The Review of Transmission，Management in General practice and Humanity Factors involved in Hepatitis C Virus Infection

AhmadMeesaq,AlmajduiMajedAbdulazizS,GhandooraLualKhalilI,RaeiMaazAhmedM,AlhussainHadiMobarakS

【中圖分类号】R368 【文献标识码】A 【文章编号】2095-6851（2017）11--01

Introduction

Hepatitis C virus （HCV） infection affects more than 3% of the global population and poses a high economic burden. Between 130 and 150 million people are chronically infected with hepatitis C.Hepatitis C virus （HCV） remains the leading infectious cause of liver-related mortality in the developed world and accounts for approximately 700，000 deaths per year due to decompensated cirrhosis or hepatocellular carcinoma （HCC）1.HCV causes chronic hepatitis in 60%–80% of the patients， and 10%–20% of those patients develop cirrhosis over 20–30 years of HCV infection. About 1%–5% of the patients with liver cirrhosis may develop liver cancer and 3%–6% may decompensate during the following 20–30 years. The risk of death in the following year after an episode of decompensation is between 15% and 20%.HCV-associated disease is one of the leading causes of HCC and the main indications for liver transplantation.In addition， HCV infection increases the risk of type 2 diabetes mellitus and is associated with a number of extra-hepatic manifestations （arthralgia， cryoglobulinemia， skin manifestations， sicca syndrome and thyroid disorders） and increases the risk for circulatory diseases， kidney diseases， renal failure， cancers of the esophagus， prostate and thyroid and all-cause mortality.Chronic Hepatitis C Virus （HCV） is a growing public health concern. HCV is transmitted through exposure to infected blood and cannot be spread through intact skin or mucous membranes2. Globally， there are approximately 170 million people diagnosed with chronic HCV ， with 3 to 4 million new cases per year3. It has been estimated that approximately 30% of individuals infected with HCV are unaware that they have the disease . Approximately 350，000 deaths per year are attributed to a HCV related cause3.

History

Since its discovery in 19893， the hepatitis C virus （HCV） has been shown to be responsible for a chronic infection in up to 80% of infected people， with a possible evolution to major complications including cirrhosis and primary hepatocellular carcinoma3. According to the geographic area， 10% to 90% of liver transplants are due to complicated chronic hepatitis C.HCV is an RNA mono-stranded enveloped virus belonging to the Flavivirus family. Eleven genotypes are currently recognized with many subtypes within a same genotype. The infidelity of the HCV RNA-dependent RNA polymerase is mainly responsible for the huge variability of the viral genome， leading to the constitution of a quasi-species in chronically infected subjects.This variability together with a poor understanding of the pathophysiology of chronic HCV infection explains the present inability at developing an effective prophylactic vaccine.However， different therapeutic strategies have been elaborated since 20 years for curing HCV infection with the hope of eradicating definitively the infection when the treatment is initiated before the installation of severe liver lesions.endprint

Prevalence of HCV Infection

The worldwide prevalence of HCV infection was 2.8% in 2005 and 1.6% in 2014， equating to about 115 million persons positive for antibody to hepatitis C （anti-HCV） and 1.1% equating to about 80 million persons positive for HCV RNA4. The prevalence varies among geographic regions： regions with a high prevalence of over 3.5% include Central Asia （including Mongolia and China）， SouthEast Asia （including Pakistan and Thailand）， and North Africa （including Egypt）. Low prevalence （below 1.5%） regions are Asia （including South Korea and Japan）， North America （including the United States）， and South America4.

Transmission Dynamics

Hepatitis C virus （HCV） is a blood-borne pathogen that has a worldwide distribution and infects millions of people. Its transmission is mainly mediated by blood and by other fluids contaminated with blood.HCV is usually transmitted via blood in which viral load may be very high. This observation explains the impressive historical epidemic of HCV infections that occurred via blood products in transfused patients when no specific screening test was available for identifying infected donors. By contrast， sexual intercourse is not an efficient way for transmitting HCV， except in subjects with very high-risk sexual practices5. In addition to drug injection or nasal sniffing， all the situations exposing to contaminated blood may lead to HCV infection， including tattooing， piercing， use of razors and manICUre devices.The major mode of transmission of HCV are following：

1：Transmission of HCV from Infected to Non-infected Patients

There are many ways to transfer the virus from infected peoples to non-infected peoples.

（a）Transfusion of Blood

The administration of blood productsappears as a major risk factor for acquiring HCV infection in many parts of the world. In developed countries，with thesystematic implementation of laboratory test for the detection of HCV RNA by nucleic acid testing， the risk of acquiring HCV via blood products decreased dramatically. In developing countries the situation is more alarming： according to the WHO database on blood safety 39 countries performed no routine screening of HCV in blood products in 2012 and 47% of donations were tested in settings without quality insurance6. The eradication of HCV transmission blood screening is very necessary.

