Feasibility, safety, efficacy and potential scaling-up of sofosbuvir-based HCV treatment in Central and West Africa: (TAC ANRS 12311 trial).

Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.

Deep mutational scanning of hepatitis B virus reveals a mechanism for cis-preferential reverse transcription.

Hepatitis B virus (HBV) is a small double-stranded DNA virus that chronically infects 296 million people. Over half of its compact genome encodes proteins in two overlapping reading frames, and during evolution, multiple selective pressures can act on shared nucleotides. This study combines an RNA-based HBV cell culture system with deep mutational scanning (DMS) to uncouple cis- and trans-acting sequence requirements in the HBV genome. The results support a leaky ribosome scanning model for polymerase translation, provide a fitness map of the HBV polymerase at single-nucleotide resolution, and identify conserved prolines adjacent to the HBV polymerase termination codon that stall ribosomes. Further experiments indicated that stalled ribosomes tether the nascent polymerase to its template RNA, ensuring cis-preferential RNA packaging and reverse transcription of the HBV genome.

Prevalence of hepatitis B and C viruses among migrant workers in Qatar.

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

Discovery and mechanistic study of Imperatorin that inhibits HBsAg expression and cccDNA transcription.

Chronic hepatitis B virus (HBV) infection remains a significant global health challenge due to its link to severe conditions like HBV-related cirrhosis and hepatocellular carcinoma (HCC). Although current treatments effectively reduce viral levels, they have limited impact on certain HBV elements, namely hepatitis B surface antigen (HBsAg) and covalently closed circular DNA (cccDNA). This highlights the urgent need for innovative pharmaceutical and biological interventions that can disrupt HBsAg production originating from cccDNA. In this study, we identified a natural furanocoumarin compound, Imperatorin, which markedly inhibited the expression of HBsAg from cccDNA, by screening a library of natural compounds derived from Chinese herbal medicines using ELISA assay and qRT-PCR. The pharmacodynamics study of Imperatorin was explored on HBV infected HepG2-NTCP/PHHs and HBV-infected humanized mouse model. Proteome analysis was performed on HBV infected HepG2-NTCP cells following Imperatorin treatment. Molecular docking and bio-layer interferometry (BLI) were used for finding the target of Imperatorin. Our findings demonstrated Imperatorin remarkably reduced the level of HBsAg, HBV RNAs, HBV DNA and transcriptional activity of cccDNA both in vitro and in vivo. Additionally, Imperatorin effectively restrained the actions of HBV promoters responsible for cccDNA transcription. Mechanistic study revealed that Imperatorin directly binds to ERK and subsequently interfering with the activation of CAMP response element-binding protein (CREB), a crucial transcriptional factor for HBV and has been demonstrated to bind to the PreS2/S and X promoter regions of HBV. Importantly, the absence of ERK could nullify the antiviral impact triggered by Imperatorin. Collectively, the natural compound Imperatorin may be an effective candidate agent for inhibiting HBsAg production and cccDNA transcription by impeding the activities of HBV promoters through ERK-CREB axis.

Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B.

This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.

Severe acute liver disease in adults: Contemporary role of histopathology.

Liver biopsies have consistently contributed to our understanding of the pathogenesis and aetiologies of acute liver disease. As other diagnostic modalities have been developed and refined, the role of biopsy in the management of patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute hepatitis, including acute liver injury (ALI), has changed. Liver biopsy remains particularly valuable when first-line diagnostic algorithms fail to determine aetiology. Despite not being identified as a mandatory diagnostic tool in recent clinical guidelines for the management of ALF or ACLF, many centres continue to undertake biopsies given the relative safety of transjugular biopsy in this setting. Several studies have demonstrated that liver biopsy can provide prognostic information, particularly in the context of so-called indeterminate hepatitis, and is extremely useful in excluding conditions such as metastatic tumours that would preclude transplantation. In addition, its widespread use of percutaneous biopsies in cases of less severe acute liver injury, for example in the establishment of a diagnosis of acute presentation of autoimmune hepatitis or confirmation of a probable or definite drug-induced liver injury (DILI), has meant that many centres have seen a shift in the ratio of specimens they are receiving from patients with chronic to acute liver disease. Histopathologists therefore need to be equipped to deal with these challenging specimens. This overview provides an insight into the contemporary role of biopsies (as well as explant and autopsy material) in diagnosing acute liver disease. It outlines up-to-date clinical definitions of liver injury and considers recent recommendations for the diagnosis of AIH and drug-induced, autoimmune-like hepatitis (DI-AIH).

