Symptoms of cryptogenic cirrhosis are no different than the symptoms in any other type of cirrhosis: jaundice, abdominal swelling, weight loss, fever and blood in the stool are the predominant features. Before the liver has reached a cirrhotic stage, if the patient is affected by NASH, potential symptoms are non-specific and involve fatigue and weight loss.

• Weakness

  Affected individuals may experience fatigue, weakness, loss of appetite, weight loss, nausea, edema, dilation of blood vessels and jaundice. In addition, these individuals may develop portal hypertension. [ivami.com]

  We hypothesize that the low concentration of gammaglobulins together with the weak INF-gamma response normally observed in young foals may have favored the clinical manifestation with diarrhea. [ncbi.nlm.nih.gov]

  They include swelling and pain in the abdomen, fatigue, weakness, nausea, vomiting, loss of appetite, bloody stools, unexplained loss of weight, jaundice, rashes, and discoloration of the skin. [liverbasics.com]

  Other symptoms of the disease are more general, including fatigue, overall weakness, weight loss, bloody stools, swelling of the abdomen. Continued below.... [fattyliverdiseasecures.com]

  Affected individuals can experience fatigue, weakness, loss of appetite, weight loss, nausea, swelling (edema), enlarged blood vessels, and yellowing of the skin and whites of the eyes (jaundice).People with cryptogenic cirrhosis may develop high blood [icdlist.com]

• Disability

  Based on the KPS score at the time of transplant, we grouped patients into 3 groups: severely disabled if KPS score was between 10% (moribund) and 30% (severely disabled), mild to moderate disability if KPS score was 40% to 60%, and minimal or no disability [journals.lww.com]

  It is believed that "about half (50%) of children with learning disabilities and approximately 60% of children with congenital disabilities (disabilities which are apparent from birth) do not have a definitive diagnosis to explain the cause of their difficulties [en.wikipedia.org]

  “Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.”. [ko.wikipedia.org]

  Whether it comes from a virus or a liquor bottle, cirrhosis is a potentially disabling disease. You probably won't notice any symptoms at first, but as the damage builds, you'll feel weak and exhausted. [consumer.healthday.com]

• Congestive Heart Failure

  CARDIAC CIRRHOSIS Prolonged, severe, right-sided congestive heart failure leads to chronic liver injury and cardiac cirrhosis. [medicscientist.com]

  The non liver causes formed 21.1 % which include malignancy and peritoneal tuberculosis and the congestive heart failure 16.9% and chronic renal failure 12.6%. [tishreen.edu.sy]

  heart failure with liver congestion – Repeated episodes of congestive heart failure with liver congestion can cause cirrhosis of the liver; or Cirrhosis of unknown origin – In about 10% of cases, no cause for cirrhosis is found. [mydr.com.au]

  Classic causes of transudative ascites are portal hypertension secondary to cirrhosis and congestive heart failure. Table 1. [hepatitiscnewdrugs.blogspot.com]

  Swelling of the abdomen (ascites) and/or the lower extremities (edema) due to retention of fluid is common among patients with cirrhosis, although other diseases can cause them commonly, for example, congestive heart failure. [medicinenet.com]

• Chills

  Photo Credit Dolly Faibyshev for The New York Times Work Out and Chill? Cool temperature workouts may be the answer for those who want to exercise without becoming a hot mess. [nytimes.com]

  Additionally, she denied fevers, chills, nausea, vomiting and dysuria at that time. On admission, patient hemoglobin was 7.2, which later dropped to 5.7, down from her baseline of 13.4. [healio.com]

  Some patients with SBP have no symptoms, while others have fever, chills, abdominal pain and tenderness, diarrhea, and worsening ascites. [medicinenet.com]

• Non-Alcoholic Cirrhosis

  The last is obviously indicated for alcoholic cirrhosis, but in fact it is recommended for cryptogenic or non- alcoholic cirrhosis as well, because alcohol intake will certainly risk further damage even if alcohol is not the cause of the cirrhosis to [fattyliverdiseasecures.com]

