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Abstrak :
ABSTRACT
The effects of dietary food fortified with orotic acid (1.0%) on liver function were studied in rats. The rats fed with orotic acid promoted liver triglyceride content markedly, that was 5-fold higher than that of the control. The liver malondialdehyde (MDA) content increased by 10%, but the gluthation peroxidase (GSH-Px) activity decreased by 50%. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities increased by 25% and 30%, respectively. Therefore, the decreased GSH-Px activity was associated with the promotions of AST, ALT, and the liver MDA levels. In conclusion: dietary orotic acid promotes lipid peroxidation but reduces the rate of the antioxidant enzyme. Therefore, dietary food fortified with orotic acid attenuates the liver function.

Abstrak :
Latar Belakang Perlemakan hepatitis non-alkoholik (NASH) merupakan bagian dari spektrum penyakit perlemakan hati non-alkoholik (NAFLD) yang dimulai dari perlemakan hati murni dan bisa berlanjut menjadi sirosis hati. Hipotesis terjadinya NASH hingga saat ini adalah teori Two Hit. Dikatakan bahwa sindrom resistensi insulin (obesitas, DM tipe II, dan dislipidemi) memegang peranan penting dalam terjadinya NASH. Sampai saat ini studi tentang resistensi insulin pada NASH belum pernali dilaporkan di Indonesia. Tujuan Penelitian Mendapatkan gambaran klinik dan besar kejadian resistensi insulin pada penderita NASH. Desain Penelitian Studi ini merupakan studi abscrvasional yang bersifat deskriptif-analitik dengan desain potong lintang perbandingan. Pasien dan Metode Didapatkan 30 pasien yang berobat ke poliklinik hepatologi di beberapa Rumah Sakit di Jakarta dengan perlemakan hati (dari hasil USG) yang bersedia menjalani pemeriksaan antropometrik, dan pemeriksaan darah perifer untuk kadar gula puasa, preftl lipid, fungsi hati dan insulin puasa. Penderita dengan riwayat minuet alkohol, narkoba, serologi virus hepatitis positif, dan ANA posilifdieksklusi. Gambaran NASH diperiksa oleh tiga ahli patologi anatomi (menurut criteria Brunt). Untuk analisa resistensi insulin (dengan reagen insulin ultrasensitif) diperiksa pada 30 penderita NASH yang dibandingkan dengan 30 kontrol normal dengan metode ELISA. Untuk analisa statistik digunakan program SPSS untuk Window versi 12 dengan uji statistik nonparametrik (Mann-Whitney). Hasil Dari 30 penderita NASH, hipertensi ditemukan pada 8 (26,7%) subyek, dispepsia pada 14 (46,7%) subyek, berat badan berlebih pada 6 (20%) subyek, obesitas pada 19 (63,3%) subyek, gangguan fungsi hati pada 20 (67%) subyek, hipertrigliseridemi pada 19 (63,3%) subyek, DM tipe II pada 5 (16,7%) subyek, dan sindroma metabolik pada 9 (30%) subyek. HOMA-IR didapatkan lebih tinggi pada kelompok subyek dengan NASH bila dibandingkan kontrol normal (p = 0,001). Resistensi insulin ditemukan pada 16 (53,3%) dari 30 penderita NASH (dengan batas HOMA-IR < 3,02). Simpulan Kebanyakan penderita NASH memiliki minimal satu dari komponen metabolik. Resistensi insulin mungkin mempunyai peran pada penderita NASH. Dibutuhkan sampel lebih banyak dan penelitian lebih lanjut mengenai resistensi insulin di hati.

