Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV-specific T cells, which is regulated by various co-suppressor molecules. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is among these co-suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV-specific T cells. CTLA-4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA-4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA-4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA-4 may contribute to HBV infection, as well as the development of HBV-induced cirrhosis and hepatocellular carcinoma.

This case report explores the intricate diagnostic challenges encountered in a 30-year-old male patient with abdominal pain, jaundice, and a history of acetaminophen use. Initially presenting as a potential case of drug-induced hepatitis due to acetaminophen overdose, the diagnosis took an unexpected turn when the patient tested positive for hepatitis B surface antigen. The case highlights the complexity of diagnosing acute hepatitis, considering multiple potential etiologies, including viral and drug-induced factors. Differential diagnoses for this case involve considering drug-induced hepatitis, autoimmune hepatitis, various viral hepatitis types, and the potential contribution of cocaine-induced hepatitis as individual possibilities or in combination. This case emphasizes the need for a comprehensive evaluation, the consideration of multiple potential causes, and the importance of ongoing monitoring and follow-up to ensure optimal patient care in cases of acute hepatitis.

OBJECTIVE: The aim of the current study was to obtain comprehensive genomic information on viral hepatitis B (HBV)-related hepatocellular carcinoma (HCC) and identify potential biomarkers of early recurrence in patients receiving curative surgery.
METHODS: A total of 104 patients with HBV-related HCC receiving curative surgery at Kaohsiung Chang Gung Memorial Hospital between January 2017 and December 2020 were identified, including 52 patients each with and without recurrence. Next-generation sequencing was performed to investigate genomic alterations caused by surgical resection of specimens. The Kaplan-Meier method was used to estimate disease-free survival and overall survival.
RESULTS: The landscape of gene mutations in HCC patients of our cohort showed a median number of single nucleotide variants of 250, a median number of insertions and deletions of 22, and a median number of protein-coding mutations of 185. The 10 most frequently mutated genes were TP53 (43%), TTN (39%), MUC16 (28%), PCLO (25%), OBSCN (22%), ADGRV1 (19%), ALB (18%), SYNE1 (18%), DNAH17 (17%), and RYR1 (17%). The tumour mutation burden was 4.8 mutations per megabase, and high microsatellite instability was reported in only three patients. In addition, the mutational signatures showed that aristolochic acid exposure was highly implicated in our HCC cohort. Five mutant genes, TBC1D4, ITGA4, RPS6KA3, VWA8, and FMN2, were more frequent in the recurrence group than that in the non-recurrence group.
CONCLUSIONS: Our results present an in-depth genomic analysis of HBV-related HCC. The study findings provide an improved understanding of the related molecular mechanisms and identify potential biomarkers associated with early tumour recurrence after curative resection.

UNASSIGNED: Diffuse large B-cell lymphoma (DLBCL) involving the breast, spleen, and bone in a male patient with hepatitis B virus (HBV) infection is extremely rare in clinical practice.
UNASSIGNED: We report a case of DLBCL involving the breast, spleen, and bone (triple expression of Bcl-2+, Bcl-6+, and 70% positive C-mcy) in a male patient with HBV admitted to our hospital. The patient was treated with EPOCH×4, lenalidomide+EPOCH×2 chemotherapy, intermittent methotrexate intrathecal injections to prevent central invasion, and autologous stem cell transplantation (ASCT). The patient is currently in complete remission, and the follow-up time was 43 months.
UNASSIGNED: A patient with DLBCL involving the breast, spleen, and bone can be treated with a combination of multiple regimens. If the patient\'s economic conditions permit it, ASCT can be considered.

