Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease

Rasmussen, Ditlev Nytoft; Thiele, Maja; Johansen, Stine Liv; Kjærgaard, Maria; Lindvig, Katrine Prier; Israelsen, Mads; Antonsen, Steen; Detlefsen, Sönke; Krag, Aleksander; Anastasiadou, Ema; Arumugam, Manimozhiyan; Bork, Peer; Hansen, Torben; Hartoft, Christina; Israelsen, Hans; Karsdal, Morten A.; Legido‐Quigley, Cristina; Melberg, Hans Olav; Trebicka, Jonel; Mann, Mathias; Matthijnssens, Jelle

doi:10.1016/j.jhep.2021.05.037

Cited by 92 publications

(95 citation statements)

References 38 publications

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“…A recent study demonstrated that the FIB4-index has good accuracy in predicting the risk of liver-related events (AUC of 0.821), with similar results to other biomarkers (FibroTest, Forns index, non-alcoholic fatty liver fibrosis score (NFS)). Therefore, in the absence of hepatic elastography, blood tests are a good alternative for the diagnosis and prognosis of ALD, given their accessibility in primary and secondary care [42].…”

Section: Discussionmentioning

confidence: 99%

Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Teniente-Serra

Fuster

Quirant‐Sánchez

et al. 2022

JCM

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Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 ± 109 cells/µL vs. 170 ± 105 cells/µL) in both groups. The T cells percentage was lower (80.3 ± 5.6% vs. 77 ± 7%; p = 0.03) and the NK cells percentage was higher (9.7 ± 5% vs. 13 ± 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r = –0.65, p < 0.01) and with ALF (r = −0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression.

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Section: Discussionmentioning

confidence: 99%

Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Teniente-Serra

Fuster

Quirant‐Sánchez

et al. 2022

JCM

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“…Instead, we suggest increased vigilance for the progression of disease, especially in the shorter term. An increased vigilance is also supported by a recent study of primarily non‐cirrhotic ALD patients, where 31% were hospitalized for an infection after a median time of 49 months, although correlations between histology and infections were not reported 31 . It is not clear why the rate of infections was elevated also in patients without cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

“…An increased vigilance is also supported by a recent study of primarily non‐cirrhotic ALD patients, where 31% were hospitalized for an infection after a median time of 49 months, although correlations between histology and infections were not reported. 31 It is not clear why the rate of infections was elevated also in patients without cirrhosis. Possible explanations could be progression to cirrhosis, but also unmeasured confounding such as low socio‐economic status and a higher exposure to pathogenic environments.…”

Section: Discussionmentioning

confidence: 99%

Risk of infections and their role on subsequent mortality in biopsy‐proven alcohol‐related liver disease

et al. 2022

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Background and Aims The risk for infection in alcohol‐related liver disease (ALD) has rarely been investigated at a population level, nor if the underlying liver histopathology is associated with infection risk. We examined the rate of hospital‐based infections in a nationwide cohort of biopsy‐proven ALD, and the subsequent risk of death. Methods Population‐based cohort study in Sweden comparing 4028 individuals with an international classification of disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 19,296 matched general population individuals. Swedish national registers were used to ascertain incident infections in secondary or tertiary care and subsequent mortality until 2019. We used Cox regression, adjusted for sex, age, education, country of birth, diabetes, and number of hospitalizations in the year preceding liver biopsy date, to estimate hazard ratios (HRs) in ALD and histopathological subgroups compared to reference individuals. Results Median age at ALD diagnosis was 59 years, 65% were men and 59% had cirrhosis at baseline. Infections were more common in patients with ALD (84 cases/1000 person‐years [PY]) compared to reference individuals (29/1000 PYs; adjusted hazard ratio [aHR] 3.06, 95% CI = 2.85–3.29). This excess risk corresponded to one additional infection per 18 ALD patients each year. The rate of infections was particularly high in individuals with cirrhosis (aHR = 3.46) and in those with decompensation (aHR = 5.20). Restricting our data to those with an infection, ALD (aHR = 3.63, 95%CI = 3.36–3.93), and especially ALD cirrhosis (aHR = 4.31, 95%CI = 3.89–4.78) were linked to subsequent death. Conclusions Individuals with biopsy‐proven ALD have a three‐fold increased rate of infections compared with the general population. The risk of death after an infection is also considerably higher in individuals with ALD.

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“…Liver fibrosis represents the early pre-cirrhotic stages of chronic liver disease, which in general is asymptomatic and characterized by slow progression through years to decades [6]. Significant fibrosis (≥F2) and advanced fibrosis (≥F3) represents important landmarks in the naturals history of disease since they associates strongly with future liver associated morbidity and mortality [22,39,40,41], and thus represent an important point for timely intervention to prevent further progression [28,29], and also at a regulatory level has been accepted as relevant cut points [42,43]. Liver biopsy represents the gold standard for assessment of liver fibrosis, however, several tools for the non-invasive assessment of liver fibrosis have been developed and can substitute a liver biopsy for assessment of fibrosis (▶ Fig.…”

Section: Clinical Approach To Diagnosis Of Early Alcohol Related Liver Diseasementioning

confidence: 99%

Diagnostic challenges in patients with alcohol-related liver disease

Krag

Roskams²,

Pinzani

et al. 2022

Z Gastroenterol

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Alcohol is globally the leading risk factor for cirrhosis and is subsumed under the term alcohol-related liver disease (ALD). However, only ca. 10% of people with harmful alcohol consumption (>40 gram alcohol per day) develop cirrhosis, while 15% have normal liver histology. Unfortunately, laboratory parameters and ultrasound hold little value to neither rule-in nor rule out alcohol related liver fibrosis. While several indices with combinations of liver associated markers such as FIB4 seem to be promising, non-invasive test strategies are urgently needed with cut-off’s that can be applied to guide clinical decision making. The aims of this review article are to highlight novel developments for the diagnosis of ALD and to identify topics of controversy and potential future directions. In the last 15 years, elastography to measure liver stiffness (LS) has significantly improved our screening strategies for cirrhosis. LS values below 6 kPa are considered as normal and exclude ALD. LS of 8 and 12.5 kPa represent generally accepted cut-off values for F3 and F4 fibrosis. Especially, transient elastography (TE) has been assessed in numerous studies, but similar performance can be obtained with point shear wave elastography, 2 SD shear wave elastography or MR elastography. Important confounders of elevated LS such as inflammation should also be considered and alcohol withdrawal not only improves liver inflammation but also LS. Liver stiffness measurement has signficiantly improved early diagnosis and follow-up of fibrosis in patients with ALD and patients with diagnosed manifest but clinically compensated cirrhosis should undergo further clinical examinations to rule out complications of portal hypertension. In addition, surveillance for the occurrence of hepatocellular carcinoma is recommended in all cirrhotic patients.

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Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease

Cited by 92 publications

References 38 publications

Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Risk of infections and their role on subsequent mortality in biopsy‐proven alcohol‐related liver disease

Diagnostic challenges in patients with alcohol-related liver disease

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