Review

Alcohol, psoriasis, liver disease, and anti-psoriasis drugs

Nicoletta Cassano, MD, Michelangelo Vestita, MD, Doriana Apruzzi, MD, and
Gino A Vena, MD

2nd Dermatology Clinic, Department of Abstract

Biomedical Sciences and Human
Oncology, University of Bari, Bari, Italy
Correspondence
Gino A. Vena, MD
2nd Dermatology Clinic
University of Bari
Policlinico Piazza Giulio Cesare 11
70124 Bari
Italy
E-mail: g.vena@dermatologia.uniba.it
Conflict of interest: The authors declare
no conflict of interest.
Over the last years, data have been accumulating regarding a possible association
between alcohol and psoriasis. While it is still unclear whether alcohol misuse represents a
true risk factor or merely an epiphenomenon of the cutaneous disease, a number of studies
support the role of ethanol and its metabolites as triggering factors of psoriasis. A drinking
habit also appears to exacerbate a preexisting psoriasis, and the magnitude of alcohol
consumption may be related to both a higher incidence and severity of psoriasis. Evidence
also shows that deaths from alcohol-related causes are significantly more frequent in
patients with psoriasis than in normal controls. Alcohol consumption may adversely affect
psoriasis through multiple mechanisms, such as increased susceptibility to infections,
stimulation of lymphocyte and keratinocyte proliferation, and production of proinflammatory
cytokines. Moreover, alcohol misuse can predispose to a greater risk of liver disease and
potential drug interactions. Alcoholic and non-alcoholic liver diseases have both been found
to be common in psoriatic patients. Tumor necrosis factor (TNF)-alpha, a key cytokine in
psoriasis pathogenesis, has been found to have a crucial role in alcoholic hepatitis, and
small preliminary studies have evaluated the effect of anti-TNF therapy in this condition.
However, the use of anti-TNF-a drugs in alcoholic hepatitis is still controversial and needs
to be further investigated. In this review, the relationship between alcohol and psoriasis will
be reviewed and discussed, taking also into account recent findings related to liver disease
and therapeutic implications.

effect of alcohol on psoriasis, early reports showed con-

Introduction
Psoriasis is a chronic, immune-mediated, multisystem,
inflammatory disorder that has a complex multifactorial
pathogenesis resulting from the interaction between
genetic and environmental factors. The immunopathogen-
esis of the disease is associated with a T-helper (Th)1 and
Th17 response, with overproduction of proinflammatory
cytokines, including interleukin (IL)-2, IL-12, IL-17,
IL-21, IL-22, IL-23, interferon (IFN)-gamma, and tumor
necrosis factor (TNF)-alpha. The course is chronic with
flares related to endogenous and/or environmental trig-
gers. In fact, several factors have traditionally been asso-
ciated with psoriasis outbreaks, such as physical and
psychological stresses, metabolic factors, smoking, admin-
istration of peculiar drugs, infections, and traumas.
While alcohol has been suspected to act as a promoting
factor in various medical conditions, the actual data
related to its precise role in psoriasis have been scarce
and somewhat contradictory until recently. Specifically,
even if many authors had long theorized a detrimental
flicting results.1–4 However, hints indicating a significant
correlation, derived from several large epidemiological
studies, have been accumulating over the last years. In
particular, large Scandinavian surveys found both a
higher alcohol intake and an increased prevalence of alco-
holism among psoriatic patients.5,6 Detailing the
tendency, women were found to drink more following the
diagnosis of psoriasis, probably reflecting the negative
impact of the skin disease on life quality. This evidence
might represent a stress response, elicited by the patient
in order to cope with the disease.
Possibly, the rising incidence of alcohol misuse (= alco-
hol intake over the recommended weekly limit) and
addiction (= dependent drinking, when alcohol is both
physically and psychologically addictive and it is possible
to become dependent) in the general population has
played a role in tightening the association with psoria-
sis,7,8 although it is difficult and impractical to quantify
its exact influence. As a matter of fact, even if several
studies have shown an accrued alcohol consumption in 1323

