Mental health and quality of life in patients with chronic liver disease: a single-center structural equation model.

BACKGROUND: Chronic liver disease (CLD) is one of the leading disease burdens in Pakistan. Until now, there has only been limited focus in the country on providing health services through tertiary services in urban cities, whereas there is almost no research in Pakistan on the mental health and quality of life of CLD patients. This study aimed to understand which predictors influence the mental health and quality of life of CLD patients in order to advise better policy protection. METHODS: Data was collected from CLD patients at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan. A total of 850 respondents were part of the final sample. The age of respondents ranged from 18 to 79 years and included the following diagnosis: (i) Chronic Viral Hepatitis (n = 271), (ii) Cirrhosis (n = 259), (iii) Hepatocellular Carcinoma (n = 193), and (iv) Non-viral Liver Disease (n = 127). RESULTS: Mean results reveal that females as well as illiterate patients need more support for mental health and communication with their physician; whereas men need more support to develop coping strategies. Structural equation modelling results reveal that the severity of symptoms (ß = 0.24, p < 0.001), coping strategies (ß=-0.51, p < 0.001), and doctor communication (ß=-0.35, p < 0.001) predict mental health. Quality of life is associated with the severity of symptoms (ß=-0.36, p < 0.001), coping strategies (ß = 0.26, p < 0.05), and doctor communication (ß = 0.09, p < 0.05). CONCLUSIONS: A 'bio-psycho-social-spiritual' model is recommended for Pakistan's CLD patients which includes the integration of social officers to provide support in four key areas to secure mental health and quality of life of patients.

Economic Burden and Quality of Life of Hepatocellular Carcinoma in Greater China: A Systematic Review.

Background: Hepatocellular carcinoma (HCC) accounts for more than 85%-90% of primary liver cancer globally, and approximately 45% of deaths from HCC occur in greater China. This disease poses a significant economic burden for patients, payers and society and significantly affects patients' quality of life (QoL). However, such impact of HCC in greater China has not been well characterized. This review was conducted to analyze the current evidence about the economic and humanistic impact of HCC in greater China for informing national disease management and identifying clinical gaps yet to be resolved. Methods: A systematic search literature using seven databases (Web of Science, PubMed, Medline, Cochrane Central, China National Knowledge Infrastructure, Wanfang, and Weipu) was performed to identify interventional and observational studies that reported the impact of HCC on cost or QoL and published before April 6, 2021. The focus population included adult patients with HCC in greater China. This review excluded any studies that focused on any specific treatment. Study quality was assessed using the Effective Public Health Practice Project tool. Results: Of 39,930 studies retrieved, 27 were deemed eligible for inclusion. The methodologies, perspectives and data sources used in studies were heterogeneous. In greater China, while few studies reported the health expenditures of HCC patients and investigations about economic burden at national level was lacking, the significant economic impact of HCC on patients and their families had been reported. Health-related costs increased as the disease deteriorated. Additionally, HCC also has a negative impact on the QoL of patients, mostly in terms of physical, cognitive, social functioning and severe symptoms. Conclusions: HCC has brought significant economic and QoL burden to patients in greater China. Both physical and psychological factors predicted QoL in patients with HCC in greater China. Future studies should explore the disease-related economic effects on Chinese patients and their families, the effects of physical and psychological factors on QoL and the relationships of physical and psychological factors in the region.Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?RecordID=278421, PROSPERO: CRD42021278421.

A randomized clinical trial of guided self-help intervention based on mindfulness for patients with hepatocellular carcinoma: effects and mechanisms.

BACKGROUND: Compared with face-to-face mindfulness-based interventions (MBIs), online mindfulness interventions may be more convenient for patients with limited resources and can provide self-help mindfulness methods to improve the quality of life of cancer patients. This study investigated the effects of guided self-help mindfulness-based interventions (GSH-MBIs) on psychological distress, quality of life and sleep quality in patients with hepatocellular carcinoma and explored the underlying mechanisms. METHODS: A total of 122 patients with hepatocellular carcinoma were randomly divided into the intervention group or the conventional treatment group. Psychological distress, quality of life, sleep quality, psychological flexibility and perceived stress were evaluated in the groups before the intervention at baseline, after the intervention, at 1-month follow-up and 3-month follow-up. The intervention's effects over time and the potential mediating effects were analysed using generalized estimating equations (GEE). RESULTS: GEE results indicated significant time-group interaction effects on psychological distress (P < 0.001) and sleep quality (P < 0.001). The intervention significantly improved psychological flexibility (ß, -2.066; 95% CI, -3.631, -0.500) and reduced perceived stress (ß, -2.639; 95% CI, -4.110, -1.169). Psychological flexibility and perceived stress played a mediating role in the observed results. CONCLUSION: GSH-MBIs can improve psychological distress and sleep quality via changing the psychological flexibility and perceived stress in hepatocellular carcinoma patients.

Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial.

BACKGROUND: Single-agent nivolumab showed durable responses, manageable safety, and promising survival in patients with advanced hepatocellular carcinoma in the phase 1-2 CheckMate 040 study. We aimed to investigate nivolumab monotherapy compared with sorafenib monotherapy in the first-line setting for patients with advanced hepatocellular carcinoma. METHODS: In this randomised, open-label, phase 3 trial done at medical centres across 22 countries and territories in Asia, Australasia, Europe, and North America, patients at least 18 years old with histologically confirmed advanced hepatocellular carcinoma not eligible for, or whose disease had progressed after, surgery or locoregional treatment; with no previous systemic therapy for hepatocellular carcinoma, with Child-Pugh class A and Eastern Cooperative Oncology Group performance status score of 0 or 1, and regardless of viral hepatitis status were randomly assigned (1:1) via an interactive voice response system to receive nivolumab (240 mg intravenously every 2 weeks) or sorafenib (400 mg orally twice daily) until disease progression or unacceptable toxicity. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, NCT02576509. FINDINGS: Between Jan 11, 2016, and May 24, 2017, 743 patients were randomly assigned to treatment (nivolumab, n=371; sorafenib, n=372). At the primary analysis, the median follow-up for overall survival was 15·2 months (IQR 5·7-28·0) for the nivolumab group and 13·4 months (5·7-25·9) in the sorafenib group. Median overall survival was 16·4 months (95% CI 13·9-18·4) with nivolumab and 14·7 months (11·9-17·2) with sorafenib (hazard ratio 0·85 [95% CI 0·72-1·02]; p=0·075; minimum follow-up 22·8 months); the protocol-defined significance level of p=0·0419 was not reached. The most common grade 3 or worse treatment-related adverse events were palmar-plantar erythrodysaesthesia (1 [<1%] of 367 patients in the nivolumab group vs 52 [14%] of patients in the sorafenib group), aspartate aminotransferase increase (22 [6%] vs 13 [4%]), and hypertension (0 vs 26 [7%]). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. Four deaths in the nivolumab group and one death in the sorafenib group were assessed as treatment related. INTERPRETATION: First-line nivolumab treatment did not significantly improve overall survival compared with sorafenib, but clinical activity and a favourable safety profile were observed in patients with advanced hepatocellular carcinoma. Thus, nivolumab might be considered a therapeutic option for patients in whom tyrosine kinase inhibitors and antiangiogenic drugs are contraindicated or have substantial risks. FUNDING: Bristol Myers Squibb in collaboration with Ono Pharmaceutical.

The impact of hepatocellular carcinoma diagnosis on patients' health-related quality of life.

BACKGROUND: Patients with hepatocellular cancer (HCC) are known to have worse health-related quality of life (HRQL) than the general population. However, the change in HRQL from before the diagnosis to after diagnosis remains unknown and is difficult to estimate. We aimed to compare HCC cases with matched controls to evaluate the differences in change in HRQL from before to after HCC diagnosis. METHODS: We performed propensity score-matched analysis using the self-reported HRQL data from the Surveillance, Epidemiology, and End Results registries (SEER) data linked with Medicare Health Outcomes Survey (MHOS) data (1998-2014). Cases were selected as Medicare beneficiaries (aged ≥65 years) who were diagnosed with HCC between their baseline assessment and follow-up assessment. Matched controls were selected from the same data resource and the same time period to include subjects without cancer diagnosis by propensity scores. HRQL was assessed using the Medical Outcomes Study Short Form-36 (SF-36). RESULTS: The study included 62 subjects who developed HCC and 365 matched controls. Compared to their baseline HRQL scores, after diagnosis of HCC, subjects were more likely to report declines in scores related to the mental component of HRQL. When stratified by time since diagnosis, mental component remained significantly lower as the disease advanced. In contrast, only general health aspects of physical health worsened after HCC diagnosis. CONCLUSIONS: Diagnosis of HCC has a profound negative impact on patients' HRQL. Mental health component deteriorated significantly over time. The need of including mental health services within a multidisciplinary HCC care model is clearly evident.

