The latest medical research on Liver Cancer

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about liver cancer gathered by our medical AI research bot.

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Contribution of a Genetic Risk Score to Ethnic Differences in Fatty Liver Disease.

Liver International

Susceptibility to fatty liver disease (FLD) varies among individuals and between racial/ethnic groups. Several genetic variants influence FLD risk, but whether these variants explain racial/ethnic differences in FLD prevalence is unclear. We examined the contribution of genetic risk factors to racial/ethnic-specific differences in FLD.

A case-control study comparing FLD patients (n=1,194) and population-based controls (n=3,120) was performed. Patient characteristics, FLD risk variants (PNPLA3-rs738409+rs6006460, TM6SF2-rs58542926, HSD17B13-rs80182459+rs72613567, MBOAT7/TMC4-rs641738, and GCKR-rs1260326), and a multi-locus genetic risk score (GRS) were examined. The odds of FLD for individuals with different risk factor burdens were determined.

Hispanics and Whites were over-represented (56% vs. 38% and 36% vs. 29%, respectively) and Blacks under-represented (5% vs. 23%) among FLD patients, compared to the population from which controls were selected (P<0.001). Among cases and controls, Blacks had a lower, and Hispanics a greater, net number of risk alleles than Whites (P<0.001). GRS was associated with increased odds of FLD (ORQ5vsQ1 =8.72 [95%CI=5.97-13.0], P=9.8x10-28 ), with the association being stronger in Hispanics (ORQ5vsQ1 =14.8 [8.3-27.1]) than Blacks (ORQ5vsQ1 =3.7 [1.5-11.5], P-interaction=0.002). After accounting for GRS, the odds of FLD between Hispanics and Whites did not differ significantly (OR=1.06 [0.87-1.28], P=0.58), whereas Blacks retained much lower odds of FLD (OR=0.21, [0.15-0.30], P<0.001).

Blacks had a lower and Hispanics a greater FLD risk allele burden than Whites. These differences contributed to, but did not fully explain, racial/ethnic differences in FLD prevalence. Identification of additional factors protecting Blacks from FLD may provide new targets for prevention and treatment of FLD.

Portal pressure is of significant prognostic value in primary biliary cholangitis.

Liver International

In other forms of chronic liver disease, measurement of portal pressure is of prognostic value, but this has not yet been established in primary biliary cholangitis (PBC). The aim of the study is to determine the prognostic value of hepatic venous pressure gradient (HVPG) in relation to liver-related survival outcomes, as well as to the development of hepatic decompensation, esophageal varices and variceal bleeding.

Baseline HVPG and liver biopsies were obtained in 86 patients followed for 10 years in a controlled trial of colchicine treatment, and subsequently in a long-term observational cohort study for a further 30 years.

There were 49 Hepatic deaths in addition to 10 Liver Transplants (Hepatic death/transplant; n= 59). Some of these were associated with a significant variceal bleed within 3 months of death or transplant (Portal hypertension-associated death or transplant; n=19). There were 63 deaths from all causes. During follow up, esophageal varices developed in 26 patients, whilst 17 bled from varices and 32 developed hepatic decompensation over a median follow up of 18.1 years (1.9-28.5). Baseline HVPG was highly predictive of all 6 clinical outcomes and contributed significant predictive information additional to that provided by Mayo score and Ludwig stage.

Measurement of baseline portal pressure is of significant prognostic value in primary biliary cholangitis.

Uptake of hepatitis B antiviral treatment: a panel data analysis of 31 provinces in China (2013-2020).

Liver International

China has made substantial efforts aimed to promote the uptake of antiviral treatment of hepatitis B (HB). It is unclear whether these policies achieved the desired impact. This study adopted medicines procurement data of 31 provinces to generate the first evidence about the number of standard antiviral treatment of HB overtime at both national and provincial levels in China.

We performed the panel data analyses and quasi-experimental design with the time-varying difference-in-difference method combined with the event study approach to estimate the uptake of HB antiviral treatment before and after national policy changes.

The overall trends in HB antiviral treatment at the national level increased incrementally during 2013-2020. There were 2.8862 million 12-month (person-year) antiviral standard treatment in 2020, which was only 8.93% of the eligible people estimated to need treatment. The number of monthly antiviral standard treatment increased by 42.4% (P=0.001) overall following the nationwide adoption of the '4+7' pilot pooled procurement prices in 2019, which brought substantial price reduction of core antivirals.

