What is the rationale for treatment in Chronic Liver Disease (CLD) patients?

Treatment Rationale in Chronic Liver Disease (CLD)

All patients with chronic liver disease should be considered for antiviral treatment, with specific regimens determined by disease etiology, liver function status, and presence of complications. 1

Assessment and Staging of Liver Disease

• Liver disease severity assessment is essential prior to therapy initiation, as it determines treatment approach, prognosis, and likelihood of response 1
• Identifying patients with cirrhosis is particularly important as their prognosis is altered, treatment options may be limited, and they require surveillance for hepatocellular carcinoma (HCC) 1
• Liver biopsy remains recommended whenever it may contribute to patient management or for grading and staging liver disease when clinical signs or imaging evidence of cirrhosis are absent 1
• Non-invasive tests (NITs) may be used to assess advanced liver disease, though specific cut-off values are not well established 1

Treatment Approach Based on Disease Etiology

For Hepatitis Delta Virus (HDV) Infection:

• All patients with chronic hepatitis D (CHD) and compensated liver disease should be considered for treatment with pegylated interferon alpha (PegIFNα) 1
• PegIFNα for 48 weeks is the preferred treatment schedule, though personalized durations may be considered based on HDV RNA and HBsAg kinetics 1
• Bulevirtide (BLV) is a newer treatment option for CHD with compensated liver disease, typically administered at 2 mg once daily for long-term treatment 1
• The combination of PegIFNα and BLV may be considered in patients without PegIFNα intolerance or contraindications 1

For HBV Co-infection:

• Nucleos(t)ide analogues (NAs) should be given to patients with:
  • Decompensated cirrhosis regardless of HBV DNA detectability 1
  • Compensated cirrhosis with detectable HBV DNA 1
  • Non-cirrhotic disease if HBV DNA levels exceed 2,000 IU/ml 1

Management of Complications

Hepatic Encephalopathy:

• Hepatic encephalopathy should be treated as a continuum ranging from unimpaired cognitive function through coma 1
• A four-pronged approach is recommended: initiating care for altered consciousness, identifying alternative causes, correcting precipitating factors, and commencing empirical treatment 1, 2
• Lactulose is first-line treatment, titrated to achieve 2-3 soft stools per day, with rifaximin as second-line or additional therapy for recurrent episodes 1, 2
• Identifying and correcting precipitating factors is crucial, resolving up to 90% of cases 2

Bone Disease:

• Calcium (1,000–1,500 mg/day) and vitamin D (400–800 IU/day) supplementation should be provided to patients with chronic liver disease 1
• Bisphosphonates may increase bone mass in patients with primary biliary cholangitis (PBC) and are generally well-tolerated in liver patients 1
• Physical activity is recommended, particularly exercises designed to improve spine mechanics 1

Hepatocellular Carcinoma Surveillance:

• HCC surveillance should be performed with abdominal ultrasound every 6 months in patients with CHD with advanced fibrosis or cirrhosis, regardless of anti-HDV therapy 1

Monitoring and Follow-up

• Patients with chronic liver disease should receive regular work-up at least every 6-12 months 1
• Virological parameters measured should ideally include quantitative assays for HBsAg, HBV DNA, and HDV RNA in patients with viral hepatitis 1
• Factors that indicate higher risk of liver disease progression include elevated aminotransferases and GGT levels, advanced stage of liver disease, persistence of viremia, high serum HBV DNA levels, and viral coinfections 1
• Cofactors of chronic liver injury such as alcohol abuse, obesity, and diabetes should also be considered and addressed 1, 3

Special Considerations

• Patients with decompensated cirrhosis should be evaluated for liver transplantation 1, 4
• For patients who have undergone liver transplantation for CHD, hepatitis B immunoglobulin (HBIG) combined with a high genetic barrier NA should be administered post-transplantation 1
• Patient-centered care approaches are increasingly important in CLD management, focusing on integrated practice units, meaningful patient-reported outcomes, and palliative care integration when appropriate 3

Pitfalls to Avoid

• Relying solely on ALT levels to determine disease severity, as liver disease can progress even with repeatedly normal ALT levels 1
• Using isolated blood ammonia determination for diagnosis, staging, or prognosis of hepatic encephalopathy 1, 2
• Failing to identify and correct precipitating factors in hepatic encephalopathy, which account for 90% of cases 1, 2
• Overlooking the importance of secondary prophylaxis after the first episode of hepatic encephalopathy 2