Hepatitis C Virus Research Articles

Hepatitis B Virus-Associated Liver Carcinoma: The Role of Iron Metabolism and Its Modulation.

Hepatitis B virus (HBV) infection is a significant contributor to the development of hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide. Iron, a central co-factor in various metabolic pathways, plays an essential role in liver function, but its dysregulation can lead to severe health consequences. Accumulation of iron within hepatic cells over time is linked to increased liver injury and is strongly associated with sensitive exposure to a range of conditions, including cirrhosis, fibrosis and ultimately, HCC. This review explores the intricate interplay between iron metabolism and HCC within the context of HBV infection. Hepatic iron overload can arise from liver injury and disruptions in iron homeostasis, causing hepatic necrosis, inflammation, and fibrosis, ultimately culminating in carcinogenesis. Moreover, alterations in serum iron components in HBV-related scenarios have been observed to impact the persistence of HBV infection. Notably, the progression of HBV-associated liver damage exhibits distinct characteristics at various stages of liver disease. In addition to elucidating the complex relationship between iron metabolism and HCC in the context of HBV infection, this review also investigates the prognostic implications of systemic iron levels for HCC. Furthermore, it aims to provide a comprehensive understanding of the intricate interplay between iron metabolism and HCC, extending the discussion to the context of hepatitis C virus (HCV) infection. By shedding light on these multifaceted connections, this review aims to contribute to our understanding of the pathogenesis of HBV-associated HCC and potentially identify novel therapeutic avenues for intervention.

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a primary liver cancer predominantly arising in individuals with chronic liver diseases such as cirrhosis or chronic hepatitis B virus (HBV) infection. Accounting for approximately 75% of primary liver tumors, HCC's global epidemiology is significantly influenced by HBV and hepatitis C virus (HCV) infections, alcohol and tobacco use, metabolic syndrome, diabetes, obesity, and aflatoxin B1 exposure. Preventive measures, including HBV vaccination and direct-acting antivirals for HCV, have reduced incidence rates, particularly in younger populations. Early diagnosis through surveillance in high-risk groups is critical, employing imaging modalities like ultrasound, CT, and MRI, alongside biomarkers such as alpha-fetoprotein (AFP). Prognostic assessments utilize scores like Child-Pugh and ALBI. Treatment strategies for HCC are multifaceted, involving surgical resection, locoregional therapies (e.g., transarterial chemoembolization), and systemic therapies, including targeted and immunotherapies. Despite advancements, treatment efficacy remains a challenge, necessitating ongoing research into novel therapeutic approaches and predictive biomarkers to enhance personalized treatment and improve outcomes for HCC patients.

Predictors of Acute Kidney Injury Resolution and Associated Clinical Outcomes Among Hospitalized Patients with Cirrhosis.