Health-related quality of life in locally advanced hepatocellular carcinoma treated by either radioembolisation or sorafenib (SARAH trial).

BACKGROUND: The aim of this ancillary study of the SARAH trial is to compare health-related quality of life (HRQoL) in patients with locally advanced or inoperable hepatocellular carcinoma (HCC) treated with transarterial radioembolisation (TARE) or sorafenib. METHODS: This study included randomised patients who received either TARE or at least one dose of sorafenib with no major deviation in the protocol and who had at least one QoL follow-up assessment in addition to the baseline evaluation. QoL was assessed from the date of randomisation using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, until disease progression or other reasons for stopping study participation. Data were analysed using linear mixed and time-dependent models. RESULTS: A total of 285 patients were included (122 and 163, in the TARE and sorafenib groups, respectively). Questionnaire completion rates were similar (77.5% versus 80.4%, in the TARE and sorafenib groups, respectively, p = 0.25). Longitudinal HRQoL analysis showed a significant treatment and time effects for fatigue and global health status, and significant treatment, time and treatment by time interaction effects for appetite loss, diarrhoea and social functioning. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7-4.3) versus 2.6 months (95% CI 2.0-3.0) in the TARE and sorafenib groups, respectively. CONCLUSIONS: HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. These data could be used to optimise management of patients with advanced or inoperable HCC.

Relationship between hepatocellular carcinoma and depression via online database analysis.

There may be a mutually reinforcing relationship between hepatocellular carcinoma (HCC) and depression, but the mechanism is unknown. This study used bioinformatics to evaluate the relationship between HCC and depression at the genetic level. Genes associated with HCC and depression were obtained from pubmed2ensemble. Overlapping genes were annotated by gene ontology (GO) function and enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway. The cluster-1 genes obtained by Cytoscape were analyzed by GEPIA for expression and overall survival in HCC and, finally, introduced target genes to DGIdb to get associated drugs. A total of 199 genes were found to be in common between HCC and depression. GO term enrichment analysis on DAVID found the top-6 biological processes to be mainly associated with cell death and apoptosis. The top-6 cellular component terms are extracellular. The top-6 of molecular function terms are mainly associated with receptor binding. The top-6 pathways enriched by KEGG are mainly related to inflammatory response. IGF1, VEGFA, and SERPINE1 had statistical differences in expression and 10-year survival rate. There are total 45 drugs that act on VEGFA and SERPINE1. Based on our findings, we hypothesize that the mechanism of the interaction between HCC and depression may be related to cell death or apoptosis. Further studies are needed to verify this hypothesis.

A Phase 2 Study of Image-Guided Proton Therapy for Operable or Ablation-Treatable Primary Hepatocellular Carcinoma.