ª 2011 The International Society of Dermatology International Journal of Dermatology 2011, 50, 1323–1331
1324 Review Alcohol, psoriasis, liver disease and anti-psoriasis drugs
psoriatic patients when compared with controls, demon-
strating a significant difference only for men, a specific
observation linked psoriasis more closely to alcohol mis-
use, without features of dependency, rather than to full-
blown alcoholism. However, due to the self-reporting of
alcohol intake in most epidemiological studies involving
patients with psoriasis, an underestimation of the prob-
lem is likely to have occurred.9,10
Attempting to quantify alcohol’s relation to psoriasis, a
study showed that the odds ratio (OR) for developing
psoriasis in a man consuming 80 g of alcohol per day
was 2.2.9 Furthermore, a detailed survey by Higgins
et al.,11 regarding smoking and drinking habits, showed
that the OR for alcohol as an independent risk factor for
psoriasis was 8.01. The latter study also reported smok-
ing as being more common in patients with inflammatory
skin conditions, whereas higher alcohol intake was signifi-
cantly related only to psoriasis.
The strongest data linking alcohol to psoriasis as a true
risk factor might be obtained from incidence studies
rather than from prevalence analyses. An Italian multicen-
ter case–control study has suggested some important rela-
tions among psoriasis, smoking habit, and alcohol
consumption, examining patients who had been diag-
nosed with psoriasis within the previous two years.12 This
study has pointed to a moderate association with alcohol
misuse in psoriatic men, after controlling for smoking
habit. In another experience, alcohol appeared to be a
risk factor for psoriasis in young and middle-aged men
but did not act as such in female patients although still
representing a worsening factor.9
Given such indefinite evidence, it is still unclear
whether alcohol represents a true risk factor or merely is
an epiphenomenon or consequence of psoriasis.
Influence of alcohol on psoriasis
Knowledge of the complex relationship between alcohol
intake and psoriasis may lead to a better understanding
of the effect of alcohol on the skin, even if it is still
unknown whether alcohol misuse acts as a triggering or
precipitating factor.
A number of studies have been showing the possible
influence of alcohol on the severity and phenotype as well
as the course and prognosis of psoriasis, concluding that
alcohol can not only trigger psoriasis but also a drinking
habit appears to exacerbate a preexisting disease. Heavy
drinkers have a tendency to develop more severe, more
extensive, and more inflamed manifestations.3,9,10,12–15 In
particular, the relationship concerning severity and alco-
hol consumption was thoroughly assessed by Monk and
Neill in a cohort of 100 patients.3 These authors con-
cluded that patients with severe forms of psoriasis were
International Journal of Dermatology 2011, 50, 1323–1331
Cassano et al.
more commonly heavy drinkers, compared with patients
with mild forms. Another two studies found no significant
correlation between alcohol intake and skin surface
involvement in men, as opposed to female patients, where
such a correlation was statistically significant.9,10
Alcohol consumption seems to be associated not only
with a higher incidence and severity of psoriasis but also
with a distinctive nature and distribution of the dis-
ease.13,15 According to certain authors, two predominant
patterns can be identified in drinking patients: the former
includes severe inflammation with minimal scale, typically
involving the face, groin, and flexures; the latter is char-
acterized by hyperkeratotic lesions, with a predominant
acral distribution.
There are only very few studies concerning the relevant
issue of the effect of ethanol on treatment outcome. One
observation investigated this relation in 94 patients hospi-
talized because of moderate to severe psoriasis.16 The
results showed that, among men but not female patients,
less favorable response to treatment was found in those
patients who consumed more than 80 g of ethanol per
day. Regardless of alcohol abstinence during hospitaliza-
tion, previous drinking habit appeared to be a predictor
of treatment outcome, at least in men, thus showing that
the observed effect of ethanol on treatment was likely
independent from its immediate pharmacological action.
It has been suggested that a chronic drinking habit may
impair patient compliance and can cause treatment resis-
tance, therefore contributing to patient morbidity.16,17
Conversely, in a different experience, abstinence has been
found capable of inducing remission in patients with pso-
riasis, while retaking the alcohol habit was frequently fol-
lowed by psoriasis relapse.4
Regarding prognosis, an experience in over 2000 cases
showed that deaths from alcohol-related causes were sig-
nificantly more frequent in patients with psoriasis than in
normal controls. In particular, the relative risk of alcohol-
related mortality was 4.46 for men and 5.60 for women.
The higher mortality in men was a consequence of malig-
nancies, alcohol-related psychosis, alcohol dependence or
poisoning, alcoholic liver cirrhosis, hypertension, coro-
nary heart disease, chronic obstructive pneumopathy,
peptic ulcer, and suicide. Concerning women, the main
mortality causes included pancreatic cancer, alcoholic
liver cirrhosis and liver diseases in general, coronary heart
disease, chronic obstructive pneumopathy, peptic ulcer,
and thromboembolic stroke.18
It is well known that psoriasis has a relevant impact on
patients’ quality of life. The psychological and social diffi-
culties, which include stigmatization, embarrassment,
social inhibition and vulnerability, might increase the risk
of psychiatric pathologies and substance abuse.19 The
prevalence of anxiety, depression, and suicidal thoughts
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Cassano et al. Alcohol, psoriasis, liver disease and anti-psoriasis drugs Review 1325

