Vaccination (such asfor hepatitis B), avoiding alcohol,[1] losing weight, exercising, low-carbohydrate diet, controlling hypertension and diabetes may help in those with NAFLD or NASH
Cirrhosis, also known asliver cirrhosis orhepatic cirrhosis,chronic liver failure orchronic hepatic failure andend-stage liver disease, is an acute condition of theliver in which the normal functioning tissue, orparenchyma, is replaced with scar tissue (fibrosis) and regenerativenodules as a result ofchronic liver disease.[6][7][8] Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue and nodules of regeneratinghepatocytes can replace the parenchyma, causing increased resistance to blood flow in the liver'scapillaries—thehepatic sinusoids[9]: 83 —and consequentlyportal hypertension, as well as impairment in other aspects of liver function.[6][10] The disease typically develops slowly over months or years.[1]
Hepatitis B vaccine can prevent hepatitis B and the development of cirrhosis from it, but novaccination against hepatitis C is available.[1] No specific treatment for cirrhosis is known, but many of the underlying causes may be treated by medications that may slow or prevent worsening of the condition.[3] Hepatitis B and C may be treatable withantiviral medications.[1] Avoiding alcohol is recommended in all cases.[1] Autoimmune hepatitis may be treated withsteroid medications.[1]Ursodiol may be useful if the disease is due to blockage of the bile duct.[1] Other medications may be useful for complications such as abdominal or leg swelling,hepatic encephalopathy, anddilated esophageal veins.[1] If cirrhosis leads toliver failure, aliver transplant may be an option.[21] Biannual screening for liver cancer usingabdominal ultrasound, possibly with additional blood tests, is recommended[22][23] due to the high risk ofhepatocellular carcinoma arising from dysplastic nodules.[24]
Cirrhosis affected about 2.8 million people and resulted in 1.3 million deaths in 2015.[4][5] Of these deaths, alcohol caused 348,000 (27%), hepatitis C caused 326,000 (25%), and hepatitis B caused 371,000 (28%).[5] In the United States, more men die of cirrhosis than women.[1] The first known description of the condition is byHippocrates in the fifth century BCE.[25] The term "cirrhosis" was derived in 1819 from the Greek word "kirrhos", which describes the yellowish color of a diseased liver.[26]
Person with cirrhosis and associated pain in the right upper region of the abdomen
Cirrhosis can take quite a long time to develop, and symptoms may be slow to emerge.[13] Some early symptoms include tiredness, weakness, loss of appetite, weight loss, and nausea.[13] Early signs may also include redness on the palms known as palmar erythema.[11] People may also feel discomfort in the right upper abdomen around the liver.[13]
As cirrhosis progresses, symptoms may include neurological changes affecting both the peripheral and central nervous systems, disrupting the neurotransmission within the brain and causing neuromuscular fatigue.[13][27] This can consist of cognitive impairments, confusion,memory loss,sleep disorders, and personality changes.[13]Steatorrhea or presence of undigested fats in stool is also a symptom of cirrhosis.[28]
Worsening cirrhosis can cause a build-up of fluid in different parts of the body such as the legs (edema) and abdomen (ascites).[13] Other signs of advancing disease includeitchy skin, bruising easily,dark urine, andyellowing of the skin.[13]
These features are a direct consequence of liver cells not functioning:
Spider angiomata orspider nevi happen when there is dilatation ofvasculature beneath the skin surface.[29] There is a central, red spot with reddish extensions that radiate outward. This creates a visual effect that resembles a spider. It occurs in about one-third of cases.[29] The likely cause is an increase inestrogen.[29] Cirrhosis causes a rise of estrogen due to increased conversion ofandrogens into estrogen.[30]
Palmar erythema, a reddening of the palm below the thumb and little finger, is seen in about 23% of cirrhosis cases, and results from increased circulatingestrogen levels.[31]
Gynecomastia, or the increase of breast size in men, is caused by increasedestradiol (a potent type of estrogen).[32] This can occur in up to two-thirds of cases.[33]
Liver size can beenlarged, normal, or shrunken in people with cirrhosis.[36] As the disease progresses, the liver will typically shrink due to the result of scarring.[37]
Liver cirrhosis makes it hard for blood to flow in theportal venous system.[39] This resistance creates a backup of blood and increases pressure.[39] This results inportal hypertension. Effects of portal hypertension include:
