BACKGROUND: Large disparities exist in liver cancer burden trends across countries but are poorly understood. We aimed to investigate the global trajectories of liver cancer burden, explore the driving forces, and predict future trends. METHODS: Data on the liver cancer burden in 204 countries and territories from 1990 to 2019 were extracted from the Global Burden of Disease Study. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) trajectories were defined using growth mixture models. Five major risk factors contributing to changes in the ASIR or ASMR and socioeconomic determinants were explored using the identified trajectories. A Bayesian age-period-cohort model was used to predict future trends through 2035. RESULTS: Three trajectories of liver cancer burden were identified: increasing, stable, and decreasing groups. Almost half of the American countries were classified in the decreasing group (48.6% for ASIR and ASMR), and the increasing group was the most common in the European region (ASIR, 49.1%; ASMR, 37.7%). In the decreasing group, the decrease of liver cancer due to hepatitis B contributed 63.4% and 60.4% of the total decreases in ASIR and ASMR, respectively. The increase of liver cancer due to alcohol use, hepatitis C, and hepatitis B contributed the most to the increase in the increasing group (30.8%, 31.1%, and 24.2% for ASIR; 33.7%, 30.2%, and 22.2% for ASMR, respectively). The increasing group was associated with a higher sociodemographic index, gross domestic product per capita, health expenditure per capita, and universal health coverage (all P <0.05). Significant variations in disease burden are predicted to continue through 2035, with a disproportionate burden in the decreasing group. CONCLUSION Global disparities were observed in liver cancer burden trajectories. Hepatitis B, alcohol use, and hepatitis C were identified as driving forces in different regions.
Humans ; Bayes Theorem ; Liver Neoplasms ; Risk Factors ; Hepatitis C/complications* ; Hepatitis B ; Hepacivirus ; Incidence

OBJECTIVE: The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody in hospital patients, evaluate the epidemic trend of hepatitis C and formulate screening strategies. METHODS: Patient information and HCV antibody testing results were collected from January 2017 to December 2019 in 77 HCV sentinel hospitals in China. Univariate and multivariate logistic regression was used to determine the characteristics and associations. RESULTS: HCV antibody prevalence rates were distinct among patients in different departments, with a range of 0.33%-6.93%. Patients who were admitted to the liver disease-related departments (a OR = 10.76; 95% CI, 10.27-11.28), Internal Medicine (a OR = 2.87; 95% CI, 2.75-3.00), and Department of Surgery (a OR = 1.95; 95% CI, 1.87-2.04), were more likely to be tested for HCV antibody positive. HCV antibody prevalence was associated with patients aged 45 years and older (a OR = 2.74; 95% CI, 2.69-2.80), testing in infetious disease hospitals (a OR = 2.33; 95% CI, 2.26-2.40) and secondary hospitals (a OR = 1.72; 95% CI, 1.69-1.75). Patients in sentinel hospitals of the Northeast (a OR = 12.75; 95% CI, 12.40-13.11), the Central (a OR = 1.65; 95% CI, 1.61-1.70), and the West (a OR = 1.78; 95% CI, 1.73-1.83) China had higher HCV prevalence than those who were in the Eastern coastal area. CONCLUSION Those who were over 45 years old and saw doctors for liver diseases, and invasive diagnosis and treatment should be referred to HCV antibody testing.
Humans ; Middle Aged ; Prevalence ; Hepatitis C/complications* ; Hepacivirus ; Hospitals ; Hepatitis C Antibodies ; China/epidemiology* ; Risk Factors

Acute Disease ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/microbiology* ; Female ; Hepatitis B, Chronic/complications* ; Hepatitis C, Chronic/complications* ; Humans ; Hypersplenism/complications* ; Liver Cirrhosis/complications* ; Meningococcal Infections/microbiology* ; Neisseria meningitidis/isolation & purification* ; Peritonitis/microbiology*

