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Z Gastroenterol 2022; 60(01): 45-57
DOI: 10.1055/a-1713-4372
Übersicht

Diagnostic challenges in patients with alcohol-related liver disease

Diagnostische Herausforderungen bei Patienten mit alkoholischer Lebererkrankung
Aleksander Krag
1   Centre for Liver Research/Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark (Ringgold ID: RIN11286)
2   Institute of Clinical Research, University of Southern Denmark, Odense, Denmark (Ringgold ID: RIN6174)
,
Tania Roskams
3   Department of Imaging and Pathology, University of Leuven, Leuven, Netherlands
,
Massimo Pinzani
4   University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN158987)
,
Sebastian Mueller
5   Centre of Alcohol Research, University of Heidelberg, Heidelberg, Germany
6   Department of Medicine, Salem KH, Heidelberg, Germany
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Abstract

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.

Zusammenfassung

Alkohol ist weltweit der führende Risikofaktor für eine Leberzirrhose. Subsumiert werden alkoholbedingte Leberschäden unter dem Begriff der alkoholischen Lebererkrankung (ALE). Trotz riskanten Alkoholkonsum (>40 g pro Tag) entwickeln nur ca. 10% der alkoholkonsumierenden Personen über Jahre eine Leberzirrhose. Allerdings wird diese Leberzirrhose durch routinemäßige Laborparameter oder den Ultraschall oft übersehen bzw. eignet sich die konventionelle Diagnostik nur eingeschränkt zum Ausschluss einer alkoholischen Leberfibrose. Obwohl verschiedene kombinierte Leberscores wie z.B. FIB4 vielversprechend sind, werden aber daher dringend vor allem nichtinvasive Teststrategien benötigt. Ziel dieses Übersichtsartikels ist es, neue Entwicklungen zur Diagnose der ALE vorzustellen, sowie offene Fragen und zukünftige Entwicklungsstrategien zu diskutieren. In den letzten 15 Jahren ist vor allem durch die Einführung der Leberelastografie zur Messung der Lebersteifigkeit (LS) eine entscheidende Verbesserung beim Zirrhosescreening erreicht worden. LS Werte unter 6 kPa gelten als normal und schließen eine ALE aus. LS Werte von 8 und 12,5 kPa sind allgemein akzeptiere Schwellwerte für die F3 Fibrose bzw. F4 Zirrhose. Besonders die transiente Elastografie (TE) ist bisher in zahlreichen Studien validiert worden, eine ähnliche Performance wird aber auch mit der Scherwellenelastografie und der MR Elastografie erreicht. Wichtige modulierende Faktoren einer erhöhten LS wie eine Leberentzündung (Hepatitis) müssen in der Diagnostik ebenfalls berücksichtigt werden. So führt eine Alkoholentgiftung nicht nur zu einer Verbesserung der Leberentzündung sondern auch zu einem Abfall oder sogar Normalisierung der LS. Zusammengefasst kann man sagen, dass die Einführung der LS die frühe Diagnose und auch die Verlaufsbeurteilung der ALE deutlich verbessert hat. Bei Patienten mit einer manifesten aber klinisch kompensierten Leberzirrhose müssen durch weiterführende Untersuchungen mögliche Komplikationen z.B. einer portalen Hypertension ausgeschlossen werden. Außerdem sollten diese Patienten in ein HCC Screening Programm eingeschlossen werden.

