Lviv clinical bulletin 2020, 3(31): 53-61

Liver Cirrhosis: Modern Approach to the Problem

T. Bentsa

Shupyk National Medical Academy of Postgraduate Education

Introduction. Liver cirrhosis (LC) is an important medical and socio-economic problem not only in Ukraine, but throughout the world. The urgency of this disease is due to its significant spread, increase of the number of etiological factors, as well as the occurrence of severe complications, which often leads to death. The prognosis depends on several factors, such as etiology, the severity of liver damage, the presence of complications and concomitant diseases.

The aim of the study. To review the scientific literature and summarize the published studies devoted to the study of the etiology, classification, clinical picture and diagnosis of liver cirrhosis.

Materials and methods. The content analysis, the method of systemic and comparative analysis, the bibliosemantic method of studying the current scientific research on the etiology, classification, clinical picture and diagnosis of LC were used.  The search for sources was carried out in scientometric databases: PubMed-NCBI, Medline, Research Gate, Cochrane Database of Systematic Reviews for the keywords: liver cirrhosis, diagnosis, treatment. 37 literary sources were selected and analyzed.

Results. LC is currently ranked 11th among the most common causes of death. The common causes of LC are chronic alcohol intoxication and viral hepatitis B, C, and D. LC is represented by an increase in severity, which is characterized by the lesions of the liver parenchyma with necrosis, dystrophy of hepatocytes, their nodular regeneration, as well as its interstitium with diffuse proliferation of connective tissue, leading to liver failure and portal hypertension. Most patients with cirrhosis remain asymptomatic until they develop decompensated LC. Despite the existence of a number of LC classifications – by morphology, etiology, severity, course, hepatocellular insufficiency stage, the severity of the disease is usually assessed by evaluation of the hepatic functional reserve (according to the C. G. Child – R. N. Pugh classification). Patients with LC often have life-threatening conditions such as variceal hemorrhages, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome. Variceal bleeding is a major complication of portal hypertension, which is associated with significant mortality. Ascites represents the most common decompensating event in patients with LC. The appearance of ascites is strongly related to portal hypertension, which leads to splanchnic arterial vasodilation, reduction of the effective circulating volume, activation of endogenous vasoconstrictor systems, and avid sodium and water retention in the kidneys. Bacterial translocation further worsens hemodynamic alterations of patients with cirrhosis and ascites. Ascites is also associated with a high risk of developing the further complications of cirrhosis such as dilutional hyponatremia, spontaneous bacterial peritonitis and/or other bacterial infections and acute kidney injury.

Pharmacotherapy for LC should be implemented in accordance with up-to-date guidelines and in conjunction with etiology management, nutritional optimization and patients’ education. The main treatment of uncomplicated ascites is diuretics such as spironolactone in combination with a loop one. Vasoconstrictors and albumin are recommended for the treatment of refractory ascites. In its turn antibiotics play a well-established role in the treatment and prevention of spontaneous bacterial peritonitis. The administration of vasopressor terlipressin and albumin is recommended for the treatment of hepatorenal syndrome. Pharmacological therapy of variceal bleeding aims to decrease the portal pressure by acting on its pathophysiological mechanisms such as increased hepatic vascular tone and splanchnic vasodilatation. Propranolol blocks the β-1 in the heart and the peripheral β-2 adrenergic receptors. β-1 blockade of cardiac receptors reduces heart rate, cardiac output and subsequently decreases flow into splanchnic circulation. β-2 blockade leads to unopposed α-1 adrenergic activity that causes splanchnic vasoconstriction and reduction of portal inflow. Both effects contribute to reduction in portal pressure. Carvedilol is more powerful in reducing hepatic venous pressure gradient than traditional nonselective β-blockers. Endoscopic treatment in many cases is used for the variceal bleeding (eg., ligation of the esophageal varices and tissue glue usage for the gastric varices). A shunt (transjugular intrahepatic portosystemic shunting – TIPS) is used to treat severe and often repeat variceal hemorrhage or refractory ascites. Non-selective β-blockers effectively reduce variceal re-bleeding risk in LC patients with moderate/large varices.

