Alimentary Pharmacology and Therapeutics
The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic K. K. Roberts*, A. E. Cochet*, P. B. Lamb*, P. J. Brown†, D. F. Battafarano‡, E. M. Brunt§ & S. A. Harrison*
*Division of Gastroenterology and Hepatology, Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, TX, USA. † Department of Dermatology, San Antonio Military Medical Center, Fort Sam Houston, TX, USA. ‡ Division of Rheumatology, Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, TX, USA. § Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO, USA.
Correspondence to: Dr S. A. Harrison, San Antonio Military Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX 78234, USA. E-mail: stephen.a.harrison.mil@mail. mil
Publication data Submitted 8 October 2014 First decision 23 October 2014 Resubmitted 17 November 2014 Accepted 17 November 2014 EV Pub Online 18 December 2014 This article was accepted for publication after full peer-review.
SUMMARY Background Psoriasis has been linked to metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Data suggest that the prevalence of NAFLD is increased in patients with psoriasis. The aim of this study was to determine the prevalence and severity of NAFLD in this patient population. Aim To determine the prevalence of both NAFLD and non-alcoholic steatohepatitis (NASH) in patients with psoriasis. Methods Patients between the ages of 18 and 70 years with a diagnosis of psoriasis or psoriatic arthritis and followed by either the Dermatology or Rheumatology Division within the Department of Medicine at San Antonio Military Medical Center were considered for enrollment. Each patient completed a questionnaire, underwent a thorough skin evaluation, and had a right upper quadrant ultrasound and fasting blood work. If the liver enzymes were elevated or fatty liver detected on imaging, percutaneous liver biopsy was recommended. Results One hundred and twenty-nine patients were enrolled and 103 completed all necessary studies. The participants were predominantly middle aged (52.7 12) and overweight or obese (average BMI 30.1 5.9, range: 19.8–52.5 kg/ m2). 53% (n = 54) were male while 15% (n = 15) of participants identified themselves as being a diabetic. The overall prevalence of NAFLD was 47%. The overall prevalence of NASH was 22% in those who underwent biopsy. Conclusions Non-alcoholic fatty liver disease is very common among our cohort of patients with psoriasis, occurring in roughly 47% of patients. The more progressive form of the disease, NASH, is found in approximately one in five patients. Health care providers should be mindful of this association given the high prevalence of both NAFLD and NASH in this cohort of patients. Aliment Pharmacol Ther 2015; 41: 293–300
Published 2014. This article is a U.S. Government work and is in the public domain in the USA doi:10.1111/apt.13042
293
K. K. Roberts et al. INTRODUCTION Psoriasis is a chronic inflammatory disease of the skin, affecting an estimated 125 million patients worldwide and representing approximately 2% of the global population.1, 2 This disease is best known for its cutaneous manifestations; described as well-demarcated, erythematous oval plaques with adherent silvery scales.1 However, recent data have linked psoriasis with several comorbidities to include metabolic syndrome (obesity, hypertension, hyperlipidemia and insulin resistance) and cardiovascular disease.3–5 In addition, utilising non-invasive imaging, several recent reports have shown a relationship between psoriasis and non-alcoholic fatty liver disease (NAFLD), which many consider the hepatic manifestation of metabolic syndrome.6–9 While the exact aetiology of this relationship remains uncertain, it has been postulated that inflammatory cytokines such as resistin, tumour necrosis factor alpha (TNF-a), IL-6 and IL1-b play a mechanistic role in the development of insulin resistance and fatty liver as well as psoriasis2, 10; these connections imply a possible linked pathogenesis further supported by similarities between skin and liver inflammation using advanced [18F]-fluorodeoxyglucose positron emission tomography-computed tomography techniques.11 NAFLD, the most common cause of incidental elevation of liver enzymes in the Western world and in rapidly developing countries,12 encompasses a spectrum of disease states ranging from isolated fatty liver to non-alcoholic steatohepatitis (NASH) with increasing levels of fibrosis and ultimately cirrhosis. NAFLD itself is defined as the accumulation of macrovesicular fat in more than 5% of hepatocytes in those who do not consume alcohol in harmful amounts (19 IU/mL in women or >30 IU/mL in men) were offered a liver biopsy. Participants with a negative ultrasound and unremarkable laboratory evaluation were considered as completed study patients and no liver biopsy was offered. A coagulation panel and complete blood count were drawn prior to liver biopsy to ensure adequate haemostasis. A study investigator, using a 14-guage BARD biopsy instrument (BARD Biopsy Systems, Tempe, AZ, USA), performed the liver biopsy. A single expert hepatologist (Dr Elizabeth Brunt) reviewed all liver biopsies and utilised the NIDDK NASH CRN method16 for grading the NAFLD Activity Score (NAS) and staging. Diagnostic categories rendered were ‘Not NAFLD’, ‘Non-NASH NAFLD’ and ‘NASH’. Subject participation was concluded approximately 1 month after the liver biopsy, and appropriate follow-up was provided for routine care of any identified conditions during the research period. Statistical analysis This was an observational study to compare demographical and biochemical variables between Not-NAFLD, Non-NASH NAFLD and NASH subjects with psoriasis. Values were reported as means and standard deviations for interval type variables and probabilities for binomial variables. Normally distributed interval type variables were compared with independent sample t-tests.
