Direct-acting antivirals (DAA) are highly effective for the management of HCV disease. This study aims to evaluate changes in health-related quality of life (HQoL) among people with HCV who were treated with DAAs using a minimal monitoring (MINMON) approach.

ACTG A5360 was a multicenter, international (Brazil, South Africa, Thailand, Uganda, and USA) trial to assess the feasibility and efficacy of MINMON approach in people with HCV. We measured HQoL using EQ-5D-3L at baseline, sustained virological evaluation visit, week 48 and week 72, and described using EQ-5D summary index (ranges:0-1) and visual analog scale (VAS) score (ranges 0-100). We used paired T-tests to evaluate the change in EQ-5D summary and multivariable linear regression for changes in VAS scores.

Overall, 394 individuals were included; most did not have cirrhosis (360; 91%) or problematic alcohol use (278; 71%). We found HQoL improvements for participants from Brazil and Thailand, but not for the USA. Participants reported high rates of pain/discomfort and anxiety/depression, with decreases over time only for Brazil. Factors associated with larger improvements in VAS scores included: cirrhosis at baseline, and non-use or problematic use of other substances (apart from tobacco/marijuana) compared to non-problematic use.

We found HQoL improvements among people with HCV following DAA treatment with variability across countries. Our findings reinforce the importance of DAA treatment, especially among those with advanced HCV disease. Continuous mental health care including depression and substance use support should be offered to individuals after HCV treatment.

NCT03512210 (22-Oct-2018) Direct-acting antivirals are highly effective for the management of hepatitis C disease. Recent studies have shown that hepatitis C treatment with direct-acting antivirals has a positive impact on quality of life. However, no studies have assessed quality of life among individuals starting direct-acting antivirals treatment across multiple countries representing high-, middle- and low-income settings. In this study, we evaluated changes in health-related quality of life among people with hepatitis C who were treated with direct-acting antivirals using a simplified treatment delivery and offering minimal in-person monitoring. We found quality of life improvements among persons with hepatitis C after direct-acting antivirals treatment, with differences across countries. Although direct-acting antivirals treatment works well and should be available to all persons with hepatitis C, we found that participants with cirrhosis (liver damage) had higher improvements in quality of life, reinforcing the importance of starting treatment among people with advanced hepatitis C. We also found high rates of anxiety and depression, pointing to the importance of adding mental health care and support to infectious diseases services.

Hepatitis B is one of the killer communicable diseases, with a global estimation of 1.1 million deaths resulting from liver diseases annually. The search for HBV therapeutics has resulted in repurposing the existing antiretrovirals (ARVs) for HBV treatment, considering their shared common replication mechanisms. This review is aimed at evaluating the potencies of some of the repurposed ARVs used for HBV treatment, analyzing the common mechanisms of viral replications in HBV and HIV, and investigating the potentials of traditional medicines as an alternative treatment for HBV patients. The topical keywords drug repurposing, drug repositioning, antiretrovirals, hepatitis B treatment, HBV, natural products, traditional medicines, title, and abstract were searched in PubMed, Web of Science, and Google Scholar. The advanced search included the five years, 2019-2024. The search result was filtered from 377 to 110 relevant articles. The evaluation reveals that CD4+ T cells are targeted by HIV, while HBV targets the liver with its associated diseases (cirrhosis and hepatocellular carcinoma (HCC)). Furthermore, treatments with the available repurposed ARVs only prevent or slow down the progression to cirrhosis, reduce the HCC incidence, and can improve the quality of life and increase life expectancy; however, they are not curative for HBV. Traditional medicines/natural product extracts or their phytochemicals exert anti-HBV effects through different mechanisms. Traditional medicines exert improved therapeutic effects when combined properly. The investigation further reveals that consideration of an in silico approach in HBV therapeutics might not only streamline drug development but also contribute to a deeper understanding of viral pathogenesis. Therefore, we recommend the integration of computational drug design methods with traditional medicine and natural product screening for discovering new bioactive HBV drug candidates.

