Effects of alcohol consumption on patients with hepatitis C virus infection

Introduction

Excessive alcohol consumption is a worldwide problem, which is associated with significant death rate (WHO, 2012). Among the potential complications of heavy ethanol intake, alcoholic liver disease (ALD)  is  one  of  the  most  prevalent  with  severe  consequences  .This  is  highlighted  by  the  fact  that  18  new  cases  of  ALD  per  100,000  inhabitants  are  diagnosed  every  year (Yang et al., 2008).  Regarding  ALD  pathogenesis,  it  is  well  known  that  ethanol  induced  liver  damage  is  augmented  by other injurious  factors  such  as  hepatitis  c  virus (HCV) increase  the  risk  of  development  of  liver    cirrhosis (Hutchinson  et   al., 2006).  Further,  it  is  traditionally  assumed  that  the  prevalence  of  HCV  infection  in  alcoholic  subjects  than  in   the  general  population,  which  is  estimated  between  0.5  and  2 percent  in  most  European  countries.  The   exact  burden  of  HCV  infection  among  alcoholic  subjects  however,  is  not  known  since  a  wide  range  of  prevalence  rates  have  been  reported  from  2.1  to  51  which  could  be  related  to  a  different  distribution  of  risks  factors  for  HCV  infection  studies.  Alcohol  can  increase  hepatitis  C  virus (HCV)  infection and  the  associated  liver  damage  by  causing  oxidative  stress  and  promoting  fibrosis  thereby  accelerating  disease  progression  in  cirrhosis.

Furthermore,  alcohol  may  exacerbate  the  side  effects  associated  with  current  antiviral  treatment  of  hepatitis  C  virus  infections  and  impair  the  body’s  immune  defiance  against  the  virus  of  the  HCV  infected  people  who  do  not  consume  alcohol,  only  a  minority  progresses  to  liver  antiviral  treatment.

HCV  is  spread  primarily  by  blood  to  blood  contact  associated  with  intravenous  drug  use,  poorly  sterilized  medical  equipment  and  needle  stick  injuries  in  healthcare  and  transfusions.  It  may  also  spread   from  an  infected  mother  to  her  baby  during  birth.  Alcohol  and  hepatitis  C  virus[HCV]  have  a  synergic  hepatotoxic  effects,  and  the  coexistence  of  these  factors  increases  the  risk  of  advanced  liver  disease.  The  main  mechanism  of  this  effects  are  increased  viral  replication   and  altered  immune  response,  although  genetic  predisposition  may  also  play  an  important  role.

Conceptual framework

Hepatitis C virus (HCV) is a small (55-65µm) in size, enveloped; positive-sense single-stranded RNA virus of the family Flavivradae.Hapatitis c virus is the cause of hepatitis c and some cancers such as liver cancer  (hepatocellular carcinoma) and lymphomas (Ferri, 2015).

During the initial infection people often have mild or no symptoms .occasionally a fever, dark urine, abdominal pain and a yellow tinged skin occurs .the virus persist in the liver in about 75% to 85% of those initially infected. Early on chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. In some cases, those with cirrhosis will develop complications such as liver failure, liver cancer (CDC, 2016).

HCV is spread primarily by blood to blood contact associated with intravenous drug use, poorly sterilized medical equipment, needle stick injuries in health care and transfusions. With blood screening, the risk from transfusion is less than one per two million. It may also be spread from a infected mother to her baby during birth. It is not spread by superficial contact. it is one of the five known hepatitis  viruses; A,B,C,D and E. Diagnosis is by blood testing to look for either Antibodies to the virus or s RNA. Testing is recommended in all people who are at risk (WHO, 2015).

There is no vaccine against hepatitis C virus. Prevention includes harm reduction efforts among people use intra venous drugs and testing donated blood. Getting access to the newer treatments however can be expensive. Those who develop cirrhosis or liver cancer may require a liver transplant. Hepatitis c is a leading reason for liver transplantation, though the virus usually reoccur s after transplantation.