has been found significantly higher among patients with
psoriasis when compared with controls.20 On the other
hand, excessive alcohol intake is considered to be associ-
ated with an increased incidence of anxiety and depres-
sion.21 A recent study explored on this topic evaluating
the link between ethanol misuse and psychological aspects
in 95 patients with psoriasis.22 This experience concluded
that a range from 17 to 30% of patients with psoriasis
had difficulties with alcohol and confirmed a modest but
significant correlation between levels of anxiety and
depression and weekly alcohol consumption. Those
patients who were aware of their drinking habit showed
significantly higher levels of anxiety, depressive symp-
toms, and psychosocial disabilities. As suggested, these
individuals might have used alcohol as a means to man-
age psoriasis-related distress. The high prevalence of psy-
chological disability and alcohol misuse in patients with
psoriasis underlines the importance of an appropriate
strategy of psychological screening and support.
Nowadays the scientific community widely recognizes
that psoriatic patients show a higher incidence of differ-
ent overlapping conditions, such as hypertension, diabe-
tes mellitus, and obesity. Recently, a study assessed how
this comorbidity risk may vary in psoriatic patients
when related to smoking habit and alcohol consump-
tion.23 The results revealed an OR of 2.11 for hyperten-
sion in smokers and drinkers. Furthermore, patients
consuming one drink/day of spirits had an OR for dia-
betes or obesity of 1.93, while the same parameter value
increased to 2.9 for those who assumed more than one
drink/day.
In conclusion, the available evidence suggests that alco-
hol consumption is associated with an increased incidence
and severity of psoriasis and appears to be related to the
development of a distinctive disease phenotype. In psori-
atic patients, alcohol misuse is also associated with a
higher prevalence of psychological issues, psoriatic com-
orbidities, and possibly to a higher mortality rate.
Mechanisms underlying the interaction
between alcohol and psoriasis
The immunopathogenesis of psoriasis is mediated by a
Th1 and Th17 response, with overproduction of several
proinflammatory cytokines. Some authors have suggested
that alcohol consumption may adversely affect psoriasis
through multiple mechanisms, for example altering
aspects of the immune response, predisposing drinkers to
infections, which are well-known triggers of psoriasis
flares, enhancing mitogen-driven lymphocyte prolifera-
tion, upregulating proinflammatory cytokines, influencing
keratinocyte proliferation and differentiation, and barrier
function. Table 1 summarizes the relevant data currently
available on these aspects.24–48

Table 1 Mechanisms underlying the interaction between alcohol and psoriasis and relevant literature findings

Mechanisms Literature evidence

Susceptibility to Alcohol intake inhibits killing of pneumococcal strains by rat polymorphonuclear leukocytes in vitro and decreases
infections24–29 the clearance of such strains from experimentally infected rat lungs.
The humoral response to antigen challenges appears to be diminished in alcoholics.
Mild neutropenia, mediated by the inhibitory effect of alcohol on the CSF activity