  Juvenile portal cirrhosis Laennec's cirrhosis, non-alcoholic Latent cirrhosis Liver cirrhosis Macronodular cirrhosis Micronodular cirrhosis Mixed micro AND macronodular cirrhosis Multilobular portal cirrhosis Nonalcoholic cirrhosis Nutritional cirrhosis [icd9data.com]

• Easy Bruising

  Cirrhosis can lead to Easy bruising or bleeding, or nosebleeds Swelling of the abdomen or legs Extra sensitivity to medicines High blood pressure in the vein entering the liver Enlarged veins called varices in the esophagus and stomach. [icdlist.com]

  Cirrhosis can cause weakness, loss of appetite, easy bruising, yellowing of the skin ( jaundice ), itching, and fatigue. Diagnosis of cirrhosis can be suggested by history, physical examination and blood tests, and can be confirmed by liver biopsy. [medicinenet.com]

• Constipation

  Laxatives, such as lactulose, decrease the risk of constipation; their role in preventing encephalopathy is limited. Alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. [en.wikipedia.org]

  […] colon cancer 大腸癌 colonoscope 大腸鏡 colonoscopy 大腸鏡検査 colorectal cancer結腸直腸癌 common bile duct (ductus choledochus, ductus choledochus, choledochus) 総胆管 confluence gallstone合流部結石（胆石） congenital dilatation of bile duct (congenital choledochal cyst)先天性胆管拡張症 constipation [tokyo-med.ac.jp]

  Precipitants of hepatic encephalopathy should be corrected (eg, hypovolemia, metabolic disturbances, GI bleeding, infection, constipation). [hepatitiscnewdrugs.blogspot.com]

• Right Upper Quadrant Pain

  [20][118] Other symptoms might be present, such as right upper quadrant pain or acanthosis nigricans, the latter being frequently observed in children with NASH, or hepatomegaly found in 30–40% of children with NAFLD.[20] Liver biopsies for diagnosis [en.wikipedia.org]

• Hematemesis

  These varices usually present with cases of hematochezia or hematemesis. Therefore, bleeding ectopic varices should be suspected in all patients with portal hypertension. [healio.com]

  胃食道逆流 gastrointestinal 胃腸の gastrojejunostomy胃空腸吻合術 gastroptosis胃下垂 glucose tolerance耐糖性 graft-versus-host disease (GVHD)移植片対宿主病 gram-negative bacilli グラム陰性桿菌 greater curvature大彎 h hamartoma過誤腫 heartburn胸やけ Helicobacter pylori ヘリコバクターピロリ hemangioma血管腫 hematemesis [tokyo-med.ac.jp]

• Heart Failure

  CARDIAC CIRRHOSIS Prolonged, severe, right-sided congestive heart failure leads to chronic liver injury and cardiac cirrhosis. [medicscientist.com]

  The non liver causes formed 21.1 % which include malignancy and peritoneal tuberculosis and the congestive heart failure 16.9% and chronic renal failure 12.6%. [tishreen.edu.sy]

  failure Patients with acute kidney injury at the time of enrollment Patients with CKD (Chronic Kidney Disease) or with S. [clinicaltrials.gov]

  failure with liver congestion – Repeated episodes of congestive heart failure with liver congestion can cause cirrhosis of the liver; or Cirrhosis of unknown origin – In about 10% of cases, no cause for cirrhosis is found. [mydr.com.au]

  Other rare causes of cirrhosis include blocked or inflamed bile ducts, severe reactions to medications or supplements such as methotrexate or Vitamin A, frequent bouts of heart failure, and inherited conditions such as cystic fibrosis, alpha-1-antitrypsin [consumer.healthday.com]

• Heart Disease

  Additional potential complications for cryptogenic cirrhosis include heart disease, renal disease and other potential complications of diabetes such as retinopathy. Additional complications depend on the underlying etiology of cryptogenic cirrhosis. [ncbi.nlm.nih.gov]

• Vascular Disease

  J Nutr, 124(10): 1934-41 [ CR ] [ PM ] [ CHE ] [ EČ ][ 2 ][ GS ] Hankey, G.J., Eikelboom, J.W. (1999) Homocysteine and vascular disease. [scindeks.ceon.rs]