PURPOSE: Because most previous data on proton therapy for hepatocellular carcinoma (HCC) were retrospectively collected from inoperable or previously treated cases, our aim was to evaluate the outcome of image-guided proton therapy (IGPT) for operable or radiofrequency ablation-treatable primary HCC. METHODS AND MATERIALS: This phase 2 study prospectively investigated the efficacy and safety of IGPT and quality of life (QoL) after IGPT for operable/ablatable HCC. The primary endpoint was overall survival, and the secondary endpoints were local control, incidence of grade ≥3 adverse events, and changes in QoL. Toxicities were evaluated with Common Terminology Criteria for Adverse Events, version 4.0. QoL scores were assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.0, and Quality of Life Questionnaire-Hepatocellular Carcinoma/Primary Liver Cancer Module. IGPT was performed using respiratory-gated techniques. RESULTS: Forty-five patients (median age: 68 years; range, 36-80 years) were enrolled between June 2013 and February 2016; 38 were considered operable and 14 were indicated for radiofrequency ablation. The major underlying liver diseases were hepatitis B (n = 16), hepatitis C (n = 13), alcoholic hepatitis (n = 3), and nonalcoholic fatty liver disease (n = 13). The Child-Pugh score was A5 in 32 patients, A6 in 9 patients, and B7 in 4 patients. Thirty-seven patients with a peripherally located tumor were given 66 Gy relative biological effectiveness in 10 fractions, and 8 patients with a centrally located tumor received 72.6 Gy relative biological effectiveness in 22 fractions. The median follow-up period of surviving patients was 60 months (range, 42-75 months). Two- and 5-year overall survival rates were 84% (95% confidence interval [CI], 74%-95%) and 70% (95% CI, 56%-84%), respectively, and local control rates were 95% (95% CI, 89%-100%) and 92% (95% CI, 84%-100%), respectively. Grade 3 radiation-induced liver disease was observed in 1 patient. No significant changes were noted in QoL scores 1 year after treatment, except for body image. CONCLUSIONS: Although the primary endpoint did not meet statistical significance as planned in the study design, IGPT is a safe and effective treatment for solitary primary HCC and may become a treatment option.

Quality of Life after Transcatheter Arterial Chemoembolization Combined with Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Compared with Transcatheter Arterial Chemoembolization alone.

AIM: The aim of this study was to assess quality of life (QoL) in patients with unresectable hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) compared to TACE plus radiofrequency ablation (RFA) done at the same sitting, and to assess tumor therapy response after these 2 palliative interventions. METHODS: 73 patients with unresectable HCC (BCLC-B) were included. Patients with tumor ≤ 5 cm were subjected to TACE (N = 45) while patients with tumors > 5 cm were subjected to TACE followed immediately by RFA (N = 28). QoL was evaluated with two validated questionnaires (EORTC QLQ-30 and EORTC HCC18). These questionnaires were filled out before intervention, 2 weeks and 2 months after intervention. Pre/post interventional changes were analyzed. The modified response evaluation criteria in solid tumor (mRECIST) were employed for the evaluation of therapeutic efficacy. RESULTS: Baseline global health status/QoL was significantly higher in TACE group (64.1%) compared to TACE-RFA group (51.2%). Two weeks after intervention: the absolute decrease in global health state was higher in TACE-RFA (- 12.1%) compared to TACE (- 6.3%, p = 0.411). Less impairment was found in TACE group compared to TACE-RFA group for physical/social functioning, fatigue and pain but it was statistically insignificant. Two months after intervention; TACE-RFA group showed significant improvement in global health score, social and physical functioning scores, as well as significant improvement in pain and fatigue compared to TACE group. The therapeutic efficacy of TACE-RFA was better than TACE alone: complete remission, partial remission, stable disease and progressive disease were 17.9%, 32.1%, 42.9% and 7.1% Vs11.1%, 22.2%, 48.9% and 17.8%, respectively). CONCLUSION: Neither TACE nor TACE-RFA showed a significant decrease in QoL in patients with unresectable HCC two weeks after intervention. However, two months after intervention; TACE-RFA showed significant improvement in global health score compared to TACE monotherapy. TACE-RFA appeared safe, effective and more favorable than TACE monotherapy.
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A closer look at quality of life in the hepatocellular carcinoma literature.

PURPOSE: Adults with hepatocellular carcinoma (HCC) have a high symptom burden. Their quality of life (QOL) has been shown to be significantly impacted by both the disease and its treatment, adding to the high symptom burden that these patients experience. The primary aims of this paper are as follows: (1) to identify how QOL is being defined in HCC literature and (2) to identify how QOL is being measured in the HCC literature using Ferrell's model of QOL. METHODS: A systematic review was completed of relevant studies published after 2014, using PubMed, CINHAL, and PsycInfo. Relevant studies were reviewed by 2 reviewers using PRISMA guidelines. RESULTS: From a total of 1312 papers obtained in the initial database search, 30 met inclusion criteria and are included in this review. From the included articles, 10% included a definition of QOL and 3% addressed the spiritual domain of QOL. Majority of study participants were in the early stage of HCC, though the majority of adults with HCC are diagnosed in the advanced stage. Only 3% of included studies included greater than 22% population of advanced stage of HCC. CONCLUSION: The results of this systematic review demonstrate the need for future research into QOL in the advanced stage of QOL. It also identified gap in the literature concerning the definition of QOL in HCC and the spiritual domain of QOL in HCC.