Innate and acquired
immunity alterations30–40
Chronic exposure stimulates proinflammatory cytokine production in various cell types and increases lymphocyte
activation and proliferation. In particular, evidence supports the increased production of TGF- a, IFN-c, IL-6
levels, indicating a shift towards a predominant Th1-type response. Alcohol has been found to increase TNF-a
release from peripheral blood monocytes and macrophages and to upregulate the proteolytic activity of TACE in
peripheral blood mononuclear cells.
Chronic alcohol intake also induces abnormal levels of cyclic nucleotides, implicated in keratinocyte
hyperproliferation (e.g. decreased cAMP levels and an increased cGMP/cAMP ratio)

Barrier function Alcohol promotes alteration of epidermal metabolism and barrier function and inhibition of the keratinocyte
alterations41–44 transglutaminase activity

Ethanol metabolite Acetone induces keratinocyte proliferation through overexpression of mRNA levels of alpha-5-integrin, cyclin D1,
activities45–48 and keratinocyte growth factor receptor.
The production of ROS during acetaldehyde synthesis modulates signal transduction cascades (i.e. MAPK/
activator protein 1, nuclear factor-kappa B, and Janus kinase-signal transducers and transcription activators),
leading to upregulation of proinflammatory cytokines and chemokines.
Acetaldehyde has been shown to increase c-Jun mRNA and protein levels and enhances Jun/activator DNA
binding activity in human oral keratinocytes

CSF, colony-stimulating factor; IFN, interferon; IL, interleukin; MAPK, mitogen-activated protein kinase; ROS, reactive oxygen
species; TACE, TNF-alpha-converting enzyme; TGF, transforming growth factor; TNF, tumor necrosis factor.

