Item Mild Moderate Severe

Item | > Mild | > Moderate | > Severe ALT(V) | > ≤Normal3times | > 3times10times | > >10times Bil(μmol/L) | > 17.1～34.2 | > 34.2～85.5 | > >85.5 A(g/L) | > ≥35 | > 3433 | > ≤32 A/G | > 1.51.3 | > 1.21.0 | > ≤0.9 rEP(%)ElectrophoresisGammaGlobulin | > ≤21 | > 22～25 | > ≥26 PTA(%) | > 7971 | > 7061 | > 60～40 (2) Subacute severe hepatitis. More than 10 days after the onset of acute jaundiced hepatitis, if prothrombin time is significantly prolonged (prothrombin activity below 40%), and one of the following conditions is met: ① Development of hepatic encephalopathy at II degree or above; ② Rapid rise in jaundice (serum bilirubin increases by >17.1 μmol/L within a few days), severe liver dysfunction (elevated serum ALT or enzyme-bile separation, inverted albumin-globulin ratio, increased gamma globulin); ③ Extreme fatigue and marked loss of appetite or nausea and vomiting, severe abdominal distension or ascites, possibly accompanied by obvious bleeding (for those without ascites and obvious bleeding, attention should be paid to whether this is the early stage of this type). (3) Chronic severe hepatitis. Clinical presentation is similar to subacute severe hepatitis, but with a history of chronic hepatitis, cirrhosis, or hepatitis B surface antigen carriage, along with physical signs and severe liver function impairment, or even if there is **no such medical history, but imaging, laparoscopy, or liver biopsy supports the presence of chronic hepatitis. To facilitate assessment of treatment efficacy and prognosis estimation, based on clinical presentation, both subacute and chronic severe hepatitis can be further divided into early, middle, and late stages. Early stage: Meets the basic criteria for acute liver failure, such as severe systemic and gastrointestinal symptoms, rapid deepening of jaundice, but no obvious encephalopathy has occurred, nor has ascites developed. Serum bilirubin ≥17.1 μmol/L, prothrombin activity ≤40%, or confirmed by pathology. Middle stage: Has hepatic encephalopathy at II degree or obvious ascites, tendency to bleed (bleeding spots or ecchymoses), prothrombin activity ≤30%. Late stage: Has refractory complications such as hepatorenal syndrome, gastrointestinal bleeding, severe bleeding tendency (ecchymoses at injection sites), severe infections, difficult-to-correct electrolyte disturbances, or hepatic encephalopathy at II degree or above, cerebral edema, prothrombin activity ≤20%.

4. Cholestatic hepatitis The onset is similar to acute jaundiced hepatitis, but the subjective symptoms are milder, often with obvious hepatomegaly, skin itching, and pale stools. Liver function tests show a significant increase in serum bilirubin, mainly direct bilirubin, presenting as obstructive jaundice, with alkaline phosphatase, γ-glutamyl transferase, and cholesterol all markedly elevated. If obstructive jaundice persists for more than three weeks and other intrahepatic or extrahepatic obstructive jaundices have been ruled out, then it can be diagnosed as acute cholestatic hepatitis. If the above clinical manifestations occur on the basis of chronic hepatitis, then it can be diagnosed as chronic cholestatic hepatitis.
5. Post-hepatitis cirrhosis In the early stages, it is difficult to confirm cirrhosis solely based on clinical data; pathological diagnosis is essential. Imaging (B-mode ultrasound, CT) and laparoscopic diagnosis are also of reference value. Anyone with chronic hepatitis who exhibits definite portal hypertension, such as abdominal wall or esophageal varices, ascites; imaging showing liver shrinkage, spleen enlargement, widening of the portal and splenic veins; and who has excluded other causes of portal hypertension, can be diagnosed as having clinical cirrhosis. ① Active cirrhosis. The clinical manifestations of chronic hepatitis still persist, especially elevated transaminases, jaundice, decreased albumin, hardening of the liver texture, progressive splenomegaly, accompanied by portal hypertension. ② Quiescent cirrhosis. Whether or not there is a history of liver disease, transaminases are normal, no obvious jaundice, hard liver, enlarged spleen, accompanied by portal hypertension and low serum albumin. II. Etiological Diagnosis (1) Etiological Classification Currently, there are at least five types of pathogens causing viral hepatitis: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV).

