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and Prevention
S. PAUL STARR, MD, and DANIEL RAINES, MD, Louisiana State University Health Sciences
Center School of Medicine at New Orleans, New Orleans, Louisiana
Cirrhosis is the 12th leading cause of death in the United States. It accounted for 29,165 deaths in 2007, with a mor-
tality rate of 9.7 per 100,000 persons. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis,
although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary care physicians
share responsibility with specialists in managing the most common complications of the disease, screening for hepa-
tocellular carcinoma, and preparing patients for referral to a transplant center. Patients with cirrhosis should be
screened for hepatocellular carcinoma with imaging studies every six
to 12 months. Causes of hepatic encephalopathy include constipation,
infection, gastrointestinal bleeding, certain medications, electrolyte
imbalances, and noncompliance with medical therapy. These should
be sought and managed before instituting the use of lactulose or
rifaximin, which is aimed at reducing serum ammonia levels. Ascites
should be treated initially with salt restriction and diuresis. Patients
with acute episodes of gastrointestinal bleeding should be monitored
in an intensive care unit, and should have endoscopy performed
C
irrhosis is the 12th leading cause nodular liver; splenomegaly; ascites; dilated
▲
Patient information:
A handout on cirrhosis and of death in the United States. It abdominal wall veins; spider angiomata;
liver damage, written by
the authors of this article,
accounted for 29,165 deaths in palmar erythema; peripheral edema; and
is provided on page 1360. 2007, with a mortality rate of 9.7 asterixis. Patients may be diagnosed inci-
per 100,000 persons.1 Cirrhosis is a major dentally through laboratory findings.
risk factor for the development of hepatocel- Elevated hepatic transaminase levels (e.g.,
lular carcinoma; the incidence of this malig- alanine transaminase, aspartate transami-
nancy tripled from 1975 to 2005.2 nase) are suggestive of ongoing hepatocyte
injury; however, these may be normal with
Clinical Presentation advanced liver disease. Elevation of serum
The clinical features of cirrhosis have been prothrombin time or International Normal-
known since ancient times. The Ebers papy- ized Ratio (INR) may indicate a decreased
rus written around 2600 BC describes asci- ability of the liver to synthesize clotting
tes, which was known to be associated with factors. Thrombocytopenia may indicate
a “hardness of the liver” and excessive alco- splenic sequestration. The total bilirubin
hol consumption.3 Signs and symptoms of level may also be elevated.
decompensated cirrhosis include abdomi- Alcohol abuse and viral hepatitis are the
nal swelling, jaundice, and gastrointesti- most common causes of cirrhosis, although
nal bleeding. Sensitivity of these findings nonalcoholic fatty liver disease is emerg-
varies from 31 to 96 percent.4 Findings on ing as an increasingly important cause.5 A
physical examination include a contracted, more detailed list of underlying etiologies
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Cirrhosis
Evidence
Clinical recommendation rating References
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.
org/afpsort.xml.
1354 American Family Physician www.aafp.org/afp Volume 84, Number 12 ◆ December 15, 2011
Cirrhosis
Yes
Consider referral to ≥ 15 or < 15 with Model for End-stage Stable?
a transplant center complications Liver Disease score
No
< 15
Antibiotic therapy
December 15, 2011 ◆ Volume 84, Number 12 www.aafp.org/afp American Family Physician 1355
Cirrhosis
1356 American Family Physician www.aafp.org/afp Volume 84, Number 12 ◆ December 15, 2011
Cirrhosis
Survival (%)
22 60
21
20 40
19
18 20
17
16 0
15 0 10 20 30 40 50
MELD score points
14 MELD score
13
12
11
MELD score = 6.43 + 3.78 Ln(serum total bilirubin [mg per dL]) +
10 11.2 Ln(INR) + 9.57 Ln(serum creatinine [mg per dL])
9
8 Child-Turcotte-Pugh score
7 A B C
6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
5
Laboratory test +1 +2 +3
4
Total bilirubin <2 2 to 3 >3
3
Serum albumin > 35 28 to 35 < 28
2
INR < 1.7 1.71 to 2.20 > 2.20
1 Ascites None Mild Severe
0 Hepatic None Grade I to II Grade III to IV
0 1 2 3 4 5 6 7 8 9 10 encephalopathy
Laboratory value
Figure 2. The Model for End-stage Liver Disease (MELD) score was originally designed to predict mortality in patients
awaiting transplant; however, it is often used to offer information about prognosis. The MELD score is calculated
by adding together the natural logarithms of the serum concentrations of bilirubin and creatinine and the Inter-
national Normalized Ratio (INR). Alternatively this nomogram may be used by looking up the laboratory value on
the horizontal axis and going up to the colored lines (green for bilirubin, yellow for creatinine, and red for INR).