Chronic infection with hepatitis C virus (HCV) has a long-term impact on hepatic consequences. A comprehensive evaluation of the global burden of HCV-related health outcomes can help to develop a global HCV prevention and treatment program.

We used the 2019 Global Burden of Disease (GBD) Study to comprehensively investigate burden and temporal trends in incidence, mortality and disability-adjusted life-years (DALYs) of HCV-related diseases, including liver cancer and cirrhosis and other liver diseases across 264 countries and territories from 2010 to 2019.

Globally, there were 152 225 incident cases, 141 811 deaths and approximately 2.9 million DALYs because of HCV-related liver cancer, and 551 668 incident cases, 395 022 deaths and about 12.2 million DALYs because of HCV-related cirrhosis in 2019. Worldwide, during the 2010-2019 period, liver cancer incidence declined, however, there was a 62% increase in cirrhosis incidence. In 2019, the Eastern Mediterranean was the region with the highest rates of incidence and mortality of both liver cancer and cirrhosis. Africa was the region with the fastest-growing trend of incidence of cirrhosis in the 2010-2019 period [annual percentage change (APC) = 2.09, 95% confidence interval (CI): 1.93-2.25], followed by the Western Pacific region (APC = 1.17, 95% CI: 1.09-1.22). Americas were the only region observing increased trends in liver cancer and cirrhosis mortality (APC = 0.70 and 0.12, respectively). We identified three patterns of temporal trends of mortality rates of liver cancer and cirrhosis in countries that reported HCV treatment rates.

Urgent measures are required for diagnosis, treatment and research on HCV-related cirrhosis at global, regional and country levels, particularly in Africa, the Western Pacific and the Eastern Mediterranean.

The traditional vaccines against hepatitis have been instrumental in reducing the incidence of some types of viral hepatitis; however, the need for cost-effective, easily distributable, and needle-free vaccine alternatives has led to the exploration of plant-based vaccines. Plant-based techniques offer a promising avenue for producing viral hepatitis vaccines due to their low-cost cultivation, scalability, and the potential for oral administration. This review highlights the successful expression of hepatitis B surface antigens in plants and the subsequent formation of virus-like particles, which have shown immunogenicity in preclinical and clinical trials. The challenges such as achieving sufficient antigen expression levels, ensuring consistent dosing, and navigating regulatory frameworks, are addressed. The review considers the potential of plant-based vaccines to meet the demands of rapid vaccine deployment in response to outbreaks and their role in global immunization strategies, particularly in resource-limited settings. This review underscores the significant strides made in plant molecular farming and the potential of plant-based vaccines to complement existing immunization methods against viral hepatitis.

Approximately 2.2% of Libyans have chronic hepatitis B (CHB) and are at the highest risk of developing end-stage disease complications. Several resource-limited countries, including Libya, may be far from achieving the WHO goal of hepatitis B elimination by 2030 as a result of several testing and linkage to care (LTC) barriers. In Libya, data about the current HBV infection situation is scarce. Therefore, our study aimed to evaluate the trends of HBV in eastern Libya, Tobruk region, and try to identify the region-specific gaps and barriers that could potentially delay the WHO goal of HBV elimination. An eighteen-year retrospective review of records of the main district medical center in the region was done to estimate the trends of HBV infection and qualitative interviews with the clinical staff of the CHB registry in the region were conducted to investigate the current status of HBV management. Out of 392,952 records, 371 (0.09%) HBV-positive were recorded and declining trends of the infection were noticed over the study period. Until late 2019, there was no linkage to care or follow-up for people with HBV infection. However, a CHB registry was established in late 2019 to manage HBV infections in the region, yet there are several barriers such as the lack of diagnostic infrastructure for liver function assessment and antiviral treatment. Despite the significant decline observed in the occurrence of HBV infection and introduction of important HBV management steps such as establishment of the CHB registry, there are still several barriers that could delay the elimination of the infection.

The objective of the study was to analyse the prevalence, incidence, and death of alcohol-associated liver disease (ALD) among adolescents and young adults globally, continentally, and nationally, focusing on trends over time.