Caput medusae are dilatedparaumbilical collateral veins due to portal hypertension.[39] Blood from the portal venous system may be forced through the paraumbilical veins and ultimately to the abdominal wall veins.Caput Medusae The created pattern resembles the head ofMedusa, hence the name.[9]
Hepatic encephalopathy (HE) occurs whenammonia and related substances build up in the blood.[45] This build-up affects brain function when they are not cleared from the blood by the liver. Symptoms can include unresponsiveness, forgetfulness, trouble concentrating, changes in sleep habits, orpsychosis. One classic physical examination finding isasterixis.[33] This is the asynchronous flapping of outstretched,dorsiflexed hands.[33]Fetor hepaticus is a musty breath odor resulting from increaseddimethyl sulfide and is a feature of HE.[46]
Increased sensitivity to medication can be caused by decreased metabolism of the active compounds.[47]
Cirrhosis has many possible causes, and more than one cause may be present.History taking is of importance in trying to determine the most likely cause.[2] Globally, 57% of cirrhosis is attributable to either hepatitis B (30%) or hepatitis C (27%).[48][49]Alcohol use disorder is another major cause, accounting for about 20–40% of the cases.[49][33]
Alcoholic liver disease (ALD, or alcoholic cirrhosis) develops for 10–20% of individuals who drink heavily for a decade or more.[50] Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.[51] This injury happens through the formation ofacetaldehyde from alcohol. Acetaldehyde is reactive and leads to the accumulation of other reactive products in the liver.[33] People with ALD may also have concurrentalcoholic hepatitis. Associated symptoms are fever,hepatomegaly,jaundice, andanorexia.[51]AST and ALT blood levels are both elevated, but at less than 300 IU/liter, with an AST:ALT ratio > 2.0, a value rarely seen in otherliver diseases.[52] In the United States, 40% of cirrhosis-related deaths are due to alcohol.[33]
Innon-alcoholic fatty liver disease (NAFLD), fat builds up in the liver and eventually causes scar tissue.[53] This type of disorder can be caused byobesity,diabetes,malnutrition,coronary artery disease, andsteroids.[53][54] Though similar in signs to alcoholic liver disease, no history of notable alcohol use is found. Blood tests and medical imaging are used to diagnose NAFLD and NASH, and sometimes a liver biopsy is needed.[40]
Chronichepatitis C, an infection with thehepatitis C virus, causes inflammation of the liver and a variable grade of damage to the organ.[45] Over several decades, this inflammation and damage can lead to cirrhosis. Among people with chronic hepatitis C, 20–30% develop cirrhosis.[45][33] Cirrhosis caused by hepatitis C and alcoholic liver disease are the most common reasons for liver transplant.[33] Both hepatitis C and hepatitis B–related cirrhosis can also be attributed with heroin addiction.[55]
Chronichepatitis B causes liver inflammation and injury that over several decades can lead to cirrhosis.[45] Hepatitis D is dependent on the presence of hepatitis B and accelerates cirrhosis in co-infection.[45]
Autoimmune hepatitis is caused by an attack of the liver bylymphocytes. This causes inflammation and eventually scarring as well as cirrhosis. Findings include elevations in serum globulins, especially gamma globulins.[33]
The liver plays a vital role in many metabolic processes in the body including protein synthesis, detoxification, nutrient storage (such asglycogen), platelet production and clearance ofbilirubin. With progressive liver damage; hepatocyte death and replacement of functional liver tissue with fibrosis in cirrhosis, these processes are disrupted. This leads to many of the metabolic derangements and symptoms seen in cirrhosis.[59]
Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are fully reversible.[citation needed]
The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal tissue, which is normally organized intolobules. This scar tissue blocks theportal flow of blood through the organ, raising the blood pressure.[59] This manifests asportal hypertension in which the pressure gradient between theportal circulation as compared to the systemic circulation is elevated. This portal hypertension leads to decreased sinusoidal flow from liver cells to nearbysinusoids in the liver, and increasedlymph production with extravasation of lymph to the extracellular space, causing ascites.[59] This also causes reduced cardiac return and central blood volume, which activates therenin-angiotensin system (RAAS) which causes kidneys to reabsorb sodium and water, causing water retention and further ascites. Activation of the RAAS also causes kidney vasoconstriction and may cause kidney injury.[59]