UNASSIGNED: To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with nonalcoholic fatty liver disease (NAFLD) versus other risk factors.
UNASSIGNED: Different clinical and tumor characteristics are associated with HCC in the setting of NAFLD in comparison to other risk factors. It is still unclear whether these differences impact patient survival after radical hepatectomies.
UNASSIGNED: Randomized controlled trials and observational studies published in the English literature between July 1980 and June 2020 were searched using multiple databases. Patients\' baseline characteristics and the hazard ratios (HRs) of the OS and DFS were extracted and meta-analyses were performed.
UNASSIGNED: Fifteen retrospective cohort studies with a total of 7226 patients were included. Among them, 1412 patients (19.5%) had NAFLD and 5814 (80.4%) had other risk factors (eg, viral hepatitis B or C, alcoholic cirrhosis, or cryptogenic cirrhosis). Summary statistics showed that patients with NAFLD had better DFS (HR = 0.81; 95% CI: 0.70-0.94; P = 0.006) and OS (HR = 0.78; 95% CI: 0.67-0.90; P = 0.001) than the control group. Subgroups analyses also indicated that the OS favored NAFLD patients versus patients with viral hepatitis B or C (HR = 0.80; 95% CI: 0.67-0.96; P = 0.017) or alcoholic and cryptogenic cirrhosis (HR = 0.68; 95% CI: 0.47-1.0; P = 0.05).
UNASSIGNED: After hepatic resections for HCC, NAFLD patients have better DFS and OS than patients with other risk factors. Subgroup analysis and meta-regression suggested that the survival advantage of NAFLD patients was more pronounced in studies published after 2015 and from Asian centers.

BACKGROUND: Islamic culture does not tolerate homosexuality and extramarital sex. This may result in ignorance of safe sex practices and a lack of proper public health education by the authorities and parents; this includes knowledge and awareness about sexually transmitted diseases (STDs), modes of transmission, protection methods, and sources of information about STDs.
METHODS: This is a cross-sectional study, a Quick Response (QR)-code-based survey. A standard web-based questionnaire was electronically delivered to our enlisted sample. The statistical analysis started by transferring data from the Excel spreadsheet (Microsoft Corporation, Redmond, Washington, United States) to the SPSS software program. We used one-way ANOVA to compare mean scores between the various groups. And we used the Pearson correlation coefficient to assess the association of age with the score. Significance was established at a p-value of 0.05 or less with a 95% confidence interval. All statistical calculations were performed using IBM SPSS Statistics for Windows, Version 27.0 (Released 2020; IBM Corp., Armonk, New York, United States).
RESULTS: The study analysed the sociodemographic characteristics and STD knowledge of 608 participants. Findings revealed a balanced gender distribution, 52.8% male and 47.2% female, the majority being single (72.0%) and with a university education (72.0%). Knowledge gaps were identified, such as confusion between genital herpes and HIV, limited understanding of chlamydia transmission, and misconceptions about human papillomavirus (HPV) and HIV. No significant differences were found based on sex, age, marital status, or father\'s education. However, higher education of mother correlated with significantly higher knowledge scores (p < 0.0001).
CONCLUSIONS: This study shed light on the limited knowledge and misconceptions surrounding STDs in Taif city. The findings highlighted knowledge gaps, including confusion between different STDs and misconceptions about transmission modes. The results revealed a positive correlation between higher maternal education and increased knowledge scores. These findings underscore the urgency for health authorities to develop awareness campaigns and educational initiatives to promote accurate information and foster healthier attitudes toward sexual activity in these regions.

Despite implementing hepatitis B immunoglobulin (HBIG) and vaccination, data suggest it would not be sufficient to reach the elimination targets. Tenofovir disoproxil fumarate (TDF) has been added to the Thai national standards of care for prevention of transmission of the hepatitis B virus during birth. To optimise national strategies in Thailand, we assessed TDF\'s effectiveness for prevention of mother-to-child transmission and conducted cost-effectiveness analyses of different TDF-based strategies.
We retrospectively reviewed medical records of mother and infant pairs whose mothers were positive for hepatitis B e-antigen (HBeAg) and received TDF to prevent maternal transmission of viral hepatitis B during 2018-2020. Based on the available data on transmission rate, we also applied a decision tree to estimate the cost-effectiveness of different TDF-based strategies to eligible mothers. These included: (1) HBIG for all hepatitis B virus (HBV) exposed infants; (2) HBIG for only infants of HBeAg-positive mothers (\'HBIG for e-positive\') and (3) without HBIG to infants (\'HBIG-free\'). The incremental cost-effectiveness ratio between the different strategies and baseline intervention without TDF was calculated. The one-way sensitivity analysis was used to adjust prevalence of HBeAg-positive mothers, cost of HBIG, cost of TDF and transmission rate.
Of 223 infants enrolled, 212 (95.0%) received HBIG, while 11 (5.0%) did not. None of the infants had chronic HBV infection. The most cost-saving intervention was \'HBIG-free\' followed by \'HBIG for e-positive\'. The one-way sensitivity demonstrated that the results were reasonably robust to changes. The cost-saving was greater with a higher hepatitis B virus surface antigen (HBsAg) prevalence. The HBIG-free strategy remained best at 0%-1.4% transmission rates, meeting the additional target for eliminations.
The study is the first cost-effectiveness analyses to provide evidence supporting an HBIG-free strategy in an antiviral era. This approach should be considered to prevent mother-to-child transmission in resource-constrained settings, particularly in countries with a high HBsAg prevalence.

