Sarcopenia, thrombosis, and renal dysfunction dominate cirrhosis complication updates

Updated guidance on three major complications affecting patients with cirrhosis—sarcopenia management in hepatic disorders, portal vein thrombosis treatment stratification, and hepatorenal syndrome therapeutic approaches—were presented at the United European Gastroenterology Week in Berlin in a joint session.

Sarcopenia: Beyond Muscle Mass Quantification

Francesca Ponziani, from Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome, noted that sarcopenia affects approximately 40% of patients with cirrhosis and represents a diagnosis requiring reassessment at each patient evaluation. The condition is defined by three criteria: loss of muscle strength, compromised muscle quantity or quality, and impaired physical performance.

Ponziani distinguished between frailty and sarcopenia, noting that "frailty is the phenotypic representation of an impaired muscle contracting function, and sarcopenia is instead referred to mainly to the loss of muscle mass." She recommended the liver frailty index—comprising handgrip strength, chair stance, and balance exercise—as the most practical clinical tool. "Frailty testing can be used in everyday clinical practice to suspect the sarcopenia and loss of muscle function and sarcopenia. Testing and quantification may be reserved for those patients that cannot be addressed by this kind of testing," she said.

The mechanisms driving sarcopenia in cirrhosis differ substantially from those in without cirrhosis. Ponziani presented data linking ammonia production to myostatin upregulation through inflammatory pathways (specifically mentioning protein p65 expression), with research showing myostatin as "a good predictor of sarcopenia" that can be used clinically when possible, she noted.

Gut microbiota dysbiosis emerged as a significant contributor. Mouse model studies demonstrated that rifaximin administration reduced myostatin levels and expression while increasing muscle mass. Ponziani's group identified reduced alpha diversity characterizing gut microbiota in patients with sarcopenia and cirrhosis, with markers of dysbiosis including increased Klebsiella, altered metabolism of nitrogen and branched amino acids, and endogenous ethanol production. Additional research showed that Ruminococcaceae depletion was associated with amino acid metabolism alterations and increased risk of sarcopenia and cirrhosis complications.

Treatment centers on three prevention levels: primary prevention to delay onset, secondary prevention with dietitian co-management and certified physical therapy, and tertiary prevention utilizing center-based rehabilitation. Ponziani noted that testosterone treatment demonstrated muscle mass reversal in limited studies, with one 2025 simulation study suggesting mortality benefits, though she noted: "We don't know the extent we can reverse this kind of alterations."

Portal Vein Thrombosis: Etiology Determines Management

Verena Keitel-Anselmino, from University Hospital, Magdeburg in Germany, presented contrasting approaches for cirrhotic versus non-cirrhotic portal vein thrombosis (PVT). The prevalence in cirrhosis reaches 14% overall, with annual incidence ranging from 4.6% to 26%, increasing with cirrhosis severity and portal hypertension. Hepatocellular carcinoma represents an independent risk factor, with one-year incidence reaching 25%, and 50% of PVT cases diagnosed when patients are listed for transplantation.

Risk factors in cirrhosis differ fundamentally from non-cirrhotic disease. "The risk factors you find in liver disease are all related to portal hypertension," said Keitel-Anselmino.  A prospective French study identified reduced portal vein blood flow (hazard ratio 3), previous variceal bleeding, low platelets, and large spleen as key risk factors, with coagulation factors showing minimal association.

PVT complications include worsened variceal bleeding with increased five-day treatment failure and six-week mortality, portal cholangiopathy, mesenteric ischemia with high mortality, and complicated liver transplantation. However, "if you don't look at a variceal bleed, there is no association with prognosis and long term cirrhosis outcome," noted Keitel-Anselmino.

A recent meta-analysis demonstrated anticoagulation reduces all-cause mortality independent of PVT severity, with significantly higher recanalization rates and stable thrombus in non-treated patients. Critically, bleeding occurrence was identical between treatment groups. Keitel-Anselmino stated: "Anticoagulation does have an effect besides the recanalization of the portal vein."

