Aliment Pharmacol Ther 2011; 33: 1104–1112
Summary
Background The role of anti‐viral therapy in prevention of hepatocellular carcinoma (HCC) recurrence is to be defined.
Aim To investigate the role ...of anti‐viral therapy in prevention of tumour recurrence after curative treatment of hepatitis B virus (HBV)‐related HCC.
Methods A systematic electronic search on keywords including HCC and different anti‐viral therapies was performed through eight electronic databases, including Medline, EMBASE and Cochrane Databases. The primary outcome was HCC recurrence after curative treatment of HBV‐related HCC. The secondary outcomes were mortality related to HCC, mortality related to liver failure and the overall mortality.
Results Nine cohort studies were included with a total number of 551 patients: 204 patients with anti‐viral treatment group and 347 patients without anti‐viral treatment (control group). There was significant difference in the incidence of HCC recurrence in favour of the anti‐viral treatment group (55% vs. 58%; odds risk (OR) = 0.59, 95% CI 0.35–0.97, P = 0.04). The risk of HCC was reduced by 41% in the anti‐viral treatment group. There were also significant differences in favour of anti‐viral treatment group in terms of liver‐related mortality (0% vs. 8%; OR = 0.13, 95% CI 0.02–0.69, P = 0.02) and overall mortality (38% vs. 42%; OR = 0.27, 95% CI 0.14–0.50, P < 0.001).
Conclusions Anti‐viral therapy has potential beneficial effects after the curative treatment of HBV‐related hepatocellular carcinoma in terms of tumour recurrence, liver‐related mortality and overall survival. Anti‐viral therapy should be considered after curative treatment of hepatocellular carcinoma.
Physical distancing has been argued as one of the effective means to combat the spread of COVID-19 before a vaccine or therapeutic drug becomes available. How far people can be spatially separated is ...partly behavioral but partly constrained by population density. Most models developed to predict the spread of COVID-19 in the U.S. do not include population density explicitly. This study shows that population density is an effective predictor of cumulative infection cases in the U.S. at the county level. Daily cumulative cases by counties are converted into 7-day moving averages. Treating the weekly averages as the dependent variable and the county population density levels as the explanatory variable, both in logarithmic scale, this study assesses how population density has shaped the distributions of infection cases across the U.S. from early March to late May, 2020. Additional variables reflecting the percentages of African Americans, Hispanic-Latina, and older adults in logarithmic scale are also included. Spatial regression models with a spatial error specification are also used to account for the spatial spillover effect. Population density alone accounts for 57% of the variation (R-squared) in the aspatial models and up to 76% in the spatial models. Adding the three population subgroup percentage variables raised the R-squared of the aspatial models to 72% and the spatial model to 84%. The influences of the three population subgroups were substantial, but changed over time, while the contributions of population density have been quite stable after the first several weeks, ascertaining the importance of population density in shaping the spread of infection in individual counties, and in their neighboring counties. Thus, population density and sizes of vulnerable population subgroups should be explicitly included in transmission models that predict the impacts of COVID-19, particularly at the sub-county level.
Summary
Background
A meta‐analysis on the risk of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) genotypes is warranted as the current data are conflicting.
Aim
To investigate the ...relative risk of HCC among the four major HBV genotypes (A–D).
Methods
A meta‐analysis was performed based on literature search from electronic databases and bibliography between 1950 and 2012. All s with keywords ‘hepatitis B’, ‘hepatocellular carcinoma’ and ‘genotype’ were screened. Studies were included if they reported HBV genotype as an exposure and HCC as an outcome.
Results
Nine hundred and eighty‐eight s were found through literature search, among them 43 studies were eligible for this meta‐analysis. A total of 14 545 patients with an average age of 43 years were included; 71% were male patients and 17% had cirrhosis. In 33 studies, HCC was found in 1541/6060 (25%) genotype C vs. 550/4417 (12%) genotype B HBV‐infected patients odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.52–2.76, P < 0.001. No difference in the risk of HCC was found among genotype A (71/517, 14%) vs. genotype D (170/1506, 11%) HBV‐infected patients in 14 studies (OR = 0.94, 95% CI = 0.67–1.32). In 10 studies, the risk of HCC was also found higher among genotype C (498/1659, 30%) than genotype A&D (103/1403, 7%) HBV‐infected patients (OR = 2.34, 95% CI = 1.63–3.34, P < 0.001). Subgenotype Ce and Cs HBV‐infected patients had similar risk on HCC (OR = 1.13, 95% CI = 0.76–1.67, P = 0.54). On funnel plot analysis, there was no significant publication bias in all comparisons.
Conclusion
Genotype C hepatitis B virus is associated with a higher risk of hepatocellular carcinoma than other major hepatitis B virus genotypes.
