inpatient / gastroenterology

Cirrhosis and Decompensations

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If You Remember Nothing Else

The most common etiologies of cirrhosis are EtOH, HCV, NAFLD/NASH. MELD uses Cr, Tbili, INR, and Na to calculate - ranges from 6-40. Decompensations are ascites, SBP, EV, HE, HCC. Common triggers for decompensation include infection, medication non-adherence, constipation, bleeding, and dehydration from diuretic use. All decompensated patients admitted should have a diagnostic paracentesis. SAAG (serum ascites albumin gradient) > 1.1 suggests the etiology of ascites is related to portal hypertension (if there is a big difference, would be more explained by oncotic pressure)

Clinical Pearls

• Cirrhosis is irreversible fibrosis leading to nodules that interfere with hepatic architecture, vasculature, and ultimately function - when liver function is impaired, its considered End-Stage Liver Disease (ESLD)
• Alcohol, HCV/HBV, and NAFLD are the most common causes of cirrhosis
• MELD Score predicts 90d mortality, used to assess for transplant; uses Cr, Tbili, INR, Na; ranges from 6-40 (should use values within last 48 hours); Child-Pugh assesses cirrhosis severity, predicts 1-2y mortality; uses Bilirubin, albumin, INR, ascites, encephalopathy
• A biopsy is the gold standard for diagnosis of cirrhosis, but imaging is often more than enough for diagnosis
• RUQUS can tell us about echogenicity/morphology of the liver, presence and appearance of ascites, vascular patency, the biliary tree morphology, evidence of HCC
• Decompensations are ascites, encephalopathy, and variceal bleeding; SBP, HCC, and varices that don’t bleed are technically not decompensations but whatever
• Ascites is the most common decompensation; from development, there is a 44% 5y mortality
• A majority of complications of cirrhosis are related to portal hypertension (varices, ascites, hydrothorax, HRS) and reduced synthetic function (low albumin and oncotic pressure, immune dysfunction, coagulopathy, portal vein thrombosis)
• Portal hypertension leads to an increase in NO and prostaglandins leading to splanchnic vasodilation - the body increases RAAS and ADH in response leading to Na and water retention; Hyponatremia severity correlates with survival
• SAAG (serum ascites albumin gradient) > 1.1 suggests the etiology of ascites is related to portal hypertension (if there is a big difference, it would be more explained by oncotic pressure)
• 10-30% of patients hospitalized with cirrhosis have SBP; diagnosed with >250 PMN/L; if cultures negative, technically called culture-negative neutrocytic ascites (CNNA); secondary peritonitis is usually polymicrobial
• SBP - 70% GNR, Klebsiella, E. Coli, 30% GPC Enterococcus, Strep Pneumo
• In general, the diuretic goal should be net neg 500-1000cc - going too fast runs the risk of AKI since ascites fluid mobilized slower than other compartments
• UNa/UK can help differentiate between too low diuretic dose vs too much Na in the diet; if UNa/UK <1, likely an ineffective dose; if >1 suggests >2g Na intake
• Do a therapeutic LVP if tense or refractory ascites or unable to use diuretics; if >5L give 6-8g albumin for every L ascites removed
• Refractory ascites can be treated with midodrine TID, serial LVPs q2 weeks, or TIPS as a bridge to OLT
• HE is neurotoxic effects of increased NH3 - leads to abnormal neurotransmission (increased GABA, decreased glutaminergic) leads to depressed AMS, and at worst edema; asterixis and milkmaid’s are signs of the neurotoxicity leading to loss of postural tone but also inattention
• Grade 1 HE - inattention, altered sleep pattern; Grade 2 - lethargy, disoriented, asterixis; Grade 3 - somnolence, AMS, asterixis; Grade 4 - Coma
• Ammonia absolute value does not add any diagnostic value - level does not correlate with severity - able to compensate for high levels over a chronic timeline
• Lactulose works by increasing stool output and maintaining acidic pH (converted to lactic acid by intestinal flora which leads to acidification which turns NH3 (ammonia) to NH4+ (ammonium) which is more easily excreted in feces; rifaximin helps reverse HE by (possibly) killing bacteria that turn NH4+ to NH3, allowing NH4 to be excreted (or just result of pH); in general, add rifaximin if refractory, or 2nd admission for HE
• Beyond rifaximin, can consider Miralax, branched-chain AA, L-ornithine L-aspartate
• EGD should be done at diagnosis and every 2 years if ongoing/worsening cirrhosis
• Gastric varices are treated similarly to EV, but are much more dangerous and have high mortality
• Window hypothesis - beta blockers have no effect on survival or prevention in early cirrhosis, but have a survival benefit in middle stages, & reduce survival in advanced cirrhosis; stop BB if SBP, refractory ascites, HRS< low BP, sepsis
• PTT and PT/INR do not correlate with the risk of bleeding or clotting in patients with cirrhosis - there is no benefit to correcting INR pre-procedure, but should shoot for goal Plt >50k if getting a risky procedure
• Avoid FFP in general unless persistent fibrinogen deficiency - large volume leads to increased portal pressures
• Can stop screening for HCC if Child-Pugh Class C and not listed for transplant due to low survival
• HCC treatment - curative surgery if Child-Pugh A and small nodule or liver transplant; can also ablate or do TACE/TARE with IR, sorafenib, immunotherapy, radiation
• Milan Criteria for transplant with HCC - one lesion <5cm or up to 3 lesions all <3cm, no extra-hepatic involvement, no major vessel involvement
• Hepatic hydrothorax is more commonly R-sided; comes from small defects in the diaphragm, do not need to have large volume ascites to build up on thoracic cavity - can do thora if the cause of dyspnea, but should avoid chest tubes
• Hepatopulmonary Syndrome - shunting through vascular dilations, often at the bases of lungs, leads to platypnea (dyspnea when upright); get TTE with late bubbles and PFTs showing decreased DLCO; the only treatment is a transplant 
• HRS - splanchinic dilation → activation of RAAS → renal vasoconstriction → decreased GFR - need to exclude other causes (prerenal - have lack of improvement after volume expansion - no shock, no exposure to nephrotoxic drugs); goal to cause vasoconstriction of splanchnics by repleting volume and giving midodrine and octreotide - goal to avoid dialysis, as usually doesn't help improve mortality
• TIPS - if refractory ascites, recurring varices, acute decompensation as bridge to liver transplant; early <72h if high risk of rebleed, “rescue” if uncontrolled bleed despite medical and EGD therapy
• PEth blood test measures phosphatidylethanol (PEth) which is an alcohol biomarker - if <10 considered negative; if >10, likely ongoing alcohol use; >210 indicates excessive use
• Palmar erythema and spider angiomata are caused by hyperestrogenism
• Spironolactone can cause gynecomastia

Trials and Literature

• Rifaximin + Lactulose vs Lactulose alone leads to improved reversal of HE (NNT 3) and improved mortality (NNT 4) (Am J Gastro 2013 )
• Does This Patient with Liver Disease Have Cirrhosis? Rational Clinical Exam

Other Resources

• Clinical Problem Solvers - CPS Cirrhosis Schema; Cirrhosis and Dyspnea
• MD Calc -Child-Pugh ; MELD Score