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Backgrounds Non-Alcoholic Steatohepatitis (NASH) is a spectrum of Non-Alcoholic Fatty Liver Disease (NAFLD) which is starting from pure fatty liver (steatosis) to hepatic cirrhosis. Most of studies about prevalence of NASH come from Western countries. The recent hypothesis of NASD which is accepted until now is the Two Hit Theory. It was noted that insulin resistance syndrome (obesity, diabetes, dyslipidemia) has an important sole in NAFLD especially in progression to become NASH. In Indonesia, study about insulin resistance in NASH has not been reported. Aims of the study To know the clinical pictures and the prevalence of insulin resistance in subjects with NASH. Study Design This study was a descriptive-analytic with a comparative cross-sectional design. Patients and Methods There were 30 outpatients who come to liver clinic in several hospitals in Jakarta, with a diagnosis of fatty liver (ultrasound examination) underwent examination of anthropometric measurement, and blood tests for fasting glucose, lipid profile, liver function and fasting insulin level. Subjects with a history of alcohol intake, drug abuser, HBsAg positive, anti I-ICV positive and ANA positive were excluded. A liver biopsy proven NASH was confirmed from every subject (according to Brunt criteria), which has been examined by three experienced pathologists. The insulin resistance measured (with ELISA method) in 30 subjects with NASH by 1-IOMA-IR was compared with 30 normal controls. All analyses were performed with SPSS for Windows version 12 A significance level of 5% was used with non-parametric test (Mann-Whitney). Results From 30 subjects with NASH, hypertension was found in 8 (26.7%) subjects, dyspepsia was found in 14 (46.7%) subjects, overweight was found in 6 (20%) subjects, obesity was found in 19 (63.3%) subjects, abnormal liver function tests was found in 20 (67%) subjects, hypertrigliseridemia was found in 19 (63.3%) subjects, DM type II was found in 6 (16.7%) subjects, and metabolic syndrome was found in 9(30%) subjects. HOMA-IR was found higher in 30 subjects with NASH compared to 30 normal controls (p= 0.001). Insulin resistance was defined when HOMA-IR was more than 3.02. Insulin resistance was found in 16 (53.3%) from 30 subjects with NASH. Conclusions Most subjects with NASH have at least one component of the metabolic syndrome. Insulin resistance might have a role in subjects with NASH. A larger sample was needed to support this study. Further study about hepatic insulin resistance is needed.

Abstrak :
ABSTRAK Hiperkolesterolemia adalah kondisi gangguan metabolik yang sering dijumpai pada masyarakat dunia. Karena berkaitan erat dengan insidensi dislipidemia dan penyakit kardiovaskular, berbagai peneliti telah mencoba untuk menemukan terapi farmakologi terbaik untuk menurunkan kadar kolesterol. Diantara beberapa obat pilihan utama adalah asam fibrat. Saat ini dikembangkan pengobatan dengan tanaman tradisional, salah satunya adalah Acalypha indica. Tanaman ini terbukti untuk penyembuhkan pneumonia, artritis, dan infeksi. Polifenol dan flavonoid yang terdapat dalam Acalypha indica diduga berperan penting dalam efek antihiperkolesterolemia yang dimilikinya. Diharapkan juga kandungan pada tanaman ini dapat menurunkan efek samping penggunaan obat konvensional. Uji preklinis ini bertujuan untuk mengetahui efek antihiperkolesterolemia dari ekstrak etanol akar Acalypha indica pada perlemakan hati, dibandingkan dengan terapi asam fibrat. Dua puluh dari dua puluh lima tikus Sprague-Dawley diinduki diit tinggi kolesterol-fruktosa selama empat minggu hingga mencapai kondisi tinggi kolesterol. Sampel dibagi menjadi lima grup berdasasrkan intervensinya, yakni kontrol positif, kontrol negatif, terapi gemfibrozil, terapi ekstrak Acalypha indica, dan terapi kombinasi gemfibrozil dan ekstrak Acalypha indica. Tikus kemudian diterminasi pada akhir periode intervensi. Hati tikus diambil dan diproses dengan blok parafin dan pewarnaan hematoksilin-eosin. Jaringan hati dinilai dengan kriteria Clinical Research Network Scoring untuk Steatohepatitis non alkoholik (NASH). Ekstrak Acalypha indica menurunkan deposisi lemak secara signifikan (p = 0,014), sama baiknya dengan terapi gemfibrozil (p = 0,003) dan terapi kombinasi (p = 0,003). Ekstrak etanol akar Acalypha indica merupakan agen antihiperkolesterolemia yang cukup menjanjikan untuk mengurangi deposisi lipid dan kejadian steatohepatitis non alkoholik pada jaringan hati tikus.