The aim of the work is to assess the prevalence of hepatitis B virus drug resistance mutations and immune escape mutations in pregnant women in the Republic of Guinea.
Blood plasma samples obtained from 480 pregnant women from different regions of the Republic of Guinea with laboratory-confirmed viral hepatitis B were studied. Nucleotide sequences for genotype identification and mutation detection were obtained using nested-PCR followed by Sanger sequencing, based on overlapping pairs of primers spanning the complete genome of the virus.
In the examined group, the viral genotype E was the most prevalent (92.92%) compared with subgenotypes A1 (1.67%), A3 (1.46%), D1 (0.63%), D2 (1.04%) and D3 (2.29%). Among the examined HBV-infected pregnant women, 188 (39.17%) had undetectable HBsAg. Drug resistance mutations were detected in 33 individuals, which amounted to 6.88%. The following mutations were found: S78T (27.27%), L80I (24.24%), S202I (15.15%), M204I/V (42.42%). The presence of polymorphic variants not described as drug resistant has also been shown in positions associated with the development of drug resistance to tenofovir, lamivudine, telbivudine and entecavir (L80F, S202I, M204R). When analyzing the MHR and the region of a determinant, mutations were detected in 318 (66.25%) of pregnant women. In 172 of them, which amounted to 54.09%, multiple mutations were found. The amino acid substitutions in 13 positions associated with HBsAg-negative hepatitis B and/or potentially affecting HBsAg antigenicity were identified.
The high prevalence of immune escape and drug resistance mutations potentially associated with false-negative result of HBsAg screening, prophylaxis failure, and virological failure of therapy that has been identified among treatment naive pregnant women imposes a serious problem.
Введение. Несмотря на все усилия по ограничению передачи вируса гепатита В (ВГВ) от матери ребёнку, понимание течения хронического гепатита В (ХГВ) у беременных женщин всё ещё ограниченно. Одним из регионов с крайне высокой распространённостью ХГВ является Африка: здесь суммарное количество больных составляет приблизительно 75 млн человек. Кроме того, серьёзным фактором, способным повлиять как на лечение, так и на вакцинную профилактику, могут являться мутации вируса. Таким образом, изучение генетической гетерогенности ВГВ является значимым. Цель работы оценить распространённость мутаций лекарственной устойчивости и мутаций ускользания от иммунного ответа ВГВ у беременных женщин в Гвинейской Республике. Материалы и методы. Исследованы образцы плазмы крови, полученные от 480 беременных женщин из разных регионов Гвинейской Республики с лабораторно подтверждённым ВГВ. Нуклеотидные последовательности для определения генотипов и выявления мутаций получали с использованием nested-ПЦР с последующим секвенированием по Сэнгеру на базе перекрывающихся пар праймеров, совместно фланкирующих полный геном вируса. Результаты и обсуждение. В обследованной группе чаще всего обнаруживали вирус генотипа Е (92,92%) по сравнению с субгенотипами А1 (1,67%), А3 (1,46%), D1 (0,63%), D2 (1,04%) и D3 (2,29%). Среди обследованных ВГВ-инфицированных беременных было выявлено 188 человек (39,17%) с неопределяемым HBsAg. Мутации лекарственной устойчивости вируса были выявлены у 33 человек, что составило 6,88%. Обнаружены следующие мутации: S78T (27,27%), L80I (24,24%), S202I (15,15%), M204I/V (42,42%). Показано также наличие полиморфных вариантов, не описанных как фармакорезистентные, в положениях, связанных с развитием лекарственной устойчивости к тенофовиру, ламивудину, телбивудину и энтекавиру (L80F, S202I, M204R). При анализе MHR и региона детерминанты мутации выявлены у 318 (66,25%) беременных. Из них у 172 человек, что составило 54,09%, обнаружены множественные мутации. Определено наличие замен в 13 позициях, ассоциированных с HBsAg-негативным ХГВ и (или) потенциально влияющих на антигенность HBsAg. Заключение. Выявленная среди терапевтически наивных беременных женщин широкая распространённость мутаций иммунного бегства и лекарственной устойчивости, способных приводить к ложноотрицательным результатам скрининга на HBsAg, безуспешной профилактике и вирусологической неэффективности терапии ВГВ-инфекции, представляет собой серьёзную проблему.

