Vassilios Papastergiou

Cost‐effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C

The cost‐effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost‐effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta‐analysis to calculate the diagnostic accuracy of various NITs using a bivariate random‐effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality‐adjusted life‐years; QALYs) using data from the meta‐analysis, literature, and national UK data. We compared the cost‐effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost‐effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more‐potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost‐effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost‐effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1‐4, the incremental treatment cost threshold for the “treat all” strategy to remain the most cost‐effective strategy would be £37,500. Above this threshold, the most cost‐effective option would be noninvasive testing with magnetic resonance elastography (ICER = £9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost‐effective strategy with currently available drugs in developed countries. (Hepatology 2014;60:832–843)

Inflammation‐based scores do not predict post‐transplant recurrence of hepatocellular carcinoma in patients within milan criteria

Increased preoperative inflammation scores, such as neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and inflammation‐based index (IBI) have been related to post‐transplant HCC recurrence. We evaluated the association between inflammation‐based scores (NLR, PLR, IBI) and post‐LT HCC recurrence as well as tumor necrosis after transarterial embolization. 150 consecutive patients who underwent transplantation for HCC within the Milan criteria between 1996 and 2010 were included; data regarding inflammatory markers, patient and tumor characteristics were analyzed. NLR, PLR, and IBI were not significantly associated with post‐LT HCC recurrence or worse overall survival. Increased NLR and PLR were associated with complete tumor necrosis in the subset of patients who received preoperative transarterial embolization (P < 0.05). Cox regression analysis revealed that absence of neoadjuvant transarterial therapy (OR = 4.33, 95% CI = 1.28‐14.64; P = 0.02) and no fulfillment of the Milan criteria in the explanted liver (OR = 3.34, 95% CI = 1.08‐10.35; P = 0.04) were independently associated with post‐LT HCC recurrence inflammation‐based scores did not predict HCC recurrence post‐LT in our group of patients. NLR and PLR were associated with better response to TAE, as this was recorded histologically in the explanted liver. Histological fulfillment of the Milan criteria and absence of neoadjuvant transarterial treatment were significantly associated with post‐LT HCC recurrence. Liver Transpl 20:1327‐1335, 2014.

Biochemical criteria at 1 year are not robust indicators of response to ursodeoxycholic acid in early primary biliary cirrhosis: results from a 29-year cohort study

In primary biliary cirrhosis (PBC), biochemical criteria at 1 year are considered surrogates of response to ursodeoxycholic acid (UDCA). However, due to the slow natural history of PBC, evaluation at 1 year may be suboptimal to assess the therapeutic response, particularly in early disease.

Prognosis and treatment of patients with acute alcoholic hepatitis

Despite alcoholic hepatitis (AH) is the most acute manifestation of alcohol-related liver disease, its treatment remains controversial. Corticosteroids, given either as monotherapy or together with N-acetylecysteine, have been associated with a moderate short-term survival benefit in patients with severe disease. The Maddrey’s discriminant function; Glasgow alcoholic hepatitis score; age, bilirubin, INR and creatinine score; and the Model for end-stage liver disease have been proposed for stratifying prognosis in AH enabling selection of the patients to treat. Definition of treatment non-responders using the Lille model after 7 days of therapy may prevent a detrimental impact of prolonged corticosteroids. Pentoxifylline is an effective alternative reducing the occurrence of hepatorenal syndrome. Emerging evidence supports use of liver transplantation in a strictly selected subset of corticosteroid non-responders.

Letter: prognostic scores in alcoholic hepatitis – authors' reply

1. Papastergiou V, Tsochatzis EA, Pieri G, et al. Nine scoring models for the short-term mortality in alcoholic hepatitis: crossvalidation in a biopsy-proven cohort. Aliment Pharmacol Ther 2014; 39: 721–32. 2. Sandahl TTD, Jepsen P, Ott P, et al. Validation of prognostic scores for clinical use in patients with alcoholic hepatitis. Scand J Gastroenterol 2011; 46: 1127–32. 3. Mathurin P, O’Grady J, Carithers RL, et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut 2011; 60: 255–60. 4. Forrest EH, Evans CDJ, Stewart S, et al. Analysis of factors related to mortality in alcoholic hepatitis and the derivation and validation of the glasgow alcoholic hepatitis score. Gut 2005; 54: 1174–9. 5. Forrest EH, Morris AJ, Stewart S, et al. The Glasgow alcoholic hepatitis score identifies patients who may benefit from corticosteroids. Gut 2007; 56: 1743–6. 6. Lafferty H, Stanley AJ, Forrest EH. The management of alcoholic hepatitis: a prospective comparison of scoring systems. Aliment Pharmacol Ther 2013; 38: 603–10. 7. Katoonizadeh A, Laleman W, Verslype C, et al. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010; 59: 1561–9. 8. Phillips M, Curtis H, Portmann B, Donaldson N, Bomford A, O’Grady J. Antioxidants versus corticosteroids in the treatment of severe alcoholic hepatitis–a randomised clinical trial. J Hepatol 2006; 44: 784–90. 9. Forrest E, Mellor J, Stanton L, et al. Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomized controlled trial. Trials 2013; 14: 262.

Letter: scoring models in alcoholic hepatitis – authors' reply

SIRS, We thank Dr Wieten and colleagues for their appreciative comments on our article regarding crossvalidation of prognostic models for short-term mortality in biopsy-proven alcoholic hepatitis (AH). 2 To confirm our findings, the authors assessed four prognostic indices in a cohort of 44 patients with clinically diagnosed AH. In their analysis, only the Glasgow AH score was prognostic for 30-day mortality. However, the relatively small sample, and possible misdiagnosis of AH due to the absence of histological confirmation, may have precluded other significant associations. Moreover, there may be criticism as to whether treatment effects could have led to the underestimation of predictive performances. Recent results from the STOPAH trial, published in abstract form, suggest that treatment with glucocorticosteroids reduce the 28-day mortality only marginally. Therefore, it is not surprising that a significant effect of glucocorticosteroids on survival was not shown in our relatively small cohort. 5 Similarly, it is reasonable to speculate that treatment effects are negligible as a source of biasing prognostic performances in present series. The most striking finding by Wieten et al. is that prognostic indices in AH may retain their prognostic ability for up to 3 years from presentation. This observation may appear unrelated to current disease management, given that the survival benefit with glucocorticosteroids does not seem to be sustained beyond 1 month. As yet, abstinence from alcohol remains the only significant predictor of long-term outcome in patients diagnosed with AH. Therefore, detailed analysis of long-term prognostic factors in patients who survive an episode of AH, should be performed separately in abstainers and non-abstainers. In that sense, it would be useful to know how many patients in the cohort of Wieten et al. maintained their abstinence post-hospitalisation. Clearly, there is an urgent need for surrogates of longterm prognosis, as they may significantly aid the development of new drugs or novel therapeutic strategies that are able to modify the long-term course of alcoholic liver disease. These include perspectives for liver transplantation in a strictly selected subset of patients.