Pentoxifylline with metformin treatment improves biochemical parameters in patients with nonalcoholic steatohepatitis

Summary Background The progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with NASH. Setting: Outpatient hepatology clinic. Methods A prospective trial was conducted. The first cohort included patients with biopsy-proven NASH, while the second cohort consisted of patients with biopsy-confirmed NAFLD. Blood tests were checked at baseline and every three months. Pentoxifylline at a dosage of 400 mg t.i.d. and Metformin at the dosage of 500 mg t.i.d. were introduced for six months in NASH group. The impact of the treatment was assessed based on biochemical results after combined treatment with low-cost medications. Results All 33 NASH patients completed 24 weeks of treatment. We observed significant improvement (p<0.05) of median values after treatment for the following parameters: serum uric acid levels decreased by 51.0 micromol/L, calcium decreased for 0.27 mmoL/L, magnesium showed an increase of 0.11 mmoL/L. Insulin resistance improved as a reduction of HOMA – IR by 1.3 was detected. A significant decrease of median in liver enzymes, alanine aminotransferase, aspartate aminotransferase and gammaglutamyltransferase by 24.0 IU/L, 9.1 IU/L, 10.8 IU/L respectively, was noted. Conclusions Pentoxifylline and Metformin may provide possible treatment option in NASH. Some new potential benefit of the therapy in improving liver function whilst decreasing cardiovascular risk was perceived.

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Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity

BMC Pediatrics ◽

10.1186/s12887-021-02595-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Luting Peng ◽

Su Wu ◽

Nan Zhou ◽

Shanliang Zhu ◽

Qianqi Liu ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Body Mass Index ◽

Liver Disease ◽

Fatty Liver Disease ◽

Liver Enzymes ◽

Early Stage ◽

Prevention Strategies ◽

Nonalcoholic Fatty Liver ◽

Nash Group

Abstract Background With the increasing number of children with obesity worldwide, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease among children. It is necessary to recognize the risk factors of NAFLD for prevention in childhood since NAFLD is asymptomatic in the early stage. Objectives. The objective of this study was to investigate possible risk factors of NAFLD in children with obesity, providing evidence for monitoring and prevention strategies at an early stage for obese children with NAFLD. Methods Data were collected from 428 children and adolescents aged 6-16 years recruited from the Children’s Hospital at Nanjing Medical University from September 2015 to April 2018 and analyzed. Based on a combination of ultrasound results and alanine transaminase levels, subjects were divided into three groups: simple obesity (SOB), simple steatosis (SS), and nonalcoholic fatty hepatitis (NASH). Blood biochemical examination included glucose, insulin, uric acid, lipid profile and liver enzymes. Results Among 428 children with obesity, 235 (54.9%) had SS and 45 (10.5%) had NASH. Body mass index, body mass index standard deviation score (BMI-SDS), waist circumference, body fat, liver enzymes, uric acid and HOMA-IR level were significantly higher in the NASH group than in the SS and SOB groups (p < 0.001). 53.3% of the SS group and 49.8% of the NASH group had metabolic syndrome, significantly more than in the SOB group (19.6%, p < 0.001). After adjustment for confounding factors, logistic regression models revealed that NASH was associated with BMI-SDS ≥ 3, gender, hyperuricemia and insulin resistance. Conclusions The prevalence of NASH in children with obesity is closely related to high BMI-SDS, gender, insulin resistance and hyperuricemia. These findings provide evidence that monitoring risk factors of childhood obesity can assist in developing prevention strategies for liver disease at an early stage.

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The Role of Vitamin E in the Treatment of NAFLD

Diseases ◽

10.3390/diseases6040086 ◽

2018 ◽

Vol 6 (4) ◽

pp. 86 ◽

Cited By ~ 21

Author(s):

Brandon Perumpail ◽

Andrew Li ◽

Nimy John ◽

Sandy Sallam ◽

Neha Shah ◽

...