Health-related quality-of-life impact of pembrolizumab versus best supportive care in previously systemically treated patients with advanced hepatocellular carcinoma: KEYNOTE-240.

BACKGROUND: Health-related quality of life (HRQoL) is an important outcome measure and prognostic indicator in hepatocellular carcinoma (HCC). KEYNOTE-240 (NCT02702401) assessed the efficacy and safety of pembrolizumab plus best supportive care (BSC) versus placebo plus BSC in patients with HCC who previously received sorafenib. This study presents the results of a prespecified exploratory analysis of patient-reported outcomes. METHODS: Patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and its HCC supplement (EORTC QLQ-HCC18) electronically at baseline; at weeks 2, 3, 4, 6, 9, 12, and 18; and then every 9 weeks until 1 year or end of treatment, and at the 30-day safety follow-up visit. RESULTS: The HRQoL population included 271 and 127 patients randomly assigned to pembrolizumab and placebo, respectively. From baseline to week 12, changes in both scores were similar between pembrolizumab and placebo; global health status/QoL scores were stable. The proportions of patients who improved, remained stable, or deteriorated across all functional domain and symptom scores were generally similar between pembrolizumab and placebo. Time to deterioration was similar between the 2 arms based on the prespecified analysis of EORTC QLQ-HCC18 domains of abdominal swelling, fatigue, and pain. CONCLUSION: Pembrolizumab preserved HRQoL during treatment for advanced HCC. Combined with efficacy and safety results from KEYNOTE-240, these findings support a positive benefit/risk profile for pembrolizumab in a second-line treatment setting for patients with HCC who previously received sorafenib.

Effects of high-quality nursing care on psychological outcomes and quality of life in patients with hepatocellular carcinoma: A protocol of systematic review and meta-analysis.

BACKGROUND: High quality nursing care (HQNC) has been reported to effectively prevent psychological disorders and improve the quality of life (QoL) in patients with hepatocellular carcinoma (HCC) during the treatment. However, the exact effect of HQNC remains controversial. This systematic review will be aimed to assess the effectiveness of HQNC on psychological disorders and QoL in patients with HCC. METHODS: Eligible prospective controlled clinical trials were searched from Google Scholar, Medline, Excerpt Medica Database (Embase), PubMed, Web of Science (WOS), Cochrane Library, China Scientific Journal Database (CSJD), China National Knowledge Infrastructure (CNKI), Chinese BioMedical Database (CBM) and Wanfang Database. Papers in English or Chinese published from January 2000 to July 2020 will be included without any restrictions. The clinical outcomes including psychological outcomes, QoL, and adverse events of HQNC in patients with HCC were systematically evaluated.Study selection and data extraction will be performed independently by two reviewers. Stata 14.0 and Review Manager 5.3 were used for data analysis. Methodological quality for each eligible study will be assessed by using Cochrane risk of bias tool. Subgroup and meta-regression analysis will be carried out depending on the availability of sufficient data. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: The results of this study may provide helpful evidence of HQNC on psychological effects and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070096.

A mixed-methods approach to understanding perceptions of hepatitis B and hepatocellular carcinoma among ethnically diverse Black communities in South Florida.

PURPOSE: Hepatitis B (HBV), the leading cause of hepatocellular carcinoma (HCC), disproportionately affects minorities. Compared to other races, Blacks more often present with advanced HCC and have decreased survival. We observed higher HBV-associated HCC rates among Blacks than reported nationally. In our center, Haitian Blacks had the highest rates of HBV-associated HCC and shorter survival compared to other Blacks. We investigated knowledge and perceptions regarding HBV and HCC among Blacks born in the United States or Haiti. METHODS: Using community partnerships, participants were recruited via word of mouth, email, social media or from Hepatology clinic. Focus groups were conducted in Haitian Creole or English and stratified by birthplace, gender and infection status. Discussions were audio-recorded and transcribed verbatim. A constant comparative method was used for data analysis; themes are based on conversational details. RESULTS: There were 55 participants; 49% were male and 27% had chronic HBV. Only 42% of Haitian Blacks knew about HBV prior to participation vs. 78% of African Americans, p 0.03. Both groups expressed that fear, mistrust of the medical establishment, denial and stigma might compel persons to avoid seeking care. Both groups attributed higher rates of late stage HCC diagnosis in Blacks to inadequate financial resources and education. Those with HBV reported confusion regarding their infection and suboptimal communication with healthcare providers. CONCLUSIONS: In two communities disproportionately affected by HBV, misconceptions about disease transmission, stigma, low health literacy and decreased access to care may limit detection for HBV. Culturally relevant community-based interventions are needed to increase HBV detection.