Treatment recommendations specify low molecular weight heparin or direct oral anticoagulants (DOACs), with DOACs showing fewer bleeding events than vitamin K antagonists in meta-analyses. "Proceed with caution in Child B and be very restrictive in Child C" for DOAC use, advised Keitel-Anselmino. Treatment duration targets recanalization (minimum six months) or indefinite treatment for transplant candidates.

For refractory cases, transjugular intrahepatic portosystemic shunt (TIPS) achieves above 90% technical success and complete recanalization, even with cavernous transformation. A case series showed 67% of thrombotic patients underwent TIPS through splenic access with high success rates and similar complication rates to standard approaches.

Hepatorenal Syndrome: Inflammation Challenges Functional Model

Professor Raj Mookerjee, from University College London, challenged the purely functional conceptualization of hepatorenal syndrome (HRS), presenting evidence for structural kidney damage and inflammation's role in pathophysiology and treatment response.

The acute kidney injury (AKI) staging system now incorporates urine output alongside creatinine changes, addressing sarcopenia's confounding effect on creatinine values in patients with cirrhosis. Stage 1 AKI (creatinine below 135 μmol/L or 1.5 mg/dL) patients demonstrate twice the survival of those with advanced stages.

Mookerjee presented kidney biopsy data showing toll-like receptor 4 staining in tubules of patients labeled with functional renal failure, though less than those with documented tubular injury. "If we look at inflammation, and we look at the role here of urine marker expression, one sees much worse outcome in those patients that are positive," he said.

Renal histology from so-called functional HRS patients revealed renal vascular injury elements and both tubular and glomerular injury. "Highlighting the functional is a label that we've applied as clinicians. But there are still structural elements to address," said Mookerjee.

Systemic inflammatory response syndrome criteria correlated with outcome regardless of infection resolution in a study segregating HRS patients by infection status. "Those who actually had a marked increase inflammatory response had poor outcome," suggesting inflammation impacts physiology and treatment response beyond reversible vasomotor elements, noted Mookerjee.

For treatment, he outlined a systematic approach: remove nephrotoxic factors (including aminoglycosides, NSAIDs, beta-blockers in advanced cases), provide volume replacement with albumin for non-colloidal properties, then initiate vasoconstrictors if AKI criteria persist after 48 hours.

Terlipressin with albumin remains the European standard, preferably administered as continuous infusion starting at 2 mg daily, increasing to maximum 12 mg daily. The CONFIRM trial demonstrated terlipressin superiority over albumin alone for reversing HRS and reducing renal replacement therapy requirements, though 90-day survival benefits did not persist.

Subanalysis revealed patients with higher acute-on-chronic liver failure (ACLF) grades, particularly grade 3, experienced significantly more respiratory failure. "There's something in the biology of evolution of that inflammatory response that makes capillaries perhaps more leaky in the context of the lung, but also much worse in terms of the overall systemic hemodynamics," explained Mookerjee.

Terlipressin reduces cardiac output by at least 15% in treated patients, as demonstrated by phase-contrast MRI studies. "In patients who've got more advanced disease, is perhaps taking that important kick that's needed from the compensation of cardiac output away," he said.  Monitoring mean arterial pressure, noting lack of sustained increase above 5 mmHg may indicate poor response.

Alternative vasoconstrictors include midodrine with octreotide (lower response than terlipressin) and noradrenaline (requiring ICU setting). TIPS remains under investigation for HRS, with the ongoing Liver Hero trial results pending.

Urinary neutrophil gelatinase-associated lipocalin emerged as a prognostic marker, with lower levels predicting better response to terlipressin-albumin therapy. "We don't have many histological correlates with this," he noted, however.

Approximately 50% of discharged AKI patients require readmission within three months for renal or metabolic complications, with higher chronic kidney disease progression risk. "I think we do need much better stratification of patients using validated markers that will help us improve outcomes in therapy," concluded Mookerjee.

Source: UEG Week 2025