Hepatocellular Carcinoma In Taiwan Research Articles

Secular Trends of Clinical Characteristics and Survival of Hepatocellular Carcinoma in Taiwan from 2011 to 2019.

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Taiwan, and in the past 30-40 years, Taiwan has been committed to its prevention and treatment. We aimed to investigate the secular trends of characteristics and the survival of HCC in recent decades after making increased efforts. Between 2011 and 2019, a total of 73,817 cases were enrolled from the TCR database. The overall male-to-female ratio was 7/3. The overall, male and female mean ages increased from 63.8 to 66.1 years, 62.0 to 64.3 years and 68.3 to 70.4 years, respectively. After dividing by viral etiologies and gender, the mean age showed increasing trends in all subgroups. The proportions of HBV-HCC, HCV-HCC, HBV+HCV-HCC and Non-HBV+non-HCV-HCC were 48.3%, 25.2%, 5.3% and 21.3% in males, compared with 25.5%, 48.6%, 5.3% and 20.5% in females, respectively. The 5-year survival rates of BCLC stages 0, A, B, C and D were 70%, 58%, 34%, 11% and 4%, respectively. The proportion of BCLC stage 0 increased from 6.2% to 11.3%. Multivariate analysis showed that being female, older age, diagnostic year, BCLC stages, hospital level, body mass index, smoking, alcohol consumption, AFP, Child-Pugh classification and HBV/HCV status were independent predictors for survival. In recent decades, the overall survival of HCC in Taiwan has been improving and might be partly associated with increased BCLC 0 and Child-Pugh A patients, while with the consequent age of patients increasing over time. The proportion of viral-related HCC is decreasing, while nonviral-related HCC is increasing.

Effects of Achieving SVR on Clinical Characteristics and Surgical Outcomes in Patients Who Developed Early-Stage HCV-Related Hepatocellular Carcinoma and Received Curative Resection: Preoperative versus Postoperative SVR.

The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative resection remain elusive. We aimed to compare the clinical presentation and postoperative prognosis among patients with early-stage HCV-related HCC and different viral status. We retrospectively analyzed 208 patients with BCLC stage 0 or A-HCC, including 44 patients who remained HCV viremic, 90 patients who developed HCC after achieving SVR (post-SVR HCC), and 74 patients who subsequently achieved SVR after resection. Patients with post-SVR HCC had a lower degree of hepatitis and better liver function than those who achieved SVR or remained viremic after resection. Notably, 75.6% of patients with post-SVR HCC did not have cirrhosis. Patients with post-SVR HCC and those achieving SVR after resection exhibited comparable recurrence rates and recurrence-free survival, while patients with persistent viremia had the worst surgical outcomes. We concluded that patients with post-SVR HCC had a better liver function but similar surgical outcomes compared with patients who achieved SVR after resection. The low prevalence of cirrhosis in patients with post-SVR HCC highlights the importance of regular surveillance after SVR.

The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes to Hepatocellular Carcinoma Susceptibility.

Metalloproteinase-7 (MMP-7) has been previously found to be up-regulated in hepatocellular carcinoma (HCC) specimens and cells, favoring epithelial-mesenchymal transition. However, the contribution of MMP-7 genotypes to HCC has not been revealed to date. The study aimed to evaluate the contribution of MMP-7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes on the risk of HCC in Taiwan, where HCC incidence is extremely high compared to worldwide data. In this case-control study, MMP-7 genotypes and their association with cigarette smoking and alcohol drinking habits were determined in 298 HCC patients and 889 healthy subjects by a typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Ever smokers and alcohol drinkers were represented with higher percentages in the case group compared to the control group. MMP-7 rs11568818 genotypes were not found differentially distributed in case and control groups (p for trend=0.5246). People of the analyzed cohort of the present study were all of CC genotypes at their rs11568819 polymorphic sites, without any CT or TT genotypes. As for gene-lifestyle interactions, people with variant genotypes at MMP-7 rs11568818 had the same odds for HCC development compared to the wild-type AA genotype, no matter whether the subjects belonged to the smoker, non-smoker alcohol drinker, or non-drinker groups. MMP-7 variant genotypes did not present any significance towards being a marker for HCC risk in Taiwanese.