ª 2011 The International Society of Dermatology International Journal of Dermatology 2011, 50, 1323–1331
1326 Review Alcohol, psoriasis, liver disease and anti-psoriasis drugs
Ethanol and its metabolites may influence the immune
response in various ways, affecting functions and mecha-
nisms of both innate and acquired immunity. Alcohol is
generally believed to suppress the immune and flogistic
response.30,31 However, recent data suggest that acute
alcohol intake decreases inflammation and immunity,
whereas chronic exposure leads to opposing effects,
inducing proinflammatory cytokine production in various
cell types, as well as increasing lymphocyte activation and
proliferation.31
Some authors have pointed out the role of ethanol
metabolites, acetaldehyde (AcH) and acetone, in the path-
ogenesis of psoriasis.45,46 AcH is a product of ethanol
oxidation, through the action of alcohol dehydrogenase
enzyme and through cytochrome p450 isoform 2E1, with
production of reactive oxygen species. Acetone is instead
formed by decarboxylation of acetoacetic acid, whose
precursor is acetyl-coenzyme A. Alcohol and its metabo-
lites can promote the production of proinflammatory
cytokines in different cell types and may increase lympho-
cyte activation and proliferation.45,46 It has been demon-
strated that ingested ethanol is secreted through human
skin and that its levels in perspiration are similar to those
found in blood and other body fluids.45 These findings
suggest that levels of ethanol detectable in human skin
might be pharmacologically active and relevant.
Of note, as well demonstrated for psoriasis, genetic
factors are also likely to play a crucial role in alcohol-
ism, with heritability estimates ranging from 50 to
60%.49 Past studies failed to disclose a significant associ-
ation of alcoholism or alcoholic liver disease with HLA
antigens. The most important genes found to influence
the risk of alcohol dependence are those encoding alco-
hol-metabolizing enzymes (alcohol dehydrogenase and
aldehyde dehydrogenase), although several other genes
are regarded as possible candidates. In particular, genetic
research has recently investigated the potential implica-
tion of corticotropin-releasing factor, c-aminobuytric acid
(GABA), cholinergic, dopaminergic, and opioidergic sys-
tems. To the best of our knowledge, until now no data
seem to show the existence of a common genetic back-
ground in psoriasis and alcoholism.
Alcohol, liver disease, and anti-psoriasis drugs
The relation between psoriasis, alcohol consumption, and
liver disease has been often discussed. From an epidemio-
logical perspective, a higher prevalence of both alcoholic
and non-alcoholic liver disease has been noted in psoriatic
patients. In particular, non-alcoholic fatty liver disease
(NAFLD) shows close pathogenetic relation to psoriasis
cytokine modifications, with a prime role of TNF-a.
Additionally, many drugs used to treat psoriasis, biologi-
International Journal of Dermatology 2011, 50, 1323–1331
Cassano et al.
cals included, can potentially damage the liver and often
cause laboratory alterations in hepatic functionality mark-
ers, posing an additional liver burden in these patients.
Liver disease and psoriasis
Alcoholic hepatitis is a clinical syndrome characterized by
jaundice and liver failure that generally occurs after dec-
ades of heavy alcohol use and may also be accompanied
by other signs and symptoms, like fever, ascites, and
proximal muscle functionality loss.
Early reports noted a larger than expected portion of
psoriatic patients with abnormal liver biopsies.50 In 1985,
Chaput et al. investigated psoriasis prevalence among
patients divided into four groups: those without liver dis-
ease; those with non-cirrhotic alcoholic liver disease;
those with alcoholic cirrhosis; and those with clinically
evident cirrhosis.51 These authors reported psoriasis to be
more frequent than expected in patients with alcoholic
cirrhosis. A more recent observation assessed the preva-
lence of psoriasis in patients with alcohol liver disease,
indicating the prevalence as much higher (up to 15%)
than the predicted value in the normal population.52
NAFLD is a condition traditionally associated with
obesity, insulin resistance, and full-blown metabolic syn-
drome, and is also very frequent among patients with
chronic plaque psoriasis, being strongly related to psoria-
sis severity and its comorbidities. Furthermore, it has
been observed that NAFLD may likely lead psoriatic
patients to develop more severe liver fibrosis than patients
with NAFLD without psoriasis,53,54 suggesting the need
to accurately screen and monitor these patients, especially
when potentially systemic hepatotoxic drugs are consid-
ered as a therapeutic option. In this context, such findings
represent further reasons to discourage alcohol misuse in
psoriatic subjects.
Several lines of evidence seem to suggest that TNF-a may
be involved in the pathogenesis of NAFLD as a key factor,
by inducing and maintaining the inflammatory process.
Inspired by this observation, a recent study has assessed the
effects of an anti-TNF-a chimeric antibody (infliximab) in
experimental steatohepatitis, induced in rats by methio-
nine- and choline-deficient diet, indicating that this drug is
capable of reducing necrosis, inflammation, and fibrosis, as
