The HCV viral hepatitis or hepatitis C
Definition: This is an RNA virus, a distant relative of flavivirus, which is the yellow fever virus, a single chain with a single reading frame, fitted with a capsid of 50-60 nm size, containing amino acids 3011 and 9033 nucleotides; has a core and a shell, and NS non-structural domains and antigen polyprotein encoded, C22, C33, C100. The virus has several HCV genotypes, which does not connote infections of different clinical significance or different prognosis, but whose distribution has important therapeutic implications, because some genotypes are more sensitive to interferon, IFN. LIPA with the test, you can distinguish six main types: 1, 1a, 1b, 1a/1b, 2, 2a/2c, 3, 4, 5a, 6a.

Geographic distribution of major genotypes in Italy in%.

areas
No. HCV1 HCV2 HCV3
NORTH (244)
51 34 11 4
CENTER (57) 56 33 9 2
SOUTH (66) 56 35 3 6
Sicily (44) 91 7 2

Epidemiology: the 0.5-1.5% of blood donors are carriers of HCV, in Japan, 1, 3% of the subjects was a carrier, in the U.S., in New York from 0.9 to 1.4% of subjects had experienced blood donors and HCV was positive in Africa to get up by 6%, a study shows that the infection may be acquired infection perinatally from an infected mother, established in this way the status of "carrier" virus in a totally asymptomatic. Those at risk are, however, hemophiliacs who were infected through blood products, necessitating factor VIII antibody and with a rate of 70%, equal with the addicts in the mood, 76% positivity in dialysis is remains at around 10-30% in some studies leading to 55%, 4% in homosexuals. Even the spouses of HCV + subjects, hemophilia, for example, were infected through sexual intercourse and how this is possible if the reports are frequent in a Spanish study 6% of partners of drug users was positive subjects. However the virus in body fluids is difficult, but the secretions of carriers of HCV with HCV RNA testing positive were infected (urine, feces, saliva, breast milk). A study of prostitutes who used condoms showed a HCV prevalence of 7% compared with the group not used it, 20%. In normal marital relationships that primacy aggura between 0 -5%, depending on the group. Medical personnel, such as surgeons have a prevalence of HCV of 6.3%, dentists in New York, for example, 17%.

So is hepatitis drug addicts and from my study suggests that co infection is already after some years of addiction. In polytransfused seroconversion to HCV varies between 50% and 85%;

Clinical forms:

course of acute hepatitis C;

hepatitis C to chronic course.



Acute hepatitis C.

The acute form has an incubation period of 5-12 weeks, on average seven weeks, the symptoms are given by general malaise, drowsiness, nausea, abdominal tenderness, the patient is jaundiced rarely, in only 25% of cases, while in the subject HIV positive form can be rapidly progressive course. Noteworthy extrahepatic manifestations such as arthritis, rashes, glomerulonephritis and periaterite nodosa, aplastic anemia. Fulminant evolution has never been observed in a study of 500 patients Diestag. A fulminant form may occur if the person is suffering from other chronic hepatitis. In one patient, positive HBsAg, polytransfused, undergone prosthetic valve surgery after a blood transfusion, was observed after 12 settinane a rise in transaminases with jaundice and intense development of encephalopathy, after 5 years had the exitus of the patient for complications cirrhotic ascites and encephalopathy. In any case, the person infected with HCV, HCV RNA appears early after just one week after the transfusion, for example, ie 5-6 weeks prior to the rise in AST, which appears after 6-7 weeks, with a peak at 8 weeks to 12 weeks and stabilization in the meantime you can with ELISA 2 and RIBA 4, detection of antibody against the viral proteins C22 and C33, already by 11 weeks, while the C100 antibody, the ELISA test generation is apparent only after 4-6 months of infection.



Hepatitis C infection.

Despite the benign primary infection, exposure to HCV is burdened with a significant risk of chronicity. It is estimated that not less than 75% of exposed subjects develop a chronic infection. It should be stressed that neither the normality of ALT and AST or a test for HCV RNA negative after the acute episode provides healing has occurred. The assessment of healing involves testing negative for HCV RNA at 18-24 months after primary infection when defenses are low, eg. in immunosuppressed and drug into the vein, where heroin use is the basis of a deficient immune response by inhibiting cell helpers. Clinically, the chronic forms are sometimes characterized by a small fluctuation of ALT and AST, for fatigue, increase of YGT and decrease in platelets, unrelated to other signs of portal hypertension, splenomegaly, varices. The biopsy finding is a 'chronic active hepatitis with mild or moderate inflammation and mild fibrosis. With the progress of the inflammatory process, however, determines the appearance of nodules of regeneration, to cirrhosis.



Diagnosis.

Relies on laboratory tests on blood, to search for a movement of transaminases, AST and ALT, total bilirubin and split, etc. YGT. It is also possible to know if there is infected, eg. after un'emotrasfusione suspect after a few weeks, with the PCR test to search for HCV RNA after 11-12 weeks, with tests of second and third generation ELISA and RIBA 4, detection of antibodies to viral proteins C22 and C33 where once there were only the 1st-generation ELISA test for antibodies to search for viral antigens C100-3 and thereafter, especially in chronic forms, once established seropositivity for HCV, you need to know if the infection is under way and the virus multiplies or, rather, has been exceeded .. Therefore it is necessary to carry out checks for HCV RNA quality and quantity to "weigh" the copy and the results of viral treatment. In fact, the healing process is long and difficult. LIPA with the test, however, it is possible to distinguish six main types: 1, 1a, 1b, 1a/1b, 2, 2a/2c, 3, 4, 5th, 6th and that for treatment with interferon (IFN). Before beginning treatment with IFN, however, consideration should be some parameters: blood count, platelets, BUN, creatinine, FT3, FT4, TSH, antibodies antitireoglobulina, antimicrosomi, ANA, SMA, ANTI-LKM, because use of IFN is not no side effects, not least problems of hypo and hyperthyroidism, and also in patients with autoimmune hepatitis or autoimmune diseases, the use of interferon may exacerbate the disease. In patients with SMA and ANA <1:320, where the predominant viral form will be used recombinant interferon, in patients with antibody titers> 1:320, will be useful corticosteroid use. Finally, subjects with anti-LKM1 may have a viral infection and autoimmune reactivity, they can be used in recombinant interferon and corticosteroids, depending on the response.