Safety and Efficacy of Drug-Eluting Beads Trans-Arterial Chemoembolization for Hepatocellular Carcinoma in Taiwan (SERENADE-T)

PurposeThe aim of this retrospective study was to evaluate the safety and efficacy of patients with hepatocellular carcinoma treated with drug-eluting bead with doxorubicin transarterial chemoembolization (DEBDOX-TACE) in Taiwan.Patients and MethodsWe retrospectively investigated 630 hepatocellular carcinoma patients who underwent DEBDOX-TACE in multiple institutions from 2011 to 2016 in Taiwan. Tumor response was assessed per modified response evaluation criteria in solid tumors, overall survival, and safety.ResultsThis study included 630 patients who underwent DEBDOX-TACE, participants’ mean age was 66 years, 68.1% males and 15.6% females. The mean doxorubicin dose administered via DEBDOX-TACE was 56 mg. Complete and partial response rates were 14.6% and 49.2%, respectively, with a disease control rate of 84.6%. The median overall survival was 29.2 months. The most common post-embolization symptom was abdominal pain (22.4%). No hepatic encephalopathy and no procedure-related death were found.ConclusionReal-world data from Taiwan demonstrated that DEBDOX-TACE for hepatocellular carcinoma can achieve high tumor response rate with low adverse events.

Exposure to Air Pollution and Survival in Follow-Up after Hepatocellular Carcinoma

Introduction: Air pollutants are classified as carcinogens by the International Agency for Research on Cancer. Long-term exposure to ambient particulate matter with an aerodiameter of 2.5 μm or lower (PM_2.5) has been reported to be linked with increased mortality due to hepatocellular carcinoma (HCC). However, the effects of air pollutants other than PM_2.5 on HCC-related mortality have not been fully investigated. Accordingly, we conducted this study to assess the effect of long-term exposure to air pollutants (PM_2.5 and nitrogen dioxide [NO₂]) on HCC-related mortality. Method: In 2005, the Taiwan Liver Cancer Network (TLCN) was established by the National Research Program for Genomic Medicine to recruit liver cancer patients from 5 major medical centers in northern, central, and southern Taiwan. The TLCN had successfully recruited 9,344 patients by the end of 2018. In this study, we included 1,000 patients randomly sampled from the TLCN to assess the effect of exposure to air pollutants on HCC mortality after HCC diagnosis. Daily averages of PM_2.5 and NO₂ concentrations were retrieved from 77 air quality-monitoring stations and interpolated to the townships of patients’ residences by using the Kriging method. The effect of air pollutants on HCC survival was assessed using a Cox proportional hazards model. Results: A total of 940 patients were included in the analysis. After adjusting for potential confounders and mutually adjusting for co-pollutants, we observed that the hazards ratio (95% confidence interval) for HCC-related mortality for every 1-μg/m³ increase in PM_2.5 concentration was 1.11 (1.08–1.14) and that for every 1-ppb increase in NO₂ concentration was 1.08 (1.03–1.13). Conclusion: Our study suggests that long-term exposure to PM_2.5 and NO₂ was associated with decreased survival time in patients with HCC in Taiwan.

Optimal Intervals of Ultrasonography Screening for Early Diagnosis of Hepatocellular Carcinoma in Taiwan

