Management of Lactic Acidosis in Chronic Liver Disease

Pathophysiology and Risk Factors

The risk of lactic acidosis is significantly higher in patients with decompensated cirrhosis and concurrent renal impairment, according to the European Association for the Study of the Liver 1, 2

The American Association for the Study of Liver Diseases recommends early identification and treatment of precipitating factors, such as bacterial infections and gastrointestinal bleeding, to manage lactic acidosis in chronic liver disease patients 3, 4
Metformin should be discontinued immediately in patients with decompensated cirrhosis, GFR < 30 mL/min/1.73m², acute kidney injury, or serious intercurrent illness, as recommended by the National Kidney Foundation 1, 2, 5, 6, 7, 8
For diabetes management in chronic liver disease patients with lactic acidosis, the American Diabetes Association recommends using insulin as the preferred agent for glycemic control, and considering GLP-1 receptor agonists in Child-Pugh class A cirrhosis only, and SGLT2 inhibitors in Child-Pugh class A and B cirrhosis 1, 5, 8

The Society of Critical Care Medicine recommends providing hemodynamic support with crystalloids as initial fluid resuscitation, and using norepinephrine as first-line vasopressor for hypotension, and vasopressin for persistent hypotension 9
The American Thoracic Society recommends providing oxygen therapy and ventilation if respiratory failure develops, and using low tidal volume strategy for patients with ARDS 3, 4, 9
The International Society of Nephrology recommends early initiation of continuous renal replacement therapy for persistent hyperammonemia, hyperkalemia, and metabolic abnormalities, and using terlipressin with albumin for hepatorenal syndrome 9, 4

The European Society for Clinical Nutrition and Metabolism recommends providing adequate nutritional support with 35 kcal/kg of body weight/day, and protein intake of 1.2-1.5 g/kg of body weight/day, and including late evening snack for patients with sarcopenia or decompensated cirrhosis 1, 2, 5

The American Association for the Study of Liver Diseases recommends treating patients with acute-on-chronic liver failure and lactic acidosis in intermediate or intensive care settings, and early referral to liver transplant centers for immediate evaluation 3, 4
The European Association for the Study of the Liver recommends against using extracorporeal liver support systems outside clinical trials, due to lack of significant survival benefits 3, 4

The American Association for the Study of Liver Diseases recommends frequent monitoring of organ function, including liver, kidney, brain, lung, coagulation, and circulation, as acute-on-chronic liver failure is a dynamic condition 3, 4

SGLT2 inhibitors can be used in patients with Child-Pugh class A and B cirrhosis but should be avoided in decompensated cirrhosis due to risks of hemodynamic instability and acute kidney injury, as recommended by the European Association for the Study of the Liver 10, 11, 12
SGLT2 inhibitors are appropriate for patients with compensated (Child-Pugh A) cirrhosis, with evidence supporting their use in Child-Pugh B cirrhosis as well, according to the American Association for the Study of Liver Diseases 13, 14

GLP-1 receptor agonists can be used in Child-Pugh class A cirrhosis only, as stated by the American Diabetes Association 10
Metformin can be used in compensated cirrhosis with preserved renal function but should be discontinued immediately if decompensation occurs or GFR falls below 30 mL/min, as recommended by the European Association for the Study of the Liver 12
Sulfonylureas should be avoided in patients with hepatic decompensation due to increased risk of hypoglycemia, according to the American Association of Clinical Endocrinologists 10

The American College of Cardiology recommends assessing for hypovolemia before initiation of SGLT2 inhibitors as they cause intravascular volume contraction through osmotic diuresis, particularly in patients with ascites, concurrent diuretic use, or baseline hypotension 15
The American College of Cardiology suggests considering temporarily reducing thiazide or loop diuretic doses when initiating SGLT2 inhibitors to avoid excessive volume depletion 15
According to the Mayo Clinic Proceedings, evaluate eGFR prior to initiation and monitor periodically, with more frequent monitoring when eGFR <60 mL/min/1.73 m², and expect an initial "eGFR dip" of 3-5 mL/min/1.73 m² that typically returns to baseline within weeks 16

The American College of Cardiology advises educating patients that diabetic ketoacidosis can occur even with normal glucose levels (150-250 mg/dL, "euglycemic DKA") and instructing them to seek immediate medical attention for nausea, vomiting, abdominal pain, or malaise 15
The Mayo Clinic Proceedings recommends discontinuing SGLT2 inhibitors 3 days before elective procedures (4 days for ertugliflozin) to prevent acute kidney injury 16

The Mayo Clinic Proceedings suggests prioritizing SGLT2 inhibitors in Child-Pugh A or B cirrhosis when cardiovascular disease, heart failure, or CKD (eGFR 30-60 mL/min/1.73 m²) coexist, due to their superior mortality reduction compared to DPP-4 inhibitors in cirrhotic patients 17
The American College of Cardiology recommends considering GLP-1 receptor agonists as an alternative to SGLT2 inhibitors in Child-Pugh class A cirrhosis, according to American Diabetes Association recommendations, and using them when SGLT2 inhibitors are contraindicated due to eGFR <30 mL/min/1.73 m² or not tolerated 15

The American College of Cardiology advises avoiding canagliflozin in patients with prior amputation, severe peripheral arterial disease, neuropathy, diabetic foot ulcers, or osteoporosis due to increased amputation and fracture risk observed in one trial 15
The Mayo Clinic Proceedings suggests that empagliflozin and dapagliflozin have more favorable safety profiles in patients with prior amputation, severe peripheral arterial disease, neuropathy, diabetic foot ulcers, or osteoporosis 16