Cirrhosis

Cirrhosis, also known asliver cirrhosisorhepatic cirrhosis,chronic liver failureorchronic hepatic failureandend-stage liver disease, is an acute condition of theliverin which the normal functioning tissue, orparenchyma, is replaced with scar tissue (fibrosis) and regenerativenodulesas a result ofchronic liver disease.Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue and nodules of regeneratinghepatocytescan replace the parenchyma, causing increased resistance to blood flow in the liver'scapillaries—thehepatic sinusoids—and consequentlyportal hypertension, as well as impairment in other aspects of liver function.The disease typically develops slowly over months or years.
Stages of cirrhosis include compensated cirrhosis and decompensated cirrhosis.Early symptoms may includetiredness,weakness,loss of appetite,unexplained weight loss, nausea and vomiting, and discomfort in theright upper quadrantof the abdomen.As the disease worsens, symptoms may includeitchiness,swelling in the lower legs,fluid build-up in the abdomen,jaundice,bruising easily, and the development ofspider-like blood vessels in the skin.The fluid build-up in the abdomen may develop intospontaneous infections.More serious complications includehepatic encephalopathy, bleeding fromdilated veins in the esophagus,stomach, orintestines, andliver cancer.
Cirrhosis is most commonly caused by medical conditions includingalcohol-related liver disease,metabolic dysfunction–associated steatohepatitis(MASH – the progressive form ofmetabolic dysfunction–associated steatotic liver disease,previously called non-alcoholic fatty liver disease or NAFLD),heroinabuse,chronichepatitis B, and chronichepatitis C.Chronic heavy drinking can cause alcoholic liver disease.Liver damage has also been attributed toheroinusage over an extended period of time as well.MASH has several causes, includingobesity,high blood pressure, abnormal levels ofcholesterol,type 2 diabetes, andmetabolic syndrome.Less common causes of cirrhosis includeautoimmune hepatitis,primary biliary cholangitis, andprimary sclerosing cholangitisthat disruptsbile ductfunction,genetic disorderssuch asWilson's diseaseandhereditary hemochromatosis, andchronic heart failure with liver congestion.
Diagnosis is based onblood tests,medical imaging, andliver biopsy.
Hepatitis B vaccinecan prevent hepatitis B and the development of cirrhosis from it, but novaccinationagainst hepatitis C is available.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.Hepatitis B and C may be treatable withantiviral medications.Avoiding alcohol is recommended in all cases.Autoimmune hepatitis may be treated withsteroid medications.Ursodiolmay be useful if the disease is due to blockage of the bile duct.Other medications may be useful for complications such as abdominal or leg swelling,hepatic encephalopathy, anddilated esophageal veins.If cirrhosis leads toliver failure, aliver transplantmay be an option.Biannual screening for liver cancer usingabdominal ultrasound, possibly with additional blood tests, is recommendeddue to the high risk ofhepatocellular carcinomaarising from dysplastic nodules.
Cirrhosis affected about 2.8 million people and resulted in 1.3 million deaths in 2015.Of these deaths, alcohol caused 348,000 (27%), hepatitis C caused 326,000 (25%), and hepatitis B caused 371,000 (28%).In the United States, more men die of cirrhosis than women.The first known description of the condition is byHippocratesin the fifth century BCE.The term "cirrhosis" was derived in 1819 from the Greek word "kirrhos", which describes the yellowish color of a diseased liver.
Cirrhosis can take quite a long time to develop, and symptoms may be slow to emerge.Some early symptoms include tiredness, weakness, loss of appetite, weight loss, and nausea.Early signs may also include redness on the palms known as palmar erythema.People may also feel discomfort in the right upper abdomen around the liver.
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.This can consist of cognitive impairments, confusion,memory loss,sleep disorders, and personality changes.Steatorrhea or presence of undigested fats in stool is also a symptom of cirrhosis.
Worsening cirrhosis can cause a build-up of fluid in different parts of the body such as the legs (edema) and abdomen (ascites).Other signs of advancing disease includeitchyskin, bruising easily,dark urine, andyellowing of the skin.
These features are a direct consequence of liver cells not functioning:
Liver cirrhosis makes it hard for blood to flow in theportal venous system.This resistance creates a backup of blood and increases pressure.This results inportal hypertension. Effects of portal hypertension include:
Some signs that may be present include changes in thenails(such asMuehrcke's lines,Terry's nails, andnail clubbing).Additional changes may be seen in the hands (Dupuytren's contracture) as well as the skin/bones (hypertrophic osteoarthropathy).