Low treatment rate is a critical issue in reaching the elimination of viral hepatitis as a public health threat in China. Affordability is an important but not the only factor that determines the uptake of hepatitis treatment. Further scaling up and acceleration of treatment uptake will need strategies to improve public awareness of HB, strengthening diagnosis, linking people who are infected to chronic care, reducing loss to follow up, and ensuring people who are eligible get timely treatment.

Hepatic ultrastructural features distinguish pediatric Wilson disease from NAFLD and autoimmune hepatitis.

Liver International

Wilson disease (WD) has diverse presentations that frequently mimic other liver diseases. Distinguishing WD from non-alcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH), can be difficult and has critical implications for medical management. This study aimed to examine the utility of histological features of WD in children compared to those with NAFLD and AIH.

A review of liver biopsy slides was performed in children with a clinical and/or genetic diagnosis of WD, seen at the Hospital for Sick Children between 1981-2019 and compared to controls with NAFLD and AIH. 37 children with WD and 37 disease controls ( 20 NAFLD; 17 AIH) were included. Three pathologists, blind to clinical details and diagnosis, reviewed all liver biopsies to reach consensus. Clinical and histopathologic features were compared between groups.

Most WD cases displayed steatosis or steatohepatitis on histology (34/37), active AIH-pattern in 1 and inactive cirrhosis in 2 cases. Electron microscopy (EM) findings of mitochondrial abnormalities including dilated tips of cristae, pleomorphism, membrane duplication and dense matrix were more frequent in the WD group as compared to disease controls (p<0.0001). In WD, dilated tips of mitochondrial cristae had a sensitivity of 91% and specificity of 86%, best among EM features.

Light microscopic findings display considerable overlap among children with WD, NAFLD and AIH. Ultrastructural findings of mitochondrial abnormalities are important to distinguish WD from NAFLD and AIH. EM examination should be considered essential in the diagnostic work-up of pediatric liver biopsies.

Epidemic characteristics of alcohol-related liver disease in Asia from 2000-2020: a systematic review and meta-analysis.

Liver International

To systematically summarize the prevalence of alcohol-related liver disease (ALD) and the alcohol-attributable proportions of liver cirrhosis and hepatocellular carcinoma (HCC) cases in Asia.

The Embase, PubMed, Web of Science, Cochrane, CINAHL, WanfangMed and China National Knowledge Infrastructure databases were searched from January 01, 2000 to December 01, 2021 for reports of ALD prevalence and alcohol-attributable proportions of liver cirrhosis/HCC in Asian populations. Study characteristics were extracted, and meta-analyses were conducted.

Our literature search identified 13 studies reporting the ALD prevalence, 62 studies reporting the alcohol-attributable proportion of liver cirrhosis and 34 studies reporting the alcohol-attributable proportion of HCC. The overall prevalence of ALD was 4.81% (95% confidence interval [CI] 3.67%, 6.09%). The ALD prevalence was higher in men (7.80% [95%CI 5.70%, 10.19%]) than in women (0.88% [95%CI 0.35%, 1.64%]) and increased significantly over time from 3.82% (95%CI 2.74%, 5.07%) between 2000 and 2010 to 6.62% (95%CI 4.97%, 8.50%) between 2011 and 2020. Among 469,640 cases of liver cirrhosis, the pooled alcohol-attributable proportion was 12.57% (95% CI 10.20%, 15.16%) . Among 82,615 HCC cases, the pooled alcohol-attributable proportion was 8.30% (95%CI 6.10%,11.21%). Significant regional differences were observed in alcohol-attributable proportions of liver cirrhosis and HCC.

The prevalence of ALD and the proportions of alcohol-related liver cirrhosis and HCC in Asia are lower than those in western populations. However, a gradual increasing trend was observed over the last 21 years. ALD is likely to emerge as a leading cause of chronic liver disease in Asia.

Transjugular intrahepatic portosystemic shunt for portal hypertension: 30 years' experience from China.

Liver International

Liver diseases are major causes of illness and death worldwide. In China, liver diseases, primarily viral hepatitis, affect approximately 300 milli...

High Plasma Levels of Betaine, a Trimethylamine N-Oxide Related Metabolite, are Associated with Severity of Cirrhosis.

Liver International

The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished due to impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered due to impaired hepatic flavin monooxygenase expression. Here we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity.

Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4,837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score.