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.
Antiviral Agents/therapeutic use* ; Carbamates ; Drug Therapy, Combination ; Genotype ; Hepacivirus/genetics* ; Hepatitis C/drug therapy* ; Hepatitis C, Chronic/drug therapy* ; Heterocyclic Compounds, 4 or More Rings ; Humans ; Liver Cirrhosis/complications* ; Prospective Studies ; RNA ; Ribavirin/therapeutic use* ; Sofosbuvir/adverse effects* ; Sustained Virologic Response ; Treatment Outcome

Objective: To explore the diagnostic value and model of serum Golgi protein 73 (GP73) in patients with hepatitis C cirrhosis. Methods: 271 cases with chronic hepatitis C virus infection who were treated in the Fifth Medical Center of PLA General Hospital from January 2010 to December 2017 were retrospectively collected as the research objects, including 126 cases with hepatitis and 145 cases with liver cirrhosis. Serum GP73 and liver stiffness measurement (LSM) based on transient elastography test were performed in all patients. Simultaneously, blood routine, liver function, coagulation function and other related indicators were collected. GP73 diagnostic efficiency for liver cirrhosis was evaluated by receiver operating characteristic curve (ROC). GP73 diagnostic value was clarified after comparison with aspartate aminotransferase/platelet ratio index (APRI), FIB-4 index (FIB-4) and LSM. Compensated hepatitis C virus-related cirrhosis diagnostic model based on serological index was established by logistic regression analysis. Results: The area under the receiver operating characteristic curve (AUC) of GP73, LSM, FIB-4 and APRI in the diagnosis of compensated hepatitis C virus-related cirrhosis were 0.923, 0.839, 0.836 and 0.800 respectively, and GP73 had the best diagnostic efficiency (P <0.001). LSM and GP73 combined use had improved the diagnostic sensitivity of cirrhosis to 97.24%. Multivariate logistic regression analysis revealed that GP73, age, and platelets were independent predictors of cirrhosis.Compensated hepatitis C virus-related cirrhosis diagnostic model (GAP) was established based on the result: LogitP=1/[1+exp(6.145+0.013×platelet-0.059×age-0.059×GP73)].AUC model for diagnosing compensated liver cirrhosis was 0.944, and the optimal cut-off value was 0.56, with sensitivity and specificity of 84.03% and 92.06%, respectively, and the diagnostic efficiency of this model was better than that of APRI, FIB-4, LSM and GP73 alone (P<0.05). Conclusion: GP73 is a reliable serum biomarker for the diagnosis of compensated hepatitis C virus-related cirrhosis. The GAP diagnostic model based on GP73, platelet count, and age can further improve the diagnostic efficiency and help to diagnose patients with compensated hepatitis C virus-related cirrhosis.
Aspartate Aminotransferases ; Biomarkers ; Fibrosis ; Hepatitis C ; Hepatitis C, Chronic/complications* ; Humans ; Infant, Newborn ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Polyesters ; ROC Curve ; Retrospective Studies

INTRODUCTION: To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive. METHODS: The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented. RESULTS: Between 2011 and 2014, of 161,658 individuals who underwent screening prior to blood donation, 95 (0.059%) were positive for HCV. Of the 42 sera available, common genotypes (GTs) were GT-3 (47.6%) and GT-1 (31.0%). Of 1,575 HD patients, 2.2% were anti-HCV positive. The HCV GT distribution was HCV GT-1 (32.4%), HCV GT-3 (20.5%) and GT-6 (8.8%). 83 halfway house inmates were screened. Of the 47 IVDUs, 36.2% were anti-HCV positive with predominant GT-3 (%). IL28B polymorphism was noted to be CC predominantly 85.3%. CONCLUSION Prevalence of HCV infection has decreased in both the BD and HD populations. However, it remains high in the IVDU population. GT-1 remains the most common in the HD population; however, GT-3 infection is now more common among the BD population in Singapore. IL28B - CC is the predominant variant among the HCV-infected individuals in Singapore.
Acute Kidney Injury ; blood ; complications ; Adult ; Alleles ; Blood Donors ; Female ; Genotype ; Hepatitis C ; epidemiology ; Humans ; Interleukins ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prevalence ; Renal Dialysis ; Singapore ; epidemiology ; Substance Abuse, Intravenous ; blood ; epidemiology ; Young Adult

OBJECTIVEThe aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle.