CamScanner Created (2) Diagnostic Criteria for Each Type of Viral Hepatitis

1. Hepatitis A For patients with acute hepatitis, a positive serum anti-HAV-IgM indicates a recent HAV infection and confirms the diagnosis. When anti-HAV-IgM is detected in the serum of patients with chronic hepatitis B or autoimmune liver disease, caution should be exercised in determining overlapping HAV infection, as it is necessary to exclude false positives caused by rheumatoid factor (RF) and other reasons.
2. Hepatitis B If any of the following conditions is met, it can be diagnosed as current HBV infection: ① Positive serum HBsAg; ② Positive serum HBV-DNA, or positive HBV-DNA polymerase; ③ Positive serum anti-HBc-IgM; ④ Positive intrahepatic HBcAg and/or HBsAg, or positive HBV-DNA. For diagnosing acute hepatitis B, it is necessary to differentiate it from acute exacerbation of chronic hepatitis B. The following dynamic indicators can be used as references: ① HBsAg titer decreases from high to low, and after disappearance, anti-HBs turns positive; ② During the acute phase, anti-HBc-IgM titer is high, while anti-HBc-IgG is negative or at a low level. **Diagnosis of chronic hepatitis B: Clinically consistent with chronic hepatitis, and at least one sign of current HBV infection is positive. Diagnosis of chronic HBsAg carriers: No clinical symptoms or physical signs, normal liver function, and HBsAg remains positive for more than six months. 3. Hepatitis C Acute hepatitis C diagnosis: Acute hepatitis patients with positive serum or intrahepatic HCV-RNA; or positive anti-HCV, but no other acute infection markers for hepatitis viruses. Diagnosis of chronic hepatitis C: Clinically consistent with chronic hepatitis, with positive serum anti-HCV, or positive serum and/or intrahepatic HCV-RNA. 4. Hepatitis D · HDV is a defective virus that relies on HBsAg for replication, and can manifest as simultaneous or overlapping infection of HDV and HBV. Acute HDV and HBV co-infection: Acute hepatitis patients, in addition to positive markers of acute HBV infection, also have positive serum anti-HD-IgM, with low-titer positive anti-HD-IgG; or positive serum and/or intrahepatic HDAg and HDV-RNA. Overlapping HDV and HBV infection: Chronic hepatitis B patients or chronic HBsAg carriers, with positive serum HDV-RNA and/or HDAg, or positive anti-HD-IgM and anti-CamScanner Created

HD-IgG at high titer, with positive intrahepatic HDV-RNA and/or HDAg. Diagnosis of chronic hepatitis D: Clinically consistent with chronic hepatitis, with persistent high titers of anti-HD-IgG, continuous positivity of HDV-RNA, and positive intrahepatic HDV-RNA and/or HDAg. 5. Hepatitis E Acute hepatitis patients with positive serum anti-HEV turning positive or titer increasing from low to high, or positive anti-HEV >1:20, or positive results from spot hybridization or PCR testing of serum and/or feces for HEV-RNA. Since reagents and methods for detecting anti-HEV-IgM have not yet been standardized, further research is needed, but detection of anti-HEV-IgM can still serve as a diagnostic reference. (3) Establishing the Diagnosis For all cases clinically diagnosed as acute, chronic, severe, cholestatic hepatitis, or post-hepatitis cirrhosis, once a specific type is confirmed through etiological or serological specific methods, then the patient is officially diagnosed as belonging to that type. Individuals infected with two or more hepatitis viruses simultaneously are referred to as co-infections. When someone already has one type of hepatitis virus infection and subsequently becomes infected with another type, it is called superinfection. The official naming format for confirmed diagnoses combines clinical classification with etiological classification, with histological examination attached afterward. For example: (1) Viral hepatitis (Type A; simultaneous infection of Type A and Type B) **Acute jaundiced type (acute non-jaundiced type) (2) Viral hepatitis (Type B; overlapping infection of Type B and Type D) Chronic (moderate) inflammation activity level 2, fibrosis level 3 (3) Viral hepatitis (Type C) Subacute severe early (middle; late) (4) HBsAg carrier recently infected with another type of hepatitis can also write as follows: ① Viral hepatitis (Type A; Type E) Acute jaundiced type ② HBsAg carrier who is negative for markers of Types A, B, C, D, and E can be diagnosed as:CamScanner Created