  These include NASH, occult ethanol intake, occult viral hepatitis, autoimmune hepatitis, occult biliary disease, hepatic vascular disease, celiac disease, mitochondriopathies, familial Mediterranean fever, systemic lupus erythematosus, Alstrom syndrome [statpearls.com]

  e.g. primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC) : 5-10% metabolic disease, e.g. hereditary hemochromatosis, Wilson disease, alpha-1-antitrypsin deficiency : 5% autoimmune hepatitis vascular disease, e.g. congestive hepatopathy [radiopaedia.org]

• Bleeding Gums

  We report the case of a 47-year-old male patient who presented with bleeding gums and melena. He was found to have pancytopenia and on evaluation, had an aplastic bone marrow. [jscisociety.com]

  This places pressure on the varices and stops the bleeding. [medicalnewstoday.com]

• Jaundice

  Age, jaundice, spiders, palmar erythema and factor V showed a statistically significant difference of the cryptogenic cirrhosis when compared with both alcoholic and viral etiologies. [ncbi.nlm.nih.gov]

  Symptoms include weakness, abdominal swelling, fever, jaundice and inexplicable weight loss. The treatment of cryptogenic cirrhosis is solely a liver transplant. [symptoma.com]

  Kidney failure Jaundice Severe itching Gallstones A small number of people with cirrhosis get liver cancer. Your doctor will diagnose cirrhosis with blood tests, imaging tests, or a biopsy. Cirrhosis has many causes. [icdlist.com]

  Jaundice. Jaundice occurs when the diseased liver doesn't remove enough bilirubin, a blood waste product, from your blood. Jaundice causes yellowing of the skin and whites of the eyes and darkening of urine. Bone disease. [mayoclinic.org]

• Hepatomegaly

  Diagnoses were based on histology in all but 3 patients (2 elderly women with liver atrophy and severe cirrhotic ascites diagnosed clinically with cryptogenic cirrhosis and 1 adult man with abnormal serum aminotransferase levels and hepatomegaly that [ncbi.nlm.nih.gov]

  Abdominal ultrasound showed hepatomegaly (5 cm × 5 cm × 5 cm) with mild ascites. The spleen, gallbladder, pancreas, kidneys, aorta, and inferior vena cava were normal. There was no retroperitoneal lymphadenopathy. [hindawi.com]

  CARDIAC CIRRHOSIS Clinic a l featu r es · Mild jaundice · Liver dysfunction · Hepatomegaly – firm, non tender • *Ascites · Peripheral edema · Oesophageal bleeding · Encephalopathy. [medicscientist.com]

  Elevations in liver enzymes and hepatomegaly have been described in patients treated with colchicine 34, and liver damage in colchicine intoxication was also reported 18. [journals.lww.com]

• Hepatosplenomegaly

  Clinical manifestations include hepatosplenomegaly, mild disturbances in the liver function tests, diarrhea, malabsorption, and weight loss 32. [journals.lww.com]

  At this point, the abdomen was not distended, but there was hepatosplenomegaly, extending 6 cm below the subcostal margin. There was no hepatic bruit or ascites. [hindawi.com]

• Scleral Icterus

  In addition, the patient had mild scleral icterus. The abdomen was distended and soft; however, an irregular and nontender hepatomegaly of 6 cm was palpable below the right subcostal margin, with no splenomegaly. [hindawi.com]

• Erythema

  Age, jaundice, spiders, palmar erythema and factor V showed a statistically significant difference of the cryptogenic cirrhosis when compared with both alcoholic and viral etiologies. [ncbi.nlm.nih.gov]

  These red signs include appearance of red longitudinal streaks on the varices, discrete cherry red spots, raised spots overlying the varices like a blood blister, and diffuse erythema surrounding varices. [healio.com]

  Specific (due to impaired liver function): Impaired protein synthesis (leukonychia [white nails], ascites, bruising) Impaired biliary excretion (jaundice, pruritus) Impaired nitrogen metabolism (hepatic encephalopathy) Impaired estrogen metabolism (palmar erythema [pathologyoutlines.com]

