Results from two French studies presented at the International Liver CongressTM 2010 press conference will help inform clinical practice in the treatment of patients with severe or acute alcoholic hepatitis.
The first study demonstrated the positive potential of performing liver transplantation for patients suffering from severe alcoholic hepatitis (SAH) earlier than the recommended 6-months rule (required minimum of recorded abstinence for an alcoholic patient to be eligible for a liver transplant). Indeed, those patients who do not respond to treatment with steroids have a 6-month survival of around 30% and most deaths actually occur within 2-months. The results show that early liver transplantation could be proposed to non-respondents, pending a very careful evaluation of selected patients.
Acute alcoholic hepatitis (AAH) however, is an absolute contraindication for liver transplantation. It has a low survival rate, with mortality remaining at around 35% at 6 months despite corticoid treatment, the current standard of care for the condition. The second study presented April 16 will help inform a potential new treatment option for those patients who do not respond to standard treatment with corticoid. Data demonstrated that treatment with combined corticoids plus N-acetyl cysteine (C+NAC) showed an increase in survival rates. There have been few, large, well-designed trials advocating the use of N-acetyl cysteine to slow progression of liver disease. This latest study adds to the growing body of evidence in the benefits of treatment with C+NAC in patients with acute liver disease.
Professor Philippe Mathurin from the Hτpital Huriez, CHRU Lille, France who presented the results commented: "Whilst the management of alcoholic hepatitis is steeped in controversy, as clinicians we have a responsibility to treat these patients in the most effective way possible, and as researchers we have a mandate to highlight new options.
These latest results across large patient cohorts are the sort of clinical studies that are vital to help guide best practice in the treatment pathway for difficult-to-treat patients with a challenging medical history. Alongside education and, ideally, prevention strategies we can achieve some successful outcomes.
About the studies
The physiopathology of AAH combines oxidative stress combined with elevated levels of TNF-alpha. The proposal of the first study was that combination of corticoid with N-acetyl cysteine (C+NAC) may rebuild anti-oxidant stocks with anti-inflammatory action. 174 patients across 11 centres in France were randomized into C+NAC or corticoid groups. The study looked at evaluating survival at months one, two, three and six as well as complications from treatment and bilirubin change (marker to evaluate progression of AAH) at day 7 and 14.
Deaths were significantly lower at month 1 for C+NAC group, with the survival rate being increased to some extent at month 2 and 6 for that patient group. The C+NAC group had lower infection and hepatorenal syndrome at both month 2 and 6.
For patients suffering from SAH, non-responders to steroids have a survival rate at 6-months of around 30%. Most deaths however occur within 2 months and early liver transplantation is the logic but controversial solution as it challenges the 6-months abstinence rule for patients. In this trial, six liver transplant centres performed early liver transplantation in patients experiencing their first episode of liver disease who had been drastically selected using the following criteria: absolute consensus of medical and paramedical staff, no co-morbidities and supportive family members. Each transplanted patient was matched to a non-transplanted non-respondent to steroids patient for the case control (control group). Overall twenty patients underwent transplantation.
Results show that 1-year survival was significantly higher in patients who had the transplant compared to the control group. Four out of five transplanted patients died from aspergillosis (a type of fungal infection). In the control group, 90% of the observed deaths occurred within the first two months. The study is still ongoing and two other patients are being evaluated for early transplantation.
- Castel et al. Early transplantation improved survival of non-responders to corticosteroids in severe alcoholic hepatitis: a challenge of the 6 month rule of abstinence. Journal of Hepatology, 2010; 52S13 DOI: 10.1016/S0168-8278(10)60031-1
- Nguyen-Khac et al. Treatment of severe Acute Alcoholic Hepatitis (AAH) with Corticoids plus N-Acetyl Cysteine (C NAC) versus Corticoid alone (C): a multicenter, randomized control trial. Journal of Hepatology, 2010; 52S38 DOI: 10.1016/S0168-8278(10)60085-2
- Louvet et al. The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology, 2007; 45 (6): 1348 DOI: 10.1002/hep.21607
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