Effect of sodium cantharidinate/vitamin B6 injection on survival, liver function, immune function, and quality of life in patients with hepatocellular carcinoma: Protocol for a meta-analysis.

BACKGROUND: Sodium cantharidinate/vitamin B6 (SC/VB6) injection, a famous insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of SC/VB6 injection on survival, liver function, immune function, and quality of life (QoL) in patients with HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of SC/VB6 for patients with HCC were searched from ten electronic databases including PubMed, Google Scholar, Cochrane Library, Excerpt Medica Database (Embase), Medline, Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ), and Wanfang Database. Papers in Chinese or English published from January 2000 to July 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall survival (OS), QoL, liver function, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the clinical trials was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of SC/VB6 on survival, liver function, immune function, and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070121.

High incidence of hepatocellular carcinoma and cirrhotic complications in patients with psychiatric illness: a territory-wide cohort study.

BACKGROUND: Because of high-risk behaviours, sedentary lifestyle and side effects of medications, psychiatric patients are at risk of viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. We aimed to study the incidence of hepatocellular carcinoma (HCC) and cirrhotic complications in psychiatric patients. METHODS: We identified consecutive adult patients in all public hospitals and clinics in Hong Kong with psychiatric diagnoses between year 2003 and 2007 using the Clinical Data Analysis and Reporting System, which represents in-patient and out-patient data of approximately 80% of the 7.4-million local population. The patients were followed for liver-related events (HCC and cirrhotic complications) and deaths until December 2017. Age- and sex-standardized incidence ratio (SIR) of HCC in psychiatric patients to the general population was estimated by Poisson model. RESULTS: We included 105,763 psychiatric patients without prior liver-related events in the final analysis. During a median (interquartile range) follow-up of 12.4 (11.0-13.7) years, 1461 (1.4%) patients developed liver-related events; 472 (0.4%) patients developed HCC. Compared with the general population, psychiatric patients had increased incidence of HCC (SIR 1.42, 95% confidence interval [CI] 1.28-1.57, P < 0.001). The SIR was highest in patients with drug-induced (SIR 3.18, 95% CI 2.41-4.11, P < 0.001) and alcohol-induced mental disorders (SIR 2.98, 95% CI 2.30-3.81, P < 0.001), but was also increased in patients with psychotic disorders (SIR 1.39, 95% CI 1.16-1.65, P < 0.001) and mood disorders (SIR 1.16, 95% CI 1.00-1.34, P = 0.047). Liver disease was the fifth most common cause of death in this population, accounting for 595 of 10,614 (5.6%) deaths. Importantly, 569 (38.9%) patients were not known to have liver diseases at the time of liver-related events. The median age at HCC diagnosis (61 [range 26-83] years) was older and the median overall survival (8.0 [95% CI 5.0-10.9] months) after HCC diagnosis was shorter in this cohort of psychiatric patients than other reports from Hong Kong. CONCLUSIONS: HCC, cirrhotic complications, and liver-related deaths are common in psychiatric patients, but liver diseases are often undiagnosed. More efforts are needed to identify liver diseases in the psychiatric population so that treatments and screening for HCC and varices can be provided to patients in need.

Outcomes in hepatocellular carcinoma patients undergoing sorafenib treatment: toxicities, cellular oxidative stress, treatment adherence, and quality of life.