129 Enrolled
103 Completed ultrasound
-7 Excluded -19 Failed to complete ultrasound or labs
27 Did not meet 76 Met biopsy biopsy criteria criteria 27 49 Elevated Steatosis liver by US enzymes -24 Refused biopsy (8 patients with NAFLD by US and 16 with 52 Completed elevated liver enzymes biopsy alone)
12 Not NAFLD
23 NASH
17 Not NASH
Figure 1 | Participant flow chart. One hundred and twenty-nine patients with known psoriasis were enrolled in the NAFLD prevalence study. Twenty-six participants either met exclusion criteria or failed to complete requested labs or ultrasound. Of the 113 individuals who completed initial assessment, 76 were offered a liver biopsy based on the presence of fatty liver on ultrasound or elevated liver enzymes. Forty of the 52 biopsies revealed histological evidence of NAFLD and 12 had no evidence of NAFLD. Twentythree of the 40 NAFLD cases were positive for NASH. Of the 12 participant found to have no evidence of NAFLD on biopsy, five had the appearance of NAFLD on ultrasound and seven had elevated liver enzymes alone. The total number of NAFLD cases was determined to be 48 (40 by biopsy plus eight patients with NAFLD by ultrasound alone who chose not to undergo biopsy). The eight patients with NAFLD by ultrasound who did not undergo biopsy were considered in the NAFLD group.
Binomial variables were compared with v2 contingency tests. Ordinal type variables were compared with Mann–Whitney rank sum tests. A P value of 30 (%) Alkaline phosphatase lg/mL, mean (s.d.) AST, U/L, mean (s.d.) ALT, U/L, mean (s.d.) HgbA1C, %, mean (s.d.) Insulin, lIU/mL, mean (s.d.) Glucose, mg/dL, mean (s.d.) HOMA-IR, mean (s.d.) Cholesterol, mg/dL, mean (s.d.) Ferritin, ng/mL, mean (s.d.) PASI, mean (s.d.) Adiponectin, lg/mL, mean (s.d.) Leptin, pg/mL, mean (s.d.) HGF, pg/mL, mean (s.d.) MCP1, pg/mL, mean (s.d.) Resistin, pg/mL, mean (s.d.) PAI-1, pg/mL, mean (s.d.) IL-6, pg/mL, mean (s.d.) TNF-a, pg/mL, mean (s.d.) IL-8, pg/mL, mean (s.d.) IL-1b, pg/mL, mean (s.d.)
Not NAFLD (n = 55) 53.4 49.2 36.33 40 10.9 78.2 5.5 7.3 3.6 5.5 27.46 23.6 69.65 24.45 26.56 5.58 10.61 94.71 2.47 183.53 112.53 2.996 92.201 17 145.81 672.99 343.13 71 252.45 26 131.38 2.58 4.97 7.13 0.61
(12.72) (4.21)
(4.62) (22.15) (9.556) (22.08) (0.40) (6.77) (9.07) (1.63) (34.32) (109.63) (2.70) (81.22) (16 585.48) (408.92) (170.11) (33 438.08) (12 000.21) (3.78) (5.63) (5.13) (1.21)
NAFLD (n = 48) 46.6 56.79 44.10 66.7 18.8 58.3 31.3 4.2 4.2 2.1 33.21 75 74.79 27.67 33.79 6.13 21.85 115.42 6.50 168.19 201.20 5.207 59.711 31 766.09 836.46 404.24 70 960.54 30 146.49 4.49 6.33 8.38 1.08
(9.75) (5.30)
(5.79) (25.49) (11.402) (16.43) (0.94) (16.89) (34.03) (5.54) (35.19) (201.51) (4.96) (39.77) (28 598.01) (475.39) (186.56) (29 992.09) (11 220.59) (5.24) (8.75) (7.59) (3.83)
P value NA 0.001
The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic K. K. Roberts*, A. E. Cochet*, P. B. Lamb*, P. J. Brown†, D. F. Battafarano‡, E. M. Brunt§ & S. A. Harrison*
*Division of Gastroenterology and Hepatology, Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, TX, USA. † Department of Dermatology, San Antonio Military Medical Center, Fort Sam Houston, TX, USA. ‡ Division of Rheumatology, Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, TX, USA. § Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO, USA.