As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.
Cirrhosis has many possible causes, and more than one cause may be present.History takingis of importance in trying to determine the most likely cause.Globally, 57% of cirrhosis is attributable to either hepatitis B (30%) or hepatitis C (27%).Alcohol use disorderis another major cause, accounting for about 20–40% of the cases.
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.
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.
The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal tissue, which is normally organized intolobules. This scar tissue blocks theportalflow of blood through the organ, raising the blood pressure.This manifests asportal hypertensionin which the pressure gradient between theportal circulationas compared to the systemic circulation is elevated. This portal hypertension leads to decreased sinusoidal flow from liver cells to nearbysinusoidsin the liver, and increasedlymphproduction with extravasation of lymph to the extracellular space, causing ascites.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.
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.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.Furthermore, HSCs secreteTIMP1andTIMP2, naturally occurring inhibitors ofmatrix metalloproteinases(MMPs), which prevent MMPs from breaking down the fibrotic material in theextracellular matrix.
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. Thespleenbecomes 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.
The diagnosis of cirrhosis in an individual is based on multiple factors.Cirrhosis may be suspected from laboratory findings,physical exam, and the person's medicalhistory. Imaging is generally obtained to evaluate the liver.A liverbiopsywill confirm the diagnosis; however, is generally not required.
Ultrasoundis routinely used in the evaluation of cirrhosis.It may show a small and shrunken liver in advanced disease.  On ultrasound, there is increasedechogenicitywith irregular appearing areas.Other suggestive findings are an enlargedcaudate lobe, liver surface nodularitywidening of thefissuresandenlargement of the spleen.An enlargedspleen, which normally measures less than 11–12 cm (4.3–4.7 in) in adults, may suggest underlyingportal hypertension.Ultrasound may also screen forhepatocellular carcinomaand portal hypertension.This is done by assessing flow in the hepatic vein.An increasedportal vein pulsatilitymay be seen. However, this may be a sign of elevatedright atrial pressure.Portal vein pulsatility are usually measured by a pulsatility indices (PI).A number above a certain values indicates cirrhosis (see table below).
Other scans includeCTof the abdomen andMRI.A CT scan is non-invasive and may be helpful in the diagnosis.Compared to the ultrasound, CT scans tend to be more expensive. MRI provides excellent evaluation; however, is a high expense.
Portable ultrasoundis a low cost tool to identify the sign of liver surface nodularity with a good diagnostic accuracy.
Cirrhosis is also diagnosable through a variety of newelastographytechniques.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 imagingandmagnetic resonance elastography.Transient elastographyandmagnetic resonance elastographycan help identify the stage of fibrosis.Compared to abiopsy, elastography can sample a much larger area and is painless.It shows a reasonable correlation with the severity of cirrhosis.Other modalities have been introduced which are incorporated into ultrasonagraphy systems. These include2-dimensional shear wave elastographyandpoint shear wave elastographywhich uses acoustic radiation force impulse imaging.
Rarely are diseases of the bile ducts, such asprimary sclerosing cholangitis, causes of cirrhosis.Imaging of the bile ducts, such asERCPorMRCP(MRI of biliary tract and pancreas) may aid in the diagnosis.
The best predictors of cirrhosis are ascites, platelet count < 160,000/mm, spider angiomata, and a Bonacini cirrhosis discriminant score greater than 7 (as the sum of scores for platelet count,ALT/ASTratio andINRas per table).
These findings are typical in cirrhosis:
FibroTestis a biomarker for fibrosis that may be used instead of a biopsy.
Other laboratory studies performed in newly diagnosed cirrhosis may include:
Markers of inflammation and immune cell activation are typically elevated in cirrhotic patients, especially in the decompensated disease stage:
The link between gut microbiota constitution and liver health (Particularly in Cirrhosis) has been well described,however specific biomarkers for prediction of Cirrhosis still requires further research. A 2014 study identified 15 microbialbiomarkersfrom thegut microbiota.These could potentially be used to discriminate patients with liver cirrhosis from healthy individuals.
Thegold standardfor diagnosis of cirrhosis is aliver biopsy. This is usually carried out as afine-needle approach, through the skin (percutaneous), orinternal jugular vein(transjugular).Endoscopic ultrasound-guided liver biopsy (EUS), using the percutaneous or transjugular route, has become a good alternative to use.EUS can target liver areas that are widely separated,and can deliver bi-lobar biopsies.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.
Once the biopsy is obtained, apathologistwill 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 tissuebetween 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.
