Management of liver cirrhosis between primary care and specialists

Table 1 Diagnostic tests, suggested etiology, and current treatment for the most frequent forms of liver cirrhosis in adult patients

Abnormal test(s)	Etiology	Treatment
γGT (high), MCV (high)	Alcohol	Abstinence
HBsAg, HBV-DNA, HBc-IgM, HDV-RNA (positivity)	HBV + Delta virus infection	Interferon α-2b, nucleoside (Lamivudine, Telbivudine, Entecavir) and nucleotide (Adefovir, Tenofovir) analogues
HCV-RNA (positivity)	HCV infection	Interferon plus ribavirin
γGT (high), alkaline phosphatase (high), AMA (positivity)	Primary biliary cirrhosis	Ursodeoxycholate
ANA, ASMA, LKM (positivity)	Autoimmune hepatitis	Prednisone, azathioprine
Ferritin (high), transferring saturation index (> 45%), liver iron content (high), HFE gene mutation for hereditary hemochromatosis (C282Y, H63D)	Hemochromatosis	Phlebotomy, deferoxamine
Ceruloplasmin (low), serum (low) and 24 h urine copper excretion (high)	Wilson’s disease	D-penicillamine, zinc
HDL-cholesterol (low), glucose (high), triglycerides (high)	NAFLD/NASH	Low caloric diet, exercise, drugs lowering insulin-resistance

AMA: Anti-mitochondrial antibody; ANA: Antinuclear antibody; ASMA: Anti-smooth-muscle antibody; γGT: γ- glutamyltransferase; HBV-DNA: Hepatitis B virus DNA; HCV-RNA: Hepatitis C virus RNA; HBsAg: Hepatitis B surface antigen; HDL: High density lipoprotein; HDV-RNA: Hepatitis delta virus RNA; LKM: Liver kidney microsomes; MCV: Mean corpuscular volume; NASH: Nonalcoholic steatohepatitis; NAFLD: Nonalcoholic fatty liver disease.

Table 2 Child-Pugh scoring system for liver cirrhosis and related indication priority for transplantation[20]

Score	1	2	3
Bilirubin (mg/dL)	< 2	2-3	> 3
Prothrombin time (INR)	< 4 sec. (< 1.7)	4-6 sec. (1.7-2.3)	> 6 sec. (> 2.3)
Albumin (g/dL)	> 3.5	3.5-2.8	< 2.8
Ascites	Absent	Mild	Severe
Encephalopathy	Absent	Mild	Severe

The Child-Pugh score is given by the sum of the score (1 to 3) of each of the five parameters. A score of 6 or lower defines the patient as class A, 7 to 9 as class B, and 10 or higher as class C.

Table 3 Current indications and contraindications to orthotopic liver transplantation in adult patients with liver cirrhosis

Indications	Contraindications
Advanced chronic liver failure	Relative
Child-Pugh score > 7	HIV seropositivity
Qualifying MELD score	Methadone dependence
	Stage 3 hepatocellular carcinoma
Acute liver failure	Absolute
Drug, toxins or virus induced fulminant hepatitis	Extrahepatic malignant disease
	AIDS
	Cholangiocarcinoma
	Severe, uncontrolled systemic infection
	Multiorgan failure
	Advanced cardiopulmonary disease
	Active substance abuse
General
No alternative available treatment
No absolute contraindications
Willingness to comply with follow-up care and family assistance

AIDS: Acquired immunodeficiency syndrome; HIV: Human immunodeficiency virus; MELD: Model for end stage liver disease.

Table 4 Standard objectives for an efficient out clinic care of cirrhotic patients

1 Early diagnosis of chronic liver disease. Identification of etiology

2   Identification of patients with chronic liver disease at risk of cirrhosis

3 Evaluation of patient’s general health status

4 Act on etiologic factors and on factors favoring disease progression. Identify treatment end-points and place the patient within his family and social setting

5 Promote family and cohabitants’ participation to primary prevention for infective forms (health education), secondary prevention for inherited or metabolic disorders, support and surveillance for toxic forms (alcohol)

6 Suggest health-dietetic measures and therapeutic remedies

7 Check parameters of effectiveness and control side effects of specific treatments (antiviral, phlebotomy, immune-depressants, β-blockers, etc.)

8 Identify and treat associated conditions (diabetes, osteoporosis, malnutrition, etc.)

9 Avoid administration of hepatotoxic drugs, drugs promoting renal sodium retention and central nervous system depressants

10 Promote vaccination against flu and pneumonia, including transplanted patients, and against hepatitis A and B virus

11  Supervise for complications by promoting clinical, biochemical and instrumental follow-up

12  Assist specialists in identifying candidates for liver transplantation

13  Assist the patient requiring legal problems

Table 5 Features of home assistance in patients with liver cirrhosis

Advantages

Decreased number of hospitalization and re-admissions

Decreased costs of treatments

Assist the patient within his familiar comfort

Criteria of eligibility

Identification of a clinical status allowing home stay

Identification of priority criteria

Presence of a valid family support or of an active aid system

Selection criteria

Use the Karnofsky Performance Status1 for patients with decompensated liver cirrhosis and limited self-sufficiency (set to < 50%)

¹The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment. This scale is often used in the primary care setting to assess the prognosis in individual patients and to decide a treatment; the lower the score, the worse the survival.

Table 6 Key messages for best management of cirrhotic patients

Statement	Evidencelevel
1 A compensated liver cirrhosis is suspected with abnormal liver function tests, low platelets count, and prolonged prothrombin time[63]	III
2 Ultrasonography is a reliable, non-invasive, fast, and cost-effective test working as a first-line tool for diagnosing liver cirrhosis[64]	II-III
3 Child-Pugh and MELD scores assess the prognosis of liver cirrhosis[19,20]	I
4 First-line treatment of patients with cirrhotic ascites includes diuretics and sodium restriction. Anti-aldosterone drugs are given with loop diuretics to increase diuretic response or when renal perfusion is impaired. Dietary salt intake should be restricted to approximately 88 mmol/day (2000 mg/d). Marked salt restriction can expose the risk of hyponatremia[32,37]	I
5 Removal of less than 5 liters of fluid does not appear to have a hemodynamic consequence. For larger paracentesis, albumin (6 to 8 g/L of fluid removed) can be administered. Albumin is indicated in patients with PBS to prevent renal failure, and in patients with hepatorenal syndrome. Albumin can be also used to treat refractory ascites. Its infusion at home is safe and cost-effective[37,65]	II
6 β-blockers (e.g. propranolol or nadolol) are recommended for prophylaxis of variceal bleeding at a dosage titrated to a 25 percent reduction in pulse rate[66]	I
7 Liver transplantation is the only definitive care for patients with major complications (ascites, bleeding, HCC) and/or MELD above 13[1]	I
8 Osteoporosis is an important systemic complication of end-stage liver cirrhosis. Management includes vitamin D and bisphosphonates[53]	II
9 Malnutrition is a negative and independent predictor of survival in patients with liver cirrhosis[67]	II
10 An integrated assistance of patients with liver cirrhosis has a better outcome than the management by generalists/specialists alone[61]	II

LEVEL I : At least one properly conducted RCT, systematic review, or meta-analysis; LEVEL II: Other comparison trials, non-randomized, cohort, case-control, or epidemiologic studies, and preferably more than one study; LEVEL III: Expert opinion or consensus statements (see text for details); MELD: Model for end-stage liver disease.