DATA SOURCESThis review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication".

STUDY SELECTIONArticles related to iron metabolism, iron overload in patients with CHC, or the effects of iron on HCV life cycle were selected for the review.

RESULTSIron overload is common in patients with CHC. The mechanisms involve decreased hepcidin levels caused by HCV through signal transducer and activator of transcription 3, mitogen-activated protein kinase, or bone morphogenetic protein/SMAD signaling pathways, and the altered expression of other iron-metabolism-related genes. Some studies found that iron increases HCV replication, while other studies found the opposite result. Most of the studies suggest the positive role of iron on HCV translation, the mechanisms of which involve increased expression levels of factors associated with HCV internal ribosome entry site-dependent translation, such as eukaryotic initiation factor 3 and La protein.

CONCLUSIONThe growing literature demonstrates that CHC leads to iron overload, and iron affects the HCV life cycle in turn. Further research should be conducted to clarify the mechanism involved in the complicated interaction between iron and HCV.

Female ; Hepacivirus ; pathogenicity ; Hepatitis C ; complications ; metabolism ; Hepcidins ; metabolism ; Humans ; Iron Overload ; etiology ; metabolism ; virology ; Male ; Signal Transduction

BACKGROUND/AIMS: The prevalence of hepatitis C virus (HCV) infection in Busan, Gyeongnam, and Jeonnam Provinces in Korea is more than twice the national average. This study aimed to examine whether demographic and lifestyle characteristics are associated with HCV infection in these areas. METHODS: A case control study was performed at three study hospitals. HCV cases were matched with two controls for sex and age. Patient controls were selected from non-HCV patients at the same hospital. Healthy controls were subjects participating in medical checkups. Conditional logistic regression models were used. RESULTS: A total of 234 matched-case and patient- and healthy-control pairs were analyzed. The significant risk factors for both controls were sharing razors (adjusted odds ratio [aOR], 2.39 and 3.29, respectively) and having more than four lifetime sexual partners (aOR, 2.15 and 6.89, respectively). Contact dockworkers (aOR, 1.91) and tattoos (aOR, 2.20) were significant risk factors for the patient controls. Transfusion (aOR, 5.38), a bloody operation (aOR, 5.02), acupuncture (aOR, 2.08), and piercing (aOR, 5.95) were significant risk factors for the healthy controls. Needle stick injuries and intravenous drug abuse were significant in the univariate analysis. CONCLUSIONS: More education concerning the dangers of sharing razors, tattoos and piercings is required to prevent HCV infection. More attention should be paid to needle stick injuries in hospitals and the community.
Acupuncture Therapy/adverse effects ; Adult ; Aged ; Blood Transfusion/adverse effects ; Body Piercing/adverse effects ; Case-Control Studies ; Equipment Reuse ; Female ; *Hepacivirus ; Hepatitis C/*epidemiology/*transmission/virology ; Humans ; Life Style ; Logistic Models ; Male ; Middle Aged ; Needlestick Injuries/complications/virology ; Odds Ratio ; Prevalence ; Republic of Korea/epidemiology ; Risk Factors ; Sexual Behavior ; Sexual Partners ; Tattooing/adverse effects ; Workplace ; Young Adult

Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed "washout" in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule > or = 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis.
Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/*diagnosis/pathology ; Contrast Media ; Female ; Hepatitis B, Chronic/complications ; Hepatitis C, Chronic/complications ; Humans ; Liver/*pathology ; Liver Neoplasms/*diagnosis/pathology ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Practice Guidelines as Topic ; Republic of Korea ; Young Adult

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated. METHODS: In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. RESULTS: During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. CONCLUSIONS: Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.
Aged ; Carcinoma, Hepatocellular/mortality/pathology/*surgery ; Catheter Ablation ; Female ; Hepatitis B/complications ; Hepatitis C/complications ; Humans ; Liver Neoplasms/mortality/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome