bubble_chart Overview

Hepatitis C is a pestilence caused by the hepatitis C virus. This disease is distributed worldwide and is primarily transmitted through blood transfusion or blood products, especially with repeated transfusions from multiple donors. In recent years, hepatitis C has also been found to be common among non-transfusion populations, mainly spreading through injections, needle sticks, wounds contaminated with HCV-infected blood, and other close contacts. It has also been confirmed that mother-to-child transmission can occur.

bubble_chart Pathogen

Research has confirmed that the HCV genome is a linear, single-stranded, positive-sense RNA virus belonging to the Flavivirus genus. It consists of a coding region, a 5'-non-coding region, and a 3'-non-coding region. The coding region includes two parts: the structural region and the non-structural region. The former is relatively conserved, while the latter is prone to variation. The structural region is divided into the C region, M region, and E region, encoding the core protein, matrix protein, and envelope membrane protein, respectively, which together form the viral particles. The non-structural region consists of the NS₁, NS₂, NS₃, NS₄, and NS₅ genes, encoding the NS₁, NS₂, NS₃, NS₄, and NS₅ proteins, respectively. Among these, the NS₁ protein may be a soluble complement-binding antigen, NS₃ is the helicase of HCV-RNA, and NS₅ is the RNA-directed RNA polymerase of HCV-RNA. Thus, the main function of the structural proteins is a characteristic feature of HCV, with the C gene being the most conserved, followed by the 5'-non-coding region, while the E gene is a highly variable region. The antigenic variation of the encoded envelope membrane protein allows the virus to evade the host's immune response.

In vitro cell culture of HCV has not yet been successful. It primarily replicates within hepatocytes.

HCV-RNA genotyping: Domestic reports indicate that the predominant HCV genotypes in China are type II and type I. Type II HCV has a poor treatment response. Further research is needed to address issues such as the varying liver injuries caused by different HCV genotypes and their responses to interferon therapy.

bubble_chart Pathogenesis

It was previously believed that HCV directly damages hepatocytes. In recent years, with the deepening of research on hepatitis C, it has been recognized that hepatitis C shares many similarities with hepatitis B, such as progression to chronicity, development of cirrhosis and hepatocellular carcinoma. Notably, hepatitis C also has chronic HCV carriers. Therefore, the prevailing view on the mechanism of HCV-induced hepatocyte damage leans toward immune-mediated injury, where cytotoxic T cell-mediated cellular immune responses play a significant role.

bubble_chart Pathological Changes

The pathological changes are essentially the same as those of hepatitis B, differing only in the location and severity of the lesions. There are no characteristic pathological changes of sexually transmitted diseases.

bubble_chart Clinical Manifestations

The incubation period for post-transfusion hepatitis C is 2–26 weeks, with an average of 7.4 weeks. The incubation period for sporadic hepatitis C remains undetermined. The clinical course is generally mild, with subclinical cases being more common, and severe hepatitis is rare. Compared to hepatitis B, the average levels of ALT and bilirubin are lower, jaundice duration is shorter, the condition is milder, and fever is less common. Common symptoms include fatigue, loss of appetite, and most cases do not present with jaundice, with isolated ALT elevation being a persistent or recurrent feature. However, the rate of progression to chronic hepatitis is higher than that of hepatitis B (40–50%), and non-jaundiced cases are more prone to chronicity than jaundiced ones. The remaining cases recover within six months, following a self-limiting course. Chronic hepatitis C often presents with recurrent ALT abnormalities, elevated AST, and rapid onset of protein metabolism disorders, while signs such as spider angiomas, palmar erythema, and splenomegaly are less pronounced than in hepatitis B.

bubble_chart Auxiliary Examination

Clinical significance of anti-HCV and HCV-RNA testing

1. Anti-HCV

Most HCV-infected individuals develop anti-HCV antibodies. Therefore, detecting anti-HCV is valuable for diagnosing hepatitis C. A positive anti-HCV result indicates HCV infection. However, current test results cannot fully distinguish between acute, chronic, or convalescent stages of infection. Antibody titers also do not reflect the intensity of HCV infection, at least not confirmed in animal studies. A positive anti-HCV may indicate recent infection or an immune state post-infection, but in most cases, it signifies current HCV infection and, to some extent, reflects the individual's infectiousness. The time from HCV infection to anti-HCV seroconversion varies greatly among individuals. Current methods detect antibodies relatively late, and during this period, the only marker of infection may be HCV RNA. Additionally, about 20% of hepatitis C patients never develop anti-HCV, so the actual infection rate is higher than the detection rate. A negative anti-HCV result does not rule out HCV infection.

Post-transfusion hepatitis C is well-documented. After HCV infection, individuals may exhibit four types of responses: ① Those transfused with high-titer anti-HCV-positive blood may test positive for anti-HCV immediately after transfusion, turning negative after 5 weeks. Later, anti-HCV autoantibodies may reappear and persist; ② Delayed anti-HCV response with sustained positivity, typically seroconverting 20–22 weeks post-transfusion or 14–16 weeks after illness onset, rapidly peaking and remaining positive for over 10 years; ③ Delayed short-term anti-HCV response, seroconverting 19–21 weeks post-transfusion or 9–11 weeks after illness onset, turning negative after 1 year; ④ No response, often seen in transient HCV infections where anti-HCV remains negative.

Currently detected anti-HCV IgM differs from IgM responses to other viruses: ① IgM appears later than IgG; ② IgM persists for a long time, at least 3–8 years or longer; ③ IgM titers correlate positively with IgG titers; ④ Secondary IgM antibody responses occur. This indicates that anti-HCV IgM cannot serve as an early diagnostic marker for HCV infection or distinguish recent from past infections. However, it may reflect chronic infection or viral carriage and can be used as a prognostic and treatment efficacy indicator.

2. HCV-RNA

Due to the low HCV load in the blood of hepatitis C patients, direct nucleic acid hybridization rarely detects HCV-RNA. Nucleic acid amplification is required first. Semi-quantitative polymerase chain reaction (HCV cDNA/PCR, or cPCR) to measure HCV RNA in the liver and serum offers high specificity, sensitivity, and speed. A positive HCV RNA result is direct evidence of HCV infection, indicates viral replication, and confirms infectiousness. Since HCV RNA appears earlier than anti-HCV, it can be used for early diagnosis and donor screening. A negative HCV RNA result suggests HCV clearance, making it useful for assessing prognosis and treatment efficacy.

bubble_chart Diagnosis

In principle, a comprehensive diagnosis should be made. Refer to epidemiological data, such as history of blood transfusion and blood product use, surgical history, and close contact with hepatitis C patients; clinical characteristics and routine laboratory tests. Definitive diagnosis relies on specific serological tests.

1. Enzyme-linked immunosorbent assay (ELISA) to detect anti-HCV in serum

Since 1989, the earliest method used to detect anti-HCV was the ELISA method, using C₁₀₀ and 5-1 as antigens, but its sensitivity and specificity were not ideal. Later, the second-generation ELISA method was introduced, adding core proteins C₂₂ and C₃₃, which improved sensitivity. Recently, third-generation reagents have been developed, incorporating the NS₅ protein, making them more sensitive than second-generation reagents.

2. HCV cDNA/polymerase chain reaction (PCR) to detect HCV-RNA in liver and serum

This method involves reverse transcribing HCV RNA into HCV DNA, amplifying it, and then observing the results via electrophoresis. Strict operational procedures must be followed to avoid laboratory contamination.

bubble_chart Treatment Measures

The general treatment is the same as for hepatitis B. Antiviral therapy is under exploration.

1. Alpha-interferon (α-IFN)

has certain efficacy in treating chronic hepatitis C. After treatment, the serum HCV RNA negative conversion rate can reach 50-80%, but about half of the patients may revert to HCV RNA positive after discontinuation, and α-interferon remains effective upon re-administration. Along with the negative conversion of HCV replication indicators, improvements in liver function and hepatic lesions can be observed, suggesting that interferon inhibits HCV but cannot completely eliminate the virus. Relapse often occurs 6-12 months after treatment. If ALT remains normal and serum HCV RNA is negative for 12 months post-treatment, a cure may be possible. The reasons for relapse include: ① different viral genotypes—generally, type III responds better to IFN therapy than type II; ② emergence of mutant strains; ③ incomplete viral clearance; ④ resistance to antiviral drugs. Some reports indicate that interferon is more effective in treating sporadic hepatitis C than post-transfusion hepatitis C. For acute hepatitis C, if ALT abnormalities persist for more than 6 months, interferon therapy should be initiated. Commonly used is interferon α-2b (Intron A), administered as follows: 3 million units intramuscularly once daily for 2 weeks, then 3 million ^units intramuscularly every other day for 14 weeks. The general treatment course lasts 3 to 6 months. Increasing the interferon dose and extending the treatment duration (12 months or longer) may improve efficacy, with a short-term response rate of 50%.

2. Ribavirin

is a broad-spectrum antiviral drug, but its efficacy in treating chronic hepatitis C is inferior to interferon. It does not significantly reduce serum and liver HCV-RNA levels.

bubble_chart Prevention

1. Screening blood donors for anti-HCV is currently an important measure to reduce post-transfusion hepatitis C.

2. Managing the source of pestilence

Isolate patients by hepatitis type and use disposable medical supplies; promote knowledge on hepatitis C prevention and treatment, and adhere to disinfection and isolation protocols.

3. Cutting off transmission routes

Sterilize medical instruments after each use and adopt disposable medical supplies; strictly control indications for blood, plasma, and blood product transfusions; ensure the quality of blood and blood products.

4. Protecting susceptible populations

Reports suggest that immunoglobulins are effective in preventing hepatitis C, with a dosage of 0.06ml/kg administered intramuscularly. The ultimate control of this disease relies on vaccine prevention. The successful molecular cloning of HCV provides the foundation for vaccine development against this disease.