The study of toxicities induced by sorafenib, as well as the identification of possible mechanisms and biomarkers of these toxicities, is important to improve the treatment and quality of life of hepatocellular carcinoma (HCC) patients. This study focused on toxicities, cellular oxidative stress, adherence, and quality of life of 11 patients with HCC treated with sorafenib. Dermatotoxicity, myelotoxicity, gastro toxicity, nephrotoxicity, pain, and fatigue were investigated. For oxidative stress analysis, the peripheral blood mononuclear cells were isolated and mitochondrial superoxide anion production was measured using MitoSOX Red test. Medication adherence was evaluated based on Morisky-Green and MedTake tests. Quality of life assessment was performed using EORTC QLQ C-30 and QLQ HCC18 questionnaires. The results showed that hand-foot syndrome (45.5%), thrombocytopenia (45.5%), diarrhea (54.5%), pain (54.5%), and fatigue (36.4%) were the most prevalent toxicities. A non-statistically significant change in the levels of superoxide anion was observed after the sorafenib treatment (Wilcoxon test, P = 0.4131). Moreover, 81.8% of patients had high adherence, 100% knew the correct indication of sorafenib, 81.8% knew the correct intake and drug regimen, and 36.4% knew the correct dose of antineoplastic. There was a significant worsening in the emotional and pain domains of quality of life after the sorafenib (Wilcoxon test, P = 0.0313 and P = 0.0313, respectively). A production of superoxide anion was not correlated with toxicities (Spearman's correlation and Mann-Whitney U tests, P > 0.05). This study suggests that oxidative stress might not be the mechanism of sorafenib toxicities.

Genetic variation in NRG 1 gene and risk of post-traumatic stress disorders in patients with hepatocellular carcinoma.

OBJECTIVE: Neuregulin 1 (NRG1) was proved to play an important role in numerous neurodevelopmental processes. In our study, we aimed to investigate the relationship between the NRG1 gene polymorphism and the cognitive function of patients with hepatocellular carcinoma (HCC) complicated with post-traumatic stress disorders (PTSD) before and after the psychological intervention. METHODS: Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) were used for cognitive function assessment. Serum level of NRG1 was detected by ELISA, and the correlation between NRG1 level and cognitive function was analyzed. The difference of cognitive function score of patients with HCC complicated with PTSD before and after psychological intervention was compared, and the relationship between rs35753505 and rs3924999 polymorphism with the score was analyzed. RESULTS: Patients with HCC complicated with PTSD showed decreased serum NRG1 level. NRG1 levels of patients in the HCC + PTSD group were positively correlated with MMSE, MoCA, and LOTCA scores. In rs35753505, the CC genotype was a risk factor for the occurrence of PTSD in patients with HCC, while in rs3924999, the GG genotype was a risk factor for the occurrence of PTSD in patients with HCC. After psychological intervention, the CC genotype at rs35753505 and the GG genotype at rs3924999 were susceptible genotypes. CONCLUSION: CC genotype at rs35753505 and GG genotype at rs3924999 of NRG1 gene increased the risk of PTSD in patients with HCC. CC and GG genotypes were susceptible after psychological intervention.

Clinico-Psychosocial Factors Predicting Hepatocellular Carcinoma Related Knowledge Among Patients with Chronic Liver Disease.

Regular clinical surveillance for hepatocellular carcinoma (HCC) among high-risk patients could lead to early detection and cure. Patient's knowledge and attitude are important to the uptake rate of this surveillance. This study is aimed at assessing the level of HCC-related knowledge among patients with chronic liver disease (CLD) who are at risk of HCC and determine predictors for poor knowledge. A cross-sectional study was conducted among inpatients with CLD at the Third People's Hospital of Kunming in China. Questionnaires were used to measure patient's sociodemographic characteristics, HCC-related knowledge, and patient-doctor-related psychometric factors. Factor analysis was performed to explore the underlying domains captured by the knowledge questionnaire. Univariate and multivariate analyses were performed to identify independent predictors for each domain. Three common factors were derived from the exploratory factor analysis, namely, "Surveillance," "Lifestyle," and "Prognosis." Patients with low educational background and a short period of having CLD were at a significantly low level of HCC-related knowledge of all three domains. On the other hand, surveillance and lifestyle but not prognosis, were associated with patient's communication confidence with doctors. Over two-thirds of high-risk patients had low knowledge of HCC. Medical providers should pay more attention to low educational groups and newly diagnosed CLD patients.