Research has shown the pivotal role of thestellate cell, that normally storesvitamin A, in the development of cirrhosis. Damage to the liver tissue from inflammation leads to the activation of stellate cells, which increases fibrosis through the production ofmyofibroblasts, and obstructs hepatic blood flow.[60] In addition, stellate cells secreteTGF beta 1, which leads to a fibrotic response and proliferation ofconnective tissue. TGF-β1 have been implicated in the process of activating hepatic stellate cells (HSCs) with the magnitude of fibrosis being in proportion to increase in TGF β levels. ACTA2 is associated with TGF β pathway that enhances contractile properties of HSCs leading to fibrosis.[61] Furthermore, HSCs secreteTIMP1 andTIMP2, naturally occurring inhibitors ofmatrix metalloproteinases (MMPs), which prevent MMPs from breaking down the fibrotic material in theextracellular matrix.[62][63]
As this cascade of processes continues, fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. Thespleen becomes congested, andenlarged, resulting in its retention ofplatelets, which are needed for normal blood clotting. Portal hypertension is responsible for the most severe complications of cirrhosis.[citation needed]
The diagnosis of cirrhosis in an individual is based on multiple factors.[33] Cirrhosis may be suspected from laboratory findings,physical exam, and the person's medicalhistory. Imaging is generally obtained to evaluate the liver.[33] A liverbiopsy will confirm the diagnosis; however, is generally not required.[45]
Ultrasound is routinely used in the evaluation of cirrhosis.[45] It may show a small and shrunken liver in advanced disease. On ultrasound, there is increasedechogenicity with irregular appearing areas.[64] Other suggestive findings are an enlargedcaudate lobe, liver surface nodularity[65] widening of thefissures andenlargement of the spleen.[66] An enlargedspleen, which normally measures less than 11–12 cm (4.3–4.7 in) in adults, may suggest underlyingportal hypertension.[67] Ultrasound may also screen forhepatocellular carcinoma and portal hypertension.[45] This is done by assessing flow in the hepatic vein.[68] An increasedportal vein pulsatility may be seen. However, this may be a sign of elevatedright atrial pressure.[69] Portal vein pulsatility are usually measured by a pulsatility indices (PI).[68] A number above a certain values indicates cirrhosis (see table below).
Other scans includeCT of the abdomen andMRI.[45] A CT scan is non-invasive and may be helpful in the diagnosis.[45] Compared to the ultrasound, CT scans tend to be more expensive. MRI provides excellent evaluation; however, is a high expense.[45]
Portable ultrasound is a low cost tool to identify the sign of liver surface nodularity with a good diagnostic accuracy.[72]
Cirrhosis is also diagnosable through a variety of newelastography techniques.[73][74] When a liver becomes cirrhotic it will generally become stiffer. Determining the stiffness through imaging can determine the location and severity of disease. Techniques includetransient elastography,acoustic radiation force impulse imaging,supersonic shear imaging andmagnetic resonance elastography.[75]Transient elastography andmagnetic resonance elastography can help identify the stage of fibrosis.[76] Compared to abiopsy, elastography can sample a much larger area and is painless.[77] It shows a reasonable correlation with the severity of cirrhosis.[76] Other modalities have been introduced which are incorporated into ultrasonagraphy systems. These include2-dimensional shear wave elastography andpoint shear wave elastography which uses acoustic radiation force impulse imaging.[16]
Rarely are diseases of the bile ducts, such asprimary sclerosing cholangitis, causes of cirrhosis.[45] Imaging of the bile ducts, such asERCP orMRCP (MRI of biliary tract and pancreas) may aid in the diagnosis.[45]
The best predictors of cirrhosis are ascites, platelet count < 160,000/mm3, spider angiomata, and a Bonacini cirrhosis discriminant score greater than 7 (as the sum of scores for platelet count,ALT/AST ratio andINR as per table).[78]
Thrombocytopenia, typically multifactorial, is due to alcoholic marrow suppression, sepsis, lack of folate, platelet sequestering in the spleen, and decreasedthrombopoietin.[52] However, this rarely results in a platelet count < 50,000/mL.[80]
Aminotransferases AST and ALT are moderately elevated, with AST > ALT. However, normal aminotransferase levels do not preclude cirrhosis.[52]
Vasoactive intestinal peptide is increased as blood is shunted into the intestinal system because of portal hypertension.