HCV and chronic illness.

In subjects with chronic HCV infection may have separate movements autoantibody, the presence of cryoglobulins, ie antibodies that precipitate at temperatures below 37 °, cryoglobulins of type 1, monomer form of monoclonal Ig, usually IgM, or chains free light, and cryoglobulins of type 2, being a component monoclonal IgM and polyclonal IgG, type 3 consisting of IgM and IgG. Cryoglobulinemia may occur in the course of lymphoproliferative disorders such as multiple myeloma, Waldenstrom's disease, or monoclonal gammapathies. In the case of chronic HCV will evenieneza types C1/C2 and purple skin. Finally there is a relationship between HCV chronic hepatitis and not Hodgking lymphomas, usually in 20-30% of cases preceded by mixed cryoglobulinemia; immunocitomi these lymphomas were low grade malignant. Probably the same HCV may intervene in the genesis. Finally you can have hepatocellular carcinoma and cutaneous manifestations of erythema type handheld naevi racemosa, Dupuytren contracture, and lichen ruber planus, ie patches of deposit of lipofuscin itchy violaceous papules and limbs.



Therapy.

The current treatment relies on the use of IFN, but must be assessed case by case basis, balancing the risk of morbidity / mortality, life expectancy and benefit. There are no age limits, but the treatment has no meaning after 60 years, as it is unlikely that chronic liver disease can not yet cause problems for the patient than his life expectancy, however side effects are always larger at a certain age. A vision appears to be represented by PEG-IFN. Treatment with IFN in addition is contraindicated in patients with:

autoimmune diseases

alcoholism

thyroiditis

Cirrhosis

renal

psicodepressione

thrombocytopenia and myelosuppression



Doses and use of alpha-IFN

A multitude of studies show good results at doses of 3-6 million units every other day or 3 times a week for 6-12 months, with response rates seen as normalization of AST and ALT from 45% to 89%, the discontinuation of therapy is burdened with a very high relapse rate, approximately 50% of subjects.



Predictors of success are:

age <45 years

disease duration less than 6 years

low levels of HCV RNA (<1,000,000 copies / ml

HCV genotype 2 or 3.



Little success if:

presence of cirrhosis

presence of hemosiderosis in liver tissue

HCV genotypes 1 and 4

high levels of HCV RNA> 1 million copies.



Another protocol of the Italian Association for the Study of Liver recommends:

IFN 6 million units x 3 times a week for 4 months if transaminases normalize, you make another round of 2 months to 6 million + 3 million for six months to a year total.

Follow up of the patient:

every month: blood count, aminotransferases

every 3 months: Quick time, protein electrophoresis, autoantibody, thyroid function. In fact to be found antithyroid antibodies (antitireoglobulina and antimicrosomiali) in 12-15% of patients with chronic HCV infection, with onset of hypothyroidism and hyperthyroidism.

Who to treat?

Naive patients (naive)

with chronic active hepatitis, moderate or severe

with cirrhosis but at stage A Child

Mild chronic active hepatitis, young people in particular cases

patients relapsers

Liver transplant patients with HBV coinfection HIV / AIDS

acutely infected

with normal transaminases.

. Incurred Answers

genotype 1 (b) IFN 3MU x twice / week x 24 weeks 02.06% success

48 weeks x 9% success

genotype x 2.3 IFN 3 MU twice / week x 24 weeks 15% success

48 weeks x 32% success

Other treatments with IFN + ribavirin, a synthetic purine nucleoside.

The protocol is:



IFN five million units x 3 times a week subcutaneously plus ribavirin 1.2 g / day in 2-3 divided doses for 6 months, this treatment is not without side effects, eg. hemolytic anemia.



New perspectives from the pegylated, a recombinant interferon. What is pegylated? It 'a process that allows the attachment of one or more chains of polyethylene glycol (PEG) adalcune bases of the molecule. This will reduce the clearance and increase the duration of pharmacological and this allows one somminitrazione per week, which is thus given:

Today, 2004, according to guidelines presented last regional congress FADO Sicily, the most effective therapy consists of pegylated interferon (2a or 2b) plus ribavirin:



Patients with genotype 1 (and 4)

- Peg-IFN 2a: 180 microg / week

2b: 1.2 -1.5 microg / kg / week plus ribavirin 1000-1200 mg / day for 48 weeks

Patients with genotype 2, 3

- Peg-IFN 2a: 180 microg / week

2b: 1.2 -1.5 microg / kg / week plus ribavirin 800 mg / day for 24 weeks



These regimens based sull'IFN remain key for the next five years. New approaches are under study because patients are not responders with genotype 1b, the most promising drugs are targeted towards enzymes present in the HCV NS3/4A serine protease and NS5B polymerase



Other schemes:

at doses of 120-130 U / 1 weekly + ribavirin 1.2 g in 2 doses / day x 3-4 months, after assessing the values of ALT and continue until completion for 7 months;

In follow-up will control the following parameters:

CBC, BUN, creatinine, ANA, AMA, ASMA, ANTI-LKM, TSH, FT3, FT4, and antibodies antimicrosomi antitireoglobulina.

dr. Italiano Claudio

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