There are different clinical practices regarding ultrasonography screening intervals for hepatocellular carcinoma (HCC) despite recommendations from international guidelines. To evaluate whether ultrasonography screening using intervals suggested by international guidelines is associated with cancer stage shifting, reductions in mortality, and improved quality of life (QoL) for patients with HCC. This nationwide comparative effectiveness research study estimated lifetime survival functions using interlinkages of 3 databases from Taiwan-the Taiwan National Health Insurance, Taiwan National Cancer Registry, and National Mortality Registry-combined with QoL measurements obtained from National Cheng Kung University Hospital. In total, 114 022 patients listed as having newly diagnosed HCC from 2002 through 2015 in the Taiwan National Cancer Registry were followed up until 2017. The QoL values of 1059 patients with HCC who visited National Cheng Kung University Hospital were prospectively measured with the European QoL-5 dimensions questionnaire from 2011 through 2019. Patients were categorized based on the time between their last ultrasonography screening and the index date (90 days prior to HCC diagnosis) as 1 of 5 subcohorts: 6 months (0-6 months), 12 months (7-12 months), 24 months (13-24 months), 36 months (25-36 months), and longer than 36 months (no screening in the previous 3 years). Data were analyzed from April 2020 to April 2021. Life expectancy, quality-adjusted life expectancy, and loss of life expectancy or loss of quality-adjusted life expectancy compared with age-, sex-, and calendar year-matched cohorts. There were 59 194 patients with Barcelona Clinic Liver Cancer staging information, including 42 081 men (mean [SD] age, 62.2 [12.6] years) and 17 113 women (mean [SD] age, 69.0 [11.2] years). There was a consistent trend showing that the longer the interval between ultrasonography examinations, the higher the loss of life expectancy and loss of quality-adjusted life expectancy for both sexes. Loss of quality-adjusted life expectancy values for male subcohorts were 10.0 (95% CI, 9.1-10.9) quality-adjusted life-years (QALYs) for ultrasonography screening intervals of 6 months, 11.1 (95% CI, 10.4-11.8) QALYs for 12 months, 12.1 (95% CI, 11.5-12.7) QALYs for 24 months, 13.1 (95% CI, 12.6-13.6) QALYs for 36 months, and 14.6 (95% CI, 14.2-15.0) QALYs for longer than 36 months. Loss of quality-adjusted life expectancy values for female subcohorts were 9.0 (95% CI, 8.3-9.6) QALYs for 6 months, 9.7 (95% CI, 9.2-10.2) QALYs for 12 months, 10.3 (95% CI, 9.8-10.7) QALYs for 24 months, 10.7 (95% CI, 10.2-11.1) QALYs for 36 months, and 11.4 (95% CI, 11.0-11.8) QALYs for longer than 36 months. Patients with underlying hepatitis B virus infection or cirrhosis had the greatest improvement in life expectancy with shorter screening intervals. Regular ultrasonography screening with intervals less than 6 to 12 months may be associated with early detection of HCC, save lives, and improve the quality of life for patients with HCC from a lifetime perspective.

Epidemiological projections of viral-induced hepatocellular carcinoma in the perspective of WHO global hepatitis elimination.

Hepatitis B is an eminent risk factor for hepatocellular carcinoma (HCC) in Southeast Asia and sub-Saharan Africa, whereas hepatitis C is a key risk factor for HCC in Western Europe and North America. Increased awareness of the global burden of viral hepatitis resulted, in May 2016, in the adoption of the first global health sector strategy on viral hepatitis by the World Health Assembly, which calls for the elimination of viral hepatitis as a public health threat by 2030. Although the incidence of liver cancer resulting from viral infections has increased since the 1990s, the implementation of public health interventions, such as hepatitis B vaccination and antiviral therapies might have reduced the global burdens of HCC. Hepatitis B immunization in infancy has been associated with a reduction in the risk of infant fulminant hepatitis, chronic liver disease, and HCC in Taiwan. Achieving viral hepatitis elimination by 2030 can be accelerated by improving the access to HCC screening programs. HCC surveillance programs in developed countries must be refined to increase an access to personalized surveillance program, whereas the limited access to surveillance and treatment of HCC in developing countries remains a significant public health issue.