Conclusions. Liver cirrhosis is one of the most dangerous multi-organ diseases of a human with multiple pathogenetic links, the causes of which invariably remain hepatitis viruses, alcohol, toxic substances, drugs, ultraviolet radiation, genetic factors, some chronic diseases of the internal organs. There are a number of classifications of liver cirrhosis – by morphology, etiology, severity, course, severity of hepatocellular insufficiency etc. Examination of this category of patients requires timeliness, scrupulousness, compliance with a comprehensive approach using modern clinical, laboratory and instrumental methods. During the objective examination of a patient a doctor traditionally draws attention to the presence of telangiectasia, palmar erythema, jaundice, “raspberry” tongue, scratching marks, gynecomastia in men, ascites and “caput medusae”, during the palpation the liver is enlarged, dense, with a sharp lower edge, spleen is enlarged. Among the laboratory methods, in addition to routine ones, the immunological tests are used, among the main instrumental examination – ultrasound, computed tomography, indirect elastometry of the liver or Fibroscan, esophagogastrofibroscopy, puncture biopsy of the liver, in particular modern ones – vibrational transient elastography and magnetic resonance elastography.

Although liver cirrhosis is the final stage of liver disease, this diagnosis cannot be considered a verdict for a patient, because today there are quite effective treatments using the principles of differentiation – the impact on the etiological factor, liver state and comorbid lesions and their complications often allows if not to cure the patient, then to prevent the negative disease course. Among them, there are diet, the use of etiotropic drugs, intestinal sanitation, correction of clinical and laboratory syndromes, portal hypertension syndrome, endothelial and autonomic dysfunction as causes of comorbid lesions and their complications.