Plasma betaine was on average 60% higher (P<0.001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (P=0.44). After liver transplantation (n=13), betaine decreased (P=0.017; P=0.36 vs. PREVEND population), whereas TMAO levels tended to increase (P=0.085) to higher levels than in the PREVEND population (P=0.003). Betaine levels were positively associated with CPT stage and MELD score (both P<0.001). The association with MELD score remained in fully adjusted analysis (P<0.001). The association of TMAO with MELD score did not reach significance (P=0.11). Neither betaine, nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted P=0.78 and P=0.44, respectively).

Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity, and decrease after liver transplantation.

Attribution of diabetes to the development of severe liver disease in the general population.

Liver International

Diabetes associates with advanced liver disease and predicts mortality regardless of the primary etiology of the liver disease. Even a family history of diabetes has been linked to advanced liver fibrosis in non-alcoholic fatty liver disease (NAFLD). However, the fraction of liver-related outcomes in the general population that are attributable to diabetes remains unclear.

The population-attributable fraction (PAF) of diabetes for liver disease as a time-dependent exposure was estimated in the Finnish FINRISK study (n = 28787) and British Whitehall II study (n = 7855). We also assessed the predictive ability of a family history of diabetes for liver-related outcomes. Incident diabetes data were from drug purchase/reimbursement and health care registries (FINRISK) or follow-up examinations (Whitehall II). Incident severe liver outcomes were identified through linkage with national healthcare registries.

Diabetes was associated with a 2-fold risk of liver-related outcomes in both the FINRISK (HR, 1.92; P < 0.001) and Whitehall II (HR, 2.37; P < 0.001) cohorts, and this remained significant after adjusting for multiple confounders. PAF analyses demonstrated that diabetes explained 12-14% of the risk for severe liver-related outcomes after 10 and 20 years of follow-up. Also, maternal diabetes increased the risk of liver-related outcomes in the FINRISK (HR, 1.43; P = 0.044) and Whitehall II (HR, 2.04; P = 0.051) cohorts.

Approximately 12-14% of severe liver-related outcomes are attributable to diabetes at the population level. The association between maternal diabetes and liver disease might suggest a mitochondrial genetic mechanism.

Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug-induced liver injury: A multicenter, randomized, phase II trial.

Liver International

Evidence for using bicyclol in drug-induced liver injury (DILI) is limited. This study aimed to explore the efficacy and safety of bicyclol in acute DILI.

This was a multicenter, randomized, double-blinded, double-dummy, active-controlled, superiority, phase II trial. Patients with idiosyncratic acute DILI were randomized 1:1:1 to low-dose bicyclol (25 mg times a day [TID]), high-dose bicyclol (50 mg TID), and polyene phosphatidylcholine (control) groups. The primary endpoint was the decrease from baseline in serum alanine aminotransferase (ALT) levels at post-treatment 4 weeks.

Overall, 241 patients were included in the full analysis set, with 81, 82, and 78 patients in the low-dose bicyclol, high-dose bicyclol, and control groups, respectively. ALT levels decreased across groups (-249.2 ± 151.1, -273.6 ± 203.1, and -180.8 ± 218.2 U/L in the low-dose bicyclol, high-dose bicyclol, and control groups, respectively; both P < 0.001, the bicyclol-dependent groups vs. control group). The ALT normalization rates at weeks 1, 2, 4, 6, and 8 were higher in the bicyclol-dependent groups than in the control group (P = 0.002 at week 1 and all P < 0.001 at weeks 2, 4, 6, and 8, respectively). The median times to ALT normalization in the low-dose bicyclol, high-dose bicyclol, and control groups were 29, 16, and 43 days, respectively. Adverse events, serious adverse events, and adverse drug reactions were similar across groups.

Bicyclol (25 and 50 mg TID) appeared efficacious and safe for treating idiosyncratic acute DILI, while bicyclol 50 mg TID showed higher efficacy.

Sex is a major effect modifier between body composition and mortality in patients with cirrhosis assessed for liver transplantation.

Liver International

Body composition predicts mortality in patients with cirrhosis. The impact of sex on this association is unknown. We investigated the impact of sex on this association in patients with cirrhosis assessed for liver transplantation.

