Low–Grade Steatosis and Major Changes in Portal Flow As New Prognostic Factors in Steroid–Treated Alcoholic Hepatitis

Abstract

The aim of this study was to assess the prevalence and prognostic value of major alterations of portal flow in patients with steroid-treated alcoholic hepatitis. Fifty patients with severe, histologically proven alcoholic hepatitis were enrolled. Clinical data, liver test results, and hepatic Doppler ultrasound findings were collected at inclusion and at month 2. Patients were followed for 1 year or until death. Major changes in portal flow were defined as reversed or alternating flow in the portal trunk and/or in intrahepatic portal branches. Changes in portal flow were observed in 24 (48.0%) of 50 and 17 (39.5%) of 43 patients at inclusion and month 2, respectively. Univariate analysis showed that age older than 50 years, steatosis less than 20% on initial liver biopsy, presence of major changes in portal flow, Child-TurcottePugh score higher than 12, factor V level higher than 45%, and hepatofugal splenic blood flow were associated with a lower 1-year survival. Cox regression analysis showed that steatosis < 20% (relative hazard [RH] ‫؍‬ 9.3, P ‫؍‬ .0009) and major changes in portal flow (RH ‫؍‬ 3.1, P ‫؍‬ .04), were independently associated with poor survival. A lcoholic hepatitis (AH) is a necrotizing inflammatory condition that is considered as an acute form of alcoholic liver injury. The severity of AH can be measured using Maddrey's discriminant function (DF, Ͼ 32). 1 In the absence of treatment, approximately 30% to 40% of patients with severe AH die within 6 months; patients who survive the initial episode of AH have a chance of long-term survival if they remain abstinent. 2 Most meta-analyses conclude that glucocorticoids are beneficial in alcoholic hepatitis, with a 1-month survival rate of 65% and 85% in untreated and steroid-treated patients, respectively, suggesting that steroids reduce mortality by approximately 20% to 25%. 3 However, the reasons why some patients are nonresponders to steroid therapy are unclear. Factors other than necrotizing inflammatory factors could be responsible for the deterioration of liver function despite both abstinence and steroid therapy. Recently, we observed that reversal of portal flow through large spontaneous portacaval shunts in candidates for liver transplantation with alcoholic cirrhosis was more frequent among patients presenting with severe liver insufficiency than in those presenting with complications of portal hypertension. 4 We therefore postulated that such major changes in portal flow might contribute to the deterioration of liver function in patients with alcoholic hepatitis. To test this hypothesis, we conducted a multicenter prospective study designed to assess the prevalence Abbreviations: AH, alcoholic hepatitis; DF, discriminant function; PT, prothrombin time; CTP, Child-Turcotte-Pugh; US, ultrasound; PV, main portal vein; RPV, right intrahepatic portal vein; LPV, left intrahepatic portal vein; SV, splenic vein; SMV, superior mesenteric vein. From the

The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids

“…Although data on the evolution of liver func-tion at 6 months were available for only a small number of such patients, we observed that approximately half of them still had severe liver insufficiency, with a median Child score of 8.5 (range, [6][7][8][9][10][11][12][13][14] and a median MELD score of 21.5 (range, 12-31) (data not shown). This suggests that, among live non-responders with a Lille score Ն 0.45, only half are no longer at risk of liver-induced death.…”

“…The following clinical and biological variables were recorded at admission, and biological data were prospectively determined during the treatment period (7,14,21, and 28 days): center, age, sex, alcohol intake, presence of encephalopathy, ascites, survival, bilirubin, prothrombin time, albumin, AST, creatinine, white blood cell count, polymorphonuclear count, and DF. All patients were followed for at least 6 months.…”

“…[7][8][9] In patients with DF Ն 32, several RCTs and a recent meta-analysis showed that corticosteroids improve shortterm survival. 1,5,[10][11][12][13][14] However, novel strategies or molecules are required, in light of the fact that approximately 40% of patients die at 6 months. 15 Therefore, improvement in the prediction of mortality in severe AH is warranted.…”

Early switch to pentoxifylline in patients with severe alcoholic hepatitis is inefficient in non-responders to corticosteroids

“…Among available therapeutic options, and although some clinicians are reluctant to use corticosteroids, compelling data have shown that this treatment improves short-term survival compared to placebo [1,[3][4][5][6][7][8]. However, novel strategies or molecules are required in light of the fact that approximately 40% of patients treated with corticosteroids die within 6 months [9].…”

Clinical and histological recovery from “life-threatening” severe acute alcoholic hepatic failure with complete hepatofugal portal blood flow

“…In contrast, Duvoux et al [10] reported that major changes in portal flow were frequent in patients with severe alcoholic hepatitis. In their study, all patients had acute-onchronic liver diseases with liver histology showing F4 (liver cirrhosis) in 88% and F3 in 12%.…”