Abnormal transaminase and lipid profiles in coexisting diseases in patients with fatty liver: a population study in Sichuan

Among chronic liver diseases, fatty liver has the highest incidence worldwide. Coexistence of fatty liver and other chronic diseases, such as diabetes, hepatitis B virus (HBV) and Helicobacter pylori (Hp) infection, is common in clinical practice. The present study was conducted to analyze the prevalence and association of coexisting diseases in patients with fatty liver and to investigate how coexisting diseases contribute to abnormal transaminase and lipid profiles. We enrolled participants who were diagnosed with fatty liver via ultrasound in the physical examination center of West China Hospital. Multivariable logistic regression was used to determine the adjusted odds ratios (ORs). We found that 23.6% of patients who underwent physical examinations were diagnosed with fatty liver. These patients had higher risks of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and hypertension and a lower risk of HBV infection. The risks of Hp infection and hyperthyroidism did not statistically differ. When fatty liver coexisted with T2DM, MetS and thyroid dysfunction, it conferred a higher risk of elevated transaminase. Fatty liver was positively correlated with triglycerides, cholesterol and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with HBV; thus, HBV had a neutralizing effect on lipid metabolism when coexisting with fatty liver. In conclusion, patients with fatty liver that coexists with T2DM, MetS and thyroid dysfunction are more prone to elevated transaminase levels. Patients with both fatty liver and HBV may experience a neutralizing effect on their lipid metabolism. Thus, lipid alterations should be monitored in these patients during antiviral treatment for HBV.

Novel Induction Therapy for Newly Diagnosed Extranodal Natural Killer/T Cell Lymphoma (ENKTL) Treated By Anti-PD-1 Antibody Plus Histone Deacetylase Inhibitor Followed By P-GemOx Regimen

Background: ENKTL is a highly aggressive NHL with a higher incidence in Asia. L-asparaginase containing chemotherapy regimens are the most frequently administered in first-line treatment with moderate to severe toxicities. In 2020 ASH meeting, we reported Sintilimab(anti-PD-1 antibody) plus Chidamide(an oral subtype-selective HDACi) yielded effective antitumor activity, durable response with mild toxicity in patients with relapsed or refractory ENKTL(SCENT trial. Abstracts 644) for the first time. We then initiated this exploratory study to investigate the efficacy and safety of Sintilimab plus Chidamide(SC) for patients with newly diagnosed ENKTL. Methods: This trial enrolled eligible patients with newly diagnosed ENKTL(ND-ENKTL); ECOG score≤ 2; at least one measurable or evaluable lesion. Trial flow chart was showed in Figure 1. All patients received 2-3 cycles of Sintilimab (200mg) plus Chidamide (30mg, twice a week). For patients with early stage, 2 cycles of SC were given, subsequent 2-4 cycles of P-Gemox administered and followed by involved field radiotherapy (IFRT). For advanced stage, patients were treated with 3 cycles of SC and 3-6 cycles of P-Gemox. The primary study endpoints are the ORR of SC and end of treatment assessed according to the lymphoma response to immunomodulatory therapy criteria (LYRIC). Key secondary endpoints included DOR, PFS, OS and safety. Adverse events (AEs) were defined according to CTCAE 5.0. Pretreatment FFPE tumor and blood samples were obtained. Samples were analyzed by capture-based NGS targeting lymphoma relevant genes. Results: From July 2019 to April 2021, 30 eligible patients were enrolled from Sun Yat-sen University Cancer Center. The median age was 49 (range, 21-81 )years, 2(6.7%) patients with ECOG score ≥2, 12(40%) patients with stage III-IV, 11(36.7%) patients with PINK-E score≥3. Nineteen stageI-II and 9 stage III-IV patients were evaluated for efficacy. For stage I-II, 14(73.7%) patients achieved response, including 13(68.4%) CR patients and 1 (5.3%) PR with SC. After 2 cycles of SC, 9(69.2%) CR patients chosen to continue SC treatment. Five (26.3%) PR patients accepted 2 cycles of P-GemOx, 4(80%) patients got CR. All patients obtained CR (100%) after IFRT(Fig.2A). For stage III-IV, 4(44.4%) patients achieved response (1 got CR), 3(33.3%) patients experienced rapid progression disease (RPD) in SC portion. The CR patient chosen to continue SC treatment. Six (66.7%) patients entered P-Gemox portion including 1 RPD patient, all (100%) patient got CR. At last follow-up, ORR was 100% (7/7) with 100% CR(Fig.2B). The median follow-up time was 8.8 (0.3-24.3) months. The estimated 1-year PFS and OS rate were all 92.9±0.5%( Fig.3 A-B). 2 RPD patients died within one month. Circulating EBV-DNA clearance after SC significantly correlated with superior outcome. Dynamics ctDNA assay is in progress, data in detail will be presented at the ASH conference. Twenty-nine(96.7%) patients reported treatment-related adverse effects (TRAEs). The most common TRAEs (≥10%) were neutropenia (43.3%), thrombocytopenia (36.7%), elevated transaminase (33.3%), and anemia (23.3%). The most common grade 3 TRAEs(≥10%) was neutropenia (13.3%), elevated transaminase (10.0%), no grade 4 TRAEs. There were 4(13.3%) cases of immune-related AEs, including 3 cases of hypothyroidism and 1 case of hyperthyroidism. Conclusion: Sintilimab plus Chidamide yielded effective antitumor activity and manageable toxicities in newly diagnosed ENKTL for the first time. It may be a promising chemo-free induction therapeutic portion for this population, especially for early-stage patients. Further investigation is needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Liver Involvement in Children with COVID-19 and Multisystem Inflammatory Syndrome: A Single-Center Bulgarian Observational Study