Long-term effectiveness of population-wide multifaceted interventions for hepatocellular carcinoma in Taiwan

Taiwan has launched a series of population-wide interventions to prevent hepatocellular carcinoma (HCC) related to hepatitis B and C virus infection since 1984. We took this opportunity to investigate the impact of each intervention on the incidence and case-fatality rate of HCC, and assessed their relative contributions to the overall reduction in mortality during this period. Population-based registry data on HCC mortality and incidence from individuals aged 0 to 84 years between 1979 and 2016 were collected before (Period 1) and after universal hepatitis B vaccination from 1984 (Period 2), universal health care from 1995 (Period 3), and viral hepatitis therapy from 2003 (Period 4). A Bayesian Poisson regression model was used for mortality decomposition analysis to estimate the respective contributions of these interventions to the reduction in age-specific incidence and case-fatality rates. Mortality declined substantially in children, young- and middle-aged groups, but only slightly decreased in the elderly group. The declining trends in mortality were in part explained by incidence reduction and in part by a remarkable decline in case-fatality rate attributed to universal health care. Hepatitis B vaccination led to a 35.9% (26.8% to 44.4%) reduction in incidence for individuals aged 30 years or below, whereas antiviral therapy reduced the incidence of HCC by 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for individuals aged 30-49 years and 50-69 years, respectively. Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups. Since 1984, a series of population-wide interventions have been launched in Taiwan to prevent viral hepatitis-related hepatocellular carcinoma, including a universal hepatitis B vaccination program (from 1984), universal health care (from 1995), and a national viral hepatitis therapy program (from 2004). Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.

Changing faces of hepatocellular carcinoma: East vs West

We read with interest the paper "The changing scenario of hepatocellular carcinoma in Italy: an update" published in an upcoming issue of Liver International.1 It is an interesting study that looked at the changing scenario of etiology, clinical presentation, management and prognosis of hepatocellular carcinoma (HCC) in Italy during the last 15 years (2004-2018). We have recently reviewed the changing clinical patterns of HCC in Taiwan (2004-2015),2 and found that we do share remarkable resemblance between the East and West. Some findings may deserve further in-depth discussion.

Real-world experience of pembrolizumab plus lenvatinib in unresectable hepatocellular carcinoma in Taiwan.

e16627 Background: Multi-kinase inhibitors and immune checkpoint inhibitors (ICIs) are treatment options of systemic therapy for unresectable hepatocellular carcinoma (HCC). Targeted therapy can potentially enhance T cell infiltration and activation, consequently, cooperate with ICIs to produce synergistic anti-tumor effects. The ongoing clinical trial shows promising data by combining pembrolizumab with lenvatinib for advanced HCC. The study tried to evaluate the treatment response and adverse events of pembrolizumab plus lenvatinib for HCC in real-world setting. Methods: From Jul. 2019, patients who received pembrolizumab plus lenvatinib for unresectable HCC in a tertiary medical center in Taiwan were prospectively enrolled. The status of HCC was either in advanced HCC or failed by prior locoregional treatment. The dosage of pembrolizumab was 100mg every 3 weeks. The starting dose of lenvatinib was 10mg per day then titrating to weight-based dose according to recommendation. Patients who had received at least 2 cycles of pembrolizumab were evaluated in this report. The tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). The treatment related adverse events (TRAEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Till the end of Jan. 2020, 27 patients had received at least 2 cycles of pembrolizumab, and 17 had evaluable post-treatment images either by CT or MRI. There were 6 (22.2%) in BCLC B, and 21 (77.8%) in BCLC C. Of them, 17 (63%) were treated as the first-line systemic treatment, 8 as the second-line and 2 as the third line systemic treatment. Of the 17 cases with post-treatment image studies, there were 6 (35.3%) in partial response (PR), 7 (41.2%) in stable disease (SD), and 4 (23.5%) in progressive disease (PD) by RECIST v1.1; and 1 (5.8%) in complete response (CR), 9 (52.9%) in PR, 3 (17.6%) in SD and 4 (23.5%) in PD by mRECIST, respectively. The objective response rate (ORR) and disease control rate (DCR) by mRECIST were 58.7% and 76.5%, respectively. The most common TRAEs in any grade were hypertension 24 (88.4%), palmar-plantar syndrome 19 (70.4%), hypothyroidism 19(70.4%). The Grade 3/4 TRAEs were 3 (11.1%) with psoriasis-like skin reaction, 3 (11.1%) with hypertension and 2 (7.4%) with palmar-plantar syndrome. Conclusions: Pembrolizumab plus lenvatinib can produce excellent ORR and DCR with tolerable safety profiles. Such combination could be a promising strategy for unresectable HCC in the future.