Schlüsselwörter

Alkoholische Lebererkrankung - Lebersteifigkeit - Leberzirrhose

Keywords

alcoholic liver disease - liver stiffness - liver cirrhosis


Publication History

Received: 11 November 2021

Accepted after revision: 02 December 2021

Article published online:
18 January 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 World Transplant Registry reports. 2018
    PubMedSearch in Google Scholar
  • 2 Wong RJ, Aguilar M, Cheung R. et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology 2015; 148 (03) 547-555
    CrossrefPubMedSearch in Google Scholar
  • 3 Burra P, Senzolo M, Adam R. et al. Liver transplantation for alcoholic liver disease in Europe: a study from the ELTR (European Liver Transplant Registry). American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2010; 10 (01) 138-148
    CrossrefPubMedSearch in Google Scholar
  • 4 Wood AM, Kaptoge S, Butterworth AS. et al. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet 2018; 391 (10129): 1513-1523
    CrossrefPubMedSearch in Google Scholar
  • 5 Simpson RF, Hermon C, Liu B. et al. Alcohol drinking patterns and liver cirrhosis risk: analysis of the prospective UK Million Women Study. Lancet Public Health 2019; 4 (11) e41-e48
    CrossrefPubMedSearch in Google Scholar
  • 6 Parker R, Aithal GP, Becker U. et al. Natural history of histologically proven alcohol-related liver disease: A systematic review. J Hepatol 2019; 71 (03) 586-593
    CrossrefPubMedSearch in Google Scholar
  • 7 Bagnardi V, Rota M, Botteri E. et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer 2015; 112 (03) 580-593
    CrossrefPubMedSearch in Google Scholar
  • 8 Rehm J, Roerecke M. Patterns of drinking and liver cirrhosis – what do we know and where do we go?. J Hepatol 2015; 62 (05) 1000-1001
    CrossrefPubMedSearch in Google Scholar
  • 9 Seitz HK, Bataller R, Cortez-Pinto H. et al. Alcoholic liver disease. Nat Rev Dis Primers 2018; 4 (01) 16
    CrossrefPubMedSearch in Google Scholar
  • 10 Rehm J, Taylor B, Mohapatra S. et al. Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis. Drug Alcohol Rev 2010; 29 (04) 437-445
    CrossrefPubMedSearch in Google Scholar
  • 11 Bellentani S, Tiribelli C. The spectrum of liver disease in the general population: lesson from the Dionysos study. J Hepatol 2001; 35 (04) 531-537
    CrossrefPubMedSearch in Google Scholar
  • 12 Israelsen M, Juel HB, Detlefsen S. et al. Metabolic and Genetic Risk Factors Are the Strongest Predictors of Severity of Alcohol-Related Liver Fibrosis. Clin Gastroenterol Hepatol 2020;
    CrossrefPubMedSearch in Google Scholar
  • 13 Mavilia MG, Wu GY. HBV-HCV Coinfection: Viral Interactions, Management, and Viral Reactivation. J Clin Transl Hepatol 2018; 6 (03) 296-305
    CrossrefPubMedSearch in Google Scholar
  • 14 Emdin CA, Haas M, Ajmera V. et al. Association of genetic variation with cirrhosis: a multi-trait genome-wide association and gene-environment interaction study. Gastroenterology 2020;
    CrossrefPubMedSearch in Google Scholar
  • 15 Carlsson B, Linden D, Brolen G. et al. Review article: the emerging role of genetics in precision medicine for patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2020; 51 (12) 1305-1320
    CrossrefPubMedSearch in Google Scholar
  • 16 Stickel F, Moreno C, Hampe J. et al. The genetics of alcohol dependence and alcohol-related liver disease. J Hepatol 2017; 66 (01) 195-211
    CrossrefPubMedSearch in Google Scholar
  • 17 Abul-Husn NS, Cheng X, Li AH. et al. A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease. N Engl J Med 2018; 378 (12) 1096-1106
    CrossrefPubMedSearch in Google Scholar
  • 18 Younossi ZM, Koenig AB, Abdelatif D. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64 (01) 73-84
    CrossrefPubMedSearch in Google Scholar
  • 19 Hazeldine S, Hydes T, Sheron N. Alcoholic liver disease – the extent of the problem and what you can do about it. Clinical medicine (London, England) 2015; 15 (02) 179-185
