Cirrhosis Blog

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion. The liver is necessary for survival; there is currently no way to compensate for the absence of liver function long term, although liver dialysis can be used short term.

This organ plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, hormone production, and detoxification. It lies below the diaphragm in the abdominal-pelvic region of the abdomen. It produces bile, an alkaline compound which aids in digestion via the emulsification of lipids. The liver’s highly specialized tissues regulate a wide variety of high-volume biochemical reactions, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital functions

Some of the following signs and symptoms may occur in the presence of cirrhosis or as a result of the complications of cirrhosis. Many are nonspecific and may occur in other diseases and do not necessarily point to cirrhosis. Likewise, the absence of any does not rule out the possibility of cirrhosis.

* Spider angiomata or spider nevi. Vascular lesions consisting of a central arteriole surrounded by many smaller vessels due to an increase in estradiol. These occur in about 1/3 of cases.
* Palmar erythema. Exaggerations of normal speckled mottling of the palm, due to altered sex hormone metabolism.
* Nail changes.
o Muehrcke’s nails – paired horizontal bands separated by normal color due to hypoalbuminemia (inadequate production of albumin).
o Terry’s nails – proximal two thirds of the nail plate appears white with distal one-third red, also due to hypoalbuminemia
o Clubbing – angle between the nail plate and proximal nail fold > 180 degrees
* Hypertrophic osteoarthropathy. Chronic proliferative periostitis of the long bones that can cause considerable pain.
* Dupuytren’s contracture. Thickening and shortening of palmar fascia that leads to flexion deformities of the fingers. Thought to be due to fibroblastic proliferation and disorderly collagen deposition. It is relatively common (33% of patients).
* Gynecomastia. Benign proliferation of glandular tissue of male breasts presenting with a rubbery or firm mass extending concentrically from the nipples. This is due to increased estradiol and can occur in up to 66% of patients.
* Hypogonadism. Manifested as impotence, infertility, loss of sexual drive, and testicular atrophy due to primary gonadal injury or suppression of hypothalamic or pituitary function.
* Liver size. Can be enlarged, normal, or shrunken.
* Splenomegaly (increase in size of the spleen). Due to congestion of the red pulp as a result of portal hypertension.
* Ascites. Accumulation of fluid in the peritoneal cavity giving rise to flank dullness (needs about 1500 mL to detect flank dullness). It may be associated with hydrocele and penile flomation (swelling of the penile shaft)[citation needed] in men.
* Caput medusa. In portal hypertension, the umbilical vein may open. Blood from the portal venous system may be shunted through the periumbilical veins into the umbilical vein and ultimately to the abdominal wall veins, manifesting as caput medusa.
* Cruveilhier-Baumgarten murmur. Venous hum heard in epigastric region (on examination by stethoscope) due to collateral connections between portal system and the remnant of the umbilical vein in portal hypertension.
* Fetor hepaticus. Musty odor in breath due to increased dimethyl sulfide.
* Jaundice. Yellow discoloring of the skin, eye, and mucus membranes due to increased bilirubin (at least 2–3 mg/dL or 30 mmol/L). Urine may also appear dark.
* Asterixis. Bilateral asynchronous flapping of outstretched, dorsiflexed hands seen in patients with hepatic encephalopathy.
* Other. Weakness, fatigue, anorexia, weight loss.

Complications

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.

* Bruising and bleeding due to decreased production of coagulation factors.
* Jaundice due to decreased processing of bilirubin.
* Itching (pruritus) due to bile salts products deposited in the skin.
* Hepatic encephalopathy – the liver does not clear ammonia and related nitrogenous substances from the blood, which are carried to the brain, affecting cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
* Sensitivity to medication due to decreased metabolism of the active compounds.
* Hepatocellular carcinoma is primary liver cancer, a frequent complication of cirrhosis. It has a high mortality rate.
* Portal hypertension – blood normally carried from the intestines and spleen through the hepatic portal vein flows more slowly and the pressure increases; this leads to the following complications:
o Ascites – fluid leaks through the vasculature into the abdominal cavity.
o Esophageal varices – collateral portal blood flow through vessels in the stomach and esophagus. These blood vessels may become enlarged and are more likely to burst.
* Problems in other organs.
o Cirrhosis can cause immune system dysfunction, leading to infection. Signs and symptoms of infection may be aspecific are more difficult to recognize (e.g. worsening encephalopathy but no fever).
o Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines (spontaneous bacterial peritonitis).
o Hepatorenal syndrome – insufficient blood supply to the kidneys, causing acute renal failure. This complication has a very high mortality (over 50%).
o Hepatopulmonary syndrome – blood bypassing the normal lung circulation (shunting), leading to cyanosis and dyspnea (shortness of breath), characteristically worse on sitting up.
o Portopulmonary hypertension – increased blood pressure over the lungs as a consequence of portal hypertension.

