Hepatitis cB17.1

Author:Prof. Dr. med. Peter Altmeyer

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Last updated on: 06.06.2022

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Synonym(s)

C-hepatitis; HC

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DefinitionThis section has been translated automatically.

Acute or chronic liver inflammation caused by the hepatitis C virus, an RNA virus usually transmitted parenterally and belonging to the flavivirus group. There are 6 known genotypes (GT1 - GT 6) and >100 subtypes of the hepatitis C virus. Acute hepatitis C infection (20% of adults) causes the typical symptoms of acute viral hepatitis, including anorexia, malaise, and jaundice. Fulminant hepatitis and death may occur. Chronic hepatitis C infection is by far the most common manifestation, affecting 80% of adult infected individuals. Multiple infections with versch. Subtypes are possible. An expired HCV infection does not protect against reinfection!

Hepatitis C is a notifiable disease. The attending physician must report the disease by name to the responsible public health department if acute hepatitis C is suspected, if the disease is present, and in the event of death.

PathogenThis section has been translated automatically.

Transmission of the virus occurs through blood or blood products (10-30% of all posttransfusional hepatitis; risk today 1:15 million blood units); increased prevalence in drug-addicted homosexual men, after organ transplantation, during hemodialysis; vertical transmission from HCV-positive mothers to the child possible (<10%).

The most important transmission routes today are the shared use of needles and syringes among drug addicts, and piercing or tattooing performed under poor hygiene conditions. The risk of transmission during unprotected sexual intercourse is estimated to be low at 1 to 2%. Transmission through saliva or excretory secretions, via open wounds or toothbrushes is unlikely.

Receptor for hepatitis C virus (HCV) in hepatocytes is CD81. Association with CLDN1 and the CLDN1-CD81 receptor complex is essential for HCV entry into the host cell. CD 81 is specifically required for the infectivity of hepatocytes by Plasmodium falciparum, which controls the entry of sporozoites into hepatocytes via the parasitophorous vacuoles and the subsequent differentiation of the parasites into exoerythrocytic forms.

Incubation period (ICZ): 2-12 weeks

Occurrence/EpidemiologyThis section has been translated automatically.

The virus was discovered in 1989. According to the WHO, up to 150 million people worldwide are chronically infected with HCV. Prevalence in Germany 0.3% (GT1=78%, GT2/3=18%, T3=4%, GT5/6=1%), in the Mediterranean region 2-3%, in Egypt 22%. Worldwide, HCV infection causes about 30% of all cirrhosis diseases and 35% of primary liver cell carcinomas.

Clinical featuresThis section has been translated automatically.

Acute HCV infection:

Note: In about 75-80% of cases hepatitis C goes unnoticed. In about 20% of the affected persons it heals without permanent damage. About 80% of patients develop a chronic course in asymptomatic infection. In about ¼ of the patients the infection proceeds symptomatically with the classic course of acute hepatitis.

Incubation period: The virus multiplies and spreads without causing clinical symptoms. (Incubation periods: HBV: 1-6 Mo.). Early highly replicative phase. HBV viruses are completely produced.

Stage of hepatic organ manifestation: Prodromal or preicteric phase: Occurrence of non-specific symptoms such as subfebrile temperatures, loss of appetite, feeling sick, nausea and vomiting, a newly developed aversion to cigarettes and fats (fat intolerance), often pain in the right upper abdomen.

Icteric hepatitis C (only 25% of infections are icteric): this phase lasts 2-4 weeks: after 3-10 days, the urine turns dark, followed by icterus. Although icterus increasingly (climax of icterus after 7-14 days) significant improvement of general condition. Hepatomegaly, liver pressure pain, liver edges remain soft and smooth. Low splenomegaly in 15-20% of patients. Itching due to cholestasis.

Anitic acute hepatitis C (75% of cases) typically manifests itself as a flu-like disease and as such is usually not recognized. Acute hepatitis C can heal after 4-8 weeks. Fulminant courses are rare with 0.5% of the cases

Chronic hepatitis C: 75-80% of hepatitis C infections are chronic (in chronic hepatitis C, the hepatitis is still not cured after 6 months). The HC virus continues to persist in the blood, lymph nodes and other organs (this multilocular viral persistence is the reason why, in hepatitis C-infected patients, after a liver transplant, the virus re-infects the new organ; the hepatitis C viruses from the lymph nodes multiply again and reinfect the transplanted liver). Untreated, chronic hepatitis C can lead to liver cirrhosis after about 25 to 30 years. A spontaneous healing is then unlikely. In most cases chronic hepatitis C goes unnoticed for many years. Non-specific symptoms such as fatigue, upper abdominal pain and reduced performance may be present. A small proportion of patients complain of itching, dry skin and joint complaints. In these patients there is a risk of developing primary hepatocellular carcinoma (2-5% probability). Alcohol consumption, fatty liver, infection with other hepatitis viruses play a "co-etiological" role.

HIV/HCV double infections are characterised by rapidly progressive clinical courses. Often cholestatic course.

HCV infection in children: only rarely chronic hepatitis and cirrhosis of the liver.

Pregnancy and hepatitis C: The risk of vertical virus transmission from mother to child is <5% during pregnancy as well as during delivery (= significantly lower than for hepatitis B). There is no reason to advise chronically infected mothers against breastfeeding - according to previous studies. However, it is important to ensure that neither the nipples of the nursing mother nor the baby's mouth have open, bloody cracks to prevent blood-blood transmission.

ImagingThis section has been translated automatically.

Sonography: Sonography allows a rough assessment of the condition of the liver. Cirrhosis, but also changes in the structure of the liver caused by hepatitis and the consequences such as splenomegaly or ascites can be detected. Exclusion of masses within the liver.

