Numerous signs and symptoms can be observed in patients with chronic liver disease (CLD) [1]:

• Fatigue - is considered as the most common symptom regardless of the underlying cause [2]. Fatigue may be severely debilitating for some patients, such as those suffering from primary biliary cirrhosis (PBC) or viral hepatitis [2]. Moreover, fatigue is strongly associated with sleep disturbances and autonomic dysfunction, mainly in the form of reduced blood pressure regulation [3].
• Cutaneous changes - Jaundice is a predominant manifestation of cirrhosis, viral hepatitis, and several other liver-related pathologies, while spider nevi, caput medusae, palmar erythema and white nails are also important cutaneous findings [3].
• Ascites - accumulation of fluid in the peritoneum can be a sign of portal hypertension, hypoalbuminemia or other metabolic changes in the liver.
• Insulin resistance - Through mechanisms that are yet to be defined, hyperinsulinemia and development of diabetes mellitus type II can occur, most frequently in hepatocellular carcinoma and chronic viral hepatitis C [4].
• Coagulation abnormalities - The liver is the site of production of virtually all coagulation factors, making thrombocytopenia and an increased tendency for bleeding an important sign of the disease, especially in hepatitis C, interferon-induced injury, and portal hypertension [5].
• Kidney disease - Membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, mixed cryoglobulinemia and polyarteritis nodosa (PAN) have all been identified in patients with chronic liver disease (particularly viral hepatitis) [6].

Cognitive symptoms, various neurological deficits, as well as pulmonary symptoms (most commonly as a result of impaired portal circulation), can also occur in CLD [1] [7].

• Anemia

  We present a 21-year-old male patient diagnosed with sickle cell anemia who developed chronic liver disease, together with a review of the literature. [ncbi.nlm.nih.gov]

  Iron deficiency, vitamin B12 and folate deficiency anemia (often seen in alcoholism or malnutrition), and anemia of chronic disease are other common causes of anemia. [clinical.diabetesjournals.org]

• Alopecia

  […] naevi 5 in area of Paracentesis Microscopy, C/S, amylase Gynaecomastia drainage of SVC Malignant cells, infections (SBP), pancreatitisHead Jaundice Parotid enlargement – EtOH liver Hepatitis serology Cause of CLD Pallor dz Other causes of Autoantibodies Alopecia [slideshare.net]

  Otospondylomegaepiphyseal dysplasia (Hyperlordosis, Lumbar hyperlordosis) Pfeiffer syndrome (Hyperlordosis) Pinheiro Freire-Maia Miranda syndrome (Hyperlordosis) Potassium-aggravated myotonia (Hyperlordosis) Primary hypergonadotropic hypogonadism-partial alopecia [144.217.79.236]

• Leukonychia

  Testicular atrophy Small irregular shrunken liver Anaemia Caput medusae Drowsiness (encephalopathy) Hyperventilation (encephalopathy) Metabolic flap/asterixis (encephalopathy) Jaundice (excretory dysfunction) Ascites (portal hypertension and hypoalbuminemia) Leukonychia [en.wikipedia.org]

  Stigmata of CLD – jaundice, clubbing, leukonychia, palmar erythema, spider naevi, Common Presentations gynaecomastia, testicular atrophy i. Swelling – ascites, pedal edema 2. [slideshare.net]

• Papule

  All patients showed an asymptomatic solitary dome-shaped reddish papule, 5-10 mm in diameter, on the face (first, second and third patients) or chest (fourth patient). [ncbi.nlm.nih.gov]

• Decerebrate Posturing

  Both patients had generalized tonic-clonic seizures, and one demonstrated decerebrate posturing and papilledema. [ncbi.nlm.nih.gov]

• Myoclonus

  These disorders include Lafora disease (myoclonus epilepsy) and type IV glycogen storage disease. Polyglucosan deposits in both conditions result in ground-glass hepatocellular inclusions resembling those seen in chronic hepatitis B virus infection. [ncbi.nlm.nih.gov]

• Cerebellar Sign

  signs (alcohol and Wilson's disease) Liver enlargement (alcohol, NAFLD, haemochromatosis) Kayser-Fleisher rings (Wilson's disease) Increased pigmentation of the skin (haemochromatosis) Signs of right heart failureNote that other diseases can involve [en.wikipedia.org]