Cirrhosis (pronounced /sɪˈroʊsɪs/, si-ROH-sis) is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrous scar tissue as well as regenerative nodules (lumps that occur as a result of a process in which damaged tissue is regenerated), leading to progressive loss of liver function. Cirrhosis is most commonly caused by alcoholism, hepatitis B and C, and fatty liver disease but has many other possible causes. Some cases are idiopathic, i.e., of unknown cause.

Ascites (fluid retention in the abdominal cavity) is the most common complication of cirrhosis and is associated with a poor quality of life, increased risk of infection, and a poor long-term outcome. Other potentially life-threatening complications are hepatic encephalopathy (confusion and coma) and bleeding from esophageal varices. Cirrhosis is generally irreversible once it occurs, and treatment generally focuses on preventing progression and complications. In advanced stages of cirrhosis the only option is a liver transplant.

The word “cirrhosis” derives from Greek κίρῥος, meaning tawny (the orange-yellow colour of the diseased liver). While the clinical entity was known before, it was René Laennec who gave it the name “cirrhosis” in his 1819 work in which he also describes the stethoscope.

Rishe E, Azarm A, Bergasa NV.
Department of Medicine, Beth Israel Medical Center.

The perception of itch in primary biliary cirrhosis (PBC) is not characterized. Patients with primary biliary cirrhosis who were members of the PBCers Organization were invited to participate in an on-line survey addressing certain characteristics of their itch. Patients used their own words in the questions that asked for descriptions. A total of 238 subjects responded to the survey; of these, 231 were women, and 165 (69%) reported itch. One hundred and twenty-four patients from the 165 (75%) reported that itch preceded the diagnosis of primary biliary cirrhosis. A total of 58 from 164 (35%) respondents described their itch as “bugs crawling”. Fifty-seven of 88 (64.7%) subjects reported that something cool relieved their itch, and 69 of 112 (61.6%) reported that heat worsened it. One hundred and seven of 164 (65.2%) respondents reported that the itch was worse at night. The most commonly prescribed medications were antihistamines and cholestyramine, and the most common type of medication reported as being associated with relief was antihistamine drugs. There was no systematic approach to the evaluation and treatment of itch in patients with primary biliary cirrhosis. Education on the subject of itch in primary biliary cirrhosis is warranted.

Møller S, Henriksen JH.
Department of Clinical Physiology, 239, Hvidovre Hospital, DK-2650 Copenhagen, Denmark. soeren.moeller@hvh.regionh.dk

Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis without adequate plasma volume expansion, transjugular intrahepatic portosystemic shunt (TIPS) insertion, peritoneovenous shunting and surgery. Cardiac failure is an important cause of mortality after liver transplantation, but improved liver function has also been shown to reverse the cardiac abnormalities. No specific treatment can be recommended, and cardiac failure should be treated as in non-cirrhotic patients with sodium restriction, diuretics, and oxygen therapy when necessary. Special care should be taken with the use of ACE inhibitors and angiotensin antagonists in these patients. The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed.

Castellares C, Barreiro P, Martín-Carbonero L, Labarga P, Vispo ME, Casado R, Galindo L, García-Gascó P, García-Samaniego J, Soriano V.
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.