As cirrhosis can be caused by many different entities which injure the liver in different ways, cause-specific abnormalities may be seen. For example, inchronic hepatitis B, there is infiltration of the liver parenchyma withlymphocytes.Incongestive hepatopathythere areerythrocytesand a greater amount of fibrosis in the tissue surrounding thehepatic veins.Inprimary biliary cholangitis, there is fibrosis around the bile duct, the presence ofgranulomasand pooling ofbile.Lastly in alcoholic cirrhosis, there is infiltration of the liver withneutrophils.
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 withsteatosisthe 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 cirrhosisor 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.
The severity of cirrhosis is commonly classified with theChild–Pugh score (also known as the Child–Pugh–Turcotte score).This system was devised in 1964 by Child and Turcotte, and modified in 1973 by Pugh and others.It was first established to determine who would benefit from elective surgery for portal decompression.This scoring system uses multiple lab values includingbilirubin,albumin, andINR.The presence ofascitesand severity ofencephalopathyis also included in the scoring.The classification system includes class A, B, or C.Class A has a favorableprognosiswhile class C is at high risk of death.
The Child-Pugh score is a validated predictor of mortality after a major surgery.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.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.
In the past, the Child-Pugh classification was used to determine people who were candidates for a liver transplant.Child-Pugh class B is usually an indication for evaluation for transplant.However, there were many issues when applying this score to liver transplant eligibility.Thus, the MELD score was created.
TheModel for End-Stage Liver Disease(MELD) score was later developed and approved in 2002.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.It is also used as a validated survival predictor of cirrhosis, alcoholic hepatitis, acute liver failure, and acute hepatitis.The variables included bilirubin,INR,creatinine, anddialysisfrequency.In 2016,sodiumwas added to the variables and the score is often referred to as MELD-Na.
MELD-Plusis a further risk score to assess severity of chronic liver disease. It was developed in 2017 as a result of a collaboration betweenMassachusetts General HospitalandIBM.Nine variables were identified as effective predictors for 90-day mortality after a discharge from a cirrhosis-related hospital admission.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.
Thehepatic venous pressure gradient(difference invenous pressurebetween incoming and outgoing blood to the liver) also determines the severity of cirrhosis, although it is hard to measure. A value of 16 mm or more means a greatly increased risk of death.
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.
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.Caffeinemay not be the important component;polyphenolsmay 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.
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.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.Carvedilolincreases survival benefit for people with cirrhosis andportal hypertension.Diuretics in combination with low salt diet reduce fluid in body which helps reduce oedema.
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.
Cirrhosis caused byWilson's diseaseis treated by removing thecopperwhich builds up in organs.This is carried out usingchelation therapysuch aspenicillamine. When the cause is aniron overload, iron is removed using achelationagent such asdeferoxamineor bybloodletting.
As of 2021, there are recent studies studying drugs to prevent cirrhosis caused bynon-alcoholic fatty liver disease(NAFLD or NASH). The drugsemaglutidewas shown to provide greater NASH resolution versusplacebo. No improvement in fibrosis was observed.A combination of cilofexor/firsocostatwas studied in people with bridgingfibrosisand cirrhosis. It was observed to have led to improvements in NASH activity with a potential antifibrotic effect.Lanifibranor is also shown to prevent worsening fibrosis.
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 ofparacetamolin people with compensated cirrhosis; it is thus considered a safe analgesic for said individuals.
Vaccination againsthepatitis Aandhepatitis Bis recommended early in the course of illness due to decline in effectiveness of the vaccines with decompensation.
Treating the cause of cirrhosis prevents further damage; for example, giving oral antivirals such asentecavirandtenofovirwhere 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.
People with cirrhosis or liver damage are often advised to avoid drugs that could further harm the liver.These include several drugs such asanti-depressants, certain antibiotics, andNSAIDs(like ibuprofen).These agents arehepatotoxicas they aremetabolizedby 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.
According to a 2018 systematic review based on studies that implemented 8 to 14 week-longexerciseprograms, 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.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.
If complications cannot be controlled or when the liver ceases functioning,liver transplantationis 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.In the United States, theMELD scoreis used to prioritize patients for transplantation.Transplantation necessitates the use of immune suppressants (ciclosporinortacrolimus).
Manifestations ofdecompensationin cirrhosis includegastrointestinal bleeding,hepatic encephalopathy,jaundiceorascites. In patients with previously stable cirrhosis, decompensation may occur due to various causes, such asconstipation,infection(of any source), increased alcohol intake,medication, bleeding fromesophageal varicesor dehydration. It may take the form of any of the complications of cirrhosis listed below.