  1. Kharchenko N, Babak O, editors. Gastroenterology. Kyiv: Drukar; 2007. 720 p. (Ukrainian)
  2. Sherlock Sh, Dooley J. Diseases of the liver and biliary tract: a practical guide (translated from English). Aprosina ZG, Mukhina NA, editors. M.: Geotar-Medicine; 1999. 864 p. (Russian)
  3. Allegretti AS, Israelsen M, Krag A, Jovani M, Goldin AH, Schulman AR et al. Terlipressin versus placebo or no intervention for people with cirrhosis and hepatorenal syndrome. Cochrane Database Syst Rev. 2017;6(6):CD005162.
  4. Argo CK, Balogun RA. Blood products, volume control and renal support in the coagulopathy of liver disease. Clin Liver Dis. 2009;13(1):73-85.
  5. Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of Liver Diseases in the World. J Hepatol. 2019;70(1):151-171.
  6. Baiges A, Hernández-Gea V, Bosch J. Pharmacologic Prevention of Variceal Bleeding and Rebleeding. Hepatol Int. 2018;12(Suppl 1):68-80.
  7. Benmassaoud A, Freeman SC, Roccarina FD, Plaz Torres MC, Sutton AJ, Cooper NJ et al. Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev. 2020;1(1):CD013123.
  8. Blachier M, Leleu H, Peck-Radosavljevic M, Valla D-C, Roudot-Thoraval F. The Burden of Liver Disease in Europe: A Review of Available Epidemiological Data. J Hepatol. 2013;58(3):593-608.
  9. Colle I, Laterre P-F. Hepatorenal syndrome: the clinical ompact of vasoactive therapy. Exp Rev Gastroenterol Hepatol. 2018;12(2):173-188.
  10. Esrailian E, Pantangco ER, Kyulo NL, Hu K-Q, Runyon BA. Octreotide/Midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci. 2007;52(3):742-748.
  11. Fernández J, Acevedo J. New antibiotic strategies in patients with cirrhosis and bacterial infection. Exp Rev Gastroenterol Hepatol. 2015;9(12):1495-1500.
  12. Fernández J, Acevedo J, Castro M, Garcia O, de Lope CR, Roca D et al. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology. 2012;55(5):1551-1561.
  13. Fernández J, Gustot T. Management of bacterial infections in cirrhosis. J Hepatol. 2012;56(Suppl 1):1-12.
  14. Fernández J, Navasa M, Gómez J, Colmenero J, Vila J, Arroyo V et al. Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. Hepatology. 2002;35(1):140-148.
  15. Ferraioli G, Wong VW-S, Castera L, Berzigotti A, Sporea I, Dietrich CF et al. Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound in Medicine and Biology Guidelines and Recommendations. Ultrasound Med Biol. 2018;44(12):2419-2440.
  16. Ginès P, Solà E, Angeli P, Wong F, Nadim MK, Kamath PS. Hepatorenal syndrome. Nat Rev Dis Primers. 2018;4(1):23. .
  17. Global, Regional, and National Age-Sex Specific Mortality for 264 Causes of Death, 1980-2016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1151-1210.
  18. Hemándes-Gea V, Berbel C, Baiges A, Garcia-Pagán JC. Acute variceal bleding: risk stratification and management (ncluding TIPS). Hepatol Int. 2018;12(Suppl 1):81-90.
  19. Imani F, Motavaf M, Safari S, Alavian SM. The Therapeutic Use of Analgesics in Patients With Liver Cirrhosis: A Literature Review and Evidence-Based Recommendations. Hepat Mon. 2014;14(10):e23539.
  20. Kimer N, Feineis M, Moller S, Bendtsen F. Beta-blockers in cirrhosis and refractory ascites: a retrospective cohort study and review of the literature. Scand J Gastroenterol. 2015;50(2):129-137.
  21. Martin-Llahi M, Pépin MN, Guevara M, Diaz F, Torre A, Monescillo A et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008;134(5):1352-1359.
  22. Mauss S, Berg T, Rockstroh J, Sarrazin C, Wedemeyer H. Hepatology: A Clinical Textbook. 6th Sydney: Flying Publisher; 2015. 655 p.
  23. O’Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA Clinical Practice Update: Coagulation in Cirrhosis. Gastroenterology. 2019;157(1):34-43.e1.
  24. Piano S, Tonon M, Angeli P. Management of ascites and hepatorenal syndrome. Hepatol Int. 2018;12(Suppl 1):122-134.
  25. Poordad FF. Presentation and Complications Associated With Cirrhosis of the Liver. Curr Med Res Opin. 2015;31(5):925-937.
  26. Romanelli RG, Stasi C. Recent Advancements in Diagnosis and Therapy of Liver Cirrhosis. Curr Drug Targets. 2016;17(15):1804-1817.
  27. Runyon BA. AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49(6):2087-2107.
  28. Runyon BA. Ascites and spontaneous bacterial peritonitis. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Feldman M, Friedman LS, Brandt LJ, 9th ed. Philadelphia: Saunders Elsevier; 2010:1517-1541.
  29. Santos J, Planas R, Pardo A, Durández R, Cabré E, Morillas RM et al. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety. J Hepatol. 2003;39(2):187-192.
  30. Sanyal A, Younossi ZM, Bass NM, Mullen KD, Poordad F, Brown RS et al. Randomised clinical trial: rifaximin improves health-related quality of life in cirrhotic patients with hepatic encephalopathy – a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2011;34(8):853-861.
  31. Sersté T, Francoz C, Durand F, Rautou P-E, Melot C, Valla D et al. Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: a cross-over study. J Hepatol. 2011;55(4):794-799.
  32. Singh S, Muir AJ, Dieterich DT, Falck-Ytter YT. American Gastroenterological Association Institute Technical Review on the Role of Elastography in Chronic Liver Diseases. Gastroenterology. 2017;152(6):1544-1577.
  33. Stine JG, Wang J, Cornella SL, Behm BW, Henry Z, Shah NL et al. Treatment of Type-1 Hepatorenal Syndrome with Pentoxifylline: A Randomized Placebo Controlled Clinical Trial. Ann Hepatol. 2018;17(2):300-306.
  34. Strunk H, Marinova M. Transjugular Intrahepatic Portosystemic Shunt (TIPS): Pathophysiologic Basics, Actual Indications and Results With Review of the Literature. Rofo. 2018;190(8):701-711.
  35. Tripathi D, Stanley AJ, Hayes PC, Travis S, Armstrong MJ, Tsochatzis EA et al. Transjugular intrahepatic portosystemic stent-shunt in the management of portal hypertension. Gut. 2020;69(7):1173-1192.
  36. Tyagi P, Sharma P, Sharma BC, Puri AS, Kumar A, Sarin SK Prevention of hepatorenal syndrome in patients with cirrhosis and ascites: a pilot randomized control trial between pentoxifylline and placebo. Eur J Gastroenterol Hepatol. 2011;23(3):210-217.
  37. Wang H, Liu A, Bo W, Feng X, Hu Y. Terlipressin in the treatment of hepatorenal syndrome: A systematic review and meta-analysis. Medicine (Baltimore). 2018;97(16):e0431.