J.-P. Cervoni

C-Reactive protein predicts short-term mortality in patients with cirrhosis

BACKGROUND & AIMS We aimed at improving prediction of short-term mortality in cirrhotic inpatients by evaluating C-reactive protein (CRP) as a surrogate marker of systemic inflammatory response syndrome (SIRS). METHODS One-hundred and forty-eight consecutive cirrhotic patients with Child-Pugh score ≥ B8 and without hepatocellular carcinoma were prospectively included and followed for 182 days. The primary end point was 6-month survival. RESULTS Main baseline characteristics were as follows: alcoholic liver disease in 88.5%; bacterial infection in 37%; hepatorenal syndrome in 7% of cases. CRP range was 1-240 mg/L (median 26 mg/L); 42 patients (28.4%) had SIRS as defined by ACCP/SCCM-criteria. CRP levels were higher in patients with SIRS (50 vs. 21 mg/L; p<0.0001), infection (46 vs. 27 mg/L; p<0.0001), and alcoholic hepatitis (44 vs. 32 mg/L, p=0.049). Forty-two patients died within the first 6 months of follow-up. Short-term mortality was associated with extrahepatic co-morbidities (p=0.002), high MELD score (p<0.001; AUROC=0.67), renal failure (p=0.008), elevated blood lactates (p<0.001), and high baseline CRP levels (p=0.003; AUROC=0.63; best cut-off value at 29 mg/L). Among patients with baseline CRP ≥ 29 mg/L, 32 still had CRP ≥ 29 mg/L at day 15 (group A). Group A was associated with 6-month mortality in the overall population (p<0.001) and also through sensitivity analyses restricted to patients without infection or alcoholic hepatitis. Multivariate analysis (Cox) adjusted for age identified three predictors of mortality: high MELD score (HR=1.08; 95% CI: 1.03-1.12; p<0.001), extrahepatic co-morbidities (HR=2.51; 95% CI: 1.31-4.84; p=0.006), and CRP level (group A) (HR=2.73; 95% CI: 1.41-5.26; p=0.003). The performance of the three variables taken together for predicting death was 0.80 (AUROC). CONCLUSIONS In Child-Pugh score ≥ B8 cirrhotic patients, persistent CRP levels ≥ 29 mg/L predicted short-term mortality independently of age, MELD, and co-morbidities, and better than infection or clinically-assessed SIRS.

Response-guided peg-interferon plus ribavirin treatment duration in chronic hepatitis C: Meta-analyses of randomized, controlled trials and implications for the future†‡

Response‐guided pegylated interferon (peg‐IFN) plus ribavirin (P/R) therapy trials on genotype (G)1 and G2/G3 hepatitis C virus–infected patients provide contradictory results. We conducted meta‐analyses of randomized, controlled trials to address (1) the benefit of a 72‐week extended‐duration therapy in G1‐slow responders and (2) adequate shortened duration therapy in G1 and G2/G3‐rapid responders. Seventeen trials were selected, including 624 G1 rapid responders, 570 G1 slow responders, and 2,062 G2/G3 rapid responders. Virologic outcomes and treatment discontinuation data were collected from published articles and by asking investigators. Pooled estimates of sustained virologic response (SVR), relapse, and dropouts were calculated using the random effects model, considering the variability of shortened duration, ribavirin dose, genotype, and baseline viral load. In G1 slow responders, a 72‐week extended duration increased SVR (+10.7%; 95% CI [confidence interval]: +4.4% to + 17.1%), decreased relapse (−12.3%; 95% CI: −25.4% to 0%), and did not significantly increase drop‐out rates (+4.5%; 95% CI: −0.6% to + 9.6%). The benefit of extended duration was lower when using a weight‐based ribavirin regimen (+8.7%; 95% CI: +1.7% to + 15.8%). In G1 rapid responders, a 24‐week shortened duration decreased SVR (−12.5%; 95% CI: −19.2% to −5.8%) and increased relapse rates (+8.8%; 95% CI: +2.9% to + 14.8%). Such differences were not significant in patients with baseline viral load <400,000 UL/mL (−4.4%; 95% CI: −9.8% to + 1%). In G2/G3 rapid responders, SVR was more common for standard 24‐week duration than for shortened durations (+4.1%; 95% CI: +0.1% to + 8.5), but this benefit was not significant when ribavirin was weight‐adjusted and the short duration was 16 weeks (−1.7%; 95% CI: −6.1% to + 2.7%) and for G2 patients (+1.6%; 95% CI: −0.2% to + 5.5%). Conclusion: Long durations of P/R therapy improve SVR, regardless of genotype. This effect is nonetheless negligible in rapid responders, with the most favorable conditions for SVR (G2, G1 with low viral load, and G3 with weight‐adjusted ribavirin regimen). (HEPATOLOGY 2011;)

Assessment of adrenal function in cirrhotic patients using concentration of serum-free and salivary cortisol

Objective: Because over 90% of serum cortisol is bound to albumin and corticosteroid‐binding globulin (CBG), changes in these proteins can affect measures of serum total cortisol levels in cirrhotics without altering serum‐free and salivary cortisol concentrations.

Dihydrolipoamide dehydrogenase deficiency: a still overlooked cause of recurrent acute liver failure and Reye-like syndrome.

The causes of Reye-like syndrome are not completely understood. Dihydrolipoamide dehydrogenase (DLD or E3) deficiency is a rare metabolic disorder causing neurological or liver impairment. Specific changes in the levels of urinary and plasma metabolites are the hallmark of the classical form of the disease. Here, we report a consanguineous family of Algerian origin with DLD deficiency presenting without suggestive clinical laboratory and anatomopathological findings. Two children died at birth from hepatic failure and three currently adult siblings had recurrent episodes of hepatic cytolysis associated with liver failure or Reye-like syndrome from infancy. Biochemical investigation (lactate, pyruvate, aminoacids in plasma, organic acids in urine) was normal. Histologic examination of liver and muscle showed mild lipid inclusions that were only visible by electron microscopy. The diagnosis of DLD deficiency was possible only after genome-wide linkage analysis, confirmed by a homozygous mutation (p.G229C) in the DLD gene, previously reported in patients with the same geographic origin. DLD and pyruvate dehydrogenase activities were respectively reduced to 25% and 70% in skin fibroblasts of patients and were unresponsive to riboflavin supplementation. In conclusion, this observation clearly supports the view that DLD deficiency should be considered in patients with Reye-like syndrome or liver failure even in the absence of suggestive biochemical findings, with the p.G229C mutation screening as a valuable test in the Arab patients because of its high frequency. It also highlights the usefulness of genome-wide linkage analysis for decisive diagnosis advance in inherited metabolic disorders.

Thrombose portale par diffusion de cyanoacrylate au décours de l'obturation de varices gastriques hémorragiques.

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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.