The study analysed data from the Global Burden of Disease (GBD) study between 2000 and 2019. It examined ALD's prevalence, incidence, and death in adolescents and young adults aged 15-29, segmented by region, nation, and sociodemographic index. The analysis utilised Joinpoint regression modelling to calculate the annual per cent change (APC) in the rate of these parameters over time.

In 2019, there were 281,450 ALD prevalences, 18,930 incidences, and 3190 deaths among adolescents and young adults globally. From 2000 to 2019, the age-adjusted prevalence rate per 100,000 increased in the 25-29 age group (APC: +0.6%, p = 0.003), remained stable among ages 20-24 (p = 0.302) and ages 15-19 (p = 0.160). Prevalence increased significantly from age 15-19 to 20-24 (19-fold increase) and from age 20-24 to 25-29 (2.5-fold increase). ALD prevalence rates increased in all age groups in adolescents and young adults in Africa and the Eastern Mediterranean region. Around three-quarters of countries and territories experienced an increase in ALD incidence rates in young adults.

Over two decades, the burden of ALD among adolescents and young adults has increased globally. The study emphasises the importance of public health policies aimed at reducing alcohol consumption and preventing ALD among younger populations.

It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data.

This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality.

Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001).

Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests.

The Korea Disease Control and Prevention Agency.

The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease.

Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019.

Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV.

Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries.

Liver disease poses a substantial burden in Latin America. This burden is primarily attributed to a high level of alcohol consumption and the increasing prevalence of risk factors associated with metabolic dysfunction-associated steatotic liver disease (MASLD), such as sedentary lifestyles, easy access to ultra-processed foods, obesity, and type 2 diabetes mellitus. These epidemiological trends are cause for concern, especially considering that there are significant challenges in addressing them due to disparities in access to liver disease screening and care. In this article, we aim to provide an overview of the current situation regarding liver disease in Latin America. We also discuss recent multinational proposals designed to address the growing MASLD burden via its integration into existing non-communicable diseases policies, at both local and global levels. Additionally, we emphasize the urgent need to establish effective public health policies that target both MASLD risk factors and excessive alcohol consumption. Furthermore, we discuss the development of liver transplantation programs, areas for improvement in medical education and research capabilities, and how the fostering of extensive collaboration among all stakeholders is crucial for addressing liver disease in the region.

Cirrhosis was the leading cause of morbidity and mortality in adults, but data on the burden and trends were sparse in children and adolescents. We aimed to assess the trends in 204 countries and territories over the past 30 years in children and adolescents aged 0-19 years.

Data on cirrhosis was collected by the Global Burden of Disease (GBD) 2019 database from 1990 to 2019. We reported on the number, rates, and average annual percentage changes (AAPCs) of incidence and disability-adjusted life-years (DALYs) of cirrhosis at global, regional, and national level.

Globally, the incident numbers of cirrhosis in children and adolescents increased from 204,767 in 1990 to 241,364 in 2019, an increase of 17.9%, with an AAPC 0.13(0.10 to 0.16). Prevalence (AAPC = - 2.27[- 2.39 to - 2.15]), mortality (AAPC = - 1.68 [- 1.86 to - 1.5]), and DALYs rate (AAPC = - 1.72[- 1.88 to - 1.56]) of cirrhosis have decreased significantly. Cirrhosis incident rates varied between different ages. Cirrhosis caused by alcohol use (AAPC = 1[0.8 to 1.1]; incidence cases increased 48%), hepatitis C (AAPC = 0.4 [0.4 to 0.5]), NAFLD (AAPC = 0.5 [0.3 to 0.6]) have been increasing, while only hepatitis B (- 0.3[- 0.4 to - 0.2]) decreasing. Incidence cases of cirrhosis were increased in low (101.6%) and low-middle sociodemographic index (SDI 21.1%) areas, while decreasing in middle and above SDI areas. At the regional level, the largest increases count was observed in Sub-Saharan Africa.