（b）Transmission in Hemodialysis Unit

The spreading of HCV infection is historically high in patients having hemodialysis.In developed countries， a significant decrease was observed during the last decades： from 10.4% in 1995 to 7.8% in 2002 in the United States； from 13.5%， 42% and 20% in 1991 to 6.8%， 30% and 16% in 2000 in Belgium， France and Italy， respectively[21].endprint

（c）Transmission by Sharing non-sterile Syringes

The unsafe therapeutic injections have been one of the major ways of spread HCV infection in the past and continue to be responsible for transmission both in developed and developing countries.During the 20th century， unsafe injections using contaminated syringes or needles were responsible for large epidemics that explain the high prevalence of HCV infections in Egypt，India and Italy.HCV contamination related to acupunctureproceeds of the same ignorance of the infectious risk attached to blood.

（d）Transmission by Organ Transplantation

Transplantation of organ or tissue from an infected donor may result in an HCV infection in the recipient. Because systematic HCV serology testing is performed in donors. However， in 2000 in Oregon， United States： a donor who was seronegative for HCV was sampled during the “window period” of his HCV infection （the patient was tested retrospectively positive for HCV RNA）， which led to the contamination of 8 recipients （3 organ and 5 tissue recipients）7.

（f）Vertical Transmission

There are several several potential transmission routes from an infected woman to her newborn： intrauterine， intrapartum， and postnatal.The most recent systematic review and meta-analysis showed that the risk was 1.7% among children born to all HCV antibody–positive women and 4.3% among children of HCV RNA–positive women . Presence of maternal HCV viremia is a critical factor in mother-to-child transmission of HCV and maternal HIV co-infection is an important risk factor.Other factors， such as mother's age， parity， HCV genotype， and breastfeeding， do not appear to be associated with the risk . Although there is some evidence that prolonged rupture of membranes may increase vertical transmission risk and cesarean delivery is not currently recommended as a risk-reducing intervention8.

2：Transmission from HCV Patients to Healthcare Workers

The probability of HCWs to be exposed to blood has HVC is higher than the general population because the prevalence of HVC persistent infection in hospitalize patients. The meta-analysis of 26 longitudinal studies performed by Henderson between 1991 and 2002.He recorded 2357 exposures for 44 HCV infections， which resulted in a percentage of contamination of 1.9. So the risk of exposure to HCV is approximately 10-fold less than the HBV risk， and approximately 10-fold higher than the HIV risk9. The most common ways of transfer of HCV from infected individuals to HCWs are following ： （a） Needle-stick injury containing blood from an infected patient. （b） During surgery exposure to contaminated blood.（c） Exposure to mucosal secretion containing blood. （d） Get injury from suture needles during suturing.endprint

3：Transmission from HCWs to Non-Infected Peoples

In 1991，the first cases of transmission of HCV from infected HCWs to non-infected patients were recognized . After the discovery of hepatitis B vaccine ， HCV has become the more prevalent blood-borne viral agent at risk to be transmitted occupationally by HCWs. Between 1991 and 2005， approximately 400 patients got HCV infection from 20 HCWs. The transmission of HCV commonly occurred during invasive procedures such as cardiothoracic surgery and gynecologist-obstetricians surgeries.

Clinical Manifestations

According to Centers for Disease Control and Prevention （CDC）， nearly 80% patients have no experience of symptoms with acute hepatitis C infection. In some cases， patients have experienced of symptoms after the virus has infected them which are following： （1）Fever （2） Anorexia and （3） fatigue.

Long-term infection with the hepatitis C virus （HCV） is known as chronic hepatitis C. Chronic hepatitis C is usually a silent" infection for many years， until the virus damages the liver enough to cause the signs and symptoms of liver disease. Among these signs and symptoms are：（1）Nausea/vomiting （2）Stomachache （3）Myalgia （4）Arthralgia （5） Jaundice （6）Ascites （7）Weight Loss （8） Bleeding （9） Bruising （10） Confusion （11）Drowsiness （12）Slurred speech （13）Dark color urine and （14） Spider angioma.

Screening，Diagnose and Assessment

The CDC recommends screening for HCV infections with an HCV antibody test when people： （1） Have ever injected illegal drug. （2） Received a blood transfusion or organ transplantation before 1992.（3） Babies born to mother with hepatitis C . （3） Abnormal liver function test with no identified cause. （4） Have ever received clotting factors before 1987. （5） Have evidence of chronic liver disease.（6） Long term dialysis. （7） HCWs who have been exposed to blood or accidental needle stick. （8） Sexual pattern diagnosed with hepatitis C infection. （9） Anyone born from 1945 to 1965. （10） Anyone who has been in prison.

An HCV antibody test is used to screen for past exposure and current infection.The Centers for Disease Control and Prevention （CDC） recommends that all positive antibody tests be followed by an HCV RNA test that detects viral RNA in the blood to determine whether or not the person has an active infection.

（1）HCV RNA test

RNA quantitative detects and measures the number of viral RNA particles in the blood. This test used to confirm the presence of the virus and diagnose an active infection. Viral load tests are also used before and during treatment to help determine response to therapy by comparing the amount of virus before and during treatment. RNA qualitative is used to distinguish between a current or past infection. It is reported as a positiveor detected if any HCV viral RNA is found； otherwise， the report will be negativeor not detected.endprint

（2）Viral Genotyping

It is used to determine the kind， or genotype， of the HCV present to help guide treatment. There are 5 major types of HCV and more than 50 subtypes identified； the most common， genotype 1， accounts for about 75% of cases. The drugs selected for treatment depend in part on the genotype of HCV infecting a person.