Summary
Background
The rs738409 GG variant in patatin‐like phospholipase 3 (PNPLA3) is associated with non‐alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if ...it contributes to the development of NAFLD through affecting dietary pattern.
Aim
To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD.
Methods
Liver fat and fibrosis were assessed by proton‐magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food‐frequency questionnaire.
Results
The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern.
Conclusions
The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.
The discovery of vitamin E (α-tocopherol) began in 1922 as a vital component required in reproduction. Today, there are eight naturally occurring vitamin E isoforms, namely α-, β-, γ- and ...δ-tocopherol and α-, β-, γ- and δ-tocotrienol. Vitamin E is potent antioxidants, capable of neutralizing free radicals directly by donating hydrogen from its chromanol ring. α-Tocopherol is regarded the dominant form in vitamin E as the α-tocopherol transfer protein in the liver binds mainly α-tocopherol, thus preventing its degradation. That contributed to the oversight of tocotrienols and resulted in less than 3% of all vitamin E publications studying tocotrienols. Nevertheless, tocotrienols have been shown to possess superior antioxidant and anti-inflammatory properties over α-tocopherol. In particular, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase to lower cholesterol, attenuating inflammation via downregulation of transcription factor NF-κB activation, and potent radioprotectant against radiation damage are some properties unique to tocotrienols, not tocopherols. Aside from cancer, vitamin E has also been shown protective in bone, cardiovascular, eye, nephrological and neurological diseases. In light of the different pharmacological properties of tocopherols and tocotrienols, it becomes critical to specify which vitamin E isoform(s) are being studied in any future vitamin E publications. This review provides an update on vitamin E therapeutic potentials, protective effects and modes of action beyond cancer, with comparison of tocopherols against tocotrienols. With the concerted efforts in synthesizing novel vitamin E analogs and clinical pharmacology of vitamin E, it is likely that certain vitamin E isoform(s) will be therapeutic agents against human diseases besides cancer.
Summary
Background
Safety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB).
Aim
To review and evaluate the ...latest evidence on the safety profiles of the six approved nucleoside analogues.
Methods
Relevant articles related to nucleoside analogue safety were selected for review following extensive language‐ and date‐unrestricted, electronic searches of the literature.
Results
Nephrotoxicity has been well reported in patients receiving older generations of nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate (TDF). Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real‐life setting. Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. Real‐life data demonstrated increased risk of hip fracture in patients receiving adefovir but not TDF. The newly approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles compared to TDF. Long‐term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. Muscular toxicity may be seen in telbivudine‐treated patients so regular monitoring is advised. Peripheral neuropathy and lactic acidosis are rare adverse events. Latest international guidelines support the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not contraindicated during TDF therapy.
Conclusions
Long‐term safety profile of nucleoside analogues is now better defined with more data from large real‐life cohorts and clinical trials with long‐term follow‐up. The new nucleotide analogue, TAF is now available with favourable renal and bone safety profiles.
Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) affects 20%‐40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. ...Electronic medical records facilitate large‐scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases.
Aim
To develop and validate a laboratory parameter‐based machine learning model to detect NAFLD for the general population.
Methods
We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton‐magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver‐operating characteristic curve (AUROC) of models in validation group were compared.
Results
Six predictors including alanine aminotransferase, high‐density lipoprotein cholesterol, triglyceride, haemoglobin A1c, white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83‐0.90) and 0.88 (0.84‐0.91) in the training and validation groups respectively. Using dual cut‐offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%‐96%) sensitivity and 90% (86%‐93%) specificity with corresponding negative and positive predictive values of 96% (91%‐98%) and 69% (59%‐78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate.
Conclusions
NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies.
Linked ContentThis article is linked to Gallacher et al and McPherson and Yip papers. To view these articles visit https://doi.org/10.1111/apt.14217 and https://doi.org/10.1111/apt.14234.
The present study tested whether the relationships among resilience, life satisfaction, and depression could be explained by positive views toward the self, the world, and the future (positive ...cognitive triad). Structural equation modeling and mediation analyses were conducted based on 1,419 college students in Hong Kong. The model of positive cognitive triad as mediator between resilience and well-being fit the data (comparative fit index = .94, Tucker-Lewis index = .93, root-mean-square error of approximation = .08). Findings showed resilience to be significantly related to positive cognitions about the self, the world, and the future. Individuals who had higher level of resilience held significantly more positive cognitions and reported significantly higher levels of life satisfaction and lower levels of depression. The utility of the positive cognitive triad as the mechanism through which resilience enhances well-being was supported. Applications in cultivating resilience and positive cognitions in counseling services are discussed.
The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine ...aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty‐one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and ...clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.
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