Causes of hepatitis C

Hepatitis C is caused by infection with the hepatitis c virus .the virus can cause both acute  and chronic hepatitis infection, ranging in severity from a mild illness lasting a few weeks to a serious life long illness. The infection spreads when blood contaminated with the virus enters the blood stream of an unaffected person.

Signs and symptoms of hepatitis C

Acute infection

Hepatitis C infection causes acute symptoms in 15% of causes. Symptoms are generally mild and vague, including a decreased appetite, fatigue, nausea, muscle or joint pains and weight loss and rarely does acute liver failure result (Bailey, 2010). Most cases of acute infection are not associated with jaundice. The infection result spontaneously in 10-50% of cases which occurs more frequently in individuals who are young and female.

Chronic infection

About 80% of those exposed to the virus develop a chronic infection (Nelson et al., 2011).This is defined as the presence of detectable Viral Replication for at least 6 months. Most people experience minimal or no symptoms during the initial few decades of the infection. Chronic hepatitis c can be associated with fatigue after several years may cause cirrhosis or liver cancer. The liver enzymes are normal in 7-53%.

Extrahapatic complications

The most common problem due to hepatitis C but not involving the liver is mixed cryoglobulinemia (usually the type II form) an inflammation of small and medium sized blood vessels (Dammacco and Sanonno, 2013). Hepatitis C is also associated with the auto-immune disorder

Occult infection

Persons who have been infected with hepatitis C may appear to clear the virus but remains infected. The virus is not detectable with conventional testing but can be found with ultra-sensitive (Carreno, 2006).The original method of detection was by demonstrating Viral genome within the liver biopsies but newer methods include an antibody test for the virus .Core protein and the detection of the viral genome after first concentrating the viral and particles by ultra centrifugation. A form of infection with persistent moderately elevated serum liver enzymes but without antibodies to hepatitis C has also been reported.

This type of infection may be found in people with anti I-hepatitis C antibodies but with normal serum levels of liver enzymes in antibody, negative people with ongoing elevated liver enzymes of unknown cause.

Morphology

The protein of the virus are arranged along the genome in the following order N terminal Core-Envelope(EI)-E2-P7-nonstructural protein 2(NS2)-NS3-NS4A-NS4B-NS5A-NS5B-C terminal. The mature nonstructural proteins (NS2 to NS5B) generation relies on the activity of viral protein aces. The  NS2/NS3 junction is cleaved by a metal dependent autocatalytic proteinase encoded within NS2 and the N-terminus of NS3.The remaining cleavages downstream from the site are catalyzed by a serine proteinase also contained within the N-terminal region of NS3.

The core protein has 191 amino acids and can be divided into three domains on the basis of hydrophobicity. Domain 1(residues 1-117) contains mainly basic residues with two short hydrophobic regions, domain 2 (residues 118-174) is less basic and more hydrophobic and its C-terminus is at the end of p21; domain 3(residues 175-191) is highly hydrophobic and acts as a signal sequence for E1 envelope protein.

Both  envelop protein (E1 and E2) are highly glycolated and important in cell entry.E1 serves as the fusogenic subunit and E2 acts as the receptor binding protein E1 has 4-5n-linked glycan and E2 has 11 N-glycosylation sites. The P7 protein is responsible for viral genome replication but plays a critical role in virus morphogenesis. This protein is a 63 Amino acid membrane spanning protein which locates itself in the endoplasmic reticulum. Cleavage of P7 is mediated by the endoplasmic reticulum is signal peptidases. Two transmembrane domains of P7 are connected by cytoplasmic loop and are oriented towards the endoplasmic reticulum’s lumen

Replication

Replication of HCV involves several steps. The virus replicates mainly in the hepatocytes of the liver where it is estimated that daily each infected cell produces appropriately fifty vireos (virus particles) with a calculated total of one trillion viruses generated. The virus may also replicate in peripheral blood mononuclear cells, potentially accounting for high level of immunological disorders found in chronically infected HCV patients (Ziesel et al., 2010). HCV has a wide variety of genotype and mutates rapidly due to a high error rate on the part of the virus `RNA-dependent RNA polymerase. The mutation rate produces so many variants of the virus. It is considered a gvasispecies rather than a conventional virus species. Once inside the hepatocyte, HCV take over portions of the intracellular machinery to replicates. The virus replicate on intracellular lipid membranes.