SARS-CoV-2 infection may precede and cause various autoimmune and inflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C). Therefore, we aimed to observe the clinical presentation and laboratory, instrumental and other constellations in children with MIS-C, including liver involvement. We present the outcomes from a single-center prospective observational study in which 89 children was included (60 with proven COVID-19, 10 symptomatic with confirmed COVID-19 contact and 19 diagnosed with MIS-C). Laboratory, instrumental, immunological, and clinical investigations were performed. Only 12% (n = 4) from the COVID-19 group (except the ICU cases), we found elevated AST and/or ALT (up to 100). All of the children with elevated transaminase were overweight or obese, presenting along with moderate COVID-19 pneumonia. The majority of children with MIS-C showed typical laboratory constellations with higher levels of IL-6 (120.36 ± 35.56 ng/mL). About half of the children in the MIS-C group (52%, n = 11) showed elevated transaminases. Eleven children (57.9%) presented with abdominal pain, eight (42.1%) with ascites, two (10.5%) with hepatosplenomegaly, and four (21.1%) with symptoms such as diarrhea. Mesenteric lymphadenitis was observed more often in patients with elevated LDH (327.83 ± 159.39, p = 0.077). Ascites was associated with lymphopenia (0.86 ± 0.80, p = 0.029) and elevated LDH. Hepato-splenomegaly was also more frequent in children with lymphopenia (0.5 ± 0.14, p = 0.039), higher troponin (402.00 ± 101.23, p = 0.004) and low ESR. Diarrhea was more frequent in patients with lower CRP (9.00 ± 3.44 vs. 22.25 ± 2.58, p = 0.04), and higher AST and ALT (469.00 ± 349.59 vs. and 286.67 ± 174.91, respectively, p = 0.010), and D-dimer (4516.66 ± 715.83, p = 0.001). Our data suggest that the liver can also be involved in MIS-C, presenting with typical laboratory and instrumental outcomes.

Gemfibrozil-Induced Polyuria

Gemfibrozil is a lipid-regulating agent used mainly to treat patients with hypertriglyceridaemia, especially those at risk for acute pancreatitis. Like any other pharmacological agent, gemfibrozil has known adverse effects, mainly gastrointestinal, such as cholelithiasis, gallstones, elevated transaminase, and other non-specific symptoms including dyspepsia, nausea and vomiting. Other reported adverse reactions are dizziness and vertigo, myopathy and rhabdomyolysis, angioedema, urticaria and rash. As far as we knew, gemfibrozil does not have urinary tract adverse reactions. In this report, we present a case of polyuria secondary to gemfibrozil with a score of 9 on the Naranjo scale, and a literature review.

Enoxaparin-induced hepatotoxicity: clinical cases and literature review

Low molecular weight heparins, in particular enoxaparin, have a wide range of applications, including prevention and treatment of deep vein thrombosis. The most common adverse effects of these drugs are bleeding and thrombocytopenia, but a clinician should be aware of another less common but not less important adverse effect such as an elevated transaminase level. In 2019, we observed two cases of enoxaparin-induced hepatotoxicity. In the first one, enoxaparin 0.4 ml subcutaneously twice a day was prescribed to a 40-year-old woman as a bridge therapy to discontinue warfarin before elective surgery. In the second case, a 27-year-old man received enoxaparin 0.4 ml subcutaneously twice a day for the prevention of deep vein thrombosis. The elevation of transaminase level for more than 3 times above the norm was noted in both patients which required discontinuation of the drug.

Methotrexate in rheumatology – efficacy and safety of the therapy

Methotrexate is currently the safe and effective drug used in chronic arthritis and other rheumatic diseases. Avoiding the use of methotrexate in everyday rheumatic treatment can lead to significant health complications. There is no time frame for the use of methotrexate, the drug can be used successfully for many years. The therapeutic dose of the drug is usually 25–30 mg/week. The most common side effects are gastrointestinal disorders and elevated transaminase levels. The efficacy and safety of methotrexate have been confirmed in many clinical trials and in everyday clinical practice.