Keyword(s):

Vitamin E ◽

Nonalcoholic Steatohepatitis ◽

Medical Literature ◽

Ease Of Use ◽

Alpha Tocopherol ◽

Diabetic Patients ◽

Nonalcoholic Fatty Liver ◽

Therapeutic Choice ◽

The Impact

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

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Mouse Models of Nonalcoholic Steatohepatitis: Head-to-Head Comparison of Dietary Models and Impact on Inflammation and Animal Welfare

Gastroenterology Research and Practice ◽

10.1155/2020/7347068 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Andreas Kroh ◽

Vanina Ivanova ◽

Hannah Drescher ◽

Julia Andruszkow ◽

Thomas Longerich ◽

...

Keyword(s):

Mouse Model ◽

Animal Welfare ◽

Mouse Models ◽

Nonalcoholic Steatohepatitis ◽

Cell Sorting ◽

High Fat Diet ◽

Histopathological Examination ◽

Clinical Status ◽

Nonalcoholic Fatty Liver ◽

The Impact

A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate mouse model is one of the most important steps in the design of NASH studies. In addition to the histopathological and metabolic findings of NASH, a sufficient mouse model should guarantee a robust clinical status and good animal welfare. Three different NASH diets, a high-fat diet (HFD60), a western diet (WD), and a cafeteria diet (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline and before scheduled sacrifice, and liver inflammation was analyzed via fluorescence-associated cell sorting and histopathological examination. Clinical health conditions were scored weekly to assess the impact on animal welfare. The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare. Furthermore, the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3+ NK1.1+ cells. The WD represents a model of advanced-stage NASH, and the HFD60 is a strong model of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. However, the CAFD should not be considered a NASH model.

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Influence of combined treatment with mianserin and simvastatin on selected biochemical serum parameters of liver and kidney function in rats

Current Issues in Pharmacy and Medical Sciences ◽

10.12923/j.2084-980x/26.3/a.04 ◽

2013 ◽

Vol 26 (3) ◽

pp. 263-266

Keyword(s):

Total Protein ◽

Biochemical Parameters ◽

Day Treatment ◽

Combined Treatment ◽

Creatinine Concentration ◽

Serum Parameters ◽

Combined Administration ◽

Liver And Kidney ◽

The Impact

The aim of the present study was to assess the impact of combined 14-day treatment with mianserin (10 mg/kg) and simvastatin (1 or 10 mg/kg) on selected biochemical liver and kidney parameters in rats (AST and ALT activities and the concentrations of AFP, total protein, urea, creatinine and ß2-M). The results showed the increase in both transaminases activities, creatinine concentration and the decrease of AFP, total protein and ß2-M concentrations. The results indicate that 14-day combined administration of mianserin with simvastatin negatively affects the liver functioning. The observed changes in kidney biochemical parameters may suggest a risk of renal dysfunction during long-term combined treatment with these drugs.

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Circulating miRNA is a useful diagnostic biomarker for nonalcoholic steatohepatitis in nonalcoholic fatty liver disease

Scientific Reports ◽

10.1038/s41598-021-94115-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tae Hyung Kim ◽

Yoonseok Lee ◽

Young-Sun Lee ◽

Jeong-An Gim ◽

Eunjung Ko ◽

...

Keyword(s):

