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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NR1H4 rs35724 G>C Variant Modulates Liver Damage in Nonalcoholic Fatty Liver Disease.

Liver International

Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G>C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis.

We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms was genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n=124).

The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic confounders and for enrolling center, was protective against severity of steatosis (GG vs CC OR 0.77, 95% C.I. 0.62-0.95; p=0.01), steatohepatitis (GG vs CC OR 0.62, 95% C.I. 0.47-0.83; p=0.001) and severity of fibrosis (GG vs CC OR 0.83, 95% C.I. 0.67-0.98; p=0.04). The C allele was associated with higher total circulating cholesterol (p=0.01). Patients carrying the NR1H4 rs35724 C allele had significantly higher hepatic mRNA levels of FXR and associated with higher hepatic FGFR4 and Cyp39A1 that are in turn involved in bile acid synthesis.

Increased hepatic FXR expression due the NR1H4 rs35724 C allele is linked to higher serum cholesterol but protects against steatosis, steatohepatitis and liver fibrosis. The translational relevance of these results for patient risk stratification and FXR- targeted therapy warrants further investigation.

Determinants of HCV-related complications in Italian primary care patients.

Liver International

This study aimed to assess the demographic and clinical determinants of liver complications in Hepatitis C virus (HCV)-positive patients in primary care setting.

Using the Health Search database, we selected a cohort of patients aged ≥14 being diagnosed with HCV between 2002 and 2017. Patients were followed up until the occurrence of cirrhosis and other disease progressions such as esophageal varices, hepatocellular carcinoma, and/or liver transplantation. The candidate determinants for the risk of HCV-related complications included sex, age, smoking status, liver fibrosis (measured by fibrosis 4 index (FIB-4)), infections by the human immunodeficiency virus (HIV), hepatitis B virus (HBV), other forms of hepatitis, abuse of alcohol or of illicit substances or drugs, obesity, metabolic syndrome, diabetes mellitus and renal disease. Cox regression was used to test the association between candidate determinants and the outcome.

The cohort included 8,299 HCV-positive patients (50.93% men) with an overall prevalence rate equal to 0.61%. At least one HCV-related complication was found in 12.2% of patients, with a mean time-to-event equal to 8.1 year. Along with male sex and advanced age, a FIB-4 greater than 3.25 and the presence of diabetes were associated with a greater risk of HCV-related complications.

Our study shows that patients with certain demographics and clinical characteristics are more prone to incur in HCV-related complications. The knowledge and early identification of these determinants by GPs may result in reducing disease progression and related healthcare costs through a closer monitoring.

Epidemiological trends of HBV and HDV coinfection among Viennese HIV+ patients.

Liver International

Despite vaccination recommendations, hepatitis B (HBV) and D (HDV) coinfections are common in HIV+ individuals.

HBV immunization status (anti-HBs) as well as HBV (HBsAg/HBV-DNA) and HDV (anti-HDV) coinfection rates were assessed in 1870 HIV+ individuals at HIV diagnosis (baseline, BL) and last follow-up (FU).

68 (3.6%) HIV patients were never tested for HBV. At BL, 89/1802 (4.9%) HIV patients were HBV-coinfected. 415(23.0%) showed virological HBV-clearance [HBsAg(-)/anti-HBc(+)/anti-HBs(+)] and 210(11.7%) presented with anti-HBc(+) only. 710(39.4%) were HBV-naïve [HBsAg(-)/anti-HBs(-)/anti-HBc(-)/HBV-DNA(-)], but only 378 (21.0%) received vaccinations with detectable anti-HBs(+) titers. Among the 89 HBV/HIV-coinfected patients, only 52 (58.4%) were tested for HDV: 11/49 (22.4%) had anti-HDV(+) and 3/12 (25.0%) showed HDV-RNA-viremia. During a median FU of 6.5 (IQR 7.2) years, 44 (4.6%) of the 953 re-tested BL HBV-negative patients acquired new HBV-infection (including 15/304, 4.9% of vaccinated patients). 22/89 (24.7%) patients cleared their HBsAg, resulting in 60/1625 (3.7%) HIV/HBV individuals at FU: 34 (56.7%) showed HBV-DNA suppression and 15 (25.0%) were HBV-viremic, while 12/89 (13.5%) remained without a FU test. Vaccinations induced anti-HBs(+) in 137 of the retested 649 (21.1%) BL HBV-naïve patients.

HBV-testing is well established among Viennese HIV+ patients with HBV-coinfection rates around 4-5%. HBV-vaccinations are insufficiently implemented since anti-HBs titers were detected in only 21.1% of HBV-naive HIV(+) patients and new HBV infections occured in previously vaccinated patients. HDV-testing is not systematically performed despite up to 25% of HIV/HBV-patients may show HDV-coinfection.

Adverse events as potential predictive factors of activity in advanced hepatocellular carcinoma patients treated with lenvatinib.

Liver International

BACKGROUND & AIM: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in HCC patients treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome.

We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of adverse events, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS).

The appearance of arterial hypertension G≥2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, p = 0.0188], while decreased appetite G≥2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, p = 0.0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, p = 0.0149), while decreased appetite G≥2 predicted decreased PFS (HR 1.36, 95% CI 1.04-1.77, p = 0.0277).

