Table 2 Summary of updated diagnosis for liver diseases

Viral hepatitis

1. Acute: presenting with abdominal pain, nausea, vomiting, fever, and other atypical symptoms.

2. Chronic: manifesting symptoms associated with cirrhosis.

3. The source or route of infection can be identified.³⁹²

1. Abnormal levels of biochemical indicators related to liver function, such as ALT, AST, and ALP.

2. Testing for viral antibodies or viral load is conducted to determine the presence of HAV, HDV, and HEV IgM or IgG; HBsAg, HBeAg, HCV-Ab; Viral RNA of HBV, HCV, and HGV.³⁹³

The classification of hepatitis is based on etiological factors, disease duration, disease severity, and other relevant aspects.³⁹²

ALI

Following direct or indirect exposure to various risk factors for liver injury, there was a rapid deterioration in liver function within a span of two weeks, accompanied by associated clinical symptoms such as weakness, decreased appetite, nausea, vomiting, epigastric pain, jaundice, and others.⁴⁰³

1. Serum ALT, ALP, GGT, and TBil alterations serve as the primary laboratory indicators for diagnosing ALI.

2. Liver failure is diagnosed when the following criteria are met: 1) Presence of severe gastrointestinal symptoms; 2) Progressive deepening of jaundice (serum TBil ≥ 171 μmol/L or daily increase ≥ 17.1 μmol/L); 3) Manifestation of bleeding tendency with PTA ≤ 40% or INR ≥ 1.5; and 4) Development of hepatic encephalopathy (degree II or higher), along with other complications.⁴⁰⁵

The definition of mild ALI is typically characterized by 2 ULN ≤ ALT < 5 ULN, while moderate ALI is usually defined as 5 ULN ≤ ALT < 15 ULN. Severe ALI, on the other hand, is indicated by an INR ≥ 2.0, ALT ≥ 10 ULN, and TBiL ≥ 3.0 mg/dL.^405,407

MASLD

Excessive alcohol consumption should be ruled out, along with other causes of fatty liver disease, in patients presenting at least one component of Metabolic Syndrome (BMI ≥ 24 kg/m,² blood pressure ≥ 130/85 mmHg, diabetes mellitus). Additionally, serum TG levels should be checked for values ≥ 1.70 mmol/L and high-density lipoprotein levels for values ≤ 1 mmol/L.⁴²¹

1. Biochemical analysis index: FIB-4 > 1.3, ALT > 40 U/L.

2. Ultrasonic examination, such as LSM ≥ 8 kPa, CAP > 248 dB/m.

3. Liver biopsy histological examination.^421,422

The liver biopsy histology of patients with MASLD revealed the presence of hepatic steatosis ≥ 5%, accompanied by concurrent lobular inflammation and balloon-like degeneration. Based on the extent of fibrosis, it can be categorized into early MASH (F0-1), fibrotic MASH (F2-3), and MASH cirrhosis (F4).^422,423

ALD

1. Prolonged or excessive alcohol consumption history.

2. Manifestations can range from being asymptomatic to presenting with symptoms such as right upper quadrant abdominal pain, anorexia, asthenia, unintended weight loss and jaundice. With disease progression, signs indicative of cirrhosis become evident.

3. Exclude alternative etiologies for hepatic injury.⁴³⁴

1. ALT, AST, GGT, and MCV levels exhibit elevation, while the ratio of AST/ALT > 1.5.

2. Liver ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), or transient elastography reveal characteristic manifestations indicative of fatty liver disease or liver fibrosis.^434,436

Maddrey discriminant function, model of end-stage liver disease (MELD) score, Glasgow alcoholic hepatitis score (GAHS).⁴³⁴

Autoimmune liver disease

The symptoms are typically mild in nature. Common manifestations include fatigue, abdominal discomfort, pruritus, icterus, hepatomegaly, nausea, anorexia, and acholic stools. More severe complications may encompass decompensated cirrhosis symptoms such as ascites and hepatic encephalopathy.

1. Serological testing: PBC (AMA, AMA-M2, anti-GP210 Ab, anti-SP100 Ab), AIH (ANA, ASMA, anti-SLA/LP, anti-LKM-1 and anti-LC-1 Abs, IgG and/or gamma-globulin), PSC (AMA and IgG4 levels).^134,444

2. Elevated levels of serum aminotransferases, ALP and GGT were observed.

3. Histopathological examination of liver biopsy.⁴⁴⁷

4. Imaging studies including CT, MRI, MRCP.⁴⁴⁵

1. Paris diagnostic criteria.

2. IAIHG simplifies the scoring system.

Genetic and rare liver diseases

1. General symptom: unexplained aberrant hepatic function, hepatomegaly, cholestasis, neurological manifestations or additional systemic symptoms, hepatic cirrhosis, liver failure.

2. Unique clinical manifestations, such as Kayser-Fleischer ring, emphysema and other signs.¹⁹³

1. Laboratory tests (e.g. liver function test, serum ceruloplasmin, serum α1-antitrypsin).

2. Imaging examination, ultrasound (e.g. CT and MRI)

3. Liver biopsy histological examination.

4. Genetic analysis.^104,141,460

The grading of patients with advanced cirrhosis or liver failure should be conducted in accordance with their condition.¹⁰⁰

Cirrhosis

The progression from an initially asymptomatic or mildly symptomatic compensatory phase of cirrhosis to a decompensated phase with portal hypertension and impaired liver function is frequently accompanied by complications, such as esophageal varices, gastrointestinal bleeding, ascites, hepatic encephalopathy, and jaundice.⁴⁶²

1. Histological examination of liver biopsy.

2. Indirect markers of fibrosis: FIB-4 > 2.67; BARD > 3, APRI > 1.5, Forns > 6.9, NAS > 0.676.

3. LSM ≥ 8 kPa.¹⁵⁵

The Child-Pugh classification was employed to assess the severity of liver cirrhosis in patients based on parameters including prothrombin time, ascites, serum bilirubin levels, serum albumin concentration, and hepatic encephalopathy.⁴⁶²

HCC

1. Risk factors such as viral hepatitis, fatty liver, alcoholic hepatitis, or aflatoxin exposure may contribute to the development of the condition.

2. In the early stage, there are typically no specific symptoms present. However, as the disease progresses, individuals may experience liver pain followed by an upper abdominal mass, weakness, wasting syndrome, abdominal distension, fever, bleeding tendency, lower limb edema and potential bone metastasis which could include tenderness.

1. Histological examination of liver biopsy.

2. Imaging techniques including ultrasound combined with dynamic enhanced CT and MRI scanning, as well as digital subtraction angiography.

3. Nuclear medicine imaging examinations such as PET/CT and SPECT/CT.^477,478

4. Elevated levels of AFP (>20 ng/mL), DCP (>40 mAU/mL) and AFP-L3 (>10%).⁴⁷⁹

5. Diagnosis using circulating microRNA, circulating tumor cell, cfDNA, circulating tumor DNA, and free DNA methylation biomarker panels either individually or in combination.

1. Classification of Liver Cancer (BCLC) at Barcelona Clinic,

2. Hong Kong Liver Cancer Stage (HKLC) stage,

3. BALAD staging.⁴⁸⁹