Background: Acute kidney injury (AKI) is one of the common complications of liver cirrhosis. It occurs in nearly 20% of patients with cirrhosis who are hospitalized. Prior literature demonstrated that the AKI occurrence in patients with cirrhosis is independently associated with higher mortality. However, there are data assessing predictors and outcomes of AKI resolution in hospitalized patients with cirrhosis. Therefore, the aim of the current study was to identify clinical predictors of AKI resolution among inpatients with cirrhosis that are easily obtained and to evaluate the clinical outcomes of those patients. Methods: The current study is a retrospective cohort of patients with cirrhosis who were hospitalized and had AKI between 2012 and 2020 at a tertiary referral center. Patients included in this study were identified using the International Classification of Diseases 9 codes and then they were manually verified by two independent chart reviewers. AKI was classified according to the AKI Network (AKIN) serum creatinine (Cr) criteria, with AKIN resolution defined as AKIN stage 1 or lower at the time of discharge, while unresolved AKIN was defined as AKIN stage 2 or 3 at the time of discharge. For univariate analysis, Fisher's exact and the two-sample T-test were utilized. For multivariable analysis, stepwise logistic regression was performed to evaluate variables associated with AKIN resolution. Survival curves were estimated and compared using the Kaplan-Meier method and Log-Rank Test. A p-value cutoff of 0.05 was used for statistical significance. Results: Between 2012 and 2020, there were 140 patients who were included (59% males). The majority of patients had viral hepatitis (54%) as the cirrhosis etiology with 80% of them having hepatitis C virus. Most patients had fluid-responsive AKI (49%), and stage 1 AKIN (69%). In terms of outcomes, the majority of patients (117 patients; 84%) had AKIN resolution at the time of discharge. In the multivariable analysis, after adjusting for clinical meaningful variables, our study shows that higher albumin value at the time of admission (adjusted Odds Ratio "aOR" = 3.28; p = 0.01) and non-metabolic dysfunction-associated steatotic liver disease (non-MASLD) cirrhosis (aOR = 9.43; p < 0.01) were variables associated with higher odds of AKIN resolution at the time of discharge. Conversely, we show that a higher Cr value at the time of admission was associated with lower odds of AKIN resolution at the time of discharge (aOR = 0.31; p < 0.01). When evaluating mortality, patients with unresolved AKIN at the time of discharge had higher rates of in-hospital mortality (p < 0.01) compared to those with resolved AKIN. Survival curve analyses using the Kaplan-Meier method indicated that patients with resolved AKIN experienced higher 90-day survival rates (p < 0.01). Additionally, those with resolved AKIN demonstrated greater transplant-free survival compared to patients with unresolved AKIN at both the 1-year (p = 0.04) and 3-year (p < 0.01) follow-ups. Conclusions: When evaluating clinical predictors of AKIN resolution in admitted patients with cirrhosis, our study showed that a higher admission albumin value and non-MASLD etiology of cirrhosis were associated with higher odds of AKIN resolution at the time of discharge. Conversely, a higher admission Cr value was associated with lower odds of AKIN resolution at the time of discharge. We also demonstrate that AKIN resolution during index admission was associated with improved short- and long-term transplant-free survival (up to 3 years). Our findings warrant external validation in larger cohorts to further evaluate the impact of inpatient AKI resolution on cirrhosis outcomes. Our findings can help clinicians predict AKIN outcomes and encourage more aggressive management of AKI, especially in high-risk patients, which can improve mortality.

Increasing trends in hepatitis E hospitalisations in Spain, 1997 to 2019.

BackgroundHepatitis E, a viral hepatitis caused mainly by the ingestion of raw or undercooked food, is not a notifiable disease in Spain.AimTo analyse the temporal trends, epidemiological characteristics and factors associated with severe disease from hepatitis E hospitalisations in Spain from 1997 to 2019.MethodsHospitalisation records were obtained from the Spanish National Hospital Discharge Database. Temporal trends and seasonality were analysed by Poisson regression in years 1997-2015 and 2016-19, given changes in hospital discharge databases. Multivariate logistic regression was used to identify factors associated with severe disease.ResultsHepatitis E hospitalisation incidence increased from 0.22 cases per 1,000,000 inhabitants in 1997 to a maximum of 2.95 in 2018. Seasonality was observed during 2016-19 period, with more cases in the second and third quarters of the year. The incidence was higher in men vs women, and in the population aged over 40 years. Factors independently associated with death were age ≥ 50 years (adjusted odds ratio (aOR): 2.43), chronic liver disease (aOR: 4.29), HIV infection (aOR: 3.00) and hepatitis B/C (aOR: 2.11).ConclusionsHepatitis E hospitalisations have increased in Spain in recent years, being more severe in cases with older age, chronic hepatic diseases and HIV infection. A greater incidence in men over 40 years and a possible seasonality were observed. Further studies are needed to assess the seasonality, geographical distribution and impact of the disease to guide public health actions for prevention and control.

The Camden and Islington Viral Hepatitis Identification Tool (CIVHIT): Use of a Clinical Database Case-Finding Tool for Hepatitis B, Hepatitis C and HIV in Primary Care.