Vasodilators are increased (such as nitric oxide and carbon monoxide) reducing afterload with compensatory increase in cardiac output, mixed venous oxygen saturation.[81]
Renin is increased (as well as sodium retention in kidneys) secondary to a fall in systemic vascular resistance.[82]
FibroTest is a biomarker for fibrosis that may be used instead of a biopsy.[83]
Other laboratory studies performed in newly diagnosed cirrhosis may include:
The link between gut microbiota constitution and liver health (Particularly in Cirrhosis) has been well described,[91] however specific biomarkers for prediction of Cirrhosis still requires further research. A 2014 study identified 15 microbialbiomarkers from thegut microbiota.[92] These could potentially be used to discriminate patients with liver cirrhosis from healthy individuals.
Thegold standard for diagnosis of cirrhosis is aliver biopsy. This is usually carried out as afine-needle approach, through the skin (percutaneous), orinternal jugular vein (transjugular).[93] Endoscopic ultrasound-guided liver biopsy (EUS), using the percutaneous or transjugular route, has become a good alternative to use.[94][93] EUS can target liver areas that are widely separated,[95] and can deliver bi-lobar biopsies.[94] A biopsy is not necessary if the clinical, laboratory, and radiologic data suggest cirrhosis. Furthermore, a small but significant risk of complications is associated with liver biopsy, and cirrhosis itself predisposes for complications caused by liver biopsy.[96]
Once the biopsy is obtained, apathologist will study the sample. Cirrhosis is defined by its features onmicroscopy: (1) the presence of regenerating nodules of hepatocytes and (2) the presence offibrosis, or the deposition ofconnective tissue between these nodules. The pattern of fibrosis seen can depend on the underlying insult that led to cirrhosis. Fibrosis can also proliferate even if the underlying process that caused it has resolved or ceased. The fibrosis in cirrhosis can lead to destruction of other normal tissues in the liver: including thesinusoids, thespace of Disse, and other vascular structures, which leads to altered resistance to blood flow in the liver, andportal hypertension.[97]
No fibrosis, but mild zone 3 steatosis, in which collagen fibres (pink–red, arrow) are confined to portal tracts (P) (Van Gieson's stain)[98]
Histopathology of steatohepatitis with mild fibrosis in the form of fibrous expansion (Van Gieson's stain)[98]
Histopathology of steatohepatitis with moderate fibrosis, with thin fibrous bridges (Van Gieson's stain)[98]
Histopathology of steatohepatitis with established cirrhosis, with thick bands of fibrosis (Van Gieson's stain)[98]
Trichrome stain, showing cirrhosis as a nodular texture surrounded by fibrosis (wherein collagen is stained blue).
Macroscopically, the liver is initially enlarged, but with the progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm, and if associated withsteatosis the color is yellow. Depending on the size of the nodules, there are three macroscopic types: micronodular, macronodular, and mixed cirrhosis. In the micronodular form (Laennec's cirrhosis or portal cirrhosis), regenerating nodules are under 3 mm. In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. Mixed cirrhosis consists of nodules of different sizes.[101]
Micronodular cirrhosis, with diffuse areas of pallor
The severity of cirrhosis is commonly classified with theChild–Pugh score (also known as the Child–Pugh–Turcotte score).[102] This system was devised in 1964 by Child and Turcotte, and modified in 1973 by Pugh and others.[103] It was first established to determine who would benefit from elective surgery for portal decompression.[102] This scoring system uses multiple lab values includingbilirubin,albumin, andINR.[104] The presence ofascites and severity ofencephalopathy is also included in the scoring.[104] The classification system includes class A, B, or C.[104] Class A has a favorableprognosis while class C is at high risk of death.