① Acute (chronic) viral hepatitis (etiology undetermined) or ② Chronic hepatitis (viral or autoimmune undetermined) III. Pathological Histological Diagnosis Acute hepatitis is mainly characterized by inflammation, degeneration, and necrosis, with little fibrosis; chronic hepatitis, in addition to inflammation and necrosis, exhibits varying degrees of fibrosis, and may even progress to cirrhosis. We recommend classifying both acute and chronic hepatitis based on etiology. For chronic hepatitis, we also classify the degree of inflammatory activity and the degree of fibrosis (G04) and stage (S04), striving for specific criteria. This approach not only helps standardize procedures but also facilitates dynamic observation, monitoring treatment efficacy, accumulating research data, and deepening our understanding of the natural patterns of various types of viral hepatitis. Appendix: Grading and Staging Standards for Chronic Hepatitis

| > Degree of Inflammatory Activity(G) | > Degree of Fibrosis(S)

Level | Portal Area and Surroundings | > Intrahepatic Lobules | > Stage | > Degree of Fibrosis 0 | > No Inflammation | > No Inflammation | > 0 | > None 1 | > Portal Area Inflammation | > Degeneration and a Few Necroses | > 1 | > Expansion of Portal Area, Fibrosis | > (CPH) | | | 2 | > Mild PN | > Degeneration, Spot and Focal Necrosis or Preference | > 2 | > Fibrous Separation around Portal Area, Fibrous Septa | > | > Acidophilic Bodies | | > Formation, Preservation of Lobular Structure | > (Light CAH) | | | 3 | > Moderate PN | > Severe Degeneration and Necrosis or BN Seen | > 3 | > Fibrous Septa Accompanied by Disruption of Lobular Structure(dis- | > | | | > Tortion), No Cirrhosis | > (Medium CAH) | | | 4 | > Severe(PN) | > BN Range Wide, Involving Multiple | > 4 | Early Cirrhosis or Definite Cirrhosis | > (Severe CAH) | > Lobules, Lobular Structure Distorted(More | | | | > Lobular Necrosis) | | For liver biopsy specimens, we recommend making consecutive sections, and in addition to routine HE staining, performing reticular fiber staining to show the degree of intrahepatic fibrosis, while also conducting immunohistochemical staining. Institutions with the necessary resources can, as needed, carry out in situ hybridization and in situ PCR to help determine the pathogen and the state of viral replication. (1) Acute Viral Hepatitis

1. Acute mild hepatitis The main lesions are located within the lobules, manifested as hepatocyte swelling (edema), acidophilic change, fatty change (mainly seen in hepatitis C), spot and focal necrosis, acidophilic

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bodies, infiltration of mononuclear cells in the hepatic sinusoids, proliferation of sinusoidal endothelial cells (often more pronounced in hepatitis C). Some cases show a certain degree of intrahepatic bile stasis, with bile plugs in the hepatic capillaries, necrotic foci, and small clusters of pigment-phagocytic cells in the sinusoids. Patients with jaundice exhibit these changes more obviously, sometimes lasting for a longer period. Inflammation in the portal area is often not prominent in hepatitis B, whereas it is more noticeable in other types; in hepatitis A and E, the portal area often shows more plasma cell infiltration, while in hepatitis A, lymphocytes and plasma cells are often seen infiltrating the periphery of the hepatic lobules. In some cases, hepatocyte shedding occurs, resembling fragmented necrosis. Inflammation in the portal area is more obvious in hepatitis C, sometimes presenting as follicular-like lymphocyte aggregation, with damage to the epithelial cells of the small bile ducts.

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2. Acute hepatitis with bridging necrosis, also known as more severe acute hepatitis. Group
   Histological changes, apart from central zone band-like necrosis, are otherwise similar to those of mild acute hepatitis. The prognosis is relatively good; necrotic lesions can gradually recover, and it rarely progresses to chronic hepatitis.