Transmission of hepatitis C

The primary route of transmission in the developed world is intravenous drug use (IDU) while in the developing world the main methods are blood transfusion and unsafe medical procedures. The cause of transmission remain unknown in 20% of cases, however many of these are believed to be accounted for by IDU.

Drug use

Intravenous drug use (IDU) is a major risk factor for hepatitis C in many part of the world. Out of 77 countries reviewed 25(including the United States) were found to have prevalence of hepatitis C in the intravenous drug user population of between 60% and 80% (Nelson et al., 2011).

Health care exposure

Blood transfusion, transfusion of blood products or organ transplants without HCV screening carries significant risk of infection, Those who experienced a needle stick injury from someone who was HCV positive have about 1.8% chances of subsequently contracting the disease themselves. The risk is greater if the needle in question is hollow and the punctured wound is deep.

Hospital equipment has also been documented as a method of transmission of hepatitis c including reuse of needles and syringes, multiple- use medications vials; infusion bags and improperly sterilized surgical equipment among others.

Sexual intercourse

Whether hepatitis can be transmitted through sexual activity is still controversial (Tohmme and Holmerg, 2010). Sexual activity and hepatitis C, and multiple sexual partners are risk factors for hepatitis C.

Body modification

Tattooing is associated with two or three fold increased risk of hepatitis C .This can be due to improper sterilized equipment or contamination of the dyes being used, tattoos or piercings performed either before the mid-1980s, “underground” or non professionally are of serious concern, since sterile techniques in such settings may be lacking. The risk also appears to be greater for large tattoos.

Shared personal item

Personal care items such as razors, tooth-brushes and manicuring or pair during equipment can be contaminated with blood , sharing such items can potentially leads to exposure to HCV. Appropriate caution should be taken regarding any medical condition that results in bleeding as cuts and sores.

Mother to child transmission of hepatitis C

Mother-to-child transmission of hepatitis C occurs in less than 10% of pregnancies. There are no measures that alter this risk. It is not clear when transmission occurs during pregnancy, but it may occur both during gestation and at delivery. A long labour is associated with a greater risk of transmission (Alter 2007). There is no evidence that breastfeeding spread spreads HCV, however to be caution, an infected mother is advised to avoid breastfeeding if her nipples are cracked and bleeding, or if her viral loads are high.

Virology

In hepatitis C virus (HCV) is a small enveloped single stranded positive RNA virus. It is a member of the hepacivirus genus in the family flavivridae. There are seven major genotypes of HCV, which are known as genotype 1-7. The genotypes are divided into several sub types with the number of sub types depending on the genotypes. In the United States, about 70% of cases are caused by genotype 1, 20% by genotype 2 and about 1% by each of the other genotypes. Genotype 1 is also the most common in South America and Europe.

The half life of the virus particles in the serum is around 3 hours maybe as short as 45minutes in an infected person, about 10¹² virus particles are produced each day in addition to replication in the liver, the virus can multiple in the lymphocyte.

Pathogenesis     

HCV is a non cytopathic virus that enters the liver cells and undergoes replication simultaneously causing cell necrosis by several mechanisms including immune- mediated cytolysis. In addition to various other phenomena such as hepatic steatosis, oxidative stress and insulin resistance. The proteins/peptide encoded by different sub-genomic regions of the HCV genome and their quasispecies influenced the above mechanism and thus have a significant role in HCV pathogenesis and disease condition (Irshad and Dhar, 2006).

