Copyright ©The Author(s) 2019.
World J Gastroenterol. Feb 28, 2019; 25(8): 888-908
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.888
Table 2 Summary of further pharmacological agents with potentially therapeutic effects
TreatmentPotential mechanism of actionIndications and Evidence
Human Serum Albumin (HAS)Oncotic properties: Acts as a plasma expander to counteract splanchnic arterial vasodilatation in cirrhosis; Non-oncotic properties: Modulation of the inflammatory response through binding of reactive oxygen species and NO. Also affects capillary integrity. Furthermore, cirrhosis affects the capacity of albumin to bind endogenous and exogenous substances, which may be compensated for by albumin infusion.A recent meta-analysis found that HAS infusion in combination with antibiotics decreases the incidence of renal failure and mortality in patients with SBP; Several studies demonstrate that HAS infusion together with vasoconstrictors reduces mortality in patients with type 1 HRS; A meta-analysis by Bernardi et al showed that HAS infusion was effective in preventing paracentesis-induced circulatory dysfunction; A multicentre RCT by Caraceni et al[148] (n = 440) in cirrhotic patients with uncomplicated ascites showed that long-term HAS plus diuretics prolonged survival compared to diuretics alone[142-148].
Faecal microbiota transplant (FMT)As described previously, cirrhosis and its progression have been closely linked to gut dysbiosis with a predominance of pathogenic bacterial taxa and SIBO. Amelioration or even reversion of dysbiosis may be achieved through direct manipulation of the intestinal microbiome using FMT.Although FMT has been extremely successful in repopulating the healthy intestinal microbiome of patients with C. difficile diarrhoea and has even been endorsed in guidelines for the treatment of recurrent C. difficile diarrhoea, studies of FMT in patients with liver disease are smaller and more limited. A pilot study suggested a reduced burden of HE in patients given a single FMT enema compared to standard-of-care therapy. Currently, Woodhouse et al[126] are in the process of conducting a randomised, single-blinded, placebo-controlled trial in 32 cirrhotic patients in order to assess the safety and tolerability of FMT delivered by upper GI endoscopy[126,149-151].
Caffeine/ CoffeeCaffeine antagonizes the A2a adenosine receptor on hepatic stellate cells, the effector cells of fibrogenesis. Activation of the A2a adenosine receptor has been directly associated with matrix production in rodent models. However, decaffeinated coffee has also been shown to lower transaminases. Hence there may be additional anti-fibrotic constituents of coffee such as polyphenols which are potent anti-inflammatories and anti-oxidants.Both retrospective and prospective observational studies have indicated that an inverse dose-response relationship exists between coffee consumption and cirrhosis risk as well as cirrhosis-related complications. Corrao et al[155] retrospectively analysed 274 decompensated cirrhotic patients and 458 matched controls with chronic liver disease, finding that daily consumption of one cup of coffee conferred an odds ratio of 0.47, while daily consumption of four cups of coffee even conferred an odds ratio of 0.16 for cirrhosis risk. Similarly, a prospective cohort study of patients with advanced hepatitis C induced liver disease found that liver-related mortality and complication rates declined with increasing coffee consumption (12.1/100 person years for > 1 cup/d; 8.2/100 for 1-3 cups/d; 6.3/100 for > 3 cups/d; p-trend = 0.001). A recent prospective cohort study analysed non-invasive liver stiffness measurements in the general Dutch population (n = 2424), observing that coffee consumption was inversely correlated with liver stiffness. Similarly, recent data from a meta-analysis showed a favourable effect of coffee consumption on risk of HCC development (RR 0.55, 95% CI 0.44-0.67). At present, no guidelines exist regarding the prescription of coffee to patients with cirrhosis or chronic liver disease[152-158].