Watt, K D

This study investigated the combined effect of handgrip strength (HGS) and non-alcoholic fatty liver disease (NAFLD) on pulmonary function using the Korea National Health and Nutrition Examination Survey (KNHANES) from 2016 to 2018. For the present study, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), the FEV1/FVC ratio, handgrip strength (HGS) and the hepatic steatosis index (HSI) to estimate NAFLD were obtained from nationwide cross-sectional surveys. For HGS, subjects were divided into higher HGS (upper 50%) and lower HGS (lower 50%). For NAFLD, subjects were divided into the NAFLD cohort (HSI > 36) and the normal cohort (HSI ≤ 36). Of 1651 subjects (men, n = 601), 25.5% of subjects (n = 421) met the HSI > 36. Based on the normal cohort with high HGS, the normal cohort with low HGS showed an increased risk of reduced FVC (OR = 3.062, 95% CI = 2.46–4.83, p < 0.001) and the NAFLD cohort with low HGS showed a further increased risk of reduced FVC (OR = 4.489, 95% CI = 3.43–7.09, p < 0.001). However, the risk of reduced FVC was not significantly increased in NAFLD with high HGS (OR = 1.297, 95% CI = 0.67–2.50, p = 0.436). After adjusted for covariates such as age, sex, smoking, FBG, HDL-C, TG, SBP, DBP, CRP and alcohol consumption, the results remained similar. More importantly, these results were consistent in the obesity-stratified analysis. The current findings of the study suggest that higher muscle strength is associated with a lower risk of reduced pulmonary function in individuals with NAFLD.

AbstractBackground and aimsNonalcoholic steatohepatitis (NASH) is associated with metabolic conditions that increase the risk of de novo malignancy following transplant. Patients often have more than one underlying liver disease, which could change the risk of de novo malignancy. This study assessed the incidence of NASH overlap and its effect on de novo malignancy in liver transplant recipients.MethodsData was analyzed from the United Network for Organ Sharing database for all liver transplant recipients from 1997 to 2017 for NASH alone or in combination with another liver disease.ResultsThere is an increasing prevalence of NASH overlap. Of the 98,679 patients included in the analysis, 1238 had a de novo malignancy identified (7.4% by 5 years post‐transplant). The cumulative incidence of de novo malignancy increases in primary sclerosing cholangitis (PSC)/NASH overlap after 5 years and was increased in alcohol‐related liver disease (ALD)/NASH through 10 years compared to ether disease alone. NASH overlaps with “other” diseases experience a cumulative incidence similar to NASH and not the “other” disease. An increased risk of de novo solid organ malignancy was associated with older age, male gender, previous malignancy, and multiorgan transplant.ConclusionThe prevalence of liver transplant recipients with NASH overlap is increasing. These patients may experience different long‐term outcomes than patients with either diagnosis alone. De novo malignancy risk can be influenced by multiple factors and metabolic comorbidities. Further study of patients with overlap diagnoses is important moving forward to guide individualized care and cancer screening programs.

Prostate‐specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68Ga‐PSMA‐11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68Ga‐PSMA‐11 PET was prospectively performed in patients with treatment‐naïve HCC on a digital PET scanner using cyclotron‐produced 68Ga. Uptake was graded qualitatively and semi‐quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor‐associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10‐5) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = −0.753; P = 1.58 × 10‐6). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68Ga‐PSMA‐11 standardized uptake value: SUVmax (median [range] 9.2 [4.9‐28.4]), SUVmean 4.7 (2.4‐12.7), and tumor‐to‐liver background ratio 2 (1.1‐11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68Ga‐PSMA‐11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