    CrossrefPubMedSearch in Google Scholar
  • 20 Lackner C, Spindelboeck W, Haybaeck J. et al. Histological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver disease. J Hepatol 2017; 66 (03) 610-618
    CrossrefPubMedSearch in Google Scholar
  • 21 Mueller S, Seitz HK, Rausch V. Non-invasive diagnosis of alcoholic liver disease. World J Gastroenterol 2014; 20 (40) 14626-14641
    CrossrefPubMedSearch in Google Scholar
  • 22 Hagstrom H, Thiele M, Roelstraete B. et al. Mortality in biopsy-proven alcohol-related liver disease: a population-based nationwide cohort study of 3453 patients. Gut 2021; 70 (01) 170-179
    CrossrefPubMedSearch in Google Scholar
  • 23 Taylor RS, Taylor RJ, Bayliss S. et al. Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Gastroenterology 2020; 158 (06) 1611-1625 e12
    CrossrefPubMedSearch in Google Scholar
  • 24 D'Amico G, Morabito A, D'Amico M. et al. Clinical states of cirrhosis and competing risks. J Hepatol 2018; 68 (03) 563-576
    CrossrefPubMedSearch in Google Scholar
  • 25 European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69 (02) 406-460
    CrossrefPubMedSearch in Google Scholar
  • 26 Gines P, Graupera I, Lammert F. et al. Screening for liver fibrosis in the general population: a call for action. Lancet Gastroenterol Hepatol 2016; 1 (03) 256-260
    CrossrefPubMedSearch in Google Scholar
  • 27 Guirguis E, Grace Y, Bolson A. et al. Emerging Therapies for the Treatment of Non-Alcoholic Steatohepatitis: A Systematic Review. Pharmacotherapy 2020;
    CrossrefPubMedSearch in Google Scholar
  • 28 Seto WK, Lo YR, Pawlotsky JM. et al. Chronic hepatitis B virus infection. Lancet 2018; 392 (10161): 2313-2324
    CrossrefPubMedSearch in Google Scholar
  • 29 Spearman CW, Dusheiko GM, Hellard M. et al. Hepatitis C. Lancet 2019; 394 (10207): 1451-466
    CrossrefPubMedSearch in Google Scholar
  • 30 Serste T, Cornillie A, Njimi H. et al. The prognostic value of acute-on-chronic liver failure during the course of severe alcoholic hepatitis. J Hepatol 2018; 69 (02) 318-324
    CrossrefPubMedSearch in Google Scholar
  • 31 Arroyo V, Moreau R, Kamath PS. et al. Acute-on-chronic liver failure in cirrhosis. Nat Rev Dis Primers 2016; 92: 16041
    CrossrefPubMedSearch in Google Scholar
  • 32 Mookerjee RP, Lackner C, Stauber R. et al. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis. J Hepatol 2011; 55 (05) 1103-1111
    CrossrefPubMedSearch in Google Scholar
  • 33 European Association for the Study of the. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol 2018; 69 (01) 154-181
    CrossrefPubMedSearch in Google Scholar
  • 34 Altamirano J, Miquel R, Katoonizadeh A. et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014; 146 (05) 1231-1239 e1
    CrossrefPubMedSearch in Google Scholar
  • 35 Katoonizadeh A, Laleman W, Verslype C. et al. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010; 59 (11) 1561-1569
    CrossrefPubMedSearch in Google Scholar
  • 36 Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature 2020; 587 (7835): 555-5566
    CrossrefPubMedSearch in Google Scholar
  • 37 Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol 2020;
    CrossrefPubMedSearch in Google Scholar
  • 38 Thiele M, Johansen S, Gudmann NS. et al. Progressive alcohol-related liver fibrosis is characterised by imbalanced collagen formation and degradation. Aliment Pharmacol Ther 2021;
    CrossrefPubMedSearch in Google Scholar
  • 39 Simon TG, Roelstraete B, Khalili H. et al. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut 2020;
    CrossrefPubMedSearch in Google Scholar
  • 40 Hagstrom H, Nasr P, Ekstedt M. et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol 2017; 67 (06) 1265-1273
    CrossrefPubMedSearch in Google Scholar
  • 41 Rasmussen DN, Thiele M, Johansen S. et al. Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease. J Hepatol 2021;
    CrossrefPubMedSearch in Google Scholar