Child-Pugh Score in Relation to Liver Function, Prognosis and Post-op Mortality[104][102]
Child-Pugh Class
Points
Liver Function
Prognosis
Abdominal surgery post-operative mortality
Child-Pugh Class A
5–6 points
Good liver function
15–20 years
10%
Child-Pugh Class B
7–9 points
Moderately impaired liver function
30%
Child-Pugh Class C
10–15 points
Advanced liver dysfunction
1–3 years
82%
The Child-Pugh score is a validated predictor of mortality after a major surgery.[102] For example, Child class A patients have a 10% mortality rate and Child class B patients have a 30% mortality rate while Child class C patients have a 70–80% mortality rate after abdominal surgery.[102] Elective surgery is usually reserved for those in Child class A patients. There is an increased risk for Child class B individuals and they may require medical optimization. Overall, it is not recommended for Child class C patients to undergo elective surgery.[102]
In the past, the Child-Pugh classification was used to determine people who were candidates for a liver transplant.[102] Child-Pugh class B is usually an indication for evaluation for transplant.[104] However, there were many issues when applying this score to liver transplant eligibility.[102] Thus, the MELD score was created.
TheModel for End-Stage Liver Disease (MELD) score was later developed and approved in 2002.[105] It was approved by the United Network for Organ Sharing (UNOS) as a way to determine the allocation of liver transplants to awaiting people in the United States.[106] It is also used as a validated survival predictor of cirrhosis, alcoholic hepatitis, acute liver failure, and acute hepatitis.[107] The variables included bilirubin,INR,creatinine, anddialysis frequency.[107] In 2016,sodium was added to the variables and the score is often referred to as MELD-Na.[108]
MELD-Plus is a further risk score to assess severity of chronic liver disease. It was developed in 2017 as a result of a collaboration betweenMassachusetts General Hospital andIBM.[109] Nine variables were identified as effective predictors for 90-day mortality after a discharge from a cirrhosis-related hospital admission.[109] The variables include all Model for End-Stage Liver Disease (MELD)'s components, as well as sodium, albumin, total cholesterol, white blood cell count, age, and length of stay.[109]
Key prevention strategies for cirrhosis are population-wide interventions to reduce alcohol intake (through pricing strategies, public health campaigns, and personal counseling), programs to reduce the transmission of viral hepatitis, and screening of relatives of people with hereditary liver diseases.[111]
Little is known about factors affecting cirrhosis risk and progression. However, many studies have provided increasing evidence for the protective effects of coffee consumption against the progression of liver disease. These effects are more noticeable in liver disease that is associated with alcohol use disorder. Coffee has antioxidant and antifibrotic effects.Caffeine may not be the important component;polyphenols may be more important. Drinking two or more cups of coffee a day is associated with improvements in theliver enzymesALT,AST, andGGT. Even in those with liver disease, coffee consumption can lower fibrosis and cirrhosis.[112]
Generally, liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. A recommended diet consists of high-protein, high-fiber diet plus supplementation with branched-chain amino acids.[113] Close follow-up is often necessary. Antibiotics are prescribed for infections, and various medications can help with itching. Laxatives, such aslactulose, decrease the risk of constipation.Carvedilol increases survival benefit for people with cirrhosis andportal hypertension.[114] Diuretics in combination with low salt diet reduce fluid in body which helps reduce oedema.[115]
Alcoholic cirrhosis caused by alcohol use disorder is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis.[citation needed]
As of 2021, there are recent studies studying drugs to prevent cirrhosis caused bynon-alcoholic fatty liver disease (NAFLD or NASH). The drugsemaglutide was shown to provide greater NASH resolution versusplacebo. No improvement in fibrosis was observed.[116] A combination of cilofexor/firsocostat was studied in people with bridgingfibrosis and cirrhosis. It was observed to have led to improvements in NASH activity with a potential antifibrotic effect.[117] Lanifibranor is also shown to prevent worsening fibrosis.[118]