(II) Chronic Viral Hepatitis
The pathological diagnosis of chronic hepatitis should include the etiology and be classified into mild, moderate, and severe degrees according to the extent of lesion.

1. Mild chronic hepatitis (including original CPH, CLH, and mild CAH): G1–2, S0–2
   (1) Hepatocellular degeneration, punctate and focal necrosis, acidophilic bodies.
   (2) Inflammatory cell infiltration in the portal areas, with or without enlargement; mild piecemeal necrosis may be observed.
   (3) Lobular architecture remains intact.
2. Moderate chronic hepatitis (equivalent to original moderate CAH): G3, S2–3
   (1) Marked inflammation in the portal areas, accompanied by moderate piecemeal necrosis.
   (2) Severe intrahepatic inflammation, with bridging necrosis.
   (3) Fibrous septa form, and most lobular structures are preserved.
3. Severe chronic hepatitis (equivalent to original severe CAH): G4, S3–4
   (1) Severe inflammation in the portal areas or accompanied by severe piecemeal necrosis. (2) Extensive bridging necrosis involving most lobules.
   (3) Numerous fibrous septa, leading to disorganized lobular architecture or early cirrhosis.
   PN: Piecemeal necrosis (PN). CLH portal area inflammation—G scan all-in-one created by King Scan

0–1, intrahepatic inflammatory activity can range from G1 to G3. When there is inconsistency between portal and intrahepatic inflammatory activity grades, the higher grade shall prevail.
Mild: Partial involvement of portal areas, with limited disruption of the limiting plate.
Moderate: Extensive involvement of portal areas, with up to 50% disruption of the limiting plate; the periphery of the lobules is more noticeably affected.
Severe: Widespread inflammation around the enlarged portal areas, extending deep into the central zone of the lobules, with severely irregular lobular boundaries.
Residual single hepatocytes or hepatocytes arranged in acinar patterns surrounded by fibrous tissue may be observed. BN: Bridging necrosis (BN). It is a more extensive form of confluent necrosis, categorized into three types based on the connection site:
(1) Portal-to-portal (P-P) BN, mainly formed by portal inflammation and PN.
(2) Portal-to-central (P-C) BN, where the central zone of the hepatic acinus merges with portal inflammation and necrosis, often accompanied by PN, frequently disrupting lobular structure.
(3) Central-to-central (C-C) BN, where necrotic foci in the central zones of two lobules merge; this type of BN tends to heal more easily. The pathological diagnosis of chronic hepatitis includes etiology and degree of lesion (grading and staging).

(III) Severe Hepatitis

1. Acute severe hepatitis: Clinically presents as severe hepatitis, with massive hepatocellular necrosis (necrotic area ≥ 2/3 of the liver parenchyma), submassive necrosis, or large focal hepatic necrosis, accompanied by severe hepatocellular edema.
2. Subacute severe hepatitis: Pathologically characterized by mixed old and new submassive necrosis (necrotic area ≤ 50%); clumps of regenerating hepatocytes appear at the periphery of the lobules; bile duct proliferation occurs, often merging with proliferating hepatocytes, leading to severe cholestasis, especially prominent in the peribiliary ducts and interlobar bile ducts.
3. Chronic severe hepatitis: Lesion characteristics involve the appearance of massive (whole-lobule) or submassive fresh hepatic parenchymal necrosis on the basis of pre-existing chronic liver disease (chronic hepatitis or cirrhosis).

Scan All-in-One Created (IV) Cirrhosis

1. Active cirrhosis: Cirrhosis accompanied by obvious inflammation.
2. Quiescent cirrhosis: Few inflammatory cells in the septa surrounding pseudo-lobules.

IV. Principles of Treatment for Viral Hepatitis
Although many therapies exist for viral hepatitis, due to the lack of rigorous randomized controlled trials, it is difficult to definitively conclude the efficacy of many drugs. In the future, attention should be paid to evaluating existing treatments for hepatitis, eliminating those with unclear effects, and seeking more reliable and effective methods. Treatment should be tailored according to different pathogens, clinical types, and histological damage. Continued exploration of integrated traditional Chinese and Western medicine approaches is encouraged, with emphasis on mobilizing healthcare professionals and patients, fostering close cooperation, and improving therapeutic outcomes.