Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (48 page)

•
Alcohol
(~60–70%): Laennec’s cirrhosis; micronodular •
Viral hepatitis
(~10%): chronic HBV, HCV, HDV infection •
Autoimmune hepatitis
: female, ↑ IgG,
ANA, antismooth muscle Ab •
Metabolic diseases
(~5%): hemochromatosis, Wilson’s disease, ɑ
₁
-AT deficiency •
Biliary tract diseases
(~5%): primary biliary cirrhosis, secondary biliary cirrhosis (calculus, neoplasm, stricture, biliary atresia), primary sclerosing cholangitis •
Vascular diseases:
Budd-Chiari syndrome, R-sided CHF, constrictive pericarditis, sinusoidal obstruction syndrome •
Nonalcoholic fatty liver dis. (NAFLD
, 10–15%) cause of most “cryptogenic cirrhosis”

Clinical manifestations

• Subclinical or may p/w liver dysfunction (jaundice, coagulopathy, encephalopathy) and/or portal HTN (ascites, varices); 35% p/w fever (SBP, acute EtOH); 25% p/w hematemesis
Physical exam

• Liver:
initially
enlarged, palpable (L lobe predom), firm;
eventually
shrunken and nodular • Signs of liver failure: jaundice (bili >2), spider angiomata & palmar erythema (↑ estra-diol), Dupuytren’s contractures, white nail lines (Muehrcke’s lines) & proximal nail beds (Terry’s nails), ↑ parotid & lacrimal glands, gynecomastia, testicular atrophy, asterixis, encephalopathy, fetor hepaticus, clubbing, hypertrophic osteoarthropathy • Signs of portal hypertension: splenomegaly, ascites, dilated superficial abdominal veins (caput medusae), epigastric Cruveilhier-Baumgarten venous hum
Laboratory studies

•
↑ bilirubin
, ↑
PT
(poor correlation w/ bleeding; factor VIII nl as not synthesized by liver), ↓ alb, ± ↑ aminotransferases (AST > ALT if late) and ↑ AΦ (variable), ↓ Na, ↑ γ-glob • Anemia (marrow suppression, hypersplenism, Fe and/or folate defic.), neutropenia (hypersplenism), thrombocytopenia (hypersplenism, ↓ Tpo production by liver, EtOH tox)
Workup

• Abdominal
U/S w/ Doppler:
liver size (↑ L & caudate lobe), r/o HCC, ascites, ✓ patency of portal, splenic and hepatic veins • Assess fibrosis: biomarkers (eg, FibroSURE = panel of 6 markers validated in HCV, ↑ score predictive of fibrosis); U/S or acoustic radiation force impulse or MR elastography • Determine etiology: hepatitis serologies (HBsAg, anti-HBs, anti-HCV), autoimmune hepatitis studies (IgG, ANA, anti–smooth muscle Ab), Fe and Cu studies, ɑ
₁
-AT, AMA • ± Liver bx: percutaneous or transjugular (consider if ascites or coagulopathy) used to dx etiology and presence of cirrhosis
Ascites
(see “Ascites” for details on dx eval;
Hep
2009;29:2087)
• Due to portal HTN (defined as hepatic venous pressure gradient [HVPG] >5 mmHg) • Develops in 60% w/in 10 y; ~50% mortality at 5 y • Treatment (
Am J Gastro
2009;104:1802): ↓ Na intake (1–2 g/d); free H
₂
O restrict if Na <125

Diuretics
: goal 1 L/d; urine Na/K >1 implies effective aldo block; spironolactone ± furosemide in 5:2 ratio (eg, 100 & 40 mg daily); ↑ doses in proportion

 NSAID as interferes w/ diuretic action (common cause of refractory ascites)

• Refractory ascites (
Clin Gas Hep
2011;9:931): seen in 5–10% of Pts; 2-y survival is 25%

Diuretic resistant on 2g Na diet or diuretic-induced complic (Cr >2, Na <125, ↑ or ↓ K, enceph)

Large-volume paracentesis (LVP)
; if >5 L, replace w/ 8–10 g/L of alb → ↓ risk of paracentesis-induced circ. dysfxn (AKI & lyte abnl) & ? ↓ mortality (
Hep
2012;55:1172)

Beware LVP if SBP as ↑ risk of ARF → consider dx tap to r/o SBP first

Transjugular intrahepatic portosystemic shunt (TIPS)
(
Clin Gas Hep
2011;9:936)

↓ ascites in 75%, ↑ CrCl, ↑ enceph, survival benefit over LVP remains controversial

Contraindic: grade II enceph, CHF or pulm HTN, active infxn or biliary obstruction

Complications include
technical
: bleeding, fistula;
related to stent
: thrombosis w/in 24 h rare, 1 y patency w/ coated stents ~80%, infxn (endotipsitis);
shunting
: new or ↑ enceph in 20–30%, hemolysis (
Hep
2010;51:306)

• Hepatic hydrothorax: 2° diaphragmatic defect; often unilateral, R > L, ± ascites

Treatment:  chest tube due to ↑ complications; Rx same as ascites

Spont
empyema
can occur (even w/o SBP) → dx thoracentesis; Rx same as for SBP

Spontaneous bacterial peritonitis
(SBP; see “Ascites” for details;
J Hep
2010;53:397)
• Develops in ~20%; 20% mortality; risk factors: AFTP <1 g/dL, hx of SBP, current GIB