Despite the availability of effective treatment and vaccines for hepatitis B virus (HBV) and C virus (HCV), many people are still infected and remain unaware of their infection. The Camden and Islington Viral Hepatitis Identification Tool (CIVHIT), a computer-based search tool, was introduced in 60 general practices (GPs) in April 2014 to support identification, testing and treatment of individuals at high risk for blood-borne viruses (BBVs). CIVHIT searched electronic medical records (EMRs), flagging all those with codes linked to risk factors or medical conditions associated with BBVs. CIVHIT was associated with a 78.5% increase in BBV tests in primary care in both boroughs. This translated to a 55.8% rise in new diagnoses. HBV testing saw the largest increase resulting in twice as many people diagnosed. Only 23.2% of HBV and 14.9% of HCV-positive tests were referred to secondary care. In an index practice, the most common flag was a history of STIs (477/719, 66.3%). Individuals with previous or current drug use and those with a known hepatitis contact were more likely to be offered a test compared to those flagged due to a history of STI. HIV and HBV testing was lower in males following a test offer. There was an increased likelihood of testing for HBV and HCV with increasing age. Additionally, individuals with previous or current drug use and individuals with a known hepatitis contact were more likely to test for HCV compared to individuals flagged due to STI history. CIVHIT shows promise to assist with the elimination of BBVs.

A case of complete response to radiotherapy combined with durvalumab and tremelimumab in a patient with unknown primary hepatocellular carcinoma arising in the lumbar spine.

A 58-year-old man visited an orthopedic clinic complaining of pain in his right lower back and numbness in his lower limbs for one month. Imaging tests revealed a tumorous lesion from the left side of the second lumbar vertebra to the paraspinal muscles. CT-guided biopsy of the tumor was performed, and immunostaining results diagnosed hepatocellular carcinoma (HCC). Although the liver showed signs of chronic liver damage, no primary tumor was found within the liver or in other organs. Blood tests showed negative hepatitis virus markers for both HBV and HCV. The tumor markers AFP, AFP-L3, and DCP were high. Because he developed spinal cord compression syndrome due to a lumbar tumor, radiation therapy and denosumab administration were performed. Subsequently, systemic therapy with durvalumab plus tremelimumab was started. In the year following the start of treatment, the tumor has shrunk, and no new lesions have been observed. Tumor markers have also decreased. We have experienced a case of HCC in the lumbar spine without a primary tumor in the liver. This is a very rare case, and the combination therapy with durvalumab and tremelimumab resulted in a complete response, which we consider to be a valuable case.

Editorial: Epidemiology and Control of Hepatitis Viruses

Five hepatitis viruses—hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV)—have a huge impact on human health with their ability to cause acute and often chronic infection [...]

Loss to follow-up of patients after antiviral treatment as an additional barrier to HCV elimination

BackgroundEliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it.MethodsPatients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study.ResultsIn the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy.ConclusionsIn a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.

Cost-Effectiveness of Treating Hepatitis C in Clients on Opioid Agonist Therapy in Community Pharmacies Compared to Primary Healthcare in Australia.

Meeting the World Health Organisation 2030 target of treating 80% of people with hepatitis C virus (HCV) in Australia requires accessible testing and treatment services for at-risk populations. Previous clinical trials, including those in Australia, have demonstrated the efficacy of outreach programmes to community pharmacies offering opioid agonist therapy (OAT). This analysis evaluates the potential cost-effectiveness of introducing an outreach programme in community pharmacies. Using a decision analytic model, we estimated the impact of adding a temporary hepatitis C outreach and treatment programme in community pharmacies to the standard treatment pathway available through general practice. We compared the expected number of tests, diagnoses, cures and costs occurring through the addition of this outreach and treatment programme to those expected through general practice alone over a 12-month time horizon. We examined costs from the perspective of the health system and conducted one-way and probabilistic sensitivity analyses to assess uncertainty in model parameters and test key assumptions. In the model adding the outreach programme pathway increased the number of tests from 4178 to 8737, the number of diagnoses from 615 to 1285 and the number of cures from 223 to 777 among people on OAT over a 12-month period. Each additional cure achieved through the addition of the outreach programme was estimated to incur $48,964 (AUD 2023) to the health system, with > 85% of these costs attributable to medication and dispensing expenses. The average cost per cure was estimated to be $49,152 through routine care and $49,018 in the outreach programme. Although outreach models of care incur large upfront costs, they can capture otherwise unreached populations and result in comparable or favourable cost per cure, due to higher levels of engagement and lower rates of loss to follow-up.

