Irsan Hasan

Diagnostic value of a group of biochemical markers of liver fibrosis in patients with non-alcoholic steatohepatitis

OBJECTIVE: The objectives of this study were to investigate the use of non‐invasive biochemical markers to evaluate the severity of liver fibrosis in patients with non‐alcoholic steatohepatitis (NASH).

Combination of alpha-1-acid glycoprotein and alpha-fetoprotein as an improved diagnostic tool for hepatocellular carcinoma.

BACKGROUND To evaluate the diagnostic value of alpha-1-acid glycoprotein (AAG) and the combination with alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) patients. METHODS AAG was measured in serum of 65 HCC patients and 54 chronic liver diseases (CLD) patients by using proteomic approach. Sensitivity and specificity of AAG and its combination with AFP were determined and compared with AFP alone for the diagnosis of HCC. RESULTS The expression concentration of AAG was significantly higher in HCC patients than chronic liver disease with sensitivity (77%) and accuracy (83%). Receiver operating characteristic analysis yielded the following AUC: AFP 0.750 (CI 95% 0.663-0.837), AAG 0.907 (CI 95% 0.855-0.960) and AFP+AAG 0.943 (CI 95% 0.897-0.988). At a specificity of 90%, the combination of AFP+AAG had sensitivity 89% and accuracy 90%, which was higher than sensitivity (52.3%) and accuracy (70%) when using AFP alone. CONCLUSION The combination of AAG and AFP shows high sensitivity and improves the accuracy of HCC diagnosis.

Genotype diversity of hepatitis C virus (HCV) in HCV-associated liver disease patients in Indonesia

Background: Hepatitis C virus (HCV) genotype distribution in Indonesia has been reported. However, the identification of HCV genotype was based on 5′‐UTR or NS5B sequence.

Hepatitis C virus genotype in blood donors and associated liver disease in Indonesia.

Objective: The aim of this study was to investigate the distribution of hepatitis C virus (HCV) genotype and the possible association between genotype and HCV-associated liver disease in Indonesia. Methods: 32 anti-HCV-positive asymptomatic carriers (AC), 55 chronic hepatitis (CH), 41 liver cirrhosis (LC), and 35 hepatocellular carcinoma (HCC) patients were included in this study. HCV genotyping was performed by phylogenetic analysis of the NS5B and 5′-UTR regions. Results: The HCV subtype 1b (36.5%), based on NS5B region, was the most prevalent, followed by subtypes 3k (15.4%), 2a (14.4%), 1a (12.5%) and 1c (12.5%), and 2e (4.8%). Subtypes 2f, 3a, 3b, and 4a were also found in some of the samples. HCV subtypes 3k (40.0%) and 1a (35.0%) were the two major subtypes in AC. HCV subtype 1b was not found in AC, but it was common in CH (31.3%), LC (50.0%), and HCC (57.1%). Conclusion: HCV subtype 1b was prevalent in samples of HCV-associated liver disease patients, including CH, LC and HCC. The percentage of subtype 1b was increased with the disease severity (AC < CH < LC < HCC).

Alpha-1-acid glycoprotein as potential biomarker for alpha-fetoprotein-low hepatocellular carcinoma

BackgroundThe outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. We determined the performances of α -1-acid glycoprotein (AAG) and des-γ-carboxy prothrombin (DCP) for the diagnosis of HCC, especially for α-fetoprotein (AFP)-low HCC.MethodsOf the 220 patients included in this retrospective study, 124 had HCC, and 61 (49%) of these were AFP-low HCC (AFP ≤ 20 ng/mL). The remaining 96 patients, including 49 with chronic hepatitis B or C and 47 with cirrhosis, were considered as control. Plasma AAG was analyzed using high performance liquid chromatography (HPLC) and confirmed using Western blot technique.ResultsWhen all patients with HCC were evaluated, the area under receiver operating characteristic (ROC) curves for AAG (0.94, 95% CI: 0.91-0.97) and DCP (0.92, 95% CI: 0.88-0.95) were similar (P = 0.40). AAG had better area under ROC curve (0.96, 95% CI: 0.94-0.99) than DCP (0.87, 95% CI: 0.81-0.93) for AFP-low HCC (P < 0.05). At the specificity 95%, the sensitivity of AAG was higher in AFP-low HCC than in AFP-high HCC (82% and 62%, respectively). In contrast, higher sensitivity was obtained from DCP in discriminating HCC patients with low AFP than that in high AFP (57% and 90%, respectively).ConclusionOur cross-sectional study showed that AAG was better performance in diagnosing HCC patients with low AFP, while DCP did better in those with high AFP.

