Systemic abnormalities in liver disease

Table 1 Difference between HPS and PPHTN modified from Rodríguez-Roisin et al[4]

	HPS	PPHTN
Prevalence	11%-32% of patients with liver cirrhosis	2% of patients with portal hypertension
Pathogenesis	Increased intrapulmonary shunting	Unknown
Intrapulmonary vascular dilatations	(+)	(-)
Pulmonary arterial hypertension	(-)	(+)
Symptom	Dyspnea, platypnea	Dyspnea on exertion, syncope, chest pain
Clinical manifestations	Cyanosis	No cyanosis
	Orthodeoxia	Accentuated pulmonary component of IIs
	Spider nevi	Systolic murmur, edema
ECG findings	None	RVH, RBBB, right axis deviation
Arterial blood gas levels	Moderate-to-severe hypoxemia (< 60-80 mmHg)	No/mild hypoxemia
Chest radiography	Normal	Cardiomegaly, hilar enlargement
CEE	Positive finding; left atrial opacification for > 3-6 heart beats after right atrial opacification	Usually negative finding
99mTcMAA shunting index	≥ 6%	< 6%
Pulmonary hemodynamics	Normal/low PVR	Elevated PVR mPAP > 25 mmHg at rest or > 30 mmHg with exercise
OLT	Indicated in severe stages	Only indicated in mild-to-moderate stages

HPS: Hepatopulmonary syndrome; PPHTN: Portopulmonary hypertension; RVH: Right ventricle hypertrophy; IIs: Second heart sound; ECG: Electrocardiography; RBBB: Right bundle-branch block; AaPO₂: Alveolar arterial oxygen gradient; CEE: Contrast-enhanced echocardiography;

^99mTcMAA: Technetium-99m-labelled macroaggregated albumin; PVR: Pulmonary vascular resistance; mPAP: Mean pulmonary artery pressure; OLT: Orthotopic liver transplantation.

Table 2 New diagnostic criteria for hepatorenal syndrome in cirrhosis[146]

Cirrhosis with ascites

Serum creatinine > 133 &mgr;mol/L (1.5 mg/dL)

No improvement of serum creatinine level (decrease to ≤ 133 &mgr;mol/L) after at least 2 d with diuretic withdrawal and volume expansion with albumin. The recommended dose of albumin is 1 g/kg of body weight per day up to a maximum of 100 g/d

Absence of shock

No current or recent treatment with nephrotoxic drugs

Absence of parenchymal kidney disease as indicated by proteinuria > 500 mg/d, microhematuria (> 50 red blood cells per high-power field) and/or abnormal renal ultrasonography

Table 3 Drugs that may need to be administered at reduced doses in patients with liver cirrhosis[187]

Drugs with high first-pass effect	Drugs metabolized mainly by
	CYP 1A2	CYP3A4	CYP2C9
Amitriptyline	Acetaminophen	Quinidine	Diclofenac
Bromocriptine	Caffeine	Amiodarone	Ibuprofen
Diltiazem	Mexiletine	Lidocaine	Mefenamic acid
Flumazenil	(R)-Warfarin	Midazolam	Tolbutamide
Fluorouracil	Imipramine	Diazepam	Phenytoin
Imipramine	Theophylline	Amitriptyline	Phenobarbital
Isosorbide dinitrate	Propranolol	Imipramine	(S)-Warfarin
Labetalol	Tamoxifen	Carbamazepine	Losartan
Lidocaine	Estradiol	(R)-Warfarin	Piroxicam
Morphine		Erythromycin
Nifedipine		Clarithromycin
Pentazocine
Propranolol
Verapamil