Our main findings are that the occurrence of arterial hypertension G ≥ 2 is a predictor of longer survival, whereas decreased appetite G ≥ 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, in order to improve patients' quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.

Racial Differences in primary sclerosing cholangitis mortality is associated with Community Socioeconomic Status.

Liver International

Natural history and outcomes data in PSC are mostly derived from cohorts where Blacks have been underrepresented. It is unknown if there are differences in mortality between Blacks and Whites with PSC.

PSC patients seen at our institution from June 1988 to Jan 2019 were identified by merging prospective ERCP hepatology-clinic databases and liver-transplant registry. Data on race, clinical events, and death was obtained through chart review. Data on community health were collected using indices from county health rankings. Cumulative incidence of death was calculated using liver transplant (LT) as a competing risk.

Out of 449 patients, 404 were White and 45 were Black. The median-duration of follow-up was 7 yrs (IQR:3, 13). Black patients were younger at presentation than White patients (36.3 vs 42.5 yrs., p=0.013). Disease severity as indicated by Mayo Risk Score categories (low 27% vs 31%, intermediate 54% vs 49% and high 19% vs 19%, p=0.690), comorbidity burden and frequency of cirrhosis (42% vs 35%, p=0.411) were similar between Blacks and Whites. Cumulative incidence of liver-related death, with LT as a competing risk was significantly higher in Blacks compared to Whites (sHR 1.80, 95%CI 1.25, 2.61, p=0.002). There was a significant interaction between race and community socioeconomic factors that attenuated the racial difference in mortality (sHR 1.01, 95%CI 0.99, 1.04, p=0.345).

Blacks with PSC present at a younger age with a similar disease severity as Whites but have higher liver related mortality that is mediated in part through community health.

Outcomes and potential surrogate markers for future clinical trials of non-alcoholic steatohepatitis cirrhosis.

Liver International

Non-alcoholic steatohepatitis has emerged as a major public health problem, and the burden of non-alcoholic steatohepatitis cirrhosis is projected ...

EASL versus LI-RADS: Intra-individual Comparison of MRI with Extracellular Contrast and Gadoxetic Acid for Diagnosis of Small HCC.

Liver International

Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study (EASL) criteria for hepatocellular carcinoma (HCC) diagnosis have been updated in 2018. We aimed to compare the HCC diagnostic performance of LI-RADS and EASL criteria with extracellular contrast agents-MRI (ECA-MRI) and hepatobiliary agents-MRI (HBA-MRI).

We prospectively evaluated 179 participants with liver cirrhosis (n=105) or non-cirrhotic chronic hepatitis B (CHB) (n=74) who underwent both ECA-MRI and HBA-MRI before surgery for de novo nodule(s) measuring 10-30 mm. We compared the HCC diagnostic performance of EASL and LR-5 in both MRIs.

In an analysis of 215 observations (175 HCCs, 17 non-HCC malignancies, and 23 benign lesions) identified from cirrhotic or non-cirrhotic CHB participants, LR-5 with ECA-MRI provided the highest sensitivity (80.7%), followed by EASL with ECA-MRI (76.2%), LR-5 with HBA-MRI (67.3%), and EASL with HBA-MRI (63.0%, all P<.05). The specificities were comparable (89.4%-91.5%). When the analysis is limited to participants with pathological cirrhosis (123 observations), the sensitivity of LR-5 with ECA-MRI was similar to that of EASL with ECA-MRI (82.7% vs. 80.2%, P=.156), but higher than LR-5 with HBA-MRI (65.1%) or EASL with HBA-MRI (62.8%, both P<.001), with comparable specificities (87.5%-91.7%).

The LR-5 with ECA-MRI yielded the highest sensitivity with a similar specificity for HCC diagnosis in liver cirrhosis and non-cirrhotic CHB participants, while the sensitivities of LR-5 and EASL with ECA-MRI are similar for liver cirrhosis participants. This indicates non-invasive diagnosis criteria can differ by contrast agents and presence of liver cirrhosis.

Risk of non-tumoral portal vein thrombosis in patients with HCV-induced cirrhosis after sustained virological response.

Liver International

Sustained virologic response (SVR) to direct-acting antivirals (DAA) ameliorates portal hypertension, improves hepatic function and may reverse the procoagulant state observed in patients with cirrhosis. However, an unexpected incidence of portal vein thrombosis (PVT) immediately after antiviral therapy has recently been reported. Therefore, we analyzed the long-term impact of SVR on the development of non-tumoral-PVT.

Our study comprised two well-characterized prospective cohorts ('HCV-Cured':n=354/'HCV-Active':n=179) of patients with HCV-cirrhosis who underwent standardized ultrasound surveillance. In the main analysis, the event of interest was de novo non-tumoral-PVT and events known to modify its natural history (OLT, TIPS, death, tumoral-PVT and anticoagulation) were considered as competing risk. Adjusted models were built using propensity scores for baseline covariates. Moreover, predictive factors were investigated by conventional multivariate analysis.