Intensive care utilization in patients with end-stage liver disease: A population-based comparative study of cohorts with and without comorbid hepatocellular carcinoma in Taiwan

BackgroundEnd-of-life intensive care may be futile and can be a cause of distress to both patients and their families. This study aimed to understand the utilization of intensive care and its associated factors in patients with End-stage liver disease (ESLD) during terminal hospitalization. MethodsPopulation-based retrospective cohort study using the National Health Institute Research Database of Taiwan. All adult patients with ESLD who died during their hospitalization in 2010–2013 were included. FindingsOf the 14,247 patients with ESLD, the majority (60·8%) was comorbid with hepatocellular carcinoma (HCC). Patients with ESLD only were younger, more deprived, more alcohol-related, and less likely to receive palliative care prior to terminal hospitalization (6·0% vs 29·2% with HCC). Compared to patients with comorbid HCC, relatively more patients without HCC were admitted to ICU (59·6% vs 22·3%), receiving CPR (11·1% vs 4·3%) and mechanical ventilation (36·3% vs 12·5%) during terminal hospitalization. Etiology of alcoholic hepatitis, esophageal varices, septicemia, pneumonia and respiratory failure, and renal failure were associated with a higher probability of ICU admission (adjusted rate ratio (aRR) range: 1·09–2·09). Prior palliative care was associated with lower probability of ICU admission (aRR range: 0·24–0·38). InterpretationThe intensive care utilization by patients with ESLD in their terminal hospitalization was substantial in Taiwan. Those who are not comorbid with HCC need more attention, especially in terms of their palliative care needs, choices regarding intensive care, and their healthcare utilization. FundingNational Institute of Health Research Health Applied Research Collaboration (ARC) South London.

Direct-acting antivirals for patients with chronic hepatitis C and hepatocellular carcinoma in Taiwan.

The treatment of chronic hepatitis C (CHC) has evolved from interferon (IFN)-based therapy to direct acting antivirals (DAAs). The effect of antiviral treatment on outcome of hepatocellular carcinoma (HCC) patients with CHC has not been well analyzed in Taiwan. From April 2015 to May 2018, 199 HCC patients with CHC undergoing DAAs treatment, including 127 having prospectively longitudinal observation, were enrolled. Among them, 107 BCLC 0/A patients achieving curative treatment of HCC were further compared with a historical cohort of 42 HCC patients experienced pegylated interferon (Peg-IFN) plus ribavirin for CHC after curative treatment. The sustained virological response (SVR) rates were 95.0% in BCLC stage 0/A (114/120), 97.1% in BCLC B (68/70), and 77.8% in BCLC C (7/9). The median recurrence-free survivals (RFS) between the DAA and IFN arms were of no difference by counting either from antiviral treatment (29.3mo vs 39.2mo, p=0.764) or from curative treatment (65.8mo vs 44.0mo, p=0.130), respectively. Achievement of SVR was the key independent factor associated with RFS and overall survival. The pattern of recurrence was also similar between the DAA and IFN arms. For intermediate stage HCC patients, the median time to tumor progression was 9.2 months from the initiation of DAA therapy, and 90% of patients maintained in BCLC B till 12 months after the DAA treatment. The SVR is high within BCLC B HCV-HCC patients by DAAs treatment. The risk of HCC recurrence and progression is not increased by DAAs.

Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients.