The role of artificial intelligence in the management of liver diseases.

Universal neonatal hepatitis B virus (HBV) vaccination and the advent of direct-acting antivirals (DAA) against hepatitis C virus (HCV) have reshaped the epidemiology of chronic liver diseases. However, some aspects of the management of chronic liver diseases remain unresolved. Nucleotide analogs can achieve sustained HBV DNA suppression but rarely lead to a functional cure. Despite the high efficacy of DAAs, successful antiviral therapy does not eliminate the risk of hepatocellular carcinoma (HCC), highlighted the need for cost-effective identification of high-risk populations for HCC surveillance and tailored HCC treatment strategies for these populations. The accessibility of high-throughput genomic data has accelerated the development of precision medicine, and the emergence of artificial intelligence (AI) has led to a new era of precision medicine. AI can learn from complex, non-linear data and identify hidden patterns within real-world datasets. The combination of AI and multi-omics approaches can facilitate disease diagnosis, biomarker discovery, and the prediction of treatment efficacy and prognosis. AI algorithms have been implemented in various aspects, including non-invasive tests, predictive models, image diagnosis, and the interpretation of histopathology findings. AI can support clinicians in decision-making, alleviate clinical burdens, and curtail healthcare expenses. In this review, we introduce the fundamental concepts of machine learning and review the role of AI in the management of chronic liver diseases.

Tubulointerstitial nephritis with IgM-positive plasma cells complicated by liver failure.

Tubulointerstitial nephritis (TIN) is characterized by inflammation of the renal interstitium with the infiltration of immune cells, mainly consisting of T cells. Recently, patients with TIN with the predominant infiltration of immunoglobulin M (IgM)-positive plasma cells were reported, coined IgMPC-TIN. Here we report the case of a 70-year-old woman diagnosed with Fanconi syndrome and renal tubular acidosis. Renal biopsy revealed IgMPC-TIN. Her renal dysfunction and clinical findings improved after corticosteroid therapy. However, the patient died of progressive liver failure and spontaneous bacterial peritonitis. In laboratory tests, viral hepatitis was excluded, and autoantibodies associated with liver diseases were negative. Generally, IgMPC-TIN is often complicated by primary biliary cholangitis (PBC), whereas her autopsy revealed the local infiltration of IgM-positive plasma cells, obliterative portal venopathy, and nodular regenerative hyperplasia in liver. This case is the first demonstration that IgMPC-TIN is also seen in liver disease with nodular regenerative hyperplasia, although IgMPC-TIN is more common in anti-M2 antibody-positive disease.

Hepatitis A, B, and C in Brazilian Afro-Descendant Communities from Northeast Brazil: A Seroepidemiological Survey

Background: Viral hepatitis is a disease that is more prevalent among individuals residing in remote regions and in contexts of social vulnerability. The objective of this study was to ascertain the seroprevalence of hepatitis A (HAV), B (HBV), and C (HCV) in vulnerable communities in the rural area of São João do Piauí (SJP), northern Brazil. Methods: Immunoenzymatic assays were employed to detect the presence of anti-HAV (total and IgM), HBsAg, anti-HBc, anti-HBs, and anti-HCV serological markers in serum samples. Samples that yielded positive results were subjected to further analysis using real-time polymerase chain reaction (PCR). Results: A total of 492 individuals, ranging in age from 3 to 101 years, were consecutively recruited from eight rural communities. The majority of individuals were female (51.2%), over 30 years of age (57.1%), self-identified as Black/Brown (92.2%), and resided in Afro-Brazilian communities, designated as “quilombos” (68.1%). The seroprevalence of anti-HAV was 69.5% (95% CI: 65.4–73.6%), while that of anti-HBc was 4.7% (95% CI: 2.8–6.6%), and that of anti-HBs was 35.2% (95% CI: 30.1–39.4%), and 0.2% (95% CI:0.0–0.6%) for anti-HCV. Conclusions: The seroprevalence rates observed were higher than the national average, and a significant proportion of individuals in the target age groups were susceptible to HBV, despite the availability of vaccination. These findings highlight potential shortcomings in the management of vaccine-preventable diseases, which could have implications for public health.

Diversity, geographical distribution and predictive factors of Hepatitis C virus genotypes and subtypes in Rwanda

BackgroundExisting data on the prevalence of hepatitis C virus (HCV) genotypes and subtypes in Rwanda need to be strengthened. The aim of this study was to identify HCV genotypes and subtypes among HCV-infected patients, as well as their geographical distribution in Rwanda, and to identify the social and economic factors that could influence HCV epidemiology which would make it possible to target national preventive and management actions for infected patients. MethodsThis study included 560 patients with confirmed chronic HCV infection. Patients were recruited from various health facilities in the four provinces of Rwanda as well as in the City of Kigali and had never received treatment with direct-acting antiviral (DAAs). HCV viral loads were measured using Cobas® AmpliPrep/Cobas® TaqMan® HCV Quantitative Test, version 2.0. HCV genotyping was performed using an in-house sequencing protocol targeting the NS5B central region. Genotypic HCV prevalence was correlated with patient geographic location, sociodemographic, behavioral, lifestyle, and clinical factors. ResultsHCV genotype 4 was detected in 99.3% of the patients, while genotype 3 was identified in 0.7%. A total of eight (8) HCV subtypes were detected, with 4k being the predominant subtype nationwide (49.5%), followed by subtypes 4r (21.2%), 4q (16.2%), 4v (7.9%), 4b (2.0%), 4l (1.8%), 4c and 3h represent 0.7% each. Our findings reveal subtype distribution variations among provinces. Subtype 4k was prevalent across regions, particularly in Kigali (64.0%) and the Eastern Province (61.6%). Subtype 4q was more common in the northern province (40.7%), 4r in the southern (43.9%) and western provinces (37.1%), and 4v in the eastern province (17.8%). Farmers exhibit a distinct infection profile compared to other occupations, showing a lower prevalence of subtype 4k but a higher prevalence of subtype 4r. ConclusionsOur study revealed that HCV infection is unevenly distributed in Rwanda, dominated by HCV genotype 4, with considerable heterogeneity in the repartition of the different subtypes. We found potential associations between rural/urban lifestyles and HCV subtype profiles. Determined HCV distribution and diversity can serve as basis not only for HCV infection awareness and prevention campaigns, but also success and guidance for personalized treatment.

Prevalence of Hepatitis E Virus Infection among Blood Donors in a Tertiary Healthcare Facility in Osun State, Nigeria

Hepatitis E virus (HEV) is currently the most common cause of viral hepatitis in developing countries. While prospective blood donors are routinely screened for HIV, Hepatitis B and C globally in endemic areas, HEV is not included in the protocol, despite the increase in global prevalence of HEV. Till date, only a handful of studies exist on the prevalence of HEV in Nigeria. The aim of this study was to fill this knowledge gap by determining the prevalence of HEV among blood donors at the LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria. A total of 102 consenting individuals were enrolled into the study between ages 20 and 55. A volume of 5ml blood sample was collected, and the serum harvested, stored at 20°C until ready for analysis. A double antibody sandwich HEV ELISA was performed to analyze the sera in duplicate for HEV antigen, using an ELISA Kit. Of the 102 samples analyzed, 15 (14.7%) tested positive for HEV antigen, confirming the presence of HEV infection among blood donors in the study population. There was significant association between HEV seropositivity and contact with animals (P=0.010) and alcohol consumption (P=0.000), which means there was a higher chance of donors who consumed alcohol or have had contact with animals to get infected with HEV. However, age, educational status, occupation and gender did not show any statistically significant association with HEV infection. The prevalence of HEV seropositivity was high (14.7%) and a cause for concern as HEV continues to be a major public health issue especially in developing countries.

A National Survey of Pharmacist Involvement in Hepatitis C Virus Management in the United States.

Models estimate that the United States will not meet its 2030 hepatitis C virus (HCV) elimination goal. Engagement of healthcare providers including pharmacists is critical for HCV elimination efforts. We aimed to characterise the involvement of pharmacists in HCV management. The study design was a cross-sectional survey. Investigators sent the questionnaire to pharmacy and HCV organisations' listservs and limited responses to licensed pharmacists with direct patient care. Questions assessed setting, HCV screening, prescribing, and management; and opinions, and perceived barriers and facilitators to pharmacists' HCV management. Two hundred and nine survey respondents across 45 states reported managing 24 patients/month, with 5.3 (±4.4) years' experience in HCV, and identified pharmacist-managed HCV at their site since 2013 (±5.8 years). Most practice at academic medical centres (29%, 58/203) under collaborative practice agreements (67%, 127/189), as ambulatory care pharmacists (70%, 131/187), in primary care (50%, 65/131). Many pharmacists provide screening, linkage to care, and/or referral (81%, 157/194); 99.5% (190/191) perform treatment evaluation and selection; 98% (180/183) provide treatment education, 93% (171/183) initiate treatment, and 90% (162/180) provide on- and/or post-treatment monitoring. Respondents indicated collaboration with prescribers as most helpful in their role in HCV management, whereas lack of reimbursement was a main barrier. Satisfying components include HCV cure, care and education provision; frustrations include socioeconomic factors impeding patients' follow-up and prior authorisations/insurance barriers. Survey results show the variety of pharmacists' roles in direct HCV patient care and may be used to increase other providers' awareness of pharmacists' services and contributions to HCV elimination efforts.

Contamination of Hepatitis E Virus in Pig Livers of Different Market Types Collected from Seven Provinces of China.

Foodborne transmission of the Hepatitis E virus (HEV) is becoming an important public health problem in China, but the food associated with the HEV transmission route remains unclear. Pig liver is among the suspected food products involved in HEV transmission. Our research aimed to survey the contamination rate and genotype identification of HEV in pig livers from different types of markets in selected provinces of China. reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to screen for HEV in pig livers, nest RT-PCR was used for partial amplification of opren reading frame (ORF) 2, followed by sequencing, and phylogenetic analysis to determine the genotype of positive samples. A total of 787 pig liver samples from 7 provinces were collected. The average positive rate of HEV was 8.13% (64/787), Inner Mongolia (14.29%, 1/7) and Hebei province (14.29%, 23/161) showed the highest positive rate. There was a significant difference among the provinces (p < 0.01). Three major market types (wholesale market, supermarket, and butcher's shop) were included in this study, and the positive rates were 5.28% (21/398), 15.86% (23/145), and 8.20% (20/244), respectively. There was no significant difference among the three market types. Eleven of the positive samples were partially sequenced and identified genotypes 4a, 4d, and 3a.

The role of NF-κB signaling pathway in viral hepatitis and gastroenteritis: pathogenesis and therapeutic applications

The role of NF-κB signaling pathway in viral hepatitis and gastroenteritis: pathogenesis and therapeutic applications

Hepatocellular Carcinoma in Acute Hepatic Porphyria: A Meta-Analysis of Observational Studies.