  […] present here is a 36-year-old female with a liver transplant at age 25 for cryptogenic cirrhosis (maintained on tacrolimus, cyclosporine and prednisone) who presented with a 2 month history of a 10 cm tender reticulated necrotic plaque with surrounding erythema [e-ijd.org]

• Epistaxis

  Although the GI bleed could be explained by portal hypertension and gastropathy, the epistaxis was likely due to a bleeding diathesis secondary to thrombocytopenia. [jscisociety.com]

• Tremor

  Although she had hepatic encephalopathy that included confusion, tremor, and slurred speech, diagnosis of Wilson's disease was ruled out because urinary cooper excretion and hepatic copper concentrations were below the range found in symptomatic Wilson's [ncbi.nlm.nih.gov]

  The word essential is sometimes synonymous with idiopathic (as in essential hypertension, essential thrombocythemia, and essential tremor ) and the same is true of primary (as in primary biliary cholangitis, or primary amenorrhea ), with the latter term [en.wikipedia.org]

  […] shock wave lithotripsy (ESWL)体外衝撃波結石破砕術（ESWL） extrahepatic bile duct肝外胆管 f facial pallor 顔面蒼白 familial polyposis coli家族性大腸ポリポーシス症候群 fatty degeneration脂肪変性 feces (stool)糞便 fibroma線維腫 fissure of anus (anal fissure)裂肛、痔裂 fistula瘻孔 fistula ani痔瘻 flapping tremor [tokyo-med.ac.jp]

  Cirrhosis, tremor, psychiatric disturbances and other neurological difficulties occur if the condition is not treated early. Treatment is with oral medication, which increases the amount of copper that is eliminated from the body in the urine. [medicinenet.com]

• Memory Impairment

  Others have chronic memory impairment in spite of medical management. Both groups of patients are subject to episodes of worsened encephalopathy. [hepatitiscnewdrugs.blogspot.com]

• Dark Urine

  Hepatitis B Electron micrograph of hepatitis B virus Specialty Infectious disease, gastroenterology Symptoms None, yellowish skin, tiredness, dark urine, abdominal pain[1] Complications Cirrhosis, liver cancer[2] Usual onset Symptoms may take up to 6 [en.wikipedia.org]

• Testicular Pain

  These 10 criteria include weight loss ≥4.5 kg, livedo reticularis, testicular pain/tenderness, myalgias, nerve disease, elevated diastolic blood pressure, elevated kidney blood tests BUN or creatinine, positive HBV or HCV, arteriogram showing the aneurysms [e-ijd.org]

The diagnosis of cryptogenic cirrhosis is established by excluding other potential causes. A detailed medical history will help reveal underlying conditions such as diabetes, or a possible alcoholic habit, which could account for the condition. Furthermore, since certain drugs are known to cause cirrhosis, a physician should always inquire about intake of medications such as amiodarone, methyldopa, methotrexate etc.

NAFLD is also a condition that can lead to a cirrhotic liver and proper attention should be reserved for this possibility. Diagnosis is established with the aid of ultrasonography (US), computed tomography (CT) scans without contrast, an magnetic resonance imaging (MRI) scan and a liver biopsy. A typical CT scan will reveal a homogenous parenchyma with low density, MRI will illustrate bright areas representing fatty deposits and a US scan will display less specific findings, such as a normal echotexture and a bright parenchyma. Even though a liver biopsy is not performed in all cirrhosis candidates, due to possible complications (hemorrhage), and does present certain limitations depending on the location of the specimen, it remains as the gold standard for the definitive diagnosis [5] [6] [7] [8] [9] [10] [11] [12].

Another possibility that has to be excluded for cirrhosis to be defined as cryptogenic is the existence of an autoimmune hepatitis. A proper diagnostic approach involves the quantification of gammaglobulin levels, antinuclear antibodies, LKM1 antibodies and smooth muscle antibodies.