  • 42 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/noncirrhotic-nonalcoholic-steatohepatitis-liver-fibrosis-developing-drugs-treatment.
    PubMed
  • 43 Rinella ME, Tacke F, Sanyal AJ. participants of the AEW. et al. Report on the AASLD/EASL Joint Workshop on Clinical Trial Endpoints in NAFLD. Hepatology 2019; 70 (04) 1424-1436
    CrossrefPubMedSearch in Google Scholar
  • 44 Zheng J, Guo H, Zeng J. et al. Two-dimensional shear-wave elastography and conventional US: the optimal evaluation of liver fibrosis and cirrhosis. Radiology 2015; 275 (01) 290-300
    CrossrefPubMedSearch in Google Scholar
  • 45 Udell JA, Wang CS, Tinmouth J. et al. Does this patient with liver disease have cirrhosis?. JAMA 2012; 307 (08) 832-842
    CrossrefPubMedSearch in Google Scholar
  • 46 Lindvig K, Krag A, Thiele M. Early detection of alcohol-related liver disease. Ugeskr Laeger 2021; 183 (14) V12200947
    PubMedSearch in Google Scholar
  • 47 Madsen BS, Thiele M, Detlefsen S. et al. PRO-C3 and ADAPT algorithm accurately identify patients with advanced fibrosis due to alcohol-related liver disease. Aliment Pharmacol Ther 2021; 54 (05) 699-708
    CrossrefPubMedSearch in Google Scholar
  • 48 Thiele M, Madsen BS, Hansen JF. et al. Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease. Gastroenterology 2018; 154 (05) 1369-1379
    CrossrefPubMedSearch in Google Scholar
  • 49 Eddowes PJ, Sasso M, Allison M. et al. Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2019; 156 (06) 1717-1730
    CrossrefPubMedSearch in Google Scholar
  • 50 Nguyen-Khac E, Thiele M, Voican C. et al. Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol 2018; 3 (09) 614-625
    CrossrefPubMedSearch in Google Scholar
  • 51 Papatheodoridi M, Hiriart JB, Lupsor-Platon M. et al. Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease. J Hepatol 2020;
    CrossrefPubMedSearch in Google Scholar
  • 52 Herrmann E, de Ledinghen V, Cassinotto C. et al. Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis. Hepatology 2018; 67 (01) 260-272
    CrossrefPubMedSearch in Google Scholar
  • 53 Imajo K, Honda Y, Kobayashi T. et al. Direct comparison of US and MR elastography for staging liver fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2020;
    CrossrefPubMedSearch in Google Scholar
  • 54 Heimbach JK, Kulik LM, Finn RS. et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018; 67 (01) 358-380
    CrossrefPubMedSearch in Google Scholar
  • 55 de Franchis R, Baveno VIF. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63 (03) 743-752
    CrossrefPubMedSearch in Google Scholar
  • 56 Petta S, Sebastiani G, Bugianesi E. et al. Non-invasive prediction of esophageal varices by stiffness and platelet in non-alcoholic fatty liver disease cirrhosis. J Hepatol 2018; 69 (04) 878-885
    CrossrefPubMedSearch in Google Scholar
  • 57 Augustin S, Pons M, Maurice JB. et al. Expanding the Baveno VI criteria for the screening of varices in patients with compensated advanced chronic liver disease. Hepatology 2017; 66 (06) 1980-1988
    CrossrefPubMedSearch in Google Scholar
  • 58 Stafylidou M, Paschos P, Katsoula A. et al. Performance of Baveno VI and Expanded Baveno VI Criteria for Excluding High-Risk Varices in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2019; 17 (09) 1744-1755 e11
    CrossrefPubMedSearch in Google Scholar
  • 59 Filingeri V, Francioso S, Sforza D. et al. A retrospective analysis of 1.011 percutaneous liver biopsies performed in patients with liver transplantation or liver disease: ultrasonography can reduce complications?. European review for medical and pharmacological sciences 2016; 20 (17) 3609-3617
    PubMedSearch in Google Scholar
  • 60 Abdi W, Millan JC, Mezey E. Sampling variability on percutaneous liver biopsy. Arch Intern Med 1979; 139 (06) 667-669
    CrossrefPubMedSearch in Google Scholar
  • 61 Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003; 38 (06) 1449-1457