Elastography/ ARFI: Transient elastography is an ultrasound method to determine liver stiffness (associated with the degree of liver fibrosis). It can be repeated at regular intervals without great effort to monitor the course of the disease.

LaboratoryThis section has been translated automatically.

Microbiology

Serology: 1-2ml serum

Direct detection:

  • PCR for the amplification of HCV DNA after prior reverse transcription of HCV RNA. Detects active HCV infection. Positive 20 days after infection.
  • Quantification of HCV-RNA by PCR to assess the effect of therapy and determine the duration of therapy.
  • HCV genotype determination (serologically or by PCR) for prognosis and determination of therapy. Determination of double infections with relevance to therapy.

Serological antibody detection:

  • IgG-AK: are detectable from week 4-6 by ELISA. Lifelong persistence in chronic hepatitis. Correlation with bigamy. In case of healing under medication no AK is detectable.
  • IgM-AK: often not detectable in mild courses of acute hepatitis C. With acute attacks of chronic hepatitis C. Hepatitis C only detectable in 50% of patients.

Genotyping:

  • In addition to the viral load, the so-called hepatitis C genotype is important for the response to treatment. Currently, genotypes 1 to 6 are distinguished. In Germany, genotype 1 is the most common (78%) and, together with genotypes 2 and 3, represents almost the entire pool of HCV infections.

General laboratory:

BSG↑; CRP↑; Liver function tests: Bilirubin mostly elevated: 2-3mg/dl; Increase of transaminases (500-3.000U/l); GPT>GOT (GOT/GPT = so called de Ritis Quotient <1); Cholestasis parameter ↑. Possibly only a slight increase of the gamma-GT. Furthermore: determination of prothrombin time or INR; increase of serum iron, possibly increase of gamma globulin fraction in electrophoresis. Blood count: possibly lymphocytosis. Virus serology to determine virus type and antigen/antibody status.

Liver values increase early during the prodromal phase, reach their peak before the icterus is maximal and then slowly decrease during the convalescence phase. Bilirubin excretion in urine usually precedes the icterus. Hyperbilirubinemia is differently pronounced in acute viral hepatitis. However, their differentiation has no clinical benefit. Alkaline phosphatase is usually only moderately elevated, strong elevations suggest the suspicion of extrahepatic cholestasis and trigger imaging procedures (e.g. sonography).

ANA positive in 20% of cases, LKM1 antibodies (antibodies against Liver Kidney Microsome Antigen - especially positive in autoimmune hepatitis) can also become positive.

Alpha-fetoprotein: Since patients with chronic hepatitis C have a significantly increased risk of primary hepatocellular carcinoma, alpha-fetoprotein should be determined as a tumor marker at regular intervals of 6 months. An increase in alpha-fetoprotein can indicate liver carcinoma.

HistologyThis section has been translated automatically.

Analysis of the inflammatory activity and the degree of connective tissue remodelling (fibrosis/cirrhosis). Necessary in chronic hepatitis C.

DiagnosisThis section has been translated automatically.

Clinic, imaging techniques, microbiology with virus typing; general laboratory.

Complication(s)This section has been translated automatically.

Extrahepatic complications:

S.a. Hepatitis C Skin changes

TherapyThis section has been translated automatically.

Antivirals and pegylated interferon alpha are used to treat hepatitis C. A protective vaccination against hepatitis C does not exist. In contrast to hepatitis A and B, healed hepatitis C does not leave behind any permanent immunity. Reinfections are possible.

Acute hepatitis:

  • Monotherapy with pegylated interferon-alpha (1x/week) for 24 weeks. Therapy success >95%; HCV-RNA negative 12 weeks after end of therapy.

Chronic hepatitis:

  • Indication for antiviral therapy. Always combination therapy. Combination of substances and duration of therapy depends on genotype, antiviral pre-therapy and stage of liver disease (cirrhosis stage) (therapy in special centres). Interferon-based therapies are no longer used in chronic hepatitis C infection:

virustatics:

  • Protease inhibitors (Graoprevir, Paritaprevir, Simeprevir)
  • NS5A inhibitors (Ledipasvir, Elbasvir, Daclatasvir, Ombitasvir, Velpatasvir). Note: NS5B is the acronym for "Nonstructural protein 5A", a zinc-binding proline-rich hydrophilic phosphoprotein of the hepatitis C virus.
  • NS5B inhibitors (Non-nucleosidic polymerase inhibitors: sofosbguvir, dasabuvir)
  • NS3A/NS4A inhibitors (Simeprevir, Paritravir)
  • Combinations of NS5A/NS5B inhibitors or multi-inhibitors against NS3, NS5A/NS4A, NS3A.
  • Note: In most cases, combination therapy is carried out with ribavirin (ribavirin blocks the multiplication of hepatitis C viruses). The type of combination therapy and duration depend on the genotype of the virus, antiviral pre-therapy (if necessary, exclusion of resistance), stage of hepatitis. These therapies are well tolerated and have a low rate of side effects. Healing rates of up to 99 percent, depending on pre-treatment and degree of fibrosis/cirrhosis. Disadvantage (high therapy costs).

ProphylaxisThis section has been translated automatically.

In Germany, blood preserves are checked for hepatitis C as standard. Persons who come into contact with blood or blood products for professional reasons (such as nursing staff, doctors, nurses, paramedics) should carefully protect themselves from direct contact. Protective gloves are also recommended when caring for people infected with hepatitis C. Objects that have come into contact with blood or other body fluids of the infected person should be thoroughly treated with virostatic disinfectants. Dispose of cannulas in shatterproof containers. In case of frequently changing sexual partners, condoms should be used consistently.

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Last updated on: 06.06.2022