well as serum transaminase, TGF-beta and malondialde-
hyde levels.55 Another experience has supported the poten-
tial of infliximab in reversing steatosis and improving
signal transduction in liver tissue of rats fed with a high-fat
diet.56 Adalimumab, a human anti-TNF-a monoclonal
antibody, has also been shown to suppress the activity of
non-alcoholic steatohepatitis (NASH), with rapid normali-
zation of liver function tests, in a patient who was treated
with the drug because of rheumatoid arthritis.57
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Cassano et al.
Effect of anti-psoriasis drugs on the liver
Numerous anti-psoriasis drugs, such as methotrexate, ret-
inoids, and anti-TNF monoclonal antibodies, are known
to be associated with liver toxicity. Some data showed
patients with psoriatic arthritis (PsA) to have a higher risk
of methotrexate-related hepatotoxicity, revealed by an
increase in hepatic enzyme levels, compared with patients
with rheumatoid arthritis. It has been therefore proposed
that psoriatic patients may also be highly susceptible to
methotrexate-induced hepatic adverse effects.58 More-
over, psoriatic patients burdened by risk factors for liver
disease and treated with methotrexate, even at low dos-
ages, have a higher chance of developing severe liver
fibrosis compared with those without such risk factors.59
The molecular basis for methotrexate hepatotoxicity is
currently not completely known, although an interaction
with DNA and an effect on folate depletion have been
suggested.60 In this frame of activity, alcohol may poten-
tiate the folate deficiency caused by methotrexate.
However, data are currently insufficient to determine a
dose–response relationship between alcohol use and meth-
otrexate hepatotoxicity, and therefore no safe limit of
alcohol intake can be recommended.60 Another example
of influence of alcohol upon systemic therapy in psoriasis
is represented by the alcohol-induced conversion of acitre-
tin into etretinate, a metabolite that shares the teratogenic
activity of acitretin with a more prolonged half-life.61 In
spite of these considerations, alcohol seems to have
played no role in the cases of acute or chronic aggressive
hepatitis that occurred during treatment with retinoids or
methotrexate.62
Other drugs, such as cyclosporine A, azathioprine, and
nonsteroidal anti-inflammatory drugs, used as possible
therapies in psoriasis and PsA, are all variably associated
with transient and generally modest increase in liver
enzyme levels. However, no alcohol–drug interactions
have been reported for these drugs.
Regardless of their beneficial effects on NAFLD and
NASH, the use of anti-TNF-a biologicals, and in particu-
lar that of monoclonal antibodies (especially infliximab),
has been associated with hepatotoxicity, sometimes
related to the concomitant use of other drugs (methotrex-
ate) or to viral reactivation (especially for hepatitis B
virus). Nevertheless, a direct and/or immune-mediated
liver injury has been hypothesized. In particular, elevated
liver enzyme levels represent a common adverse event
reported with the use of monoclonal antibodies, whereas
increase of bilirubin levels and hepatobiliary disorders,
such as cholecystitis and cholelithiasis, were found to be
uncommon.63–65 Jaundice and non-infectious hepatitis,
some with aspects of autoimmune hepatitis, have also
been observed during the post-marketing experience of
ª 2011 The International Society of Dermatology
Alcohol, psoriasis, liver disease and anti-psoriasis drugs Review 1327
infliximab, along with sporadic cases of liver failure,
which led to liver transplantation or death.64 Etanercept,
an anti-TNF receptor fusion protein, instead has been
rarely linked to the elevation of liver enzymes, and no
cases of liver injury closely related to the drug have been
reported so far.66 Considering the above-mentioned data,
etanercept treatment may constitute a safe alternative in
case of hepatotoxicity induced by anti-TNF antibodies,
as confirmed by some case reports.67–70 These observa-
tions suggest an absence of hepatic cross-toxicity between
anti-TNF antibodies and etanercept, making possible the
treatment with the latter in patients who have manifested
infliximab or adalimumab-related liver dysfunction.
To conclude, in the context of the predisposition of
psoriatic patients to develop non-alcoholic liver disease,
the hepatoxic risk of many anti-psoriasis drugs and the
overlap of an alcohol misuse habit could easily overbur-
den the liver metabolic processes, interfering with drug
metabolism and directly promoting alcohol-related liver
injuries. As no safe quantities of alcohol can be presently
recommended in psoriatic patients, such habit should
always be discouraged, especially when potentially hepa-
totoxic therapies are being considered.
Anti-TNF Drugs in Alcohol-Related Disorders
It is well known that TNF-a is implicated in a great num-
ber of metabolic processes. Therefore it is not surprising
that its levels may be altered in certain conditions related
to alcohol misuse and addiction, such as alcoholic hepati-
tis, or sleep and hemodynamic disturbances. Based on
these premises, it has been theorized that the use of anti-
TNF-a drugs may be beneficial in such instances.
Kupfer cell-derived TNF-a appears to play a primary