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,laxativesorenemas,thiamineand occasionallysteroids,acetylcysteineandpentoxifylline.Administration ofsalineis 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 careis 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.
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.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 resuscitatedecisions and life support, and potentiallyhospice.Despite proven benefit, people with cirrhosis are rarely referred to palliative care.
Cirrhosis is known to cause immune dysfunction in numerous ways. It impedes the immune system from working normally.
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.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).
TheAmerican Gastroenterological Association(AGA) provided recommendations in 2021 in regards tocoagulopathymanagement of cirrhotic patients in certain scenarios.
Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention).Diureticsmay 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.
Where salt restriction and the use of diuretics are ineffective thenparacentesismay be the preferred option.This procedure requires the insertion of a plastic tube into the peritoneal cavity.Human serum albuminsolution 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.
For portal hypertension, nonselectivebeta blockerssuch aspropranololornadololare 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 transplantationor as a palliative measure.Balloon-occluded retrograde transvenous obliteration can be used to treat gastric variceal bleeding.
Gastroscopy(endoscopic examinationof the esophagus, stomach, andduodenum) is performed in cases of established cirrhosis. If esophageal varices are found, prophylactic local therapy may be applied such assclerotherapyor banding, andbeta blockersmay be used.
Hepatic encephalopathyis a potential complication of cirrhosis.It may lead to functional neurological impairment ranging from mild confusion tocoma.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.
Most pharmaceutical approaches to treating hepatic encephalopathy focus on reducing ammonia levels.Per 2014 guidelines,the first-line treatment involves the use oflactulose, a non-absorbable disaccharide which decreases thepHlevel 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.Rifaximin, an antibiotic that inhibits the function of ammonia-producing bacteria in the gastrointestinal tract,is recommended for use in combination with lactulose as prophylaxis against recurrent episodes of hepatic encephalopathy.
In addition to pharmacotherapy, providing proper hydration and nutritional support is also essential.Appropriate quantities of protein uptake is encouraged.Several factors may precipitate hepatic encephalopathy, which include alcohol use, excess protein, gastrointestinal bleeding, infection, constipation, and vomiting/diarrhea.Drugs such as benzodiazepines, diuretics, or narcotics can also precipitate encephalopathic events.A low protein diet is recommended withgastrointestinal bleeding.
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.The median survival after the development of hepatic encephalopathy is 0.9 years.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).
Hepatorenal syndromeis a serious complication of end-stage cirrhosis when kidney damage is also involved.The annual risk of developing hepatorenal syndrome in those with cirrhosis is 8% and once the syndrome develops the median survival is 2 weeks.
Portal hypertensive gastropathyrefers to changes in themucosaof thestomachin people with portal hypertension, and is associated with cirrhosis severity.
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).Moreover, infections in cirrhosis are major triggers for other complications (ascites, variceal bleeding, hepatic encephalopathy, organ failures, death).
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).
Cirrhosis associated immune dysfunction is caused by reducedcomplementcomponent synthesis in the liver includingC3,C4and reduced total complement activity (CH50).The complement system is a part of theinnate immune systemand 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.Cirrhosis is also associated with reducedKupfer cellfunction, further increasing the risk for infections. Kupfer cells are residentmacrophagesin the liver which help to destroy pathogens.
Extrinsic factors may also increase the risk of infection in those with cirrhosis, includingproton pump inhibitoruse, alcohol use,frailty, antibiotic overuse, and hospitalizations or invasive procedures (which increase the risk of bacterial translocation to other areas of the body).
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. difficilecolitis (2.4-4%).It is estimated that 3.5% of people with cirrhosis and ascites may have asymptomatic spontaneous bacterial peritonitis.
The mortality rate for infections in those with cirrhosis is higher than that of the general population. In those with cirrhosis and severe infections withsepsisthe mortality rate is greater than 50% and in those withseptic shock, the mortality rate is 65%.
Hepatocellular carcinomais the most common primaryliver cancer, and the most common cause of death in people with cirrhosis.Screeningusing anultrasoundwith or without cancer markers such asalpha-fetoproteincan detect this cancer and is often carried out for early signs which has been shown to improve outcomes.
Each year, approximately one million deaths are due to complications of cirrhosis, making cirrhosis the 11th most common cause of death globally.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.
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.Cirrhosis is more common in men than in women.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.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.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.
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.While the clinical entity was known before,René Laennecgave it this name in an 1819 paper.