Micro-elimination of chronic hepatitis C virus in mental health settings: A prospective multicentre pragmatic trial.

INTRODUCTION: Hepatitis C virus (HCV) prevalence is high in the mental health population. We sought to evaluate testing and treatment uptake for HCV following the implementation of a universal nurse led study in inpatient and outpatient mental health populations. METHODS: From January 2018 to December 2020, we screened mental health inpatients (n = 322) and community mental health patients (n = 615) for HCV with either specialist hepatology nurses or mental health nurses (mental health nurse). RESULTS: 75.5% (464/615) of community patients and 100% (322/322) of inpatients consented to screening, with an HCV antibody-positive prevalence of 12.7% (59/464) in community patients and 19.6% (63/322) in inpatients. RNA detectable prevalence was 4.0% (22/464) and 7.5% (24/322), respectively. Community patients who were screened by specialist hepatology nurses were more likely to consent to screening (94.4% vs. 45.7%, p < 0.001) but had lower proportion of HCV antibody (10.5% vs. 20.3%, p < 0.001) and RNA detectable (4.0% vs. 7.5%, p = 0.018) when compared to mental health nurse screening. Engagement with treatment was 27.0% of community mental health patients and 45.8% of mental health inpatients undergoing treatment. All patients undergoing treatment and underwent sustained viral response (SVR) testing achieved SVR. DISCUSSION AND CONCLUSIONS: Universal screening of HCV using a nurse-led model has high rates of success in mental health patients with high proportions undergoing screening, with no reduction in the rates of SVR achieved with DAA therapy compared to the general population. Further work is needed to bridge the gap between identification of HCV and treatment among mental health patients.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Current perspectives of viral hepatitis.

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome.

BACKGROUND: Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. AIM: To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. METHODS: A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. RESULTS: Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). CONCLUSION: In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.

Case report: BTK inhibitors is effective in type II mixed cryoglobulinemia with wild-type MyD88.

This study presents two cases of type II mixed cryoglobulinemia. One case is essential, while the other is presumably associated with hepatitis B virus (HBV) infection. Both patients tested positive for monoclonal IgMκ, but negative for MyD88 mutation. They showed resistance to rituximab combined with a glucosteroid regimen, but responded positively to BTK inhibitors. These cases highlight the remarkable effectiveness of BTK inhibitors in treating refractory type II cryoglobulinemia without MyD88 mutation. The first patient achieved rapid complete remission of nephrotic syndrome within one month of starting ibrutinib, along with a significant reduction in cryoglobulin levels and abnormal clonal cells. The second patient had a rapid disappearance of rash within three days and accelerated wound healing within one week of initiating orelabrutinib, accompanied by a reduction in C-reactive protein. However, there was no reduction in cryoglobulin levels during the 12-month follow-up. These findings suggest varied mechanisms of action of BTK inhibitors in type II cryoglobulinemia through different mechanisms.

Needle Stick Injury Among Healthcare Workers in a Tertiary Care Setting in Dehradun, Sub-Himalayan Region: A Four-Year Record-Based Study.

INTRODUCTION: Needlestick injuries (NSIs) represent a significant occupational health risk in healthcare settings. These injuries, caused by contaminated sharps such as needles, vials, and scalpel blades, can lead to percutaneous exposure to infectious materials. Despite the severity of NSIs, they often go unreported, highlighting a critical gap in occupational safety protocols. AIMS: This study aimed to investigate the occurrence of NSIs among healthcare workers (HCWs) by sex, profession, and working areas. It also sought to explore the underlying reasons for these injuries and the factors contributing to their underreporting. METHODOLOGY: Adhering to the RECORD guidelines (Reporting of studies Conducted using Observational Routinely Collected Data), this record-based study involved a retrospective analysis of reported NSIs. Data were collected from voluntary reports by HCWs who experienced NSIs or exposure to potentially infectious materials such as blood and body fluids. Statistical analysis was conducted using IBM SPSS Statistics for Windows, Version 16 (Released 2007; IBM Corp., Armonk, New York) and Microsoft Excel 2010 (Microsoft Corporation, Redmond, Washington). RESULTS: Data from 142 participants indicated a higher proportion of females experiencing NSIs compared to males, with rates of 57.7% pre-COVID and 60.6% during COVID. There were notable shifts in NSI rates across professions, with increases observed among staff nurses and ward attendants/helpers. Analysis of injury circumstances revealed a decrease in sampling procedure-related injuries but an increase during intravenous procedures and biomedical waste segregation. Injuries occurring on the right-hand index finger decreased from 52.1% pre-COVID to 31% during COVID, while those on the left-hand index finger increased from 19.7% pre-COVID to 39.4% during COVID. Statistically significant associations were found between the injury site and the place of occurrence (p=0.021). Healthcare professionals commonly cleansed the site with disinfectants and used personal protective equipment (PPE) kits, with increased PPE usage noted during the COVID-19 pandemic. These findings emphasize the evolving dynamics of NSIs among HCWs and underscore the importance of tailored preventive measures during pandemics.