role in the genesis of alcoholic hepatitis. Circulating
TNF-a levels are higher in patients with alcoholic hepati-
tis than in heavy drinkers with inactive cirrhosis, heavy
drinkers without liver disease, and individuals with nei-
ther alcoholism nor liver disease, and high levels correlate
with mortality.71,72 TNF-a-induced liver cytotoxicity is
mediated through TNF receptor-1.73 The peroxidative
capacity of TNF-a in hepatocytes is restricted to the mito-
chondria and is exacerbated by alcohol-induced depletion
of mitochondrial glutathione, suggesting that mitochon-
dria are the target of TNF-a.74,75 Ethanol administration
stimulates both the release of mitochondrial cytochrome
C and the expression of the Fas ligand, leading to hepato-
cyte apoptosis by caspase-3 activation pathway.76 In
addition, the synergic action of TNF-a and Fas-mediated
apoptotic signals may increase the sensitivity of hepato-
cytes to damage, enhancing the activation of natural killer
T-cells in the liver.77
International Journal of Dermatology 2011, 50, 1323–1331
1328 Review Alcohol, psoriasis, liver disease and anti-psoriasis drugs
Sleep disturbance is one of the most important
complaints of alcoholic patients. In alcohol dependence,
markers of inflammation are associated with a lengthening
of the rapid eye movement (REM) sleep phase, which is
thought to be associated with the risk of alcoholic relapse.
Markers of inflammation, such as TNF-a and other proin-
flammatory cytokines, seem to correlate to REM sleep
amount, thus influencing the homeostatic regulation of
sleep.78–81 A randomized, placebo-controlled, double-
blind, crossover trial carried out in 18 abstinent alcohol-
dependent male adults has demonstrated that a single dose
of etanercept (25 mg) was able to cause a significant and
marked decrease of REM sleep toward values detected in
normal controls.82 Given these observations, it has been
theorized that TNF-a blockade might normalize REM
sleep in alcohol-dependent adults. Furthermore, it has
been suggested that inhibition of proinflammatory cyto-
kine signaling might represent a possible therapeutic
option when targeting sleep dysfunction,82 although other
studies are required to confirm such preliminary results.
Because TNF-a is a key mediator of hemodynamic
alterations in alcoholic hepatitis, it is not surprising that
anti-TNF-a treatment in such disease produces a highly
significant, early and sustained reduction in hepatic
venous pressure gradient, as shown in patients with alco-
holic hepatitis treated with infliximab. This action is
likely mediated by a synergic decrease in cardiac output
and intrahepatic resistance. In addiction, a reduction in
liver inflammation and an improved organ blood flow
was noted.83
In 2004, an open-label pilot study showed encouraging
results regarding the possible use of etanercept in alco-
holic hepatitis.84 Nonetheless, in a more recent phase II
placebo-controlled study performed in 48 patients with
moderate to severe alcoholic hepatitis, etanercept, admin-
istered at the dose of 50 mg/week for three weeks, was
not efficacious. Even more, the mortality rate in such
patients was significantly higher after six months as com-
pared with the placebo group.85 Consequently, taking
into account the available information, etanercept use is
not advisable for the treatment of alcoholic hepatitis. In
addition, it is recommended that physicians should exert
caution when using etanercept in patients who have mod-
erate to severe alcoholic hepatitis.66
The possible use of infliximab in patients with alcoholic
hepatitis is also the object of great controversy. A limited
number of studies in small cohorts of patients with severe
alcoholic hepatitis showed that a single infusion of inflix-
imab, at the dosage of 5 mg/kg, alone or in combination
with prednisone 40 mg/d administered for nearly 28 days,
may ameliorate the severity and complications of alco-
holic hepatitis.86–88 Regardless of these data, it must be
noted that the increased susceptibility to infections, a
International Journal of Dermatology 2011, 50, 1323–1331
Cassano et al.
known risk associated to this therapy, still poses a serious
concern.86–88
Interestingly, the possible beneficial effects of infliximab
on alcoholic hepatitis might turn to harmful when high
doses of the drug are used. This has been suggested by a
study that found that three 10 mg/kg infusions of inflix-
imab at 0, 2 and 4 weeks, in combination with predni-
sone 40 mg/d for 28 days, were associated with a higher
rate of mortality and severe infections.89 Given these
somewhat conflicting results, and the limitations of the
small studies conducted with infliximab, large randomized
controlled trials are required before infliximab (and also
other anti-TNF-a drugs) can be indicated for the treat-
ment of alcoholic hepatitis.89–92
While a few observations seem to confirm the hypothe-
sis of anti-TNF-a therapy being beneficial in treating alco-
holic hepatitis, sleep and hemodynamic alcohol-related
alterations, data are currently insufficient to endorse the
actual therapeutic efficacy and safety of anti-TNF-a bio-
logical drugs in such endeavors. Hence, further random-
ized controlled trials are needed before conclusions can
be drawn.
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