Development of Hepatic Steatosis After Chemotherapy for Non‐Hodgkin Lymphoma

Abstract

Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non‐Hodgkin lymphoma (NHL). In this retrospective case‐control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R‐CHOP) or R‐CHOP + etoposide (EPOCH‐R). Patients with liver disease or steatosis were excluded. Abdominal computed tomography was performed pretreatment and at 3‐ to 6‐month intervals and reviewed for steatosis. Patients with de novo steatosis were matched 1:1 to controls by age, sex, and ethnicity. Of 251 treated patients (median follow‐up 53 months), 25 (10%) developed de novo steatosis, with the vast majority (23 of 25; 92%) developing it after chemotherapy. Of those, 14 (61%) developed steatosis within the first 18 months posttreatment and 20 (87%) within 36 months. Cases had higher baseline body mass index (BMI; mean ± SD, 29.0 ± 6.5 versus 26.0 ± 5.2 kg/m2; P = 0.014) and hyperlipidemia (12% versus 2%; P = 0.035). Although their weights did not change during chemotherapy, BMI in cases increased by 2.4 ± 2 kg/m2 (mean ± SD) from end of treatment to steatosis compared to 0.68 ± 1.4 in controls (P = 0.003). Etoposide‐containing regimens were associated with a shorter time to steatosis (median 34 weeks versus 154 weeks; P < 0.001) despite similar baseline risk factors. Conclusion: The recovery period from NHL chemotherapy appears to be a “hot spot” for development of fatty liver, driven by early posttreatment weight gain, especially in subjects with baseline risk factors.

Clearing Steatosis Prior to Liver Surgery for Colorectal Metastasis: A Narrative Review and Case Illustration

“…We herein document the benefits of a low-calorie diet in a two-stage liver resection process. Furthermore, a study including two-stage liver resection combined with chemotherapy shows that chemotherapy produces steatosis but that it does not disappear much more than 3 weeks after stopping treatment [5]. Overall the available literature together with the present observation, support that the described 3-week hypocaloric hyper-protein diet can be used safely and efficiently in patients at risk of steatosis or with documented steatosis, and especially before surgery.…”

“…Nowadays, neoadjuvant or adjuvant treatments are routinely administered to patients undergoing surgery for colorectal cancer, including 5-fluoruracil, irinotecan, and oxaliplatin. Chemotherapy-associated steatosis (CAS) is therefore increasingly frequent, potentially limiting surgical strategies [5,6]. Although surgical techniques and patient care have improved in the recent years, hepatic steatosis is still recognized as an important risk factor for short and long-term complications and death after general surgery, and even more so after liver resection [7].…”

Effect of Chemotherapy on Fatty Liver Occurrence in Breast and Gastrointestinal Cancer Patients: A Case-Controlled Study

“…On the other hand, Hubert et al study showed that alcohol consumption and diabetes mellitus were associated with fatty liver disease and other demographic factors did not play a role (9). Ben-Yakov et al (11) showed the incidence of the fatty liver after chemotherapy was more in patients with higher BMI and pre-treatment history of hyperlipidemia than in other patients.…”

“…Ahn et al (16) reported that the frequency of fatty liver incidence was 25.8% in patients with breast cancer undergoing adjuvant chemotherapy with doxorubicin with cyclophosphamide. In another study, Ben-Yakov et al (11) examined the incidence of fatty liver in patients with non-Hodgkin's lymphoma treated with regimens containing rituximab, doxorubicin, cyclophosphamide, and prednisolone with or without etoposide, and the results showed that after treatment, up to 92% of the patients developed some degrees of hepatic steatosis.…”

<p>Sonophoresis Enhanced Transdermal Delivery of Cisplatin in the Xenografted Tumor Model of Cervical Cancer</p>

“…Nevertheless, chemotherapy results in several systemic side effects such as gastrotoxicity, myelosuppression, nephrotoxicity, ototoxicity, hepatotoxicity, cardiotoxicity, neurotoxicity and allergic reactions. [2][3][4] Cisplatin is a metallic compound that possesses square planar geometry and is a widely used antitumor drug. It is dose-dependent, with its efficacy related closely to the concentration of the drug in the tumor.…”