Computed tomography (CT) provides scans of the human body from which digitized features can be extracted. The aim of this study was to examine the role of these digital biomarkers for predicting subsequent occurrence of hepatocellular carcinoma (HCC) in cirrhotic patients. A cohort of 269 patients with cirrhosis were recruited and prospectively followed for the occurrence of HCC in Taiwan. CT scans were retrospectively retrieved and computationally processed using analytic morphomics. A predictive score was constructed using Cox regression and the generalized iterative modeling method, maximizing the log likelihood of the time to HCC development. An independent cohort of 274 patients from University of Michigan was utilized to examine the predictive validity of this score in a Western population. Of the 27 digitized features at the 12th thoracic vertebral level, six features were significantly associated with HCC occurrence. Two digitized features (fascia eccentricity and the bone mineral density) were able to stratify patients into high- and low-risk groups with distinct cumulative incidence of HCC in both the training and validation cohorts (P = 0.015 and 0.044, respectively). When the two digitized features were tested in the Michigan cohort, only bone mineral density remained an effective predictor. Digitized features derived from the CT were effective in predicting subsequent occurrence of HCC in cirrhosis patients. The bone mineral density measured on CT was an effective predictor for patients in both Taiwan and USA.

Prognostic association of demographic and clinical factors with the change rates of symptoms and depression among patients with hepatocellular carcinoma.

To identify the predictive value of demographic and clinical factors for determining changes in physical and depressive symptom among hepatocellular carcinoma (HCC) patients over time. We performed a prospective cohort study of 128 patients newly diagnosed with HCC in Taiwan. Each patient had four time-point data after the follow-up. Patients' physical symptoms were evaluated with the Edmonton Symptom Assessment System (ESAS). Psychological symptoms were evaluated with the Hospital Anxiety and Depression Scale (HADS). Clinical factors and demographic characteristics were predictors of physical and psychological symptoms, as estimated by a generalized estimating equation (GEE). We found that patients who had a smoking habit and Barcelona Clinic Liver Cancer (BCLC) Stage B disease underwent radiofrequency ablation therapy (RFA) or liver resection, and those who had higher alanine aminotransferase (GPT) level reported more symptoms from baseline to 1month. Symptoms increased from baseline to 3months in elderly patients and patients with higher GPT levels. Additionally, patients who had jobs, underwent liver resection, and had BCLC Stage C disease had increased symptoms of depression from baseline to 1month; in particular, BCLC Stage D disease had negative long-term effects on depression scores from baseline to four-time points following therapy. Advanced BCLC stage and undergoing RFA or liver resection were most closely associated with worsening physical and psychological symptoms over time. Clinical professionals should pay attention to these factors that affect physical and psychological symptoms during treatment.

Metabolic risk factors are associated with non-hepatitis B non-hepatitis C hepatocellular carcinoma in Taiwan, an endemic area of chronic hepatitis B.

Metabolic risk factors, such as obesity, fatty liver, high lipidemia, and diabetes mellitus are associated with increased risk for nonviral hepatocellular carcinoma (HCC); however, few nonviral HCC studies have stratified patients according to underlying etiologies. From 2005 to 2011, 3,843 patients with HCC were recruited into the Taiwan Liver Cancer Network. Of these patients, 411 (10.69%) who were negative for hepatitis B virus (HBV), surface antigen, HBV DNA, and anti‐hepatitis C virus (HCV) antibody were classified as non‐HBV non‐HCV (NBNC)‐HCC. Detailed clinical analyses of these patients were compared with age‐ and sex‐matched patients with HBV‐HCC or HCV‐HCC for the associated metabolic risk factors. For this comparison, 420 patients with HBV‐HCC and 420 patients with HCV‐HCC were selected from the 3,843 patients with HCC. Multivariate analyses showed fatty liver (by echography), high triglyceride levels (>160 mg/dL), and diabetes mellitus history to be significantly associated only with NBNC‐HCC and not with the matched patients with HBV‐ or HCV‐HCC. When the patients with HCC were further divided into four groups based on history of alcoholism and cirrhotic status, the group without alcoholism and without cirrhosis exhibited the strongest association with the metabolic risk factors. Based on trend analyses, patients with NBNC‐HCC with or without alcoholism were significantly different from the matched patients with HBV‐ or HCV‐HCC, except for patients with alcoholism and cirrhosis, in having more than two of the above three risk factors. Conclusion: Metabolic risk factors are significantly associated with nonviral HCC, especially for patients without alcoholism in Taiwan. Because the prevalence of viral HCC is decreasing due to the success of universal vaccination and antiviral therapy, strategies for cancer prevention, prediction, and surveillance for HCC will require modification. (Hepatology Communications 2018;2:747‐759)

Global elimination of viral hepatitis and hepatocellular carcinoma: opportunities and challenges

The most common causes of hepatitis worldwide is a group of viruses known as hepatitis A, B, C, D and E virus. Most deaths from viral hepatitis are due to...

