What is the primary cause of death in patients with decompensated liver failure, particularly those with a complex medical history such as Dyskeratosis Congenita?

Primary Causes of Death in Decompensated Liver Failure

In patients with decompensated cirrhosis, death occurs primarily from multiorgan failure in the context of acute-on-chronic liver failure (ACLF), with 28-day mortality rates ranging from 30-50%, followed by complications of portal hypertension including variceal hemorrhage, refractory ascites with hepatorenal syndrome, and sepsis from bacterial infections. 1

Mortality Mechanisms in Decompensated Cirrhosis

Acute-on-Chronic Liver Failure (ACLF)

• ACLF represents the most lethal manifestation of decompensated cirrhosis, characterized by rapid multiorgan failure with 28-day mortality of 30-50%. 1
• The syndrome requires three critical components: acute deterioration with elevated bilirubin and INR, rapid clinical decline, and at least one extrahepatic organ failure (neurologic, circulatory, respiratory, or renal). 1
• The number of simultaneously failing organs directly correlates with mortality risk—patients with single organ failure have lower mortality than those with 2-3 organ failures, while those with 4 or more organ failures approach 90% mortality at 28 days. 1
• Excessive systemic inflammation drives the cascade of organ failures, even when no precipitating event can be identified in 40-50% of cases. 1

Specific Organ Failures Leading to Death

Hepatorenal syndrome and renal failure:

• Renal failure constitutes a major cause of death, with hepatorenal syndrome representing the most severe form. 1
• One-year mortality following development of ascites reaches 49%, with progression to hepatorenal syndrome carrying 64% mortality. 1
• Patients requiring renal replacement therapy for ≥4 weeks or with estimated GFR ≤35 ml/min for ≥4 weeks have particularly poor prognosis without simultaneous liver-kidney transplantation. 1

Variceal hemorrhage:

• Variceal bleeding as an isolated complication carries 20% five-year mortality, but when combined with other decompensation events, mortality exceeds 80%. 1
• Recurrent variceal hemorrhage occurs in 60% of untreated patients within 1-2 years. 1
• Mortality is highest when bleeding occurs with bacterial infections or hepatic venous pressure gradient >20 mm Hg. 1

Hepatic encephalopathy:

• Clinical episodes of hepatic encephalopathy carry 64% one-year mortality. 1
• Encephalopathy represents a marker of advanced liver failure and frequently accompanies other organ failures in the terminal phase. 1

Sepsis and bacterial infections:

• Bacterial infections accelerate disease progression at any stage but particularly in decompensated cirrhosis. 1
• Sepsis with multiorgan failure remains a leading cause of death, driven by translocation of gut-derived bacterial products. 1
• The combination of infection with ACLF creates a particularly lethal scenario due to overwhelming systemic inflammation. 1

Special Consideration: Dyskeratosis Congenita

In patients with dyskeratosis congenita who develop decompensated liver failure, the mortality picture differs fundamentally from typical cirrhosis:

• Bone marrow failure, not liver failure, represents the principal cause of premature death in dyskeratosis congenita. 2
• Pulmonary fibrosis emerges as a major competing cause of death, particularly in late adolescence or early adulthood. 2
• These patients face multisystem mortality risks from progressive pancytopenia, pulmonary complications, and malignant transformation (myelodysplastic syndrome, leukemia, head and neck cancers). 2
• When liver failure does occur in dyskeratosis congenita, it typically manifests with severe hepatopulmonary syndrome and portal hypertension, but death usually results from bone marrow failure complications or pulmonary disease rather than isolated liver failure. 3

Prognostic Factors Determining Mortality Risk

The strongest predictor of mortality remains persistent alcohol consumption in alcoholic cirrhosis, with 71% mortality at 5 years, 84% at 10 years, and 90% at 15 years in those who continue drinking. 1

Additional high-risk features include:

• CLIF-C ACLF score and number of organ failures predict 28-day mortality with high accuracy. 1
• Presence of "pre-ACLF" state with elevated inflammatory markers (C-reactive protein, white blood cells) and high MELD scores identifies patients at imminent risk of progression to ACLF. 1
• Development of ascites as the first decompensation event, particularly in alcoholic cirrhosis, predicts rapid progression. 1

Critical Clinical Pitfall

Do not underestimate mortality risk in patients experiencing their first decompensation episode—40% of patients admitted with ACLF had no prior decompensation, and these patients have significantly higher 28-day mortality (42.2% vs. 29.6%) compared to those with prior decompensation. 1