Liver Disease ◽

Diagnostic Accuracy ◽

Fatty Liver ◽

Mirna Expression ◽

Nonalcoholic Steatohepatitis ◽

Fatty Liver Disease ◽

External Validation ◽

Circulating Mirnas ◽

Nonalcoholic Fatty Liver ◽

Nash Group

AbstractNonalcoholic steatohepatitis (NASH) is considered as a progressive form of nonalcoholic fatty liver disease (NAFLD). To distinguish NASH from nonalcoholic fatty liver (NAFL), we evaluated the diagnostic value of circulating miRNAs. Small RNA sequencing was performed on 12 NAFL patients and 12 NASH patients, and the miRNA expression was compared. After selecting miRNAs for the diagnosis of NASH, we analyzed the diagnostic accuracy of each miRNA and the combination of miRNAs. External validation was performed using quantitative reverse transcription PCR. Among the 2,588 miRNAs, 26 miRNAs significantly increased in the NASH group than in the NAFL group. Among the 26 elevated miRNAs in the NASH group, 8 miRNAs were selected, and in silico analysis was performed. Only four miRNAs (miR-21-5p, miR-151a-3p, miR-192-5p, and miR-4449) showed significant area under the receiver operating characteristic curve (AUC) values for NASH diagnosis. The combination of the four miRNAs showed satisfactory diagnostic accuracy for NASH (AUC 0.875; 95% CI 0.676–0.973). External validation revealed similar diagnostic accuracy for NASH (AUC 0.874; 95% CI 0.724–0.960). NASH represents significantly distinct miRNA expression profile compared with NAFL. The combination of serum circulating miRNAs can be used as a novel biomarker for the NASH diagnosis in NAFLD.

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Nonalcoholic Fatty Liver Disease in Patients Investigated for Elevated Liver Enzymes

Canadian Journal of Gastroenterology ◽

10.1155/2003/268528 ◽

2003 ◽

Vol 17 (1) ◽

pp. 38-42 ◽

Cited By ~ 16

Author(s):

Krikor Kichian ◽

Ross Mclean ◽

Leah M Gramlich ◽

Robert J Bailey ◽

Vincent G Bain

Keyword(s):

Liver Disease ◽

Liver Biopsy ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Nonalcoholic Steatohepatitis ◽

Fatty Liver Disease ◽

Liver Enzymes ◽

Nonalcoholic Fatty Liver ◽

Elevated Liver Enzymes ◽

History Of

Nonalcoholic fatty liver disease (NAFLD) is a common diagnosis among patients referred to gastroenterology and hepatology clinics for the evaluation of elevated liver enzymes. The diagnosis of NAFLD is supported by blood work to exclude other liver diseases, and by ultrasound evidence of fat in the liver in patients without a significant history of alcohol intake. The gold standard, however, is a liver biopsy to show the typical histological features of NAFLD, which are almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. A variety of retrospective series have linked NAFLD to obesity, diabetes, hyperlipidemia, total parenteral nutrition, jejunoileal bypass surgery and certain medications. A subset of patients with NAFLD that had an initial presentation of elevated liver enzymes was studied. Two hundred and two patients were reviewed, of whom 49 met the inclusion criteria including a liver biopsy. Patients were excluded if insufficient data were available, if the patients had a significant history of ethanol intake or if they had other coexisting liver disease. These patients were seen between 1996 and 2000 in gastroenterology and hepatology clinics in two community hospitals and one regional liver transplant centre in Edmonton, Alberta. NAFLD was associated with a spectrum of changes in the liver ranging from mild steatosis to more significant steatosis with inflammation and fibrosis. Cases of NAFLD with steatosis and mixed inflammatory infiltration but lacking ballooning degeneration or fibrosis were prevalent in young (20 to 40 years of age) patients with no other significant medical history except for obesity. NAFLD with biopsies showing significant fibrosis and ballooning cell degeneration was associated with obesity, diabetes and older age. It was concluded that, in this predominantly outpatient setting, age over 40 years and diabetes at any age are risk factors for both nonalcoholic steatohepatitis and nonalcoholic steatohepatitis with cirrhosis. It is therefore recommended that patients with raised liver enzymes and suspected NAFLD be targeted for liver biopsy in their evaluation.