Case-Control Study Examining the Association between Selective Serotonin Reuptake Inhibitors Use and Hepatocellular Carcinoma.

Objectives: The purpose of the study was to assess the relationship between selective serotonin reuptake inhibitors use and hepatocellular carcinoma in Taiwan.Methods: Using the database of the Taiwan National Health Insurance Program, we conducted a case-control study to identify 4901 subjects aged 20 years and more with newly diagnosed hepatocellular carcinoma in 2000–2013 as the cases. We randomly selected 19604 subjects aged 20 years and more without hepatocellular carcinoma as the controls. Both cases and controls were matched with sex and age. Ever use of selective serotonin reuptake inhibitors was defined as a subject who had at least a prescription for selective serotonin reuptake inhibitors before index date. Never use was defined as a subject who never had a prescription for selective serotonin reuptake inhibitors before index date. The odds ratio (OR) and 95% confidence interval (CI) for hepatocellular carcinoma associated with selective serotonin reuptake inhibitors use was estimated by the multivariable logistic regression model.Results: Among subjects with any one of the comorbid conditions associated with hepatocellular carcinoma, the adjusted OR of hepatocellular carcinoma was 0.89 (95% CI 0.75, 1.06) for subjects with ever use of selective serotonin reuptake inhibitors, comparing with never use.Conclusion: The findings indicate that among subjects with any one of the comorbid conditions associated with hepatocellular carcinoma, no significant association can be detected between selective serotonin reuptake inhibitors use and hepatocellular carcinoma.

Association between complicated liver cirrhosis and the risk of hepatocellular carcinoma in Taiwan.

Hepatic encephalopathy, ascites, and variceal bleeding are the three major complications of cirrhosis. It is well known that cirrhosis is the most important risk factor of hepatocellular carcinoma (HCC). However, little is known about whether the severity of liver cirrhosis has an effect on the incidence of HCC. This population-based cohort study aimed to explore the association between complicated cirrhosis and HCC, and identify the risk factors of HCC in patients with complicated cirrhosis. Data of the years 1997–2011 were extracted from the National Health Insurance Research Database of Taiwan. A total of 2568 patients with complicated cirrhosis without HCC at baseline were enrolled. After propensity score matching, another 2568 patients with non-complicated cirrhosis were included. Hazards Cox regression analysis by using a competing risk regression model to control for possible confounding factors was utilized to estimate the association of the complications of liver cirrhosis with the risk of HCC. We observed by using competing risk analysis that the adjusted hazard ratio (HR) for developing HCC during the follow-up period after the initial hospitalization was higher among the patients with baseline complicated cirrhosis than in those with uncomplicated cirrhosis (HR, 1.23; 95% confidence interval, CI, 1.10–1.37, p<0.001). Additionally, older patients (HR, 1.01; 95% CI, 1.01–1.02, p<0.001), males (HR, 0.84; 95% CI, 0.74–0.96, p = 0.009), and patients with alcohol-related cirrhosis (HR, 1.93; 95% CI, 1.65–2.26, p<0.001) had a statistically significant difference in the incidence of HCC. In conclusion, complicated liver cirrhosis is associated with a higher risk of HCC in Taiwan compared with cirrhosis without complications.