Global incidence rate of cirrhosis has been increasing, while the DALYs rate has been decreasing in children and adolescents. Morbidity of cirrhosis caused by hepatitis B declined, while hepatitis C, NAFLD, and alcohol use increased.

To investigate the trends in health-related quality of life (HRQoL) among hepatitis C virus (HCV) patients and to assess the longitudinal impact of antiviral therapy on their well-being.

In this prospective multicenter observational study in adults with HCV infection, sociodemographic, clinical characteristics and EQ-5D questionnaires were collected. Generalized estimating equation (GEE) models were used to assess the associations between these variables and changes in HRQoL over time.

456 patients were included, with a median age of 46.5 (36.5-57.0) years, of which 262 (57.5%) were males and 44 (9.6%) had cirrhosis. 335 patients (73.5%) receiving antiviral therapy and 61.8% achieved sustained virologic response (SVR). The baseline EQ-5D utility and EQ-VAS were 0.916 ± 0.208 and 80.6 ± 13.0. In multivariable analysis of GEE estimation, achieving SVR24 was positively associated with EQ-5D utility (p = 0.000) and EQ-VAS (p = 0.000) over time. Age and income were shown to be significant predictors of EQ-5D utility, while gender, age and genotype were associated with EQ-VAS over time.

SVR improved long-term HRQoL in HCV patients in the first few years following viral clearance. Certain sociodemographic factors, such as gender, age, income as well as genotype, significantly influenced long-term changes in patients' quality of life.

NCT01594554. Registration date: 09/05/2012.

Hepatocellular carcinoma (HCC) surveillance in low-risk patients (annual incidence <1.5%) is not recommended per the American Association for the Study of Liver Diseases guidelines. Because patients with chronic hepatitis C with non-advanced fibrosis who have achieved sustained virological response (SVR) have a low risk of HCC, HCC surveillance is not recommended for them. However, aging is a risk factor for HCC; threfore, the necessity for HCC surveillance in older patients with non-advanced fibrosis needs to be verified.

This multicenter, prospective study enrolled 4993 patients with SVR (1998 patients with advanced fibrosis and 2995 patients with non-advanced fibrosis). The HCC incidence was examined with particular attention to age.

The 3-year incidence of HCC in patients with advanced and non-advanced fibrosis was 9.2% (95% CI: 7.8-10.9) and 2.9% (95% CI: 2.1-3.7), respectively. HCC incidence was significantly higher in patients with advanced fibrosis (P < 0.001). HCC incidence stratified by age and sex was investigated in patients with non-advanced fibrosis. The HCC incidence in the 18-49, 50s, 60s, 70s, and ≥80 age groups were 0.26, 1.3, 1.8, 1.7, and 2.9 per 100 person-years in men, and 0.00, 0.32, 0.58, 0.49, and 0.57 per 100 person-years in women, respectively.

Male patients with non-advanced fibrosis aged ≥60 years have a higher risk of developing HCC and, thus, require HCC surveillance.

Cirrhosis causes a heavy global burden. In this review, we summarized up-to-date epidemiological features of cirrhosis and its complications. Recent epidemiological studies reported an increase in the prevalence of cirrhosis in 2017 compared to in 1990 in both men and women, with 5.2 million cases of cirrhosis and chronic liver disease occurring in 2017. Cirrhosis caused 1.48 million deaths in 2019, an increase of 8.1% compared to 2017. Disability-adjusted life-years due to cirrhosis ranked 16th among all diseases and 7th in people aged 50-74 years in 2019. The global burden of hepatitis B virus and hepatitis C virus-associated cirrhosis is decreasing, while the burden of cirrhosis due to alcohol and nonalcoholic fatty liver disease (NAFLD) is increasing rapidly. We described the current epidemiology of the major complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, renal disorders, and infections. We also summarized the epidemiology of hepatocellular carcinoma in patients with cirrhosis. In the future, NAFLD-related cirrhosis will likely become more common due to the prevalence of metabolic diseases such as obesity and diabetes, and the prevalence of alcohol-induced cirrhosis is increasing. This altered epidemiology should be clinically noted, and relevant interventions should be undertaken.