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ABSTRACT Hypercholesterolemia is a common metabolic disorder found worldwide. As it is highly associated with dyslipidemia and cardiovascular disease incidence, researchers have been trying to find the best pharmacological therapy to lower cholesterol level. Among the first line choices drugs are fibrate. Acalypha indica, known as ?Akar Kucing? in Indonesian language, is a traditional plant used as medicine in most Asia countries. Previously, it has been proved to help to cure pneumonia, arthritis, and infection. Polyphenol and flavonoid found in Acalypha indica are considered to play an important role in its antihypercholesterolemia effect. It is also expected to have lower side effect than conventional drugs. This preclinical trial was aimed to investigate antihypercholesterolemia effect of Acalypha indicaroot extract on fatty liver tissue, compared to fibrate treatment. Sixteen from twenty Sprague-Dawley rats were induced with high cholesterol-fructose diet for four weeks to reach fatty liver state. Samples were divided into four groups based on its intervention. Each group was processed with a four-week therapy with Acalypha indicaroot extract, gemfibrozil, combination of Acalypha indicaroot extract and gemfibrozil, and without any therapy, respectively. Rats were terminated at the end of intervention period. Liver were taken and processed with paraffin block and hematoxylin-eosin stain. Liver tissues were assessed using Clinical Research Network Scoring for Non Alcoholic Steatohepatitis (NASH). Result: Acalypha indicaroot extract significantly reduced lipid deposition in fatty liver tissue (p = 0,014), as good as fibrate therapy using gemfibrozil (p = 0,003) and fibrate-Acalypha indica therapy (p = 0,003). Acalypha indica root extract is promising for use as antihypercholesterolemia agent to reduce lipid deposition and Non Alcoholic Steatohepatitis incidence in fatty liver tissue.

Abstrak :
Background: alcohol may have additional neurotoxic ill-effects in patients with alcohol related cirrhosis apart from hepatic encephalopathy. We aimed to evaluate minimal hepatic encephalopathy (MHE) with Psychometric Hepatic Encephalopathy (PHES) score and Critical Flicker Frequency (CFF) in alcohol (ALD) and non-alcoholic steatohepatitis related (NASH) related cirrhosis. Methods: 398 patients were screened between March 2016 and December 2018; of which 71 patients were included in ALD group and 69 in NASH group. All included patients underwent psychometric tests which included number connection test A and B (NCT-A and NCT-B), serial dot test (SDT), digit symbol test (DST), line tracing test (LTT) and CFF. MHE was diagnosed when their PHES was <-4. Results: the prevalence of MHE was significantly higher in ALD group compared to NASH (69.01% vs 40.58%; P=0.007). The performance of individual psychometric tests was significantly poorer in ALD (P<0.05). Overall sensitivity and specificity of CFF was 76.62% (95%CI 65.59 – 85.52) and 46.03% (95%CI 33.39 – 59.06) respectively. Mean CFF was significantly lower in ALD than NASH (37.07 (SD 2.37) vs 39.05 (SD 2.40), P=0.001); also in presence of MHE (36.95 (SD 2.04) vs 37.96 (SD 1.87), P=0.033) and absence of MHE (37.34 (SD 3.01) vs 39.79 (SD 2.46), P=0.001). Conclusion: MHE is significantly more common in patients with ALD cirrhosis than NASH counterparts. Overall CFF values are less in alcohol related cirrhosis than NASH related cirrhosis, even in presence or absence of MHE. We recommend additional caution in managing MHE in ALD cirrhosis.