Non-invasive methods used to detect fibrosis

It is required to perform the following non-invasive procedures in cases of patients who run a high risk for NASH, in order to identify potential fibrosis:

• Age >50: quantification of AST/ALT ratio, INR and platelet count.
• Pre-existing diabetes mellitus: quantification of Retinol-Binding Protein 4 (RBP4), which is produced by adipocytes and preserved intrahepatically. Obesity leads to increased levels of RBP4, which is responsible for triggering an insulin resistance and contributing to the exacerbation of NASH.
• Obesity (BMI ≥28 Kg/m2): Transient Elastography (Fibroscan), which assesses hepatic elasticity.

• Hypoglycemia

  Hepatology 19 : 616 –627, 1994 ↵ Marks V, Teale JD: Drug-induced hypoglycemia. [care.diabetesjournals.org]

  In addition, liver cancers can produce and release a number of substances, including ones that cause an increased in red blood cell count (erythrocytosis), low blood sugar ( hypoglycemia ), and high blood calcium ( hypercalcemia ). [medicinenet.com]

  […] differential diagnosis of encephalopathy include the following: Intracranial lesions (eg, subdural hematoma, intracranial bleeding, cerebrovascular accident, tumor, abscess) Infections (eg, meningitis, encephalitis, abscess) Metabolic encephalopathy (eg, hypoglycemia [hepatitiscnewdrugs.blogspot.com]

• Hypercholesterolemia

  The comparison with the alcoholic/HCV cirrhosis group showed statistical differences regarding fasting glycemia (45.2%), hypercholesterolemia (13.3%) and female HDL levels (50.8%). [ncbi.nlm.nih.gov]

  Hypercholesterolemia was defined as TC ≥200 mg/dL(10). [scielo.br]

  Exome sequencing and directed clinical phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia. [journals.plos.org]

• Hypoalbuminemia

  Muehrcke's lines – paired horizontal bands separated by normal color resulting from hypoalbuminemia (inadequate production of albumin). [en.wikipedia.org]

  Ascites 5 Cause of Nonperitoneal Ascites Examples Intrahepatic portal hypertension Cirrhosis Fulminant hepatic failure Veno-occlusive disease Extrahepatic portal hypertension Hepatic vein obstruction (ie, Budd-Chiari syndrome) Congestive heart failure Hypoalbuminemia [hepatitiscnewdrugs.blogspot.com]

• Erythrocytosis

  In addition, liver cancers can produce and release a number of substances, including ones that cause an increased in red blood cell count (erythrocytosis), low blood sugar ( hypoglycemia ), and high blood calcium ( hypercalcemia ). [medicinenet.com]

• Enlargement of the Spleen

  Enlargement of the spleen (splenomegaly). Portal hypertension can also cause changes to and swelling of the spleen, and trapping of white blood cells and platelets. [mayoclinic.org]

  Abdominal US revealed enlarged liver and spleen and the presence of peritoneal fluid. [journals.lww.com]

  Other liver findings suggestive of cirrhosis in imaging are an enlarged caudate lobe, widening of the fissures and enlargement of the spleen. [en.wikipedia.org]

• Hepatocellular Carcinoma

  The lower occurrence of hepatocellular carcinoma and higher survival rate may indicate an indolent clinical course in CC as compared with viral cirrhosis. [ncbi.nlm.nih.gov]

• Leukocytosis

  Full blood count showed mild leukocytosis and normocytic anemia, whilst liver function tests demonstrated a mild transaminitis. Renal function tests showed raised creatinine and urea consistent with dehydration. [hindawi.com]

  Paracentesis also should be performed when SBP is suggested by the presence of abdominal pain, fever, leukocytosis, or worsening hepatic encephalopathy. [hepatitiscnewdrugs.blogspot.com]

Therapeutic schemes applied in cirrhotic patients depend on the cause of the condition. The aim of all types of treatment is to address the underlying cause, relieve the patients from its symptoms, hinder its progression and stabilize the liver. For instance, corticosteroids and azathioprine are used to treat autoimmune hepatitis, interferons are used against viral hepatitis B and C and trientine is employed in cases of Wilson's disease.