• Kidney Failure

  Symptoms may include: Fluid buildup in the belly (ascites) Vomiting blood, often from bleeding in the blood vessels in the food pipe (esophagus) Gallstones Itching Yellowing of the skin and eyes (jaundice) Kidney failure Muscle loss Loss of appetite Easy [urmc.rochester.edu]

  Liver failure that leads to kidney failure is called hepatorenal syndrome. [merckmanuals.com]

An extensive diagnostic workup is necessary to establish the underlying cause and determine the severity of liver injury. Firstly, it is mandatory to obtain a detailed patient history that will include information about the onset of symptoms and existing hepatic or extrahepatic conditions that may be responsible for their appearance. Secondly, a meticulous physical examination can reveal key features of liver injury and aid in making a presumptive diagnosis. Initial laboratory workup should include a complete blood count (CBC) with a full coagulation panel, alanine and aspartate aminotransferases (ALT and AST, respectively), alkaline phosphatase (ALP), lipid profiles, bilirubin, gamma-glutamyl transferase (γGT), glucose levels and kidney function tests (blood urea nitrogen, creatinine and urinalysis). Carbohydrate-deficient transferrin (CDT) is used to detect heavy alcohol consumption, while Hepatitis B surface and envelope antigens (HBsAg and HBeAg, respectively), as well as anti-hepatitis C (anti-HCV) antibodies, form the mainstay of viral hepatitis workup [1]. If the cause cannot be identified,then autoantibodies (antinuclear, anti-neutrophil cytoplasmic antibodies, anti-liver kidney microsomal, and anti-soluble liver antigen, or ANA, ANCA, anti-LKM and anti-SLA), parameters of iron metabolism (ferritin, total iron binding capacity, transferrin) and ceruloplasmin with urinary copper (Cu) excretion should be evaluated [1]. In addition to laboratory studies, imaging procedures can play a vital role in assessing CLD. Doppler, contrast enhanced or standard ultrasonography may be highly useful [8], while magnetic resonance imaging (MRI) and computed tomography (CT) can also provide important clues regarding the etiology and pathogenesis. As a last resort, liver biopsy can be performed and is considered to be the optimal diagnostic modality for diagnosis of non-viral causes of CLD [1].

• Erythrocytosis

  Liver biopsies of these patients show erythrocytosis, erythrophagocytosis, sinusoidal dilatation and hyperplasia in Kupffer cells. [ncbi.nlm.nih.gov]

• Sarcoptes Scabiei

  Crusted scabies is a less common variant of scabies that is highly contagious, difficult to treat and involves infestation by Sarcoptes scabiei var. hominis. [ncbi.nlm.nih.gov]

• Streptococcus Pneumoniae

  INTRODUCTION: In advanced chronic liver disease, diseases caused by common bacteria Streptococcus pneumoniae or influenza virus put people at an increased risk of serious health complications and death. [ncbi.nlm.nih.gov]

• Small Liver

  We report 3 cases in which small liver lesions were revealed on sonography with the supplemental use of a high-frequency transducer. In all 3 cases, the patients had cirrhosis or chronic liver disease. [ncbi.nlm.nih.gov]

1. Schuppan D, Afdhal NH. Liver Cirrhosis. Lancet. 2008;371(9615):838-851.
2. Swain MG. Fatigue in liver disease: Pathophysiology and clinical management. Can J Gastroenterol. 2006;20(3):181-188.
3. Newton JL, Jones DE. Managing systemic symptoms in chronic liver disease. J Hepatol. 2012;56(1):S46-55.
4. Kawaguchi T, Taniguchi E, Itou M, Sakata M, Sumie S, Sata M. Insulin resistance and chronic liver disease. World J Hepatol. 2011;3(5):99-107.
5. Poordad F. Review article: thrombocytopenia in chronic liver disease. Aliment Pharmacol Ther. 2007;26(1):5-11.
6. Hrstić I, Ostojić R. Chronic liver diseases in patients with chronic kidney disease [Article in Croatian]. Acta Med Croatica. 2011;65(4):349-353.
7. Lammert F, Wilkens G, Dietrich CG, Geier A, Wasmuth HE, Matern S. Extrahepatic manifestations of chronic liver diseases [Article in German]. Versicherungsmedizin. 2005;57(2):64-71.
8. Gerstenmaier JF, Gibson RN. Ultrasound in chronic liver disease. Insights Imaging. 2014;5(4):441-455.