This single centre retrospective cohort study included adults assessed for liver transplantation. Nutritional status was assessed using the Royal Free Hospital-Global Assessment (RFH-GA). Body composition at third lumbar vertebrae was determined. SarcopeniaSMI was defined as Skeletal Muscle Index <50cm2 /m2 in males and <39cm2 /m2 in females. SarcopeniaPMI was defined as the sex-specific 25th percentile of Psoas Muscle Index. Patients were assessed for occurrence of liver transplantation and death. Analyses were stratified by sex.

The cohort comprised 628 patients, including 199 females and 429 males. Both groups were similar in terms of baseline liver disease severity by Model for End-stage Liver Disease (MELD) (p=0.98), and nutritional status (p=0.24). SarcopeniaSMI was present in 41% of males compared to 27% of females (p<0.001). In the male cohort, when adjusted for age and MELD, sarcopeniaPMI (aHR1.74, 95%CI 1.08-2.80) and RFH-GA (aHR1.40, 95%CI 1.03-1.90) remained independent predictors of mortality. Adipose tissue had no impact on outcomes in males. In female patients, adipose tissue (TATI or VATI depending on the multivariable model) were independently associated with mortality whereas sarcopenia and malnutrition were not.

This study demonstrates that male patients were susceptible to low muscle mass, while female patients were not. Future research in this patient population should minimize sex-related bias, and present data for both groups separately.

Defining pathogenicity of NOTCH2 variants for diagnosis of Alagille syndrome type 2 by using a large cohort of patients.

Liver International

Alagille syndrome (ALGS) type 2 caused by mutations in NOTCH2 has genotypic and phenotypic heterogeneity. Diagnosis in some atypical patients with isolated hepatic presentation could be missed.

By using 2,087 patients with pediatric liver manifestations, NOTCH2 allele frequencies, in-silico prediction, protein domains, and clinical features were analyzed to define pathogenicity of NOTCH2 variants for diagnosis of ALGS type 2.

Among 2,087 patients with pediatric liver manifestations, significantly more NOTCH2 variants were absent in gnomAD in patients with elevated γ-glutamyltransferase (GGT) (P=0.041). Significantly more NOTCH2 variants which were absent in gnomAD were located in protein functional domains (P=0.038). When missense variants were absent in gnomAD and predicted to be pathogenic by at least three out of seven in-silico tools, they were found to be significantly associated with liver manifestations with elevated GGT (P=0.003). Comparing this to patients with likely-benign (LB) variants, the patients with likely-pathogenic (LP) variants significantly more as liver manifestations with elevated GGT (P=0.0001). Significantly more patients with LP variants had extra-hepatic phenotypes of ALGS compared with those patients with LB variants (P= 0.0004).

When NOTCH2 variants are absent in gnomAD, null variants and missense variants which were predicted to be pathogenic by at least three in-silico tools could be considered pathogenic in patients with high GGT chronic liver diseases.

FIB-4 and incident severe liver outcomes in patients with undiagnosed chronic liver disease: A Fine-Gray competing risks analysis.

Liver International

The Fibrosis-4 Index (FIB-4) can reliably assess fibrosis risk in patients with chronic liver disease and advanced fibrosis is associated with severe liver disease (SLD) outcomes. However, CLD is under-diagnosed in primary care. We examined the association of FIB-4 risk strata and the incidence of SLD preceding a CLD diagnosis while considering incident CLD diagnoses as competing risks.

Using primary care clinic data between 2007 and 2018, we identified patients with two FIB-4 scores and no liver disease diagnoses preceding the index FIB-4. Patients were followed from index FIB-4 until an incident SLD (a composite of cirrhosis, hepatocellular carcinoma, or liver transplantation), CLD, or were censored. Hazard ratios were computed using a Fine-Gray competing risk model.

Of 20,556 patients, there were 54.8% in the low, 34.8% in the indeterminate, 6.6% in the high, and 3.8% in the persistently high-risk FIB-4 strata. During a mean 8.2 years of follow-up, 837 (4.1%) patients experienced an SLD outcome and 11.5% of the sample received a CLD diagnosis. Of patients with an SLD event, 49% received no preceding CLD diagnosis. In the adjusted Fine-Gray model, the indeterminate (HR 1.41; 95%CI 1.17 - 1.71), high (HR 4.65; 95%CI 3.76 - 5.76), and persistently high-risk (HR 7.60; 95%CI 6.04 - 9.57) FIB-4 risk strata were associated with a higher incidence of SLD compared to the low-risk stratum.

FIB-4 scores with indeterminate and high-risk values are associated with an increased incidence of SLD in primary care patients without known CLD.