Since cirrhosis is an irreversible and untreatable condition, therapy aims at symptom relief and  primarily targets the complications of cirrhosis. Patients who have developed ascites have to restrict sodium intake, use diuretics and may also be candidates for paracentesis and shunts. In cases of diagnosed hepatic encephalopathy, antibiotics and lactulose are administered. In order to definitively address the problem of cirrhosis, the only treatment option is a liver transplant; it is important to draw attention to the fact that patients with cirrhosis due to NASH will possibly exhibit fatty deposits in the transplanted liver as well.

Even though cirrhosis is an irreversible condition, its causes can be determined in 90% of the cases: hepatitis B and C, alcoholism, diabetes, and mechanical bile duct obstruction are some of the diseases which can lead to cirrhosis. If the causes are determined early and proper treatment is administered, the fibrosing and scarring phenomena are hindered and cirrhosis remains stable. In cases of cryptogenic cirrhosis, however, since the etiology remains unknown, patients are irrevocably led to a hepatic transplant as it is the only therapeutic option.

By definition, cryptogenic cirrhosis is a condition for which no causes have been identified. The percentage of cirrhotic patients belonging in this category amounts to a 10%. Many of the cases which are termed as "cryptogenic" are in reality a result of an underlying condition known as non-alcoholic fatty liver disease or NAFLD. It is a disease characterized by fatty deposits on the liver, and NASH is its most extreme type. As the condition progresses, it leads to scarring and inflammation of hepatic tissue and the accumulation of fat (steatosis) sometimes subsides, rendering it difficult for NAFLD to be diagnosed; as a result, causes remain unknown.

Non-alcoholic fatty liver disease is triggered by many other conditions, including obesity, diabetes and hypertriglyceridemia [4]. In fact, diabetes and obesity can directly cause cirrhosis, without the onset of NASH, in some patients.

With the modernization of diagnostic tools and the advancement of medical knowledge on hepatic conditions, cryptogenic cirrhosis cases have started to decline in numbers. It is estimated that only a 10% of the patients suffering from cirrhosis have a type which is deemed cryptogenic. The condition affects primarily individuals of the senior population, namely of over 60 years old.

Scarring and fibrosis of the liver are both trademarks of a chronic, gradual hepatic condition that frequently result in cirrhosis. This is defined as an irreversible condition of the liver, also characterized by the formation of hepatocellular nodules. Fibrosis is, in fact, a direct result of the increased intrahepatic concentration of collagen (type I and III), which is produced by stellate cells. The extensive accumulation of collagen, both in the parenchymal regions and in the Disse space, leads to an imbalance of the exchange between the plasma and hepatic cells.

Cirrhosis has an important complication: portal hypertension, namely a substantial increase of the abdominal pressure, because of the hepatic incapacity to forward the blood from the portal vein to the inferior vena cava. Another significant problem caused by a cirrhotic liver is that the organ itself is subject to hypoperfusion.

The obstruction of blood flow due to a fibrosing liver alongside the destruction of hepatic cells, leads to a decreased protein synthesis, malnutrition and subsequent ascites. Furthermore, since the liver is responsible for the filtering of toxins, cirrhotic phenomena also lead to the accumulation of such by products in the organism, which find their way to the brain and lead to a condition called hepatic encephalopathy.

Only comprehensive measures can be suggested for the avoidance of cryptogenic cirrhosis, since its causes are yet to be discovered. Any individual is advised to avoid risk factors such as alcohol and acetaminophen abuse, IV drugs, unprotected sexual intercourse and the use of non-sterilized syringes at any case. Anti-hepatitis A and B vaccines should also be administered, obesity should be avoided and any type of liver condition must be treated appropriately and consistently in order to avoid the onset of cirrhosis. Relatives of patients who exhibit cirrhosis due to hemochromatosis or Wilson's disease should be tested as well and blood donation must be carried out with extreme caution, so as to eliminate occasions of disease transmission.

Cirrhosis is a chronic, incurable hepatic condition which features characteristic fibrosing alterations and irregular hepatocellular nodules [1] [2]. Cases of cirrhosis are termed "cryptogenic" when the causes leading to this condition cannot be identified.