Network pharmacology-based analysis on the key mechanisms of Yiguanjian acting on chronic hepatitis.

Chronic hepatitis (CH) encompasses a prevalent array of liver conditions that significantly contribute to global morbidity and mortality. Yiguanjian (YGJ) is a classical traditional Chinese medicine with a long history of medicinal as a treatment for CH. Although it has been reported that YGJ can reduce liver inflammation, the intricate mechanism requires further elucidation. We used network pharmacology approaches in this work, such as gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and network-based analysis of protein-protein interactions (PPIs), to clarify the pharmacological constituents, potential therapeutic targets, and YGJ signaling pathways associated with CH. Employing the random walk restart (RWR) algorithm, we identified GNAS, GNB1, CYP2E1, SFTPC, F2, MAPK3, PLG, SRC, HDAC1, and STAT3 as pivotal targets within the PPI network of YGJ-CH. YGJ attenuated liver inflammation and inhibited GNAS/STAT3 signaling in vivo. In vitro, we overexpressed the GNAS gene further to verify the critical role of GNAS in YGJ treatment. Our findings highlight GNAS/STAT3 as a promising therapeutic target for CH, providing a basis and direction for future investigations.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis.

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.

Changes in the Etiologies of Liver Cancer in Upper Egypt over a Decade from 2010 to 2020: A Single Tertiary Care Center Study.

Yasser Fouad The profile of liver diseases in Egypt is changing dramatically and viral hepatitis is declining, while the fatty liver disease is increasing dramatically. However, the impact of these changes on the profile of hepatocellular carcinoma (HCC) remains uncertain. Therefore, we determined the temporal trends in the etiologies of HCC in Egypt over a decade. We retrospectively analyzed data from consecutive patients who were diagnosed with HCC over 10 years (2010-2020) in a large center in Upper Egypt. Standard tests were utilized to diagnose hepatitis C virus (HCV) and hepatitis B virus. In the absence of other liver disorders, the presence of obesity, or diabetes in the absence of other risk factors, metabolic dysfunction-associated fatty liver disease (MAFLD) was diagnosed. A total of 1,368 HCC patients were included, in which 985 (72%) had HCV, 58 (4%) had hepatitis B virus, and 143 (10.5%) had MAFLD, 1 patient had hemochromatosis, 1 had autoimmune liver disease, and 180 (13%) patients were with unknown cause. The annual proportions of MAFLD-related HCC were increased significantly between 8.3% in 2010 and 20.6% in 2020 ( p = 0.001), while HCV-related HCC declined from 84.8 to 66.7% ( p = 0.001). Throughout the study period, there were significant increases in the age at diagnosis of HCC, the proportion of female patients, obesity, diabetes, and less severe liver dysfunction at diagnosis ( p < 0.05 for all). With the decline of HCV, MAFLD is becoming a major cause of HCC in Egypt, which has increased substantially over the past 10 years. This study urges the creation of comprehensive action strategies to address this growing burden.

Management of Hepatitis B Virus and Hepatitis C Virus Infections in Patients with Cancer Receiving Immune Checkpoint Inhibitors.