Hepatocellular carcinoma (HCC) is a long-term complication of acute hepatic porphyria (AHP) inclusive of acute intermittent porphyria [AIP], variegate porphyria [VP], or hereditary coproporphyria [HCP]. Data on HCC risk in AHP patients are limited and heterogeneous. We performed this meta-analysis with aims to (a) determine incidence of HCC in AHP and specific subtypes of AHP and (b) examine high-risk groups for HCC. Data from studies reporting HCC development in AHP patients were pooled and reported per 100 person years with 95% confidence intervals (CI). 12 observational (5 prospective) studies (11 Europe and 1 US) on 2735 patients (mean age 54.8 yrs., 62% females) with AHP (80% AIP) were analyzed. 115 HCC cases were observed with HCC incidence per 100 person years of 0.3 (0.2-0.5) in AHP, 0.4 (0.2-0.6) in AIP, 0.3 (0-0.4) in VP, and 0.2 (0.1-0.6) in HCP. The risk was 0.4 (0.2-0.6) in females, 0.3 (0.1-0.5) in males, 0.9 (0.1-1.7) in symptomatic, and 0.5 (0-1.6) in asymptomatic patients. Analyses were heterogeneous with publication bias. AHP patients with HCC were older females with a higher prevalence of cirrhosis, alcohol use, and viral hepatitis. The annual incidence of HCC in AHP patients is 0.3%, with higher risk in AIP, older females, symptomatic patients, and those with other risk factors of liver disease. Future studies pooling individual patient data and overcoming limitations of the current meta-analysis are needed as a basis for deriving a effective screening and surveillance approach for HCC in patients with AHP.

Hepatocellular Cancer Surveillance in Patients with Advanced Chronic Liver Disease

BackgroundPatients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD.MethodsFrom 3016 patients with ACLD screened in 17 European and Chinese centers, 2340 patients with liver stiffness measurement (LSM) determined using different techniques (two-dimensional shear-wave elastography [2D-SWE], transient elastography, and point shear-wave elastography) and with different disease severities were included. Cox regression was used to explore risk factors for HCC. We used these data to create an algorithm, named PLEASE, but referred to in this manuscript as “the algorithm”; the algorithm was validated in internal and two external cohorts across elastography techniques.ResultsHCC developed in 127 (5.4%) patients during follow-up. LSM by 2D-SWE (hazard ratio: 2.28) was found to be associated with developing HCC, alongside age, sex, etiology, and platelet count (C-index: 0.8428). We thus established the algorithm with applicable cutoffs, assigning a maximum of six points: platelet count less than 150×109/l, LSM greater than or equal to 15 kPa, age greater than or equal to 50 years, male sex, controlled/uncontrolled viral hepatitis, or presence of steatotic liver diseases. Within 2 years, with a median follow-up of 13.7 months, patients in the high-risk group (≥4 points) had an HCC incidence of 15.6% (95% confidence interval [CI], 12.1% to 18.7%) compared with the low-risk group, at 1.7% (95% CI, 0.9% to 2.5%).ConclusionsOur algorithm stratified patients into two groups: those at higher risk of developing HCC and those at lower risk. Our data provide equipoise to test the prospective utility of the algorithm with respect to clinical decisions about screening patients with ACLD for incident HCC. (Funded by the German Research Foundation and others; ClinicalTrials.gov number, NCT03389152.)

Application of Nanotechnology in Liver Fibrosis: An Overview

Chronic liver disease constitutes a global health issue owning to their widespread prevalence and the scarcity of effective curative treatments. They are arising from various causes, both infectious and non-infectious diseases. A rapidly evolving field of interest is the use of nanoparticle (NP) systems for the safe administration of different medications and nucleic acid for the treatment of chronic liver disorder. The review examines the pathophysiology, diagnosis and new developments in nanoparticulate systems for the treatment of liver fibrosis related chronic liver disorder. Hepatic stellate cell (HSC) activation is thought to be the primary cause of liver fibrosis. Because of their unique abilities to transfer medications and other therapeutics moieties, liposomes, nanoparticulate systems have all been extensively researched. Currently, nanoparticle technology is used for liver fibrosis. Liver fibrosis can be caused by alcoholism, hepatitis viruses, genetic disorders, steatohepatitis, autoimmune, and other non-infectious conditions including fatty liver. Advanced liver fibrosis, or cirrhosis, is defined by the formation of nodules of regenerated hepatocytes after a fibrous scar caused by the accumulation of extracellular matrix (ECM) proteins disrupts the architecture of the liver. Keywords: Liver fibrosis,Nanomedicine,Therapy,Theranostics,Application