AbstractBackground & AimsGlycogenic hepatopathy (GH) in type 1 diabetes‐mellitus (T1DM) is characterized by hepatomegaly and perturbations of liver chemistries (LC) that have not been well studied. Furthermore, misdiagnosis with other hepatic complications of T1DM, such as nonalcoholic fatty liver disease, has been described. We perform a systematic review of biopsy‐proven GH reports in T1DM patients to identify LC patterns.MethodsA systematic review identified reports of biopsy‐proven GH in patients with T1DM. We excluded GH with other liver diseases, Mauriac syndrome, or GH without T1DM. Two reviewers screened and extracted studies and assessed their methodological quality. LC elevation magnitude, AST‐to‐ALT ratio, R‐ratio to designate hepatocellular, cholestatic or mixed pattern of hepatic injury, and evolution of transaminases after glycemic control were analyzed.ResultsA total of 192 patients were included, with median age of 20 years, 73% adults, 66% females, median duration of T1DM before diagnosis 10 years, median adult body mass index 21 kg/m2, median HbA1c 12%, at least one episode of diabetic ketoacidosis 70%, and hepatomegaly 92%. ALT and AST showed moderate‐to‐severe elevation in 78% and 76%, respectively, AST/ALT >1 in 71% and hepatocellular to mixed pattern of hepatic injury in 81%. Transaminase improvement with glycemic control was the rule, regardless of other factors in multilinear regression analysis.ConclusionGH tends to have AST‐predominant elevation with a median of 13 times the upper normal limit and R‐ratio >2, which may distinguish it from other etiologies of AST‐predominant LC elevation, and in the appropriate clinical context, may obviate invasive tests.

The diagnostic criteria for cirrhotic cardiomyopathy (CCM) were recently revised to reflect the contemporary advancements in echocardiographic technology. This study evaluates the prevalence of CCM, according to the new criteria, and its impact on posttransplant cardiovascular disease (CVD). This is a single‐center retrospective matched cohort study of liver transplantation (LT) recipients who underwent LT between January 1, 2008 and November 30, 2017. A total of 3 cohorts with decompensated cirrhosis (nonalcoholic steatohepatitis, alcohol‐related liver disease, or other etiologies) were matched based on age, sex, and year of transplant after excluding patients listed without evidence of hepatic decompensation. CCM was defined, according to 2020 criteria, as having diastolic dysfunction, left ventricular ejection fraction ≤50%, and/or a global longitudinal strain (GLS) absolute value <18%. The study echocardiographers were blinded to the clinical data. Posttransplant CVD included new coronary artery disease, congestive heart failure, atrial and ventricular arrhythmia, and stroke. The study included 141 patients of whom 59 were women. The mean age at LT was 57.8 (±7.6) years. A total of 49 patients (34.8%) had CCM. Patients with CCM were at an increased risk for post‐LT CVD (hazard ratio, 2.57; 95% confidence interval, 1.2‐5.5; P = 0.016). Changes in CCM individual parameters pretransplant, such as GLS, early diastolic transmitral flow to early diastolic mitral annular velocity, and left atrial volume index were associated with an increased risk for posttransplant CVD. CCM, defined by the new diagnostic criteria, affects approximately one‐third of decompensated LT candidates. CCM predicts an increased risk for new CVD following LT. Studies into addressing and follow‐up to mitigate these risks are needed.

Linked ContentThis article is linked to Huebener et al papers. To view these articles visit https://doi.org/10.1111/apt.14627 and https://doi.org/10.1111/apt.14804.

SummaryBackgroundWith recent advances in the management of chronic liver disease and its complications, the long‐term survival in cirrhosis has improved. Therefore, the number of individuals who will spend a significant proportion of their life with end‐stage liver disease (ESLD) may continue to rise. Thus, more attention to quality of life (QOL) and its integration with traditional clinical endpoints is needed.AimsRecently, there have been many studies looking at treatment outcomes and their impact on the QOL in patients with ESLD. The aim of this review was to summarise and compare the insights gained from these intervention studies and to make concise recommendations to further promote and improve QOL in this patient population.MethodsA literature search was conducted using PubMed and Web of Science. Search terms “Quality of life” “Cirrhosis” and “end‐stage liver disease” were used as MeSH terms or searched in the title of the article.ResultsThese studies uniformly show significant improvement in health‐related QOL (HRQOL) with management of malnutrition, hepatic encephalopathy and ascites. Thus, early recognition and management of these complications are keys to better serve our patients. Early involvement of palliative care also leads to improved quality of end‐of‐life care.ConclusionsComplications of cirrhosis including malnutrition, encephalopathy, ascites and variceal bleeding lead to a decrease in HRQOL. Assessment of HRQOL has an important implication for the patient. The findings of this review illuminate the importance of using consistent tools to accurately assess QOL in patients with ESLD.