The determination of its causes plays a pivotal role in the progression of cirrhosis, as therapeutic plans greatly depend on the disease's etiology and many of its complications can be avoided. In the 21st century, given the advanced diagnostic tools and medical progress, the percentage of cryptogenic cirrhosis is substantially smaller: unknown causes are attributed to a 10% of cirrhosis cases, a number greatly diminished in comparison to statistics of the past.

One of the most common causes of cirrhosis is alcoholism. It is indeed an interesting fact that people with cryptogenic cirrhosis exhibit the same degree of fibrosis and scarring as those suffering from an alcoholic cirrhosis, even though they do not consume large amounts of alcohol. During the past years, the suggestion has been made that many cases deemed cryptogenic cirrhosis are actually caused by nonalcoholic steatohepatitis (NASH), a disease which leads to the accumulation of fat in the liver [3]. NASH patients can even be as young as children and do not consume large amounts of alcohol either. Some may not even be recreational drinkers. This disease leads to advanced cirrhosis that produces symptoms only at the progressed stages.

Generally, cirrhosis is a late-stage, untreatable liver disease, with typical structural alterations that involve scarring of the liver, fibrosis and nodules. Cirrhosis can be caused by other conditions, such as hepatitis B or C, alcoholism, obesity, diabetes, Wilson's disease and many more. In some cases, the exact causes having led to cirrhosis cannot be discovered; the condition is therefore termed "cryptogenic cirrhosis".

On many occasions, patients that are thought to have cryptogenic cirrhosis are actually individuals affected by NAFLD, which stands for non-alcoholic fatty liver disease. This condition results in the abnormal accumulation of fat in the liver and its final, most extreme stage is non-alcoholic steatohepatitis (NASH). People with NASH develop cirrhosis, with the same characteristics as people who consume excessive amounts of alcohol, even though the former are not drinkers or consume little amounts of alcohol.

Cryptogenic cirrhosis usually affects people who are older than 60 years, even though it might also be observed in some younger patients, even in children. Symptoms include weakness, abdominal swelling, fever, jaundice and inexplicable weight loss. The treatment of cryptogenic cirrhosis is solely a liver transplant.

1. Anthony PP, Ishah KG, Nayak NC, Pouslen ME, Scheuer PJ, Sorbin LH. The morphology of cirrhosis: definition, nomenclature, and classification. Bulletin of the World Health Organization 1977; 55: 521-40. 2. 
2. Anthony PP, Ishak KG, Nayak NC, Poulsen HE, Scheuer PJ, Sobin LH. The morphology of cirrhosis. Recommendations on definition, nomenclature, and classification by a working group sponsored by the World Health Organization. J Clin Pathol 1978 May;31:395-414.
3. Clark JM, Diehl AM. Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA. 2003 Jun 11;289(22):3000-4.
4. Riley TR, Taheri M, Schreibman IR. Does weight history affect fibrosis in the setting of chronic liver disease?. J Gastrointestin Liver Dis. Sep 2009;18(3):299-302.
5. Johnson PJ, McFarlane IG. Meeting repor t: International Autoimmune Hepatitis Group. Hepatology 1993 Oct;18:998-1005. 
6. Alvarez F, Berg PA, Bianchi FB. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999 Nov;31:929-38.
7. Sherlock S, Dick R, Van Leeuwen DJ. Liver biopsy today. The Royal Free Hospital experience. J Hepatol. 1985;1:75-85.
8. Tobkes AI, Nord HJ. Liver biopsy: review of methodology and complications. Digestion. 1995 Sep-Oct; 13: 267-74.
9. Ratziu V, Bugianesi E, Dixon J, et al. Histological progression of non-alcoholic fatty-liver disease: a critical reassessment based on liver sampling variability. Aliment Pharmacol Ther. 2007 Sep; 26: 821-30.
10. 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 Mar; 1: 523-5. 
11. Schlichting P, Holund B, Poulsen H. Liver biopsy in chronic aggressive hepatitis. Diagnostic reproducibility in relation to size of specimen. Scand J Gastroenterol. 1983 Jan;18(1):27-32.
12. 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 Oct;97(10):2614-8.