Table1：AssessmentofHCVtests

HCV antibodies HCV RNA HCV Infection

Negative No infection，too early after exposure ， repeated test

Positive/intermediate Negative Past infection， false positive screening

Weak/intermediate Positive Current infection

Management of HCV Infection

The goals of hepatitis C treatment are to eradicate HCV and to prevent complications of liver cirrhosis， hepatocellular carcinoma， extra-hepatic manifestations of HCV infection and death. The short-term goal of hepatitis C treatment is to achieve an SVR， defined as undetectable serum HCV RNA by a sensitive assay 12 or 24 weeks after the end of treatment. SVR was determined 24 weeks after the end of treatment using an assay with a lower limit of detection of <50 IU/mL in studies of combination therapy with Peginterferon （PegIFN）and ribavirin .Whereas it was determined 12 weeks after the end of treatment using an assay with a lower limit of detection of 10-25 IU/mL in studies on DAA therapy . According to American Association for the Study of Liver Diseases[AASLD]， the Infectious Disease Society of America[ISDA]， and the International Antiviral Society-USA[IAS-USA]， there are following recommendation10：

HCV genotype 1a infection

There are three options for treatment of patients with HCV genotype 1a infection as follows：（1） Dailyledipasvir （90 mg）/sofosbuvir （400 mg） for 12 weeks. （2）Daily daclatasvir （60 mg） and sofosbuvir （400 mg）， for 12 weeks （no cirrhosis） or 24 （cirrhosis）. （3） Daily sofosbuvir （400 mg） plus simeprevir （150 mg）， with or without weight-based RBV （1000 mg[<75 kg]to 1200 mg[≥75 kg]）， for 12 weeks （nocirrhosis） or 24 weeks （cirrhosis）.

HCV genotype 1b infection

There are generally three options for the treatment of genotype 1b as follows： （1）Daily ledipasvir （90 mg）/sofosbuvir （400 mg） for 12 weeks. （2）Daily sofosbuvir （400 mg） plus simeprevir （150 mg） for 12 weeks （no cirrhosis） or 24 weeks （cirrhosis）. （3） Daily daclatasvir （60 mg） plus sofosbuvir （400 mg） for 12 weeks （no cirrhosis） or 24 weeks（cirrhosis） （4）Daily paritaprevir （150 mg）/ritonavir （100 mg）/ombitasvir （25 mg） plus twice-daily dasabuvir （250 mg） for 12 weeks.endprint

HCV genotype 3

There are following medications used for genotype 2 treatment： （1）Daily daclatasvir （60 mg） plus sofosbuvir （400 mg） for 12 weeks（2） daily sofosbuvir （400 mg） and weight-based RBV （1000 mg[<75 kg]to 1200 mg[≥75 kg]） for 12 weeks or 16 weeks.

HCV genotype 3 and 4

For genotype 3 used following medication ： （1）Daily sofosbuvir （40mg） plus ribavirin for 24 weeks （2）Daily daclatasvir （60 mg） plus sofosbuvir （400 mg） for 12 . For genotype 4 used following medication ： （1）Dailyledipasvir （90 mg）/sofosbuvir （400 mg） for 12 weeks（2）Daily sofosbuvir （400 mg） and weight-based RBV （1000 mg[<75 kg]to 1200 mg[≥75 kg]） for 24 weeks.

Humanistic Care

Living with HCV indicates that those with HCV often feel stigmatized andunsupported in their care， relationships， and work environments， while simultaneously coping with a variety of physical and psychological symptoms.Misinformation appears to be the underlying cause of this stigma. It is likely that education， within the healthcare system， for family and friends of individuals diagnosed with HCV， and public education may reduce the stigma associated with HCV. Knowledge about the causes of HCV， as well as transmission mechanisms and transmission patterns， may reduce the feelings of stigmatization felt by those diagnosed and， in turn， may have positive implications such as more interest in being tested for HCV， increased disclosure， and improved quality of life.

Prevention

By the adaptation of the following measures the spread of HCV can be prevented： （1） Identification of patients with Hepatitis C. （2） Strict respect of standard precaution. （3） Safe injection practice. （4） Preventive measures specific ti blood products，tissue and graft. （5） Regularly testing on day 1，month 1，month 3 month 6 if exposure to HCV patients.

References

Kanwal F， Hoang T， Kramer JR， et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis Cvirus infection .2011；140（4）：1182–1188.e1.

Ontario Ministry of Health and Long-Term Care. Assessment Guide for Hepatitis C Risk Factors. Ontario Ministry of Health and Long-Term Care； 2007.

Mohd Hanafiah K.， Groeger J.， Flaxman A. D.， Wiersma S. T. Global epidemiology of hepatitis C virus infection： new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013；57（4）：1333–1342. doi： 10.1002/hep.26141.

Mohd Hanafiah K， Groeger J， Flaxman AD， Wiersma ST. Global epidemiology of hepatitis C virus infection： new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013；57：1333–1342.endprint