• Can p/w encephalopathy, abd pain, fever,
but often
(
25%
)
asx
; consider paracentesis in all hospitalized cirrhotics w/ ascites • Micro: 70% GNR (
E. coli
,
Klebs
), 30% GPC (
Enterococcus
,
S. pneumo
), nosocomial (fungi,
Pseud
); ~40% culture

• Rx: 3rd gen. ceph (eg, cefotaxime 4g/d total dose)
or
amox/clav × 5 d, if  enceph/AKI can use FQ (cipro/oflox) but avoid if already on for ppx or in ↑ FQ resist. areas IV albumin 1.5 g/kg at time of dx & 1 g/kg on day 3 → ↑ survival (
NEJM
1999;341:403) If not improving, repeat paracentesis at 48 h: ~25% ↓ PMN count = Rx success • Ppx: if h/o SBP or AFTP <1.5 + Na <130, Cr >1.2 or Child-Pugh B (
Am J Gastro
2009;4:993) norfloxacin 400 mg PO qd or Bactrim DS qd
Gastroesophageal varices
±
UGIB
(see also “GIB”;
NEJM
2010;362:823)
• Present in 60% of decompensated cirrhotics; incidence of bleeding is 24% by 2 y; bleeding risk if HVPG >12 mmHg; screen all cirrhotics at time of dx • 1° prevention of UGIB: med-to-large varices or “red wale” marks or Child-Pugh B or C

nonselective b-blockers
: ~50% ↓ risk of bleeding ± ↓ mortality; typically nadolol or propranolol (consider carvedilol if systemic HTN as ɑ1 blockade ↓ intrahepatic vasc resist.;
Hep
2010;54:2214); titrate to 25% ↓ HR; EGD  req. to document improvement

endoscopic variceal ligation
(EVL): ↓ bleeding & death
bB (
Ann Hep
2012;11:369) q1–2wk until gone → survey EGD at 3 mo → q6–12mo; adding bB only ↑ side effects

bB vs. EBL: choice based on Pt/physician preference, bB often 1st (
Hep
2008;47:1764)

• 2° prevention: for all Pts after 1st bleed b/c
50% rebleed &
30% mortality bB + EBL > either alone (
Annals
2008;149:109); TIPS if refractory or consider in Child-Pugh B or C w/in 72 h of admission for esoph variceal bleed (↑ 1-y survival;
NEJM
2010;362:2370)
Portosystemic (hepatic) encephalopathy (PSE)
(
Clin Gas Hep
2012;10:1208)
• Pathogenesis: failure of liver to detoxify NH
₃
+ other substances (eg, ADMA;
J Hep
2013;58:38) that cause cerebral edema, ↓ O
₂
consumption, ↑ ROS → brain dysfxn • Precipitants: ↑ dietary protein, constip., GIB, med nonadherence, infxn, azotemia, ↓ K, Δ volume/water, hypoxia, HCC, portosystemic shunt, meds, PVT

• Stages: (1) confusion; (2) drowsiness; (3) stupor; (4) coma • Dx: asterixis can be seen; NH
₃
poor Se for dx & monitoring Rx; remains a
clinical dx
• Treatment: identify/correct precipitants, restrict dietary protein acutely (60–80 g/d), lactulose (acidification of colon: NH
₃
→ NH
₄
⁺
) w/ goal 2–4 stools/d ± rifaximin 550 mg bid (↓ gut bacteria → ↓ NH
₃
prod); correct zinc deficiency • 2° prevention: lactulose ± rifaximin 550 bid (
Gastro
2009;137:885;
NEJM
2010;362:1071)
Hepatorenal syndrome (HRS)
(
NEJM
2009;361:1279;
Crit Care
2012;16:R23(1))
• Pathophys: renal vasoconstriction w/ ↓ renal blood flow; kidney histologically nl • Criteria: (1) cirrhosis w/ ascites; (2) Cr >1.5 mg/dL; (3)  improvement in Cr (to ≤1.5) after d/c diuretic & volume expansion (1 g/kg/d of albumin × 2 d); (4)  shock (prerenal azotemia/ATN); (5)  nephrotoxic meds; (6)  organic kidney dis (eg, GN) or obstruction

Type I
: Cr >2.5 or 1.5× baseline in <2 wk; usually occurs in severe liver failure, often following precipitating event (see later); median survival 2 wk

Type II
: more indolent course, median survival 6 mo; liver failure present < in type I

• Precipitants: GIB, overdiuresis, infection, paracentesis, drugs (aminoglycosides, NSAIDs) • Rx: Type 1: octreotide (100–200 mcg SC tid) + midodrine (7.5–12.5 mg PO tid, titrate to ↑ MAP 15 mmHg) + 20–40 g/d albumin or terlipressin + albumin (
Hep
2010;51:576); definitive Rx = liver tx. Type 2 w/ refractory ascites → TIPS.

Hepatocellular carcinoma (HCC)
(
Hep
2011;53:1020;
Lancet
2012;379:1245)
• Epi: worldwide, 6th most prevalent cancer, 3rd most frequent cancer-related death, 80% of cases due to HCV/HBV cirrhosis, in which annual risk of HCC is ~3–8% (
Gastro
2012;142:1264). ↑’d risk w/ cirrhosis of any type but esp. w/ viral, HFE, PBC, ?ɑ1-AT.