Use of a Deep Learning Approach for the Sensitive Prediction of Hepatitis B Surface Antigen Levels in Inactive Carrier Patients

Deep learning is a subset of machine learning that can be employed to accurately predict biological transitions. Eliminating hepatitis B surface antigens (HBsAgs) is the final therapeutic endpoint for chronic hepatitis B. Reliable predictors of the disappearance or reduction in HBsAg levels have not been established. Accurate predictions are vital to successful treatment, and corresponding efforts are ongoing worldwide. Therefore, this study aimed to identify an optimal deep learning model to predict the changes in HBsAg levels in daily clinical practice for inactive carrier patients. We identified patients whose HBsAg levels were evaluated over 10 years. The results of routine liver biochemical function tests, including serum HBsAg levels for 1, 2, 5, and 10 years, and biometric information were obtained. Data of 90 patients were included for adaptive training. The predictive models were built based on algorithms set up by SONY Neural Network Console, and their accuracy was compared using statistical analysis. Multiple regression analysis revealed a mean absolute percentage error of 58%, and deep learning revealed a mean absolute percentage error of 15%; thus, deep learning is an accurate predictive discriminant tool. This study demonstrated the potential of deep learning algorithms to predict clinical outcomes.

The Analysis of Hepatitis B Virus Precore/core Mutations Arising in Different States of Infection

Background: In hepatitis B virus (HBV) infection, an association between Precore/Core variations and liver disease progression has been suggested. In this study, we aimed to determine the frequency of Precore/Core mutations in HBV-infected patients at various clinical stages. Methods: Totally, 73 HBV-infected patients including 26 inactive carriers, 20 chronic active and 27 patients with liver cirrhosis/hepatocellular carcinoma were randomly selected. The HBV DNA was extracted from the sera and subjected to nested PCR for amplification of pre-core/core region. The PCR product was then sequenced by Sanger method. Results: The stop codon of W/*28 was determined as the most prevalent mutation (55%) of pre-core region. The comparison of groups also demonstrated that core substitutions at residues of S21, E40 and I105 (<0.05) correlated with the development of inactive carrier state. Furthermore, the total substitutions in Th epitopes (117-131) were significantly higher in C/HCC group than IC and CA groups (P=0.001). Conclusion: Our results indicated a high frequency of W/*28 mutation in HBV studied patients. Moreover, variations including S21, E40 and I105 and R151 that were mapped onto cellular epitopes might be related to inactive state development.

A STUDY TO DETERMINE FOLLOW-UP STRATEGY FOR DIFFERENTIATING A TRUE INACTIVE CARRIERS FROM CHRONIC HEPATITIS PATIENTS WITH HBEAG NEGATIVE BY THE HBV DNA CUTOFF VALUE

Background & Objective: As compare to true inactive carrier a significantly different prognosis generally observed in Patients with HBeAg-negative chronic hepatitis B (CHB). To differentiate this two condition accurately there are no reliable strategy. To determine follow-up strategy for differentiating a true inactive carriers from chronic hepatitis patients with HBeAg negative by the HBV DNA cutoff value. Materials and Methods: We had enrolled potential inactive carriers who were consecutive untreated patients. This inactive carriers defined as HBV DNA < 2000 IU/mL, normal ALT levels, anti-HBe-positive and definitely HBeAg-negative. HBV DNA level to ≥ 2000 IU/mL was defined as the HBV reactivation. Patients whose HBV DNA levels remained at < 2000 IU/mL were classified as true inactive carriers and patients whose HBV DNA level to ≥ 2000 were classified as false inactive carriers during the first year. Results: Among 112 inactive carrier (age, 48.3 ± 13.1 years) who were initially selected, 75 were males. As identified, 23.2 ± 7.9 IU/L and 359 ± 478 IU/mL were serum ALT and HBV DNA levels, respectively. In 24 patients there were a significant drop in HBV reactivation during the first year. Between true and false inactive carriers there were a significantly different ALT and HBV DNA levels. In patients, whose baseline HBV DNA level was ≥ 200 IU/mL as compare to patients whose baseline HBV DNA level was < 200 IU/mL, HBV reactivation developed more often during a follow-up of 354 ± 175 days. Conclusion: From true inactive carriers to differentiate patients with HBeAg-negative CHB, HBV DNA level was useful tool. As per HBV DNA level of inactive carriers applied follow-up strategies need to vary.

Differential gene expression, irrespective of circulating Hepatitis B Surface Antigen levels, between Inactive Carrier and Nucleos(t)ide Analogue-Treated Hepatitis B Virus patients

Long-term viremia control in chronic HBV patients occurs either spontaneously in inactive carrier (IC) patients or therapy-induced by nucleos(t)ide analogues (NUC). To better understand the characteristics of viremia control, we evaluated gene expression in purified leukocyte subsets from IC versus NUC-treated patients, and evaluated the putative modulatory effects of hepatitis B surface antigen (HBsAg). We observed that gene expression in NUC-treated patients differed markedly from IC patients, especially in dendritic cells, monocytes, and CD8+ T cells, while serum HBsAg levels had little effect. Nevertheless, based on our findings it cannot be excluded that HBsAg may act locally in the infected liver or preferentially affects HBV-specific cells.