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Randomized Prospective Trial Exploring the Impact of Structured Journaling in Patients With Sarcoma on the Management of Treatment-Related Adverse Events

JCO Oncology Practice ◽

10.1200/op.21.00309 ◽

2021 ◽

pp. OP.21.00309

Author(s):

N. J. Speece ◽

Menglin Xu ◽

Gabriel Tinoco ◽

David A. Liebner ◽

James L. Chen

Keyword(s):

Adverse Events ◽

Randomized Trial ◽

Symptom Management ◽

Low Cost ◽

Prospective Trial ◽

Prospective Randomized Trial ◽

Event Management ◽

Self Monitoring ◽

Patient Focus Group ◽

The Impact

PURPOSE: Treatment-related adverse events associated with systemic anticancer therapy (SACT) can deter patients with sarcoma from completing treatment. With self-monitoring, patients may be better empowered to self-advocate for improved symptom management. We hypothesized that by incorporating journaling, a structured form of self-monitoring, care team communication, and symptom management would improve. We thus designed a prospective randomized trial exploring journaling as a therapeutic adjuvant for symptom management ( NCT03258892 ). METHODS: Participants with sarcoma initiating SACT were randomly assigned to receive either a symptom management journal at the start of SACT or after completing two cycles of SACT. Symptom journals were designed jointly by a cancer patient focus group and by education experts. Journals were reviewed with clinical staff at each visit. Participant responses were obtained through questionnaires. Patient call volume was obtained through the electronic health record. RESULTS: Of 64 participants consented for the trial, 53 were evaluable for analysis. Fifty-five percent of participants reported that the journal was at least moderately useful. These participants were more likely to report improved communication scores ( P = .027), symptom management ( P = .011), and quality of life (QOL) ( P = .019). Participants who received the journal early were less likely to report a decrease in QOL as compared with the late journal group ( P = .757 v P = .035). CONCLUSION: To our knowledge, this is the first prospective randomized trial evaluating the use of structured journaling as a low-cost means to improve treatment-related adverse event management and QOL in patients with sarcoma undergoing SACT. These promising results will need to be confirmed by additional studies.

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Serum Adipokine and Ghrelin Levels in Nonalcoholic Steatohepatitis

Mediators of Inflammation ◽

10.1155/mi/2006/34295 ◽

2006 ◽

Vol 2006 ◽

pp. 1-5 ◽

Cited By ~ 18

Author(s):

Mehmet Yalniz ◽

Ibrahim Halil Bahcecioglu ◽

Huseyin Ataseven ◽

Bilal Ustundag ◽

Fulya Ilhan ◽

...

Keyword(s):

Glucose Tolerance ◽

Nonalcoholic Steatohepatitis ◽

Liver Diseases ◽

Serum Levels ◽

Control Group ◽

Serum Leptin ◽

Nonalcoholic Fatty Liver ◽

Nash Group ◽

Nonalcoholic Fatty Liver Diseases ◽

Age And Sex

Adipokines and ghrelin play role in insulin resistance, the key pathophysiological abnormality in patients with nonalcoholic fatty liver diseases. In the present study, relationship between nonalcoholic steatohepatitis (NASH) and serum adipokine and ghrelin levels was investigated. Thirty seven patients with biopsy-proven NASH and 25 age- and sex-matched controls were enrolled. Ten of NASH patients (27%) had diabetes mellitus (n=5) or impaired glucose tolerance (n=5). Body mass index (BMI) was less than 30 kg/m2in67.6%of patients, while in the remaining32.4%it was more than 30 kg/m2. Serum adiponectin, leptin, TNF-α, and ghrelin were determined. Serum leptin (15.49±4.84vs10.31±2.53) and TNF-α(12.1±2.7vs10.31±2.56) levels were significantly higher in the NASH group compared to in the control group (P<.001for each). Nevertheless, adiponectin (11.1±2.1vs17.3±2.8) and ghrelin (6.46±1.1vs7.8±1.1) levels were lower in the NASH group than in the control group (P<.001for each). Serum levels of the adipokines and ghrelin, however, were comparable in the subgroups of patients regardless of whether BMI was<30or>30or glucose tolerance was impaired or not (P>.05). Additionally, neither adipokines nor ghrelin was correlated with histopathological grade and stage (P>.05). In conclusion; there is a significant relationship between NASH and adipokines and ghrelin independent from BMI and status of the glucose metabolism. These cytokines that appear to have role in the pathogenesis of NASH, however, do not have any effect upon the severity of the histopathology.

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