Ten (2.8%) patients in the 'HCV-Cured'-cohort developed a non-tumoral-PVT during a median follow-up of 37.1 months, while 8 (4.5%) patients in the 'HCV-Active'-cohort were diagnosed with non-tumoral-PVT during a median follow-up of 42.2 months. High Child-Pugh score was the only independent risk factor for non-tumoral-PVT-development and stage A patients were at low risk. Importantly, HCV-cure did not decrease the risk of non-tumoral-PVT in inverse probability of treatment-weighted (IPTW) analysis (subdistribution hazard ratio (sHR): 1.31(95% confidence interval (95%CI): 0.43-3.97); P=0.635). In contrast, SVR was associated with a substantial reduction in mortality (IPTW-adjusted sHR: 0.453 (95%CI: 0.287-0.715); P<0.001).

The risk of non-tumoral-PVT persists after HCV-cure in patients with cirrhosis, despite improving survival. Even after etiological cure, severity of liver disease remains the main determinant of non-tumoral-PVT-development.

Association of aspirin and statin use with the risk of liver cancer in chronic hepatitis B: a nationwide population-based study.

Liver International

Aspirin and statins have been suggested to prevent hepatocellular carcinoma (HCC). However, the combined effects of aspirin and statins on HCC risk in patients with chronic hepatitis B (CHB) is not clear.

A nationwide nested case-control study was performed with data from the National Health Insurance Service gathered between 2005 and 2015 in Korea. In a cohort of 538,135 treatment-naïve, non-cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analyzed by conditional logistic regression. Separate historical cohort studies for each drug were analyzed by time-dependent Cox regression as a sensitivity analysis.

In the nested case-control study, statins (OR 0.34; 95% CI 0.32-0.37) and aspirin (OR 0.92; 95% CI 0.85-0.99) were significantly associated with a HCC risk reduction. However, dose-dependent risk reduction was observed only with statins. By sensitivity analysis in the historical cohorts, statin users (n = 244,455; HR 0.67; 95% CI 0.66-0.68) and aspirin users (n = 288,777; HR 0.81; 95% CI 0.80-0.82) had significantly lower HCC risk. In the drug-stratified analyses, statins were associated with significantly reduced risk of HCC regardless of aspirin, whereas aspirin did not show such associations.

In this nationwide population-based study of patients with CHB, statin use was consistently associated with a significant and dose-dependent reduction in HCC risk. In contrast, the association between aspirin use and HCC risk reduction was not dose-dependent and was suggested to be confounded by statins.

Coagulopathy is not predictive of bleeding in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

Liver International

Understanding factors responsible for the increased bleeding tendency in acute-on-chronic liver failure (ACLF) would improve the management of these complications. We investigated coagulation alterations in ACLF and assessed whether they were predictive of bleeding.

Cirrhosis patients with ACLF (cases) and acute decompensation (AD, controls) were prospectively recruited and underwent an extensive hemostatic assessment including standard tests, pro and anticoagulant factors, thrombomodulin-modified thrombin generation (TG), and thromboelastometry (ROTEM®). In study part 1 (case-control), we compared coagulation in ACLF vs. AD. In study part 2 (prospective), all patients were followed for bleeding and predictors of outcome were assessed.

Ninety-one patients were included (51 with ACLF, 40 with AD). Infections and ascites/renal dysfunction were the most common precipitating and decompensating events. Platelet count was lower while INR and aPTT were longer in ACLF cohort vs. AD. Regarding clotting factors, fibrinogen and factor VIII were comparable between groups while protein C and antithrombin were significantly reduced in ACLF. Endogenous thrombin potential by TG was comparable between groups. Clotting formation time and clot stability by ROTEM® were significantly lower in ACLF, indicative of a more hypocoagulable state. No hemostasis alteration could discriminate between patients who had bleeding complications during hospitalization and those who did not.

We found coagulation changes in ACLF to largely overlap with that of AD, and evidence of preserved coagulation capacity in both groups. ROTEM alterations were indicative of a more pronounced hypocoagulable state in ACLF, however no correlation was found between such alterations and bleeding.

Management of liver disease in Italy after one year of the SARS-CoV-2 pandemic: a web-based survey.

Liver International

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has severely limited the clinical activity of most hospitals around the world...

Anti-TNFα treatment in Crohn's disease: Impact on hepatic steatosis, gut-derived hormones, and metabolic status.

Liver International

An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD-treatments are agents that inhibit Tumor-Necrosis-Factor (TNF) activity, yet it is unclear why anti-TNFα agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analyzed a potential relationship between anti-TNF treatment and hepatic steatosis in CD, focusing on the gut-liver axis.

This cross-sectional study evaluated patients with established CD, with and without anti-TNFα treatment, analyzing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP), and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analyzed gut microbiota composition and mediators of bile acid (BA) signaling via stool and serum analysis.

Patients on anti-TNFα treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti-TNFα therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti-TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group-specific alterations with low levels in patients without anti-TNFα treatment. Low abundance of Firmicutes was associated with higher triglyceride levels.

Anti-TNFα treatment is associated with reduced steatosis, lower triglyceride levels, alterarions in FXR-signaling (e.g., FGF19) and microbiota composition in CD.