Correspondence to: Dr S. A. Harrison, San Antonio Military Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX 78234, USA. E-mail: stephen.a.harrison.mil@mail. mil
Publication data Submitted 8 October 2014 First decision 23 October 2014 Resubmitted 17 November 2014 Accepted 17 November 2014 EV Pub Online 18 December 2014 This article was accepted for publication after full peer-review.
SUMMARY Background Psoriasis has been linked to metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Data suggest that the prevalence of NAFLD is increased in patients with psoriasis. The aim of this study was to determine the prevalence and severity of NAFLD in this patient population. Aim To determine the prevalence of both NAFLD and non-alcoholic steatohepatitis (NASH) in patients with psoriasis. Methods Patients between the ages of 18 and 70 years with a diagnosis of psoriasis or psoriatic arthritis and followed by either the Dermatology or Rheumatology Division within the Department of Medicine at San Antonio Military Medical Center were considered for enrollment. Each patient completed a questionnaire, underwent a thorough skin evaluation, and had a right upper quadrant ultrasound and fasting blood work. If the liver enzymes were elevated or fatty liver detected on imaging, percutaneous liver biopsy was recommended. Results One hundred and twenty-nine patients were enrolled and 103 completed all necessary studies. The participants were predominantly middle aged (52.7 12) and overweight or obese (average BMI 30.1 5.9, range: 19.8–52.5 kg/ m2). 53% (n = 54) were male while 15% (n = 15) of participants identified themselves as being a diabetic. The overall prevalence of NAFLD was 47%. The overall prevalence of NASH was 22% in those who underwent biopsy. Conclusions Non-alcoholic fatty liver disease is very common among our cohort of patients with psoriasis, occurring in roughly 47% of patients. The more progressive form of the disease, NASH, is found in approximately one in five patients. Health care providers should be mindful of this association given the high prevalence of both NAFLD and NASH in this cohort of patients. Aliment Pharmacol Ther 2015; 41: 293–300
Published 2014. This article is a U.S. Government work and is in the public domain in the USA doi:10.1111/apt.13042
293
K. K. Roberts et al. INTRODUCTION Psoriasis is a chronic inflammatory disease of the skin, affecting an estimated 125 million patients worldwide and representing approximately 2% of the global population.1, 2 This disease is best known for its cutaneous manifestations; described as well-demarcated, erythematous oval plaques with adherent silvery scales.1 However, recent data have linked psoriasis with several comorbidities to include metabolic syndrome (obesity, hypertension, hyperlipidemia and insulin resistance) and cardiovascular disease.3–5 In addition, utilising non-invasive imaging, several recent reports have shown a relationship between psoriasis and non-alcoholic fatty liver disease (NAFLD), which many consider the hepatic manifestation of metabolic syndrome.6–9 While the exact aetiology of this relationship remains uncertain, it has been postulated that inflammatory cytokines such as resistin, tumour necrosis factor alpha (TNF-a), IL-6 and IL1-b play a mechanistic role in the development of insulin resistance and fatty liver as well as psoriasis2, 10; these connections imply a possible linked pathogenesis further supported by similarities between skin and liver inflammation using advanced [18F]-fluorodeoxyglucose positron emission tomography-computed tomography techniques.11 NAFLD, the most common cause of incidental elevation of liver enzymes in the Western world and in rapidly developing countries,12 encompasses a spectrum of disease states ranging from isolated fatty liver to non-alcoholic steatohepatitis (NASH) with increasing levels of fibrosis and ultimately cirrhosis. NAFLD itself is defined as the accumulation of macrovesicular fat in more than 5% of hepatocytes in those who do not consume alcohol in harmful amounts (19 IU/mL in women or >30 IU/mL in men) were offered a liver biopsy. Participants with a negative ultrasound and unremarkable laboratory evaluation were considered as completed study patients and no liver biopsy was offered. A coagulation panel and complete blood count were drawn prior to liver biopsy to ensure adequate haemostasis. A study investigator, using a 14-guage BARD biopsy instrument (BARD Biopsy Systems, Tempe, AZ, USA), performed the liver biopsy. A single expert hepatologist (Dr Elizabeth Brunt) reviewed all liver biopsies and utilised the NIDDK NASH CRN method16 for grading the NAFLD Activity Score (NAS) and staging. Diagnostic categories rendered were ‘Not NAFLD’, ‘Non-NASH NAFLD’ and ‘NASH’. Subject participation was concluded approximately 1 month after the liver biopsy, and appropriate follow-up was provided for routine care of any identified conditions during the research period. Statistical analysis This was an observational study to compare demographical and biochemical variables between Not-NAFLD, Non-NASH NAFLD and NASH subjects with psoriasis. Values were reported as means and standard deviations for interval type variables and probabilities for binomial variables. Normally distributed interval type variables were compared with independent sample t-tests.