The number of points can be read on the vertical axis, and the three numbers are added together with a correc-
tion factor of 6.43. For example, a total bilirubin level of 4 mg per dL (68.42 µmol per L) corresponds to five points.
The mortality can then be estimated by reading the smaller graph in the upper right-hand corner (for example, a
score of 40 corresponds to a less than 20 percent survival rate). The MELD score roughly corresponds to the Child-
Turcotte-Pugh score, which is found in the bottom right-hand corner.
products, and portal venous blood can bypass the liver medical record.8 In patients with active encephalopathy,
through collateral circulation (such as varices) or a med- reversible factors should be sought and managed, includ-
ically constructed shunt. ing constipation, noncompliance with medical therapy,
The symptoms of hepatic encephalopathy can be sub- infection (i.e., spontaneous bacterial peritonitis), elec-
tle; the condition should be considered in any patient trolyte imbalances, gastrointestinal bleeding, and use
with cirrhosis. Severity of hepatic encephalopathy of benzodiazepines.8 Paracentesis should be performed
should be graded (Table 317) and documented on the to rule out peritonitis as a cause of the encephalopathy.
December 15, 2011 ◆ Volume 84, Number 12 www.aafp.org/afp American Family Physician 1357
Cirrhosis
1358 American Family Physician www.aafp.org/afp Volume 84, Number 12 ◆ December 15, 2011
Cirrhosis
randomized controlled trials, clinical trials, and reviews. Also searched 12. Trevisani F, Santi V, Gramenzi A, et al.; Italian Liver Cancer Group.
were the National Guideline Clearinghouse, National Cancer Institute Surveillance for early diagnosis of hepatocellular carcinoma: is it effec-
Clinical Trials Planning Meeting, U.S. Preventive Services Task Force, and tive in intermediate/advanced cirrhosis? Am J Gastroenterol. 2007;
Cochrane Database. Search date: November 23, 2010. 102(11):2448-2457.
13. Di Martino M, Marin D, Guerrisi A, et al. Intraindividual comparison of
gadoxetate disodium-enhanced MR imaging and 64-section multide-
The Authors tector CT in the detection of hepatocellular carcinoma in patients with
cirrhosis. Radiology. 2010;256(3):806-816.
S. PAUL STARR, MD, is an assistant professor in the Department of Family
14. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the
Medicine at Louisiana State University Health Sciences Center School of treatment of small hepatocellular carcinomas in patients with cirrhosis.
Medicine at New Orleans, and the associate program director of the Loui- N Engl J Med. 1996;334(11):693-699.
siana State University Health Sciences Center Family Medicine Residency
15. Licata G, Tuttolomondo A, Licata A, et al. Clinical trial: high-dose
Program at Ochsner Medical Center in Kenner.
furosemide plus small-volume hypertonic saline solutions vs. repeated
DANIEL RAINES, MD, is an assistant professor in the Department of Medi- paracentesis as treatment of refractory ascites. Aliment Pharmacol Ther.
cine, Section of Gastroenterology at Louisiana State University Health Sci- 2009;30(3):227-235.
ences Center School of Medicine at New Orleans, where he is also acting 16. Garcia-Tsao G, Lim JK. Management and treatment of patients with cir-
chief for the Section of Gastroenterology. rhosis and portal hypertension: recommendations from the Department
of Veterans Affairs Hepatitis C Resource Center Program and the National
Address correspondence to S. Paul Starr, MD, Louisiana State University Hepatitis C Program [published correction appears in Am J Gastroen-
School of Medicine, 200 West Esplanade, Ste. 409, Kenner, LA 70065 terol. 2009;104(7):1894]. Am J Gastroenterol. 2009;104(7):1802-1829.
(e-mail: sstarr@lsuhsc.edu). Reprints are not available from the authors. 17. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Biel AT. Hepatic
encephalopathy—definition, nomenclature, diagnosis, and quantifica-
Author disclosure: No relevant financial affiliations to disclose.
tion: final report of the Working Party at the 11th World Congresses of
Gastroenterology, Vienna, 1998. Hepatology. 2002;335(3):716-721.
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December 15, 2011 ◆ Volume 84, Number 12 www.aafp.org/afp American Family Physician 1359