The Effect of Kerokan to Liver Function of Hepatitis B Patients

Kerokan is an alternative therapy done by rubbing and pressing the skin surface using oil and a blunt object. This treatment has a hepatoprotective effect as it increases heme oxygenase-1, an essential enzyme in heme catabolism. In hepatitis B, heme oxygenase-1 plays a vital role to fight oxidative stress. Hence the damage on liver cells can be reduced or even prevented. Damaged cells indicate by the production of aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) enzymes that accumulated in the bloodstream. This study aimed to investigate the effect of kerokan to liver function by analyzing SGOT and SGPT levels in hepatitis B patients. These were an experimental study with a pre-test post-test control group design conducted in the public health center in Palembang in October 2016. Statistical analysis used the unpaired t test and paired. The research subjects were 30 patients with inactive carrier and chronic hepatitis B. The levels of SGOT and SGPT were determined using the IFCC method. The levels of SGOT in control (19.53±3.44 U/L) and treatment group (20.46±4.53 U/L, Δ=0.93) after 24–48 hours were not statistically different (p=0.53). Also, the levels of SGPT in control (18.66±5.40 U/L) and treatment group (19.80±9.25 U/L, Δ=1.13) after 24–48 hours were also not statistically different (p=0.68) as well. In conclusion, the liver cells of inactive carrier and chronic hepatitis B patients were not damaged (necrosis) after kerokan therapy, and the levels of SGOT and SGPT were still in the normal range. EFEK KEROKAN TERHADAP FUNGSI HEPAR PASIEN HEPATITIS BKerokan merupakan terapi alternatif yang dilakukan dengan menggosok dan menekan permukaan kulit menggunakan minyak dan benda tumpul. Pengobatan ini bersifat hepatoprotektif, yaitu meningkatkan produksi enzim heme oxygenase-1 dalam katabolisme heme. Pada hepatitis B, heme oxygenase-1 berperan penting dalam menangkal radikal bebas sehingga dapat mengurangi atau mencegah kerusakan sel hepar. Kerusakan sel hepar diindikasikan oleh produksi enzim aspartate aminotransferase (AST/SGOT) dan alanine aminotransferase (ALT/SGPT) yang terakumulasi dalam pembuluh darah. Penelitian ini bertujuan mengetahui pengaruh kerokan pada fungsi hepar dengan menganalisis kadar SGOT dan SGPT pada pasien hepatitis B. Penelitian eksperimental ini menggunakan desain pre-test post-test control group yang dilakukan di puskesmas di Palembang pada Oktober 2016. Analisis statistik menggunakan uji t berpasangan dan tidak berpasangan. Subjek penelitian meliputi 30 pasien inactive carrier dan kronik hepatitis B. Kadar SGOT dan SGPT diukur dengan menggunakan metode IFCC. Kadar SGOT pada kontrol (19,53±3,44 U/L) dan grup perlakuan (20,46±4,53 U/L; Δ=0,93) setelah 24–48 jam tidak terdapat perbedaan signifikan (p=0,53). Selain itu, kadar SGPT pada kontrol (18,66±5,40 U/L) dan grup perlakuan (19,80±9,25 U/L; Δ=1,13) setelah 24–48 jam tidak menunjukkan perbedaan signifikan (p=0,68). Simpulan, sel hepar pada pasien inactive carrier dan kronik hepatitis B tidak mengalami kerusakan setelah terapi kerokan, serta kadar SGOT dan SGPT tetap dalam kondisi normal.

Prolonged and biphasic acute hepatitis A in hepatitis B virus carrier

Acute hepatitis A is generally a self-limited disease in healthy subjects within few weeks, but an uncommon type of prolonged and biphasic acute course of hepatitis A infection has been also described. This type of presentation is observed in about 6-10% of patients, but a small number of reports, concerning this topic, are available in literature. In addition hepatitis A virus (HAV) infection in hepatitis B virus (HBV) carriers has rarely been discussed. A 41-year-old Italian man, already known to our Department for HBV infection as an inactive carrier HBsAg(+)ve, experienced a prolonged and biphasic course of acute hepatitis A, lasting about 7 months. In this patient possible factors, causing the second flare of transaminases, were excluded (in particular autoimmunity). Liver biopsy as well HAV RNA search in blood/stools were not performed. In conclusion, the hepatologist should take into account this type of atypical course in patients with HAV-related hepatitis and should promote HAV vaccination in subjects with HBV-chronic hepatitis, to prevent possible life-threatening acute exacerbation of hepatic damage, mainly in HBV-carriers with more severe forms of liver diseases.