Epidemiology/prevalence

It is estimated that HCV infects someone 170 million people world wild, and in the united state an estimated 2.7million people have HCV infection. High prevalence of chronic hepatitis C in England is estimated to be 0.4% of adults (approximately 160000 people). During 2010, it is estimated that 16000 people died from acute infection while 196000 death occur from liver cancer secondary to the infection (Lozano, 2012). In the United States, about 2% of people have hepatitis c. in 2014, an estimated 30500 new acute hepatitis cases occurred (0.7 per 1000000 population), an increase from 2010 to 2012. In Europe, the percentage of people with chronic infection has been estimated to be between 0.13 and 3.26 (Blacheir et al., 2013).

The prevalence of HCV among alcoholics is high when compared to the general population and the rate seems to vary according to the presence or absence of coexisting liver disease. Indeed markers for HCV infection have been detected in 33% to 50% of alcoholic patients with evidence of liver injury compared to 2% to 10% in those without any sigh of liver disease (Befrits et al., 2010).

Studies by Becker et al. (2012), shows that out of 136 alcoholics subject in Zawan District of Plateau State, 58(42.6%) were positive for HCV while 4(6.3%) of the 64 non alcoholic subjects were positive. This indicates that there is higher risk of HCV infection in alcoholic subjects when compared with the non alcoholic subjects which has only 6.3% positivity. This is similar with previous report were serum markers of HCV infection were detected in up to 36^oF Brazilian patients with alcoholic cirrhosis (Stephen et al., 2013). According to Alter et al. (2007), 15(24.2%) of 62 subjects positive for HCV have elevated level of ALT, this could be due to severe liver damage.

A study by Avillar et al. (2008) which consist of 396 patients, of which 347 were men with a mean age of 44.81 years, average alcohol consumption was 163.71. The estimated prevalence of HCV in Africa is 5.3%, Egypt has the highest worldwide prevalence which is 17.5%. Egypt unusually high prevalence is attributable to the history of unsterile injection equipment used for mass treatment. WHO report 75% of HCV infected individuals developing lever disease (1.6%).

Prognosis

The responses to treatment is measured by sustained viral response(SVR), define as the absence of detectable RNA of the hepatitis C virus in blood serum for at least 24 weeks after discontinuing the treatment and rapid virological response (RVR) defined as the undetectable levels achieve within four weeks of treatment. Successful treatment decreases the future risk of hepatocellular carcinoma by 75% (Morgan et al; 2013). Prior to 2012, sustained response occurs in about 40-50% in people with HCV genotype 1 given 48 weeks of treatment. A sustained response is seen in 70-80% of people with HCV genotype 2 and 3 with 24weeks of treatment.

Diagnosis

There are a number of diagnostic test for Hepatitis C including antibody enzyme immuno assay or ELISA, recombinant immunoblot assay, and quantitative HCV RNA polymerase chain reaction(PCR).HCV RNA can be detected by PCR typically 1-2 weeks after infection, while antibodies can take substantially longer to for and thus be detected (Ozaras and Tahan, 2009).

Serology

Hepatitis C testing topically begins with blood testing to detect the presence of antibody to the HCV using an enzyme immuno assay. If this test is positive a confirmatory test is then performed to verify the immuno assay to determine the viral load. A recombinant immuno blood assay is used to verify the immuno assay, and the viral load is determined by an HCV RNA polymerase chain reaction. If there is no RNA and the immuno blood is positive, it means that the person tested had a previous infection but cleared it either with treatment or spontaneously, if the immunoblot is negative, it means that the immunoassay was wrong. It takes about 6-8weeks following infection before the immunoassay will test positive (Ray et al., 2009)

Biopsy

Liver biopsies are used to determine the degree of liver damage present. However, there are risks from the procedure .the typical changes seen are lymphocytes within parenchyma, lymphoid follicles in portal triad, and changes to the bile ducts. There are a number of blood test available that try to determine the degree of hepatic fibrosis and alleviate the need for biopsy.

Screening

It is believed only 5-50% of those infected in the united and Canada are aware of their status. Testing is recommended for those at high risk which includes injection drug users, those who has receive blood transfusion before 1992, those who have been in jail, those on long term hemodialysis and those with tattoos. Screening is also recommended with elevated liver enzymes as this is frequently only sign of chronic hepatitis