Regardless of the underlying cause of cirrhosis, consumption of alcohol and other potentially damaging substances is discouraged. There is no evidence that supports the avoidance or dose reduction ofparacetamol in people with compensated cirrhosis; it is thus considered a safe analgesic for said individuals.[119]
Vaccination againsthepatitis A andhepatitis B is recommended early in the course of illness due to decline in effectiveness of the vaccines with decompensation.[120]
Treating the cause of cirrhosis prevents further damage; for example, giving oral antivirals such asentecavir andtenofovir where cirrhosis is due to hepatitis B prevents progression of cirrhosis. Similarly, control of weight and diabetes prevents deterioration in cirrhosis due tonon-alcoholic fatty liver disease.[121]
People with cirrhosis or liver damage are often advised to avoid drugs that could further harm the liver.[122] These include several drugs such asanti-depressants, certain antibiotics, andNSAIDs (like ibuprofen).[122] These agents arehepatotoxic as they aremetabolized by the liver. If a medication that harms the liver is still recommended by a doctor, the dosage can be adjusted to aim for minimal stress on the liver.[citation needed]
According to a 2018 systematic review based on studies that implemented 8 to 14 week-longexercise programs, there is currently insufficient scientific evidence regarding either the beneficial or harmful effects of physical exercise in people with cirrhosis on all-causemortality, morbidity (including both serious and non-seriousadverse events), health-relatedquality of life, exercise capacity and anthropomorphic measures.[123] These conclusions were based on low to very low quality research, which imposes the need to develop further research with higher quality, especially to evaluate its effects on clinical outcomes.[citation needed]
If complications cannot be controlled or when the liver ceases functioning,liver transplantation is necessary. Survival from liver transplantation has been improving over the 1990s, and the five-year survival rate is now around 80%. The survival rate depends largely on the severity of disease and other medical risk factors in the recipient.[124] In the United States, theMELD score is used to prioritize patients for transplantation.[125] Transplantation necessitates the use of immune suppressants (ciclosporin ortacrolimus).
People with decompensated cirrhosis generally require admission to a hospital, with close monitoring of thefluid balance, mental status, and emphasis on adequate nutrition and medical treatment – often withdiuretics,antibiotics,laxatives orenemas,thiamine and occasionallysteroids,acetylcysteine andpentoxifylline.[126] Administration ofsaline is avoided, as it would add to the already high total body sodium content that typically occurs in cirrhosis. Life expectancy without liver transplant is low, at most three years.
Palliative care is specialized medical care that focuses on providing patients with relief from the symptoms, pain, and stress of a serious illness, such as cirrhosis. The goal of palliative care is to improve quality of life for both the patient and the patient's family and it is appropriate at any stage and for any type of cirrhosis.[127]
Especially in the later stages, people with cirrhosis experience significant symptoms such as abdominal swelling, itching, leg edema, and chronic abdominal pain which would be amenable for treatment through palliative care.[128] Because the disease is not curable without a transplant, palliative care can also help with discussions regarding the person's wishes concerning health carepower of attorney,do not resuscitate decisions and life support, and potentiallyhospice.[128] Despite proven benefit, people with cirrhosis are rarely referred to palliative care.[129]
Cirrhosis can increase the risk of bleeding. The liver produces various proteins in thecoagulation cascade (coagulation factors II, VII, IX, X, V, and VI). When damaged, the liver is impaired in its production of these proteins.[131] This will ultimately increase bleeding as clotting factors are diminished. Clotting function is estimated by lab values, mainlyplatelet count,prothrombin time (PT), andinternational normalized ratio (INR).
The AGA does not recommend for extensive pre-procedural testing, including repeated measurements of PT/INR or platelet count before patients with stable cirrhosis undergo commongastrointestinal procedures. Nor do they suggest the routine use of blood products, such as platelets, for bleeding prevention.[131] Cirrhosis is stable when there are no changes in baseline abnormalities of coagulation lab values.