Background: Patients with cancer with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded from many cancer clinical trials of immune checkpoint inhibitors (ICIs). Therefore, data are limited regarding the management of HBV and HCV infections in patients with cancer treated with ICIs. To address this gap, we reviewed the literature on management of HBV and HCV infections in patients with cancer receiving ICIs. Methods: We searched MEDLINE and PubMed for all original research articles, case reports, and systematic reviews published in English between Jul 2013 and Jul 2023 on patients with cancer with HBV or HCV infection receiving ICIs. Results: We found 28 studies (three prospective clinical trials, seven retrospective cohort studies, nine retrospective case series, and nine case reports) that evaluated the safety of ICI therapy in patients with HBV infection and cancer. The overall rate of HBV reactivation was 1.4% (38/2799), and no HBV-related deaths were reported. The frequency of HBV reactivation in patients with chronic and past HBV infections was 2% (35/1667) and 0.3% (3/1132), respectively. The risk of HBV reactivation was significantly higher among patients with chronic HBV infection not receiving antiviral prophylaxis than among those receiving antivirals (17% vs 1%, p < 0.05). Based on high-quality evidence, for patients with chronic HBV infection, antiviral prophylaxis is recommended before ICI therapy initiation. For patients with past HBV infection, monitoring and on-demand antiviral treatment are sufficient. We found 11 studies (five clinical trials, five retrospective studies, and one prospective observational study) that evaluated the safety of ICI therapy in patients with HCV infection and cancer. The overall rate of HCV reactivation was 0.5% (2/387), and no HCV-related deaths were reported. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICIs are safe for HCV-infected patients with solid tumors. Conclusions: Chronic HBV or HCV infection should not be considered a contraindication for ICI therapy. Specific risk assessment, monitoring, and management strategies are necessary to reduce the risk of ICI-related liver injury in patients with cancer and chronic HBV or HCV infection.

Overview of acute liver failure in India.

Acute liver failure (ALF) is an infrequent, but serious complication subsequent to severe acute liver injury (sALI) due to various hepatotoxic agents such as hepatotropic virus(es) and drugs such as anti-tubercular medications, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and anti-cancer and anti-epileptic therapy and due to metabolic and autoimmune disease flares. ALF after sALI presents with encephalopathy associated with prolonged international normalized ratio (INR). Mortality in ALF is high and ranges between 50% and 80%. Due to severe liver damage, multiple sequels consequent to hepatic dysfunction result in complications such as hyperammonemia that culminates in encephalopathy associated with cerebral edema; innate immune paralysis resulting in increased frequency of infections and endotoxemia causing decrease in systemic vascular resistance (SVR) and tissue hypoperfusion and damage-associated molecular patterns (DAMPs) released from damaged hepatic parenchyma inducing pro-inflammatory cytokine storm, which may cause other organ dysfunctions. Certain etiologies such as hepatitis E virus and hepatitis A virus-related ALF or paracetamol-ALF (hyper-acute presentation) have better survival than remaining causes. In addition, if etiology-specific treatment (antivirals for ALF related to hepatitis B virus (HBV) or Herpes simplex virus (HSV) or N-acetylcysteine for paracetamol) is available, then the outcome with treatment is better. About half of the patients can be salvaged with medical therapy. All patients need intensive care and organ support to provide time for the liver to regenerate. Various prognostic models to predict high probability of mortality have been described, which should be used to select patient early during the disease for liver transplantation, which is associated with high long-term survival in these sick patients. The Indian National Association for Study of the Liver (INASL) recommends the ALF-Early Dynamic (ALFED) model as a preferred prognostic model in the Indian scenario, where hepatitis viruses are a dominant etiology of ALF and occur on a naïve liver with good regenerative capacity.

Evaluación del valor clínico y económico de sofosbuvir/velpatasvir (SOF/VEL) en pacientes con hepatitis C crónica en España durante los últimos 5 años.

OBJECTIVE: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) represented a paradigm shift. In 2017, sofosbuvir/velpatasvir (SOF/VEL-Epclusa®) was approved, which showed a high cure rate in all patient, contributing to HCV elimination. The analysis aimed to quantify the clinical and economic value of SOF/VEL in HCV chronic patients since its approval in Spain. METHODS: An economic evaluation was elaborated adapting a Markov model that simulated the lifetime disease progression in of all HCV chronic patients treated with SOF/VEL (30,488 patients) since its launch (5-years), compared to previous therapies. Patients entered the model and were distributed between the fibrosis states (F0-to-F4) in treated and untreated. All patients (100%) were treated with SOF/VEL regardless of their fibrosis, and 49% with previous therapies in ≥F2. The average sustained viral response (SVR) rates 98.9% SOF/VEL versus 61.0% previous therapies. All parameters for the analysis were obtained from real-life data and literature. Only direct healthcare costs associated with disease management were included. The SOF/VEL value was measured as the number of hepatic complications avoided and their associated cost, and hepatic mortality compared to previous therapies. National Health System perspective and a 3% discount rate was applied. RESULTS: SOF/VEL decreased the number of liver complications, avoiding 92% decompensated cirrhosis, 80% hepatocellular carcinomas, and 87% liver transplants, as well as 85% liver-related mortality. Their cost associated was reduced, amounting to savings of 197Meuro. CONCLUSION: SOF/VEL adds relevant value to the HCV treatment, reducing the clinical and economic disease burden and contributing to HCV elimination in Spain.