**6. Treating the Precipitating Event**

#### *6.1. Bacterial or Fungal Infection*

The prevalence of infections in patients with ACLF, either as precipitants or complications of the syndrome, is about 50% and rises to 70% in patients with three or more OFs [43]. Bacterial infections are more frequent than fungal ones, being multidrug-resistant (MDR) pathogens involved in one-third of cases with different prevalence related to geographical region [43,44]. A complete work up for infection, including microbiological and imaging examinations, should be performed in all patients at diagnosis of ACLF before starting high-dose broad-spectrum antimicrobial therapy. The broad spectrum antibiotic treatment should be started as soon as possible. An effective antibiotic treatment is strongly associated with an improvement in survival in patients with ACLF [45,46]. Antifungal agents should be considered in patients with risk factors for fungal infections (e.g., nosocomial infections, previous antibiotic treatment, diabetes, AKI, recent endoscopy) [47,48].

### *6.2. Alcoholic Hepatitis*

Corticosteroids are the first-line treatment for severe alcoholic hepatitis. The Lille score is used to identify response to treatment. The probability of response to corticosteroids is lower in patients with ACLF respect to those without (38% and 77%, respectively) and is negatively correlated with the number of OFs at diagnosis [49].

#### *6.3. Acute Variceal Haemorrhage*

Standard medical treatment for this life-threatening precipitant is made by a vasoconstrictor (terlipressin, somatostatin or analogues such as octreotide) and endoscopic therapy (preferably variceal ligation) plus a short-term antibiotic prophylaxis with ceftriaxone [50]. In a recent multicenter international study which enrolled patients with acute variceal bleeding and ACLF, the syndrome was identified as an independent risk factor for rebleeding and short-term mortality. Pre-emptive TIPS may improve survival in this cluster of patients, but further studies are needed before recommending its routinary use [51].