129 Enrolled
103 Completed ultrasound
-7 Excluded -19 Failed to complete ultrasound or labs
27 Did not meet 76 Met biopsy biopsy criteria criteria 27 49 Elevated Steatosis liver by US enzymes -24 Refused biopsy (8 patients with NAFLD by US and 16 with 52 Completed elevated liver enzymes biopsy alone)
12 Not NAFLD
23 NASH
17 Not NASH
Figure 1 | Participant flow chart. One hundred and twenty-nine patients with known psoriasis were enrolled in the NAFLD prevalence study. Twenty-six participants either met exclusion criteria or failed to complete requested labs or ultrasound. Of the 113 individuals who completed initial assessment, 76 were offered a liver biopsy based on the presence of fatty liver on ultrasound or elevated liver enzymes. Forty of the 52 biopsies revealed histological evidence of NAFLD and 12 had no evidence of NAFLD. Twentythree of the 40 NAFLD cases were positive for NASH. Of the 12 participant found to have no evidence of NAFLD on biopsy, five had the appearance of NAFLD on ultrasound and seven had elevated liver enzymes alone. The total number of NAFLD cases was determined to be 48 (40 by biopsy plus eight patients with NAFLD by ultrasound alone who chose not to undergo biopsy). The eight patients with NAFLD by ultrasound who did not undergo biopsy were considered in the NAFLD group.
Binomial variables were compared with v2 contingency tests. Ordinal type variables were compared with Mann–Whitney rank sum tests. A P value of 30 (%) Alkaline phosphatase lg/mL, mean (s.d.) AST, U/L, mean (s.d.) ALT, U/L, mean (s.d.) HgbA1C, %, mean (s.d.) Insulin, lIU/mL, mean (s.d.) Glucose, mg/dL, mean (s.d.) HOMA-IR, mean (s.d.) Cholesterol, mg/dL, mean (s.d.) Ferritin, ng/mL, mean (s.d.) PASI, mean (s.d.) Adiponectin, lg/mL, mean (s.d.) Leptin, pg/mL, mean (s.d.) HGF, pg/mL, mean (s.d.) MCP1, pg/mL, mean (s.d.) Resistin, pg/mL, mean (s.d.) PAI-1, pg/mL, mean (s.d.) IL-6, pg/mL, mean (s.d.) TNF-a, pg/mL, mean (s.d.) IL-8, pg/mL, mean (s.d.) IL-1b, pg/mL, mean (s.d.)
Not NAFLD (n = 55) 53.4 49.2 36.33 40 10.9 78.2 5.5 7.3 3.6 5.5 27.46 23.6 69.65 24.45 26.56 5.58 10.61 94.71 2.47 183.53 112.53 2.996 92.201 17 145.81 672.99 343.13 71 252.45 26 131.38 2.58 4.97 7.13 0.61
(12.72) (4.21)
(4.62) (22.15) (9.556) (22.08) (0.40) (6.77) (9.07) (1.63) (34.32) (109.63) (2.70) (81.22) (16 585.48) (408.92) (170.11) (33 438.08) (12 000.21) (3.78) (5.63) (5.13) (1.21)
NAFLD (n = 48) 46.6 56.79 44.10 66.7 18.8 58.3 31.3 4.2 4.2 2.1 33.21 75 74.79 27.67 33.79 6.13 21.85 115.42 6.50 168.19 201.20 5.207 59.711 31 766.09 836.46 404.24 70 960.54 30 146.49 4.49 6.33 8.38 1.08
(9.75) (5.30)
(5.79) (25.49) (11.402) (16.43) (0.94) (16.89) (34.03) (5.54) (35.19) (201.51) (4.96) (39.77) (28 598.01) (475.39) (186.56) (29 992.09) (11 220.59) (5.24) (8.75) (7.59) (3.83)
P value NA 0.001