    CrossrefPubMedSearch in Google Scholar
  • 62 Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology 2000; 32 (03) 477-481
    CrossrefPubMedSearch in Google Scholar
  • 63 Maharaj B, Maharaj RJ, Leary WP. et al. Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver. Lancet 1986; 1 (8480): 523-525
    CrossrefPubMedSearch in Google Scholar
  • 64 Regev A, Berho M, Jeffers LJ. et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 2002; 97 (10) 2614-2618
    CrossrefPubMedSearch in Google Scholar
  • 65 Gilmore IT, Burroughs A, Murray-Lyon IM. et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 1995; 36 (03) 437-441
    CrossrefPubMedSearch in Google Scholar
  • 66 McGill DB, Rakela J, Zinsmeister AR. et al. A 21-year experience with major hemorrhage after percutaneous liver biopsy. Gastroenterology 1990; 99 (05) 1396-1400
    CrossrefPubMedSearch in Google Scholar
  • 67 Mathurin P, Hadengue A, Bataller R. et al. EASL Clinical Practice Guidelines: Managementof Alcoholic Liver Disease. J Hepatology 2012; 57 (02) 399-420
    CrossrefPubMedSearch in Google Scholar
  • 68 Moreno C, Mueller S, Szabo G. Non-invasive diagnosis and biomarkers in alcohol-related liver disease. J Hepatol 2019; 70 (02) 273-283
    CrossrefPubMedSearch in Google Scholar
  • 69 Nguyen-Khac E, Chatelain D, Tramier B. et al. Assessment of asymptomatic liver fibrosis in alcoholic patients using fibroscan: prospective comparison with seven non-invasive laboratory tests. Aliment Pharmacol Ther 2008; 28 (10) 1188-1198
    CrossrefPubMedSearch in Google Scholar
  • 70 Mueller S. Liver Elastography: Clinical Use and Interpretation. Springer International Publishing; 2020
    CrossrefSearch in Google Scholar
  • 71 Mueller S, Sandrin L. Liver stiffness: a novel parameter for the diagnosis of liver disease Hepatic Medicine. Evidence and Research 2010; 2: 49-67
    PubMedSearch in Google Scholar
  • 72 Mueller S. Liver Stiffness in Alcoholic Liver Disease. In: . Liver Elastography: Springer; 2020: 141-152
    Search in Google Scholar
  • 73 Mueller S, Luderer M, Zhang D. et al. Open-label study with nalmefene as needed use in alcohol dependent patients with evidence of elevated liver stiffness and/or hepatic steatosis (submitted). Alcohol and Alcoholism 2019; 55 (01) 63-70
    CrossrefPubMedSearch in Google Scholar
  • 74 Trabut JB, Thepot V, Nalpas B. et al. Rapid decline of liver stiffness following alcohol withdrawal in heavy drinkers. Alcohol Clin Exp Res 2012; 36 (08) 1407-1411
    CrossrefPubMedSearch in Google Scholar
  • 75 Gelsi E, Dainese R, Truchi R. et al. Effect of detoxification on liver stiffness assessed by fibroscan((R)) in alcoholic patients. Alcohol Clin Exp Res 2011; 35 (03) 566-570
    CrossrefPubMedSearch in Google Scholar
  • 76 Mueller J, Rausch V, Silva I. et al. PS-171-Survival in a 10 year prospective cohort of heavy drinkers: Liver stiffness is the best long-term prognostic parameter. J Hepatol 2019; 70 (01) E107
    CrossrefPubMedSearch in Google Scholar
  • 77 Mueller S, Englert S, Seitz HK. et al. Inflammation-adapted liver stiffness values for improved fibrosis staging in patients with hepatitis C virus and alcoholic liver disease. Liver International 2015; 35 (12) 2514-2521
    CrossrefPubMedSearch in Google Scholar
  • 78 Mukai M, Ozasa K, Hayashi K. et al. Various S-GOT/S-GPT ratios in nonviral liver disorders and related physical conditions and life-style. Digestive diseases and sciences 2002; 47 (03) 549-555
    CrossrefPubMedSearch in Google Scholar
  • 79 Kohlhaas A, Durango E, Millonig G. et al. Transient elastography with the XL probe rapidly identifies patients with non-hepatic ascites. Hepatic Medicine: Evidence and Research 2012; 4: 11-18
    PubMedSearch in Google Scholar
  • 80 Durango E, Dietrich C, Seitz HK. et al. Direct comparison of the FibroScan XL and M probes for assessment of liver fibrosis in obese and nonobese patients Hepatic Medicine. Evidence and Research 2013; 5: 43-52