The aim is to explore the clinical effects of combined treatment of Traditional Chinese Medicine (TCM) and western medicine in viral hepatitis B cirrhosis and the effects on microRNA (miR)-122 and miR-200a. 116 patients with chronic hepatitis B cirrhosis were admitted to our hospital. Real-time fluorescent quantitative PCR (qPCR) was employed to reveal the level of serum miR-122 and miR-200a in the three groups. The clinical effects of the two groups were compared, including alanine aminotransferase (ALT), aspartate amino transferase (AST), total bilirubin (TBIL) and alpha fetoprotein (AFP) indexes, coagulation function indexes, liver elasticity value and the main therapeutic effects. After treatment, the ALT, AST, TBIL and AFP indexes significantly decreased in both groups, which were much lower in the western medicine (WM) + TCM Group. The levels of albumin (ALB) all increased, and the increase was more significant in the WM + TCM Group. The prothrombin time (PT) was down-regulated while the prothrombin activity (PTA) was up-regulated in both groups. Both groups showed a decrease in liver elasticity after treatment, which was more obvious in the WM + TCM Group. The incidence of primary peritonitis, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding and electrolyte disturbance in the WM + TCM Group was significantly lower than those in the WM Group. The combination of Chinese and western medicine in the treatment of cirrhosis can reduce the occurrence of complications, improve the clinical symptoms and improve the clinical effects effectively, which is worthy of further study and clinical popularization. Viral hepatitis B, Liver cirrhosis, Combination of TCM and Western medicine, miR-122, miR-200a.

Acute liver injury in the setting of acute fulminant hepatitis caused by the hepatitis B virus (HBV) can occur both during primary infection and after chronic HBV reactivation. Guidelines recommend considering antiviral therapy in both cases. Antiviral therapy with a nucleoside analog may be beneficial in patients with acute liver failure from acute HBV infection, though not all studies have shown a benefit. This is a case of a 53-year-old woman with a past medical history of untreated hepatitis C with undetectable viral load and right breast cancer status post lumpectomy, who presented to the emergency department with complaints of yellowish skin and sclera discoloration with right upper quadrant pain for one week. She was a known intravenous drug abuser and binge alcohol user. Her labs were positive for hepatitis B, hepatitis E, and hepatitis C viruses. She also had elevated liver enzymes with hyperbilirubinemia showing severe acute liver injury. Computed tomography of the abdomen and pelvis with contrast was normal, and the abdominal ultrasound showed homogenous echotexture of the liver without a focal lesion. The patient was diagnosed with acute fulminant hepatitis B. After initial hemodynamic stabilization, N-acetylcysteine (NAC) and tenofovir were started, and transaminases were followed. Liver function tests showed a downtrend, and, in a few weeks, they came to baseline. Hepatitis B viral load became undetectable as well. Acute hepatitis B infection is seldom treated. The presented case depicts the use of tenofovir in the setting of severe acute liver injury due to hepatitis B. Starting antiviral therapy (especially tenofovir disoproxil fumarate) early in the disease course was shown to have very assuring results with complete resolution of symptoms and normalization of liver function tests. The treatment protocol for acute HBV deserves further investigation.