Liver disease is frequently seen in HIV+ patients as a result of coinfection with hepatitis B (HBV) or C (HCV) viruses, alcohol abuse and/or exposure to hepatotoxic drugs. The aim of this study was to assess the prevalence of liver cirrhosis, its main causes and clinical presentation in HIV+ patients. Observational, cross-sectional, retrospective study of all HIV+ individuals followed at one reference HIV outpatient clinic in Madrid. Liver fibrosis was measured in all cases using transient elastometry (FibroScan((R))). All 2168 HIV+ patients on regular follow-up (76% males, 46% injecting drug users) were successfully examined by FibroScan((R)) between October 2004 and August 2006. Liver cirrhosis was recognized in 181 (overall prevalence, 8.3%), and the main aetiologies were HCV, 82.3%; HBV, 1.6%; dual HBV/HCV, 2.8%; and triple HBV/HCV/ hepatitis delta virus (HDV) infection, 6.6%. The prevalence of cirrhosis differed among patients with distinct chronic viral hepatitis: HCV, 19.2%; HBV, 6.1%; HBV/HCV, 41.7%; and HBV/HCV/HDV, 66.7%. In 12 patients with cirrhosis (6.7%), no definite aetiology was recognized. Overall, cirrhotics had lower mean CD4 counts than noncirrhotics (408 vs 528 cells/muL respectively; P = 0.02), despite similar proportion of subjects with undetectable viraemia on highly active antiretroviral therapy. Clinical manifestations of liver cirrhosis were: splenomegaly, 61.5%; oesophageal varices, 59.8%; ascites, 22.6%; encephalopathy, 12.1%; and variceal bleeding, 6.1%. Liver cirrhosis and hepatic decompensation events are relatively frequent in HIV+ individuals. Chronic HCV and alcohol abuse, but not chronic HBV, play a major role. Transient elastometry may allow the identification of a significant number of HIV+ individuals with asymptomatic liver cirrhosis.

Gundling F, Gülberg V, Schepp W, Mann J.
Klinik für Gastroenterologie, Hepatologie und Gastroenterologische Onkologie, Klinikum Bogenhausen, Städtisches Klinikum München GmbH, München. Felix.Gundling@gmx.de

A lot of patients suffering from liver cirrhosis show a decreased renal perfusion and glomerular filtration rate. An impaired renal function is the result of complex e.g. hemodynamic disturbances, resulting of the chronic liver disease. This explains its disposition to renal dysfunction and the higher incidence of acute renal failure in liver cirrhosis. In the case of renal failure hepatorenal syndrome, apart from prerenal, renal and postrenal causes, should be included in the differential diagnosis especially when signs of portal hypertension are apparent regarding its high mortalityand fatal prognosis requiring an immediate therapeutically approach. Special attention must be due to preventive strategies to avoid renal deterioration. This includes simple steps e.g. a careful election of medication but also an adequate therapy of infection-associated complications in patients with liver cirrhosis.

Martín-Llahí M, Pépin MN, Guevara M, Díaz F, Torre A, Monescillo A, Soriano G, Terra C, Fábrega E, Arroyo V, Rodés J, Ginès P; TAHRS Investigators.
Liver Unit, Hospital Clínic, University of Barcelona School of Medicine, Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Centro de Investigacíon Biomedica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.

BACKGROUND & AIMS: Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome. METHODS: Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1-2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20-40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. RESULTS: Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone (P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases. CONCLUSIONS: As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.

Veldt BJ, Chen W, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, de Knegt RJ, Zeuzem S, Manns MP, Hansen BE, Schalm SW, Janssen HL.
Erasmus MC University Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, the Netherlands.

Recent studies suggest that diabetes mellitus increases the risk of developing hepatocellular carcinoma (HCC). The aim of this study is to quantify the risk of HCC among patients with both diabetes mellitus and hepatitis C in a large cohort of patients with chronic hepatitis C and advanced fibrosis. We included 541 patients of whom 85 (16%) had diabetes mellitus. The median age at inclusion was 50 years. The prevalence of diabetes mellitus was 10.5% for patients with Ishak fibrosis score 4, 12.5% for Ishak score 5, and 19.1% for Ishak score 6. Multiple logistic regression analysis showed an increased risk of diabetes mellitus for patients with an elevated body mass index (BMI) (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.00-1.11; P = 0.060) and a decreased risk of diabetes mellitus for patients with higher serum albumin levels (OR, 0.81; 95% CI, 0.63-1.04; P = 0.095). During a median follow-up of 4.0 years (interquartile range, 2.0-6.7), 11 patients (13%) with diabetes mellitus versus 27 patients (5.9%) without diabetes mellitus developed HCC, the 5-year occurrence of HCC being 11.4% (95% CI, 3.0-19.8) and 5.0% (95% CI, 2.2-7.8), respectively (P = 0.013). Multivariate Cox regression analysis of patients with Ishak 6 cirrhosis showed that diabetes mellitus was independently associated with the development of HCC (hazard ratio, 3.28; 95% CI, 1.35-7.97; P = 0.009). CONCLUSION: For patients with chronic hepatitis C and advanced cirrhosis, diabetes mellitus increases the risk of developing HCC.