    PubMedSearch in Google Scholar
  • 81 Roulot D, Costes JL, Buyck JF. et al. Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years. Gut 2011; 60 (07) 977-984
    CrossrefPubMedSearch in Google Scholar
  • 82 Mueller S, Millonig G, Sarovska L. et al. Increased liver stiffness in alcoholic liver disease: differentiating fibrosis from steatohepatitis. World J Gastroenterol 2010; 16 (08) 966-972
    CrossrefPubMedSearch in Google Scholar
  • 83 Mueller S. personal observation. 2019
    PubMedSearch in Google Scholar
  • 84 Anthony PP, Ishak KG, Nayak NC. et al. The morphology of cirrhosis. Recommendations on definition, nomenclature, and classification by a working group sponsored by the World Health Organization. Journal of clinical pathology 1978; 31 (05) 395-414
    CrossrefPubMedSearch in Google Scholar
  • 85 Pinzani M, Rosselli M, Zuckermann M. Liver cirrhosis. Best practice & research Clinical gastroenterology 2011; 25 (02) 281-290
    CrossrefPubMedSearch in Google Scholar
  • 86 Ramachandran A, Balasubramanian KA. Intestinal dysfunction in liver cirrhosis: Its role in spontaneous bacterial peritonitis. Journal of gastroenterology and hepatology 2001; 16 (06) 607-612
    CrossrefPubMedSearch in Google Scholar
  • 87 Bonnel AR, Bunchorntavakul C, Reddy KR. Immune dysfunction and infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2011; 9 (09) 727-738
    CrossrefPubMedSearch in Google Scholar
  • 88 Arvaniti V, D'Amico G, Fede G. et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology 2010; 139 (04) 1246-1256
    CrossrefPubMedSearch in Google Scholar
  • 89 Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet 2014; 383 (9930): 1749-1761
    CrossrefPubMedSearch in Google Scholar
  • 90 Pinzani M, Rombouts K, Colagrande S. Fibrosis in chronic liver diseases: diagnosis and management. J Hepatol 2005; 42 (Suppl. 01) S22-S36
    CrossrefPubMedSearch in Google Scholar
  • 91 Garcia-Tsao G, Friedman S, Iredale J. et al. Now there are many (stages) where before there was one: In search of a pathophysiological classification of cirrhosis. Hepatology 2010; 51 (04) 1445-1449
    CrossrefPubMedSearch in Google Scholar
  • 92 Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996; 24 (02) 289-293
    CrossrefPubMedSearch in Google Scholar
  • 93 Ishak K, Baptista A, Bianchi L. et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22 (06) 696-699
    CrossrefPubMedSearch in Google Scholar
  • 94 Wanless IR, Sweeney G, Dhillon AP. et al. Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia. Blood 2002; 100 (05) 1566-1569
    CrossrefPubMedSearch in Google Scholar
  • 95 Kim SU, Oh HJ, Wanless IR. et al. The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis. J Hepatol 2012; 57 (03) 556-563
    CrossrefPubMedSearch in Google Scholar
  • 96 Nagula S, Jain D, Groszmann RJ. et al. Histological-hemodynamic correlation in cirrhosis-a histological classification of the severity of cirrhosis. J Hepatol 2006; 44 (01) 111-117
    CrossrefPubMedSearch in Google Scholar
  • 97 Hall A, Germani G, Isgrò G. et al. Fibrosis distribution in explanted cirrhotic livers. Histopathology 2012; 60 (02) 270-277
    CrossrefPubMedSearch in Google Scholar
  • 98 Tsochatzis E, Bruno S, Isgro G. et al. Collagen proportionate area is superior to other histological methods for sub-classifying cirrhosis and determining prognosis. J Hepatol 2014; 60 (05) 948-954
    CrossrefPubMedSearch in Google Scholar
  • 99 Garcia-Tsao G, Groszmann RJ, Fisher RL. et al. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology 1985; 5 (03) 419-424
    CrossrefPubMedSearch in Google Scholar
  • 100 Ripoll C, Groszmann R, Garcia-Tsao G. et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology 2007; 133 (02) 481-488
    CrossrefPubMedSearch in Google Scholar
  • 101 Pinzani M, Rombouts K. Liver fibrosis: from the bench to clinical targets. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2004; 36 (04) 231-242