For patients with stable cirrhosis and low platelet count undergoing common low-risk procedures, the AGA does not recommend the routine use ofthrombopoietin receptor agonists for bleeding prevention.[131]
In hospitalized patients who meet standard guidelines for clot prevention, the AGA suggests standard prevention.[131]
The AGA does not recommend in routine screening forportal vein thrombosis. If there is a portal vein thrombosis, the AGA suggests treatment by anticoagulation.[131]
In the case of cirrhosis with atrial fibrillation, the AGA recommends using anticoagulation over no anticoagulation.[131]
Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention).Diuretics may be necessary to suppressascites. Diuretic options for inpatient treatment includealdosterone antagonists (spironolactone) andloop diuretics. Aldosterone antagonists are preferred for people who can take oral medications and are not in need of an urgent volume reduction. Loop diuretics can be added as additional therapy.[132]
Where salt restriction and the use of diuretics are ineffective thenparacentesis may be the preferred option.[133] This procedure requires the insertion of a plastic tube into the peritoneal cavity.Human serum albumin solution is usually given to prevent complications from the rapid volume reduction. In addition to being more rapid than diuretics, 4–5 liters of paracentesis is more successful in comparison to diuretic therapy.[132]
For portal hypertension, nonselectivebeta blockers such aspropranolol ornadolol are commonly used to lower blood pressure over the portal system. In severe complications from portal hypertension,transjugular intrahepatic portosystemic shunting (TIPS) is occasionally indicated to relieve pressure on the portal vein. As this shunting can worsen hepatic encephalopathy, it is reserved for those patients at low risk of encephalopathy. TIPS is generally regarded only as a bridge to liver transplantation[134] or as a palliative measure.[citation needed] Balloon-occluded retrograde transvenous obliteration can be used to treat gastric variceal bleeding.[135]
Hepatic encephalopathy is a potential complication of cirrhosis.[33] It may lead to functional neurological impairment ranging from mild confusion tocoma.[33] Hepatic encephalopathy is primarily caused by the accumulation of ammonia in the blood, which causes neurotoxicity when crossing the blood-brain barrier. Ammonia is normally metabolized by the liver; as cirrhosis causes both decreased liver function and increased portosystemic shunting (allowing blood to bypass the liver), systemic ammonia levels gradually rise and lead to encephalopathy.[139]
Most pharmaceutical approaches to treating hepatic encephalopathy focus on reducing ammonia levels.[140] Per 2014 guidelines,[141] the first-line treatment involves the use oflactulose, a non-absorbable disaccharide which decreases thepH level of the colon when it is metabolized by intestinal bacteria. The lower colonic pH causes increased conversion of ammonia intoammonium, which is then excreted from the body.[142]Rifaximin, an antibiotic that inhibits the function of ammonia-producing bacteria in the gastrointestinal tract,[143] is recommended for use in combination with lactulose as prophylaxis against recurrent episodes of hepatic encephalopathy.[141][144][145]
In addition to pharmacotherapy, providing proper hydration and nutritional support is also essential.[140] Appropriate quantities of protein uptake is encouraged.[146] Several factors may precipitate hepatic encephalopathy, which include alcohol use, excess protein, gastrointestinal bleeding, infection, constipation, and vomiting/diarrhea.[140] Drugs such as benzodiazepines, diuretics, or narcotics can also precipitate encephalopathic events.[140] A low protein diet is recommended withgastrointestinal bleeding.[146]
The severity of hepatic encephalopathy is determined by assessing the patient'smental status. This is generally a subjective assessment, although several attempts at creating criteria to help standardize this assessment have been published. One example is the West Haven criteria, reproduced below.
