Investigation of the effect of oral isotretinoin treatment on liver elasticity in acne vulgaris patients using shear wave elastography

Acne vulgaris; It is a chronic inflammatory disease that affects the pilosebaceous unit. It is thought to be the eighth most common disease in the world. It is mostly seen in seborrheic areas such as face, neck, back and shoulders, where pilosebaceous units are densely located. It is characterized by elementary lesions such as open and/or closed comedones and papules and/or pustules. The incidence and severity of the disease is at its highest between the ages of 16-19 in boys and between the ages of 14-17 in girls. In adulthood, it is more common in women. Four basic mechanisms play a role in acne pathogenesis; These are increased sebum production and change in its content, colonization of Cutibacterium acnes in the pilosebaceous unit, follicular hyperkeratinization and inflammation. Isotretinoin is generally the preferred agent for moderate and severe acne vulgaris, and the standard treatment dose is between 0.5-1 mg/kg/day. The target cumulative dose of the drug is 120-150 mg/kg. Although there are many treatment side effects, most of these side effects are tolerable. At the beginning of treatment, liver function tests (ALT, AST), lipid profile (LDL, HDL, triglyceride and total cholesterol), urea, creatinine and B-HCG levels should be checked, and these parameters should be monitored throughout the treatment. Liver fibrosis is a reversible wound healing response characterized by extracellular matrix accumulation after hepatic injury. It develops at different rates in almost all patients with chronic liver damage, depending on the cause of liver disease and host factors. Most chronic liver diseases are associated with fibrosis; This fibrosis is characterized by parenchymal damage and inflammation. Long-term alcohol use, biliary diseases, autoimmune hepatitis, drugs, metabolic disorders and viral hepatitis are the factors accused in the etiology of liver fibrosis. Shear Wave Elastography is a noninvasive imaging method; It is an ultrasound technique in which the tissue response to mechanical stimuli sent by an ultrasound probe is evaluated. Isotretinoin is a drug that is metabolized in the liver and stored in this organ. For this reason, it can be thought that the drug has the potential to cause inflammation and VI damage in the liver, and that this damage may progress to fibrosis in proportion to the severity of the event. This study aimed to examine whether isotretinoin use causes stiffness in the liver parenchyma using the Share Wave Elastography method and to evaluate possible parameters related to liver stiffness. A total of 40 acne vulgaris patients were included in the study; The oral isotretinoin treatment dose was determined as 0,5 mg/kg/day. Disease activity was evaluated with Global Acne Rating System scoring at the beginning of treatment and at the end of the 3rd month of treatment. The patients' demographic characteristics, smoking and alcohol use, Fitzpatrick skin types, and disease-related data were questioned and recorded. Hemogram, urea, creatinine, ALT, AST, GGT, LDL, HDL, triglyceride and total cholesterol levels were examined at the beginning of treatment and at the end of the 3rd month of treatment. To work; Between the ages of 18-65, clinically diagnosed with acne vulgaris, having a negative clinical and/or history in terms of liver fibrosis, portal hypertension, obstructive cholestasis, liver congestion, acute hepatitis, infiltrative liver diseases, hepatic and splenic inflammation, and without hepatosplenomegaly and hepatosteatosis, Patients who have not previously had HBV and/or HCV infection, whose body mass index is below 25, who are not in pregnancy or breastfeeding, who have not received systemic or topical treatment for acne vulgaris in the last 3 months, and who do not have a current diagnosis of malignancy and/or immunosuppressive status. was included. Of the 40 patients participating in the study, 27 (67,5%) were female and 13 (32,5%) were male; The average age of the patients is 21.87±2.95 years; average body mass index is 22.51±1.62 kg/m²; The average duration of acne vulgaris disease was 20.55±9.20 months. While the mean Global Acne Rating Score of the patients at the beginning of the treatment was 24.93±5.18, it was 15.37±5.23 at the end of the 3rd month of treatment; The mean score at the end of the 3rd month of treatment was statistically significantly lower than at the beginning of treatment (p<0.001). The average serum triglyceride, total cholesterol, LDL, AST and GGT levels of the patients at the end of the 3rd month of treatment were statistically significantly higher compared to the beginning of treatment (p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, respectively). ). The average serum hemoglobin and HDL levels of the patients at the end of the 3rd month of treatment were statistically significantly lower compared to the beginning of treatment (p=0.003, VII p<0.014, respectively). While the average liver stiffness value of the patients at the beginning of the treatment was 4.42±0.89 kPa (kilopascals), it was 5.59±1.01 kPa at the end of the 3rd month of treatment; The average liver stiffness value at the end of the 3rd month of treatment was statistically significantly higher compared to the beginning of treatment (p<0.001). There was a moderate, inverse correlation (r:-0.330) between triglyceride and HDL levels at the end of the 3rd month of treatment (p = 0.037). There was a moderate, same-directional (r:0.369) correlation between total cholesterol and HDL levels at the end of the 3rd month of treatment (p=0.019). There was a high, same-directional (r:0.950) correlation between total cholesterol and LDL levels at the end of the 3rd month of treatment (p = 0.000). There was a moderate, inverse correlation (r:-0.316) between HDL and GGT levels at the end of the 3rd month of treatment (p = 0.047). While the liver stiffness value was similar in both genders at the beginning of treatment; This value at the end of the 3rd month of treatment was statistically significantly higher in males compared to females (p<0.005). The average liver stiffness value of female patients at the end of the 3rd month of treatment was 1.44 times less than that of male patients (CI: -2.625; -0.371) (p:0.015). While liver stiffness values were similar in all skin types at the beginning of treatment; Liver stiffness values at the end of the 3rd month of treatment were statistically significantly lower in patients with Fitzpatrick skin type 2 than in patients with Fitzpatrick skin type 3 or 4 (p<0.045). The mean liver stiffness value of patients with Fitzpatrick skin type 2 at the end of the 3rd month of treatment was 0.7 times less than that of patients with Fitzpatrick skin type 3 or 4 (CI:-1.287; -0.033) (p:0.031). As a result, oral isotretinoin therapy may lead to stiffness of the liver parenchyma. However, this stiffness is not related to macro damage in the liver or an increase in lipid values, and different mechanisms may play a role in this phenomenon. Since, to our knowledge, this study is the first to examine whether oral isotretinoin treatment causes stiffness in the liver parenchyma, it may be useful to evaluate this issue in larger prospective studies. In addition, the pathogenesis of liver parenchymal stiffness observed in oral isotretinoin use, possible causes of stiffness and whether it is reversible are also open to research. Keywords: Acne vulgaris, isotretinoin, liver fibrosis, share wave elastography