Significant hepatic histopathology in chronic hepatitis B patients with serum ALT less than twice ULN and high HBV-DNA levels in Indonesia

OBJECTIVE:  To study the prevalence of significant hepatic histopathology in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) ≤ twice upper limit of normal (ULN) and its association with age, HBeAg status, hepatitis B virus (HBV)‐DNA level and viral genotype.

Clinical significance of hepatitis B virion and SVP productivity: relationships between intrahepatic and serum markers in chronic hepatitis B patients

Background Clinical use of hepatitis B viral (HBV) quantitative seromarker\s remains questionable since it is not precisely known whether they represent intrahepatic viral replication. Covalently closed circular DNA (cccDNA), relaxed circular DNA (rcDNA), and pregenomic RNA (pgRNA) are more likely to represent active HBV replication and their measurement can be used to derive virion productivity (VP; rcDNA/cccDNA), subviral particle (SVP) productivity (quantitative HBsAg/cccDNA), and replicative activity (RA; pgRNA/cccDNA). These can be used to compare relative HBV replication between HBeAg-negative and -positive patients. Objective To study the clinical significance of intrahepatic HBV replication phenomenon between HBeAg-negative and -positive patients and its correlation with quantitative HBV seromarkers. Method This was a prospective study between January 2010 and December 2011. Study subjects were naive chronic hepatitis B patients from Cipto Mangunkusumo and Medistra Hospitals. All patient samples underwent liver biochemistry and HBV seromarkers testing (HBeAg, quantitative HBsAg and HBV DNA levels), and patients underwent liver biopsy. Stored liver specimens were analysed for intrahepatic rcDNA, cccDNA, and pgRNA with quantification performed by real-time PCR. Comparison of HBV markers between HBsAg-positive and -negative patients was carried out using the Mann–Whitney U-test. Pearson’s correlation test was performed among HBV intrahepatic and seromarkers using their log-transformed values. Results A total of 104 patients were enrolled in this study; 54 (51.9%) were male. Patients’ mean age was 41.9 ± 11.63 years (range 19–70 years). Sixty-one patients (58.7%) were HBeAg-negative. All HBV markers were significantly higher in HBeAg-positive than HBeAg-negative patients, except for SVP productivity and RA. Serum HBV DNA was strongly correlated with intrahepatic total HBV DNA (r = 0.771), cccDNA (r = 0.774), and rcDNA (r = 0.780) while serum quantitative HBsAg showed only moderate correlation with intrahepatic total DNA (r = 0.671), cccDNA (r = 0.632), rcDNA (r = 0.675), and SVP productivity (r = 0.557). Conclusions Serum HBV DNA concentration and quantitative HBsAg might not accurately predict intrahepatic viral activity. Virion and SVP production do not occur in parallel with replicative activity.

Effect of L-ornithine-L-aspartate Therapy on Low-Grade Hepatic Encephalopathy in Patients with Liver Cirrhosis

Background: Minimal hepatic encephalopathy (MHE) is an abnormal condition of psychometric testing before hepatic encephalopathy (HE) condition reducing quality of life and survival rate. Impractical instrument, the psychometric hepatic encephalopathy score (PHES), has been recommended in diagnosing MHE. The new critical flicker frequency (CFF) has good precision and accuracy for diagnosing MHE. Oral L-ornithine-L-aspartate (LOLA) may increase ammonia detoxification. The aim of this study was to recognize the effect of oral LOLA on low-grade HE by investigating the mean value of CFF. Method: We included 31 patients with liver cirrhosis and low-grade HE (MHE, HE grade 1 and 2) at the outpatient clinic of hepatology, Cipto Mangunkusumo hospital between November 2009 and March 2010. It was a double-blind, randomized, placebo-controlled clinical trial. Oral LOLA was administered in a dose of 18 g/day, 3 times daily for 14 consecutive days. At the end of the study, there were 27 cirrhotic patients with CFF value < 38 Hz; 14 patients had received LOLA and 13 patients had placebo. Statistic analysis was performed by using the Mann-Whitney U test. Results: The mean value of CFF in LOLA group after treatment (39.3 Hz) was significantly different than the placebo group (36.04 Hz); (p = 0.027). Ammonia level decreased in LOLA group from 118.7 into 109.1 µ mol/L. In placebo group, it increased from 106.9 into 147.5 µ mol/L with p = 0.275 (before); p = 0.052 (after). Conclusion: Oral LOLA may improve the value of CFF and is likely to decrease blood ammonia level in patients with low-grade HE. Keywords: low-grade hepatic encephalopathy, oral LOLA, CFF improvement, ammonia detoxification

Correlation between Branched Chain Amino Acids to Tyrosine Ratio and Child Pugh Score in Liver Cirrhosis Patients