    CrossrefPubMedSearch in Google Scholar
  • 102 Ferrusquía-Acosta J, Bassegoda O, Turco L. et al. Agreement between wedged hepatic venous pressure and portal pressure in non-alcoholic steatohepatitis-related cirrhosis. J Hepatol 2021; 74 (04) 811-818
    CrossrefPubMedSearch in Google Scholar
  • 103 EASL-ALEH Clinical Practice Guidelines. Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63 (01) 237-264
    CrossrefPubMedSearch in Google Scholar
  • 104 Rosselli M, MacNaughtan J, Jalan R. et al. Beyond scoring: a modern interpretation of disease progression in chronic liver disease. Gut 2013; 62 (09) 1234-1241
    CrossrefPubMedSearch in Google Scholar
  • 105 Berzigotti A. Non-invasive evaluation of portal hypertension using ultrasound elastography. J Hepatol 2017; 67 (02) 399-411
    CrossrefPubMedSearch in Google Scholar
  • 106 Shi KQ, Fan YC, Pan ZZ. et al. Transient elastography: a meta-analysis of diagnostic accuracy in evaluation of portal hypertension in chronic liver disease. Liver Int 2013; 33 (01) 62-71
    CrossrefPubMedSearch in Google Scholar
  • 107 Akinyemiju T, Abera S, Ahmed M. et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA oncology 2017; 3 (12) 1683-1691
    CrossrefPubMedSearch in Google Scholar
  • 108 Lok AS, Seeff LB, Morgan TR. et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 2009; 136 (01) 138-148
    CrossrefPubMedSearch in Google Scholar
  • 109 Ripoll C, Groszmann RJ, Garcia-Tsao G. et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J Hepatol 2009; 50 (05) 923-928
    CrossrefPubMedSearch in Google Scholar
  • 110 EASL Clinical Practice Guidelines. Management of hepatocellular carcinoma. J Hepatol 2018; 69 (01) 182-236
    CrossrefPubMedSearch in Google Scholar
  • 111 Ishizawa T, Hasegawa K, Aoki T. et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 2008; 134 (07) 1908-1916
    CrossrefPubMedSearch in Google Scholar
  • 112 Trevisani F, Santi V, Gramenzi A. et al. Surveillance for early diagnosis of hepatocellular carcinoma: is it effective in intermediate/advanced cirrhosis?. Am J Gastroenterol 2007; 102 (11) 2448-2457; quiz 58
    CrossrefPubMedSearch in Google Scholar
  • 113 Nahon P, Kettaneh A, Tengher-Barna I. et al. Assessment of liver fibrosis using transient elastography in patients with alcoholic liver disease. J Hepatol 2008; 49 (06) 1062-1068
    CrossrefPubMedSearch in Google Scholar
  • 114 Kim SG, Kim YS, Jung SW. et al. The usefulness of transient elastography to diagnose cirrhosis in patients with alcoholic liver disease. Korean J Hepatol 2009; 15 (01) 42-51
    CrossrefPubMedSearch in Google Scholar
  • 115 Boursier J, Vergniol J, Sawadogo A. et al. The combination of a blood test and Fibroscan improves the non-invasive diagnosis of liver fibrosis. Liver International 2009; 29 (10) 1507-1515
    CrossrefPubMedSearch in Google Scholar
  • 116 Janssens F dSN, Piessevaux H, Horsmans Y. et al. Can transient elastography replace liver histology for determination of advanced fibrosis in alcoholic patients: a real-life study. J Clin Gastroenterol 2010; 44 (08) 575-582
    CrossrefPubMedSearch in Google Scholar
  • 117 Fernandez M, Trepo E, Degre D. et al. Transient elastography using Fibroscan is the most reliable noninvasive method for the diagnosis of advanced fibrosis and cirrhosis in alcoholic liver disease. Eur J Gastroenterol Hepatol 2015; 27 (09) 1074-1079
    CrossrefPubMedSearch in Google Scholar
  • 118 Thiele M, Detlefsen S, Sevelsted Møller L. et al. Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis. Gastroenterology 2016; 150 (01) 123-133
    CrossrefPubMedSearch in Google Scholar
  • 119 Voican CS, Louvet A, Trabut JB. et al. Transient elastography alone and in combination with FibroTest((R)) for the diagnosis of hepatic fibrosis in alcoholic liver disease. Liver Int 2017; 37 (11) 1697-1705
    CrossrefPubMedSearch in Google Scholar