4+CD45RB(high) splenocytes, but absent in the other groups. IFN-gamma secretion in response to H. pylori Ags was correlated with gastritis, although splenocytes from all groups of mice secreted some IFN-gamma. Gastritis was most severe in recipients of splenocytes from IL-10-deficient mice, and least severe in those given IFN-gamma-deficient splenocytes. Bacterial colonization in all groups was inversely correlated with gastritis. These data indicate that 1) CD4+ T cells are both necessary and sufficient for gastritis and DTH due to H. pylori in mice; 2) high expression of CD45RB is a marker for gastritis-inducing CD4+ cells; and 3) IFN-gamma contributes to gastritis and IL-10 suppresses it, but IFN-gamma secretion alone is not sufficient to induce gastritis. The results support the assertion that H. pylori is mediated by a Th1-biased cellular immune response.

Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C in naive patients: 1999 update.

The aim of this study was to update our previous meta-analysis of interferon (IFN) in the treatment of hepatitis C and to analyse new factors, namely, HCV RNA end-point, patients with cirrhosis and patients with normal ALT. We use the Der Simonian and Laird method, with heterogeneity and sensitivity analyses. Seventy-six randomized control trials (RCTs) in naive patients were found but we focused our analysis on 59 RCTs with chronic hepatitis C (26 vs. controls and 33 comparing different regimens) and on seven RCTs in acute hepatitis. Interferon-alpha (IFN-alpha) at 3 MU thrice weekly (TIW) for 12 months exhibited 39% of virological end-of-treatment response (ETR) and 17% of virological sustained response (SR), respectively, vs. 1% and 3% in untreated controls (all P < 0.001). There was a significant dose effect (in favour of 6 vs. 3 MU TIW): the virological SR at 6 months were 35% in the 6 MU group (95% CI: 24-47) and 16% in the 3 MU group (95% CI: 8-27) and were at 12 months 43% in the 6 MU group (95%CI: 31-56) and 25% in the 3 MU group (95% CI: 16-37). There was a significant duration effect (12 vs. 6 months) upon the virological SR rate both at 3 and 6 MU: 3 MU provided 14% of virological SR (95% CI: 11-19) in the 12 months group vs. 7% (95% CI: 5-11) in the 6 months group and 6 MU provided 22% (95% CI: 17-29) and 16% (95% CI: 11-22) virological SR in the 12 and 6 months groups, respectively. Cirrhotic treated patients had 17% of virological SR (95 CI: 9-24%; P < 0.001) vs. 0% in controls and provided a 20% reduction rate (95 CI: -2% to -37%, P=0.03) in hepatocellular carcinoma incidence. In acute hepatitis C, a 3-month treatment with IFN-alpha showed significant efficacy vs. controls upon the virological SR rate (32% vs. 4%, P < 0.001). In conclusion, we confirm the dose and duration effect of IFN in chronic hepatitis C, and the efficacy of IFN-alpha in the treatment of acute hepatitis and in cirrhotic patients.