Background : The determination of branched chain amino acids (BCAA) to tyrosine ratio (BTR) was available in making differentiation of chronic hepatitis from liver cirrhosis, because there was a strong association between BTR and staging (fibrosis) scores. Branched chain amino acids to tyrosine ratio have a correlation with Fischer ratio and the examination is easier because it can be done by enzymatic assay. Materials and Methods: To evaluate the correlation between BTR and Child-Pugh score, we examined the amino gram of 52 liver cirrhosis patients consisted of 26 Child-Pugh A, 19 Child-Pugh B, and 7 Child-Pugh C. The examination of amino gram was done by High Pressure Liquid Chromatograph (HPLC) analyzer. Branched chain amino acids to tyrosine ratio were compared to Child-Pugh score, albumin, ammonia level, number connection test to Fischer ratio. Results : Significant differences in BTR among Child-Pugh A, B, C were observed (Child-Pugh A 7.75 + 1.2; Child Pugh B 6.0 + 1.23 and Child Pugh C 4.38 + 3.14 (p = 0.000)). Branched chain amino acids to tyrosine ratio had a weak correlation with albumin (r = 0.292; p = 0.036), ammonia level (r = 0.376; p = 0.006) and strong correlation with Fischer ratio (r = 0.818; p = 0.000). There was no significant correlation between BTR and number connection test. Conclusion : These results showed that the determination of the molar ratio of branched chain amino acids to tyrosine well reflected the severity of liver cirrhosis and it can be used as a substitute of Fischer ratio. Keywords : Branched chain amino acids, tyrosine, liver cirrhosis

Perubahan Status Fungsi Hati, Status Nutrisi, Kadar 3-β-Hidroksi Butiran Darah, dan Keseimbangan Nitrogen pada Pasien Sirosis Hari yang Menjalankan Puasa Ramadhan

Pendahuluan. Prevalensi sirosis cukup tinggi di Indonesia yang mayoritas populasinya adalah muslim. Pada saat menjalani puasa Ramadhan yang merupakan kewajiban umat muslim terjadi berbagai proses metabolik seperti penurunan glikokogenesis, peningkatan glukoneogenesis dan ketogenesis, dapat mempengaruhi keadaan klinis, nutrisi dan bokimiawi pasien sirosis hati yang juga mengalami proses hiperkatabolik. Penelitian tentang pengaruh puasa Ramadhan pada pasien sirosis hati di Indonesia belum pernah dilakukan. Berdasarkan kenyataan diatas perlu diteliti bagaimana perubahan terhadap status nutrisi, status fungsi hati, pembentukan badan keton dan keseimbangan nitrogen pada pasien sirosis hati yang menjalankan puasa Ramadhan. Metode. Penelitian ini merupakan studi pre dan post , yang menilai perubahan pada pasien sirosis hati yang berpuasa Ramadhan: saat Ramadhan dan pasca Ramadhan. Pada subjek penelitian dilakukan pengambilan data-data dasar, anamnesis dasar. Pada minggu ke 4 saat puasa Ramadhan dilakukan pengukuran antropometrik, yaitu timbang berat badan, indeks massa tubuh (IMT), ketebalan triceps skinfold (TSF) , dan mid-upper arm circumference (MUAC) . Pada subjek juga dilakukan pengambilan darah vena untuk pemeriksaan laboratorium dan pengukuran ekskresi nitrogen urin yang ditampung dalam 24 jam. Pada minggu ke empat pasca Ramadhan subyek dievaluasi kembali dengan prosedur yang sama seperti saat Ramadhan. Hasil. Rerata (SD) indeks massa tubuh saat puasa Ramadhan adalah 25,112 (4,05) kg/m2 dan pasca Ramadhan 25,25 (4,01) kg/m2 ( p = 0,438). Didapatkan rerata (SD) midarm muscle circumference (MAMC) saat Ramadhan 25,77 (3,077) cm dan rerata (SD) pasca Ramadhan 25,96 (3,42) cm ( p =0,228). Tidak ada perbedaan bermakna secara statistik antara kadar 3-β-hidroksi butiran darah saat puasa Ramadhan dan 4 minggu pasca Ramadhan. Rerata (SD) saat puasa Ramadhan 2,44 (2,93) gram/24 jam, sedangkan rerata (SD) keseimbangan nitrogen pasca Ramadhan 0,51 (3,16) gram/24 jam ( p =0,037). Simpulan. Tidak ada perubahan status fungsi hati yang dinilai dengan Skor Child Pugh saat puasa Ramadhan dan pasca Ramadhan. Indeks massa tubuh dan ketebalan TSF membaik pasca Ramadhan. Tidak ada perbedaan kadar 3-β-hidroksi butirat darah saat puasa Ramadhan dan pasca Ramadhan. Terdapat keseimbangan nitrogen yang lebih positif saat puasa Ramadhan dibandingkan pasca Ramadhan.