Abstract 286: Forecast of the incidence and etiology of liver cancer in Taiwan, Japan, United States, and United Kingdom: toward harmonization of East and West

Abstract Background The global epidemiology of primary liver cancer (PLC), primarily hepatocellular carcinoma (HCC), has evolved significantly in the past decades because of improved control of viral hepatitis and the growing prevalence of metabolic factors. We conducted a quantitative forecast of the incidence and etiology of PLC. Methods Incidence rates of PLC were projected in two endemic Asian countries (Taiwan and Japan) and two Western countries (the United States and United Kingdom) with rigorous cancer registry. The annual incidence of PLC (ICD-10 C22.0) between 1980 and 2013 were obtained from the Taiwan Cancer Registry Database, the Japan National Cancer Center, the US SEER 9 database, Cancer Research UK, and the European Network of Cancer Registry. Incidence rates were projected to year 2035 by an age-period-cohort model with a power link function. The population attributable fractions (PAF) of chronic hepatitis B (HBV), chronic hepatitis C (HCV), alcohol consumption, obesity, and diabetes mellitus (DM) for HCC in Taiwan were projected to 2045. The prevalence of each risk factor was obtained from national surveys and projected inferentially by using a log-linear model or simple linear assumption. The relative risk of each factor was derived from pooled literature data. Results From 2013 to 2035, incidence rates of PLC in Taiwan are estimated to decrease by more than 50% in both men (49.3 to 24.2/100,000) and women (19.7 to 9.2/100,000). In Japan, incidence rates have plateaued in the 1990s, and are expected to continue to decline to 17.0/100,000 for men and 6.3/100,000 for women. Conversely, rates in the UK are projected to increase by more than 30% in both men (13.5 to 18.2/100,000) and women (6.0 to 8.1/100,000). A more modest increase is expected in the US, from 10.2 to 12.5/100,000 for men and 3.3 to 3.5/100,000 for women. In Taiwan, the PAF of HBV, the predominant risk factor of HCC, is predicted to decrease from 54.3% in 2015 to 34.4% in 2045. By 2045, the PAFs of obesity and DM are estimated to reach 11.9% and 15.4%, respectively, the latter similar to that of HCV (15.0%). Conclusion PLC incidence rates are forecast to follow a trend of convergence in four representative countries. Metabolic factors are expected to play increasingly important etiologic role in HCC even in regions currently endemic for viral hepatitis. Citation Format: Emily Han-Chung H. Hsiue, Wei-Cheng Lo, Hsien-Ho Lin, Chih-Hung Hsu, Ann-Lii Cheng. Forecast of the incidence and etiology of liver cancer in Taiwan, Japan, United States, and United Kingdom: toward harmonization of East and West [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 286. doi:10.1158/1538-7445.AM2017-286

The Contribution of Matrix Metalloproteinase-1 Genotypes to Hepatocellular Carcinoma Susceptibility in Taiwan.

Metalloproteinases (MMPs) are a family of proteases which have been shown to be overexpressed in various types of cancers. However, the contribution of MMP1 genotype to hepatocellular carcinoma (HCC) has not been well studied. This study aimed to evaluate the contribution of MMP1 promoter 1607 genotype to the risk of HCC in Taiwan, where HCC incidence is relatively high in the world. In this case-control study, MMP1 genotype and its interaction with consumption of cigarettes and alcohol in determining HCC risk was investigated among 298 HCC patients and 889 age- and gender-matched healthy controls. The percentages of ever smokers and ever alcohol drinkers were much higher in the case group than in the control group. The percentages of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype were 37.2%, 38.3% and 24.5% in the HCC group and 34.8%, 44.0% and 21.2% in the control group, respectively (p for trend=0.2048). The allelic frequency distribution analysis showed the variant 1G allele of MMP1 promoter 1607 conferred similar HCC susceptibility as the wild-type 2G allele (odds ratio (OR)=1.01, 95% confidence interval (CI)=0.84-1.22, p=0.8735). As for the gene-lifestyle interaction, there was an obvious protective effect of MMP1 promoter 1607 1G allele on the risk of HCC among non-smokers, but not non-smokers, even alcohol drinkers or non-drinkers. The 1G allele of MMP1 promoter 1607 may have a protective effect on HCC risk for non-smokers in Taiwan and further validations are needed in other population groups.