People with cirrhosis have a 40% lifetime risk of developing hepatic encephalopathy.[59] The median survival after the development of hepatic encephalopathy is 0.9 years.[59] Mild hepatic encephalopathy (also known as covert hepatic encephalopathy), in which symptoms are more subtle, such as impairments in executive function, poor sleep or balance impairment is also associated with a higher risk of hospitalization and death (18% in those with covert hepatic encephalopathy vs 3% in those with cirrhosis and no HE).[59]
Hepatorenal syndrome is a serious complication of end-stage cirrhosis when kidney damage is also involved.[148] The annual risk of developing hepatorenal syndrome in those with cirrhosis is 8% and once the syndrome develops the median survival is 2 weeks.[59]
Cirrhosis can cause immune system dysfunction, leading toinfection. Signs and symptoms of infection may be nonspecific and are more difficult to recognize (for example, worsening encephalopathy but no fever).[150] Moreover, infections in cirrhosis are major triggers for other complications (ascites, variceal bleeding, hepatic encephalopathy, organ failures, death).[150][88][90]
Those with cirrhosis are at increased risk of infections as well as increased mortality from infections. This is due to a combination of factors including cirrhosis associated immune dysfunction, reduced gut barrier function, reduced bile flow, and changes in the gut microbiota, with an increase inpathobionts (native bacteria, that under certain conditions may cause infection).[130]
Cirrhosis associated immune dysfunction is caused by reducedcomplement component synthesis in the liver includingC3,C4 and reduced total complement activity (CH50).[130] The complement system is a part of theinnate immune system and assists immune cells and antibodies in destroying pathogens. The liver produces compliment factors, but this may be reduced in cirrhosis, raising the risk of infections.Acute phase proteins (which help mount an immune response) and solublepattern recognition receptors (which help immune cells to identify pathogens) are also reduced in those with cirrhosis, leading to further immune dysfunction.[130] Cirrhosis is also associated with reducedKupfer cell function, further increasing the risk for infections. Kupfer cells are residentmacrophages in the liver which help to destroy pathogens.[130]
Extrinsic factors may also increase the risk of infection in those with cirrhosis, includingproton pump inhibitor use, alcohol use,frailty, antibiotic overuse, and hospitalizations or invasive procedures (which increase the risk of bacterial translocation to other areas of the body).[130]
Infections that are common in those in the hospital with cirrhosis includespontaneous bacterial peritonitis (with a prevalence of 27% among hospitalized patients),urinary tract infections (22-29%),pneumonia (19%), spontaneousbacteremia (8-13%), skin and soft tissue infections (8-12%) andC. difficile colitis (2.4-4%).[130][151] It is estimated that 3.5% of people with cirrhosis and ascites may have asymptomatic spontaneous bacterial peritonitis.[152]
The mortality rate for infections in those with cirrhosis is higher than that of the general population. In those with cirrhosis and severe infections withsepsis the mortality rate is greater than 50% and in those withseptic shock, the mortality rate is 65%.[130]
Each year, approximately one million deaths are due to complications of cirrhosis, making cirrhosis the 11th most common cause of death globally.[156] Cirrhosis and chronic liver disease were the tenth leading cause of death for men and the twelfth for women in the United States in 2001, killing about 27,000 people each year.[157]
The cause of cirrhosis can vary; alcohol and non-alcoholic fatty liver disease are main causes in western and industrialized countries, whereas viral hepatitis is the predominant cause in low and middle-income countries.[156] Cirrhosis is more common in men than in women.[158] The cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.
Globally, age-standardizeddisability-adjusted life year (DALY) rates have decreased from 1990 to 2017, with the values going from 656.4 years per 100,000 people to 510.7 years per 100,000 people.[159] In males DALY rates have decreased from 903.1 years per 100,000 population in 1990, to 719.3 years per 100,000 population in 2017; in females the DALY rates have decreased from 415.5 years per 100,000 population in 1990, to 307.6 years per 100,000 population in 2017.[159] However, globally the total number of DALYs have increased by 10.9 million from 1990 to 2017, reaching the value of 41.4 million DALYs.[159]
The word "cirrhosis" is a neologism derived fromGreek:κίρρωσις;kirrhosκιρρός, meaning "yellowish, tawny" (the orange yellow colour of the diseased liver) and the suffix-osis, i.e. "condition" in medical terminology.[160][161][162] While the clinical entity was known before,René Laennec gave it this name in an 1819 paper.[26]
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