Advancements and Management Strategies in Cirrhosis: A Comprehensive Review

1. Compensated and decompensated cirrhosis:
   • Cirrhosis can be classified as compensated or decompensated based on the presence or absence of complications.
   • Compensated cirrhosis has longer survival and better quality of life compared to decompensated cirrhosis.
   • Esophageal varices and other complications determine the different stages of cirrhosis.
2. Drivers of decompensation:
   • Portal hypertension is considered the main driver of cirrhosis progression.
   • Recent findings suggest that endogenous systems activation and sodium retention do not increase progressively in advanced stages of liver disease.
   • Systemic inflammation (SI) and acute on chronic liver failure (ACLF) are additional drivers of decompensation in patients with cirrhosis.
3. Pathophysiologic theory:
   • Bacterial translocation (BT) resulting from portal hypertension is thought to be the main consequence of cirrhosis.
   • SI and OS caused by BT lead to derangement of cardiovascular function and reduction of effective circulating volume.
   • This chain of events can result in the onset of ascites and other major complications of cirrhosis.
4. Mechanisms of SI and OS:
   • SI causes intense vasoconstriction and hypoperfusion of organs like the kidney.
   • Immunopathology and nutrient storage are additional mechanisms of SI on organ integrity and function.
5. Dynamics and classification of decompensation:
   • Nonacute decompensation (NAD) precedes acute decompensation (AD) and represents a transition from compensated to decompensated cirrhosis.
   • AD can lead to the development of ACLF, unstable decompensated cirrhosis (UDC), or stable decompensated cirrhosis (SDC).
   • Mortality rates vary for each classification, with ACLF having the highest rates.
6. Further investigation needed:
   • The temporal relationship from NAD to AD and the long-term outcome of patients with different classifications is not known.
   • Consensus definitions for recompensation and the outcome of recovery from decompensation are necessary.
   • Etiologic treatments and disease-modifying agents may prevent further episodes of decompensation.
7. Management of complications:
   • There have been new achievements in the management of complications of cirrhosis.
   • Specific details regarding these achievements were not provided in the given text.
8. Management of grade 1 ascites:
   • Grade 1 ascites should not be treated by medical therapy
   • Patients with grade 1 ascites have a higher risk of developing ACLF and should be followed closely
9. The long-term use of human albumin solution in the treatment of ascites:
   • Albumin has both oncotic and nononcotic properties
   • Long-term administration of human albumin solution (HAS) improves overall survival and reduces complications in patients with responsive ascites
10. The preemptive use of TIPS in the treatment of ascites:
    • TIPS provides better control of ascites but increases the risk of encephalopathy
    • The use of small-diameter covered TIPS in patients with recurrent ascites improves ascites control and transplant-free survival without increased risk of encephalopathy
11. Other options for the treatment of refractory ascites:
    • Patients who are not candidates for TIPS can be treated with the automated low-flow pump system (Alfapump)
    • Alfapump reduces the need for paracentesis and improves quality of life in patients with refractory ascites
12. Noninvasive monitoring of the effect of nonselective beta-blockers:
    • Nonselective beta-blockers lower portal pressure
    • Noninvasive monitoring of the effect of nonselective beta-blockers can help optimize their use in the management of complications
13. Monitoring the Effect of NSBBs in Patients with Cirrhosis:
    • No noninvasive parameter exists yet to evaluate the effect of NSBBs on portal pressure in patients with cirrhosis.
    • Current guidelines recommend prescribing NSBBs without monitoring their effect on portal pressure, leading to deviation from guidelines in clinical practice.
    • There is an urgent need for a noninvasive tool to monitor the effect of NSBBs on portal pressure.
14. Preventing Bacterial Infections in Patients with Cirrhosis:
    • In addition to spontaneous bacterial peritonitis, other infections can be dangerous and complicate acute-on-chronic liver failure (ACLF).
    • Norfloxacin, commonly used for prophylaxis, is facing increasing rates of bacterial resistance and safety concerns.
    • Rifaximin shows promise as an alternative antibiotic but requires well-conducted clinical trials to establish efficacy and safety.
    • Research is focusing on non-antibiotic strategies, such as Carbalive, to prevent bacterial infections in patients with cirrhosis.
15. Treating Patients with Acute on Chronic Liver Failure:
    • Patients with persistent ACLF and multiple failing organs have a poor prognosis, with mortality rates exceeding 80% at 30 days.
    • Intensive medical treatment and early liver transplantation (LT) are the main therapeutic options.
    • Controversies exist regarding unrestricted ICU support and the feasibility of early LT for patients with grade 3 ACLF.
16. ICU care for ACLF patients:
    • Patients with ACLF should receive the same ICU care as other ICU populations.
    • A recent study found no difference in ICU course and outcome between ACLF and other ICU patients matched for severity of illness.
17. Treatment of hepatic renal syndrome/acute kidney injury:
    • Patients with HRS/AKI stage >1A should receive vasoconstrictive drugs in association with albumin.
    • Terlipressin plus albumin is the first therapeutic option, given by continuous intravenous infusion.
    • Terlipressin dose should be increased if there is no response.
    • Noradrenaline is an alternative to terlipressin, but less effective in patients with HRS/AKI and ACLF.
18. Liver transplantation in ACLF grade 3:
    • LT in patients with ACLF grade 3 is feasible and associated with a clear survival benefit.
    • Transplanted patients with ACLF grade 3 have higher survival rates than nontransplanted controls.
    • Complications may be higher in patients with ACLF grade 3 at the time of LT.
    • A new score is needed to prioritize candidates with ACLF on the waiting list.
19. Factors affecting outcome after LT in ACLF:
    • Number and type of organ failures have minimal impact on survival after LT.
    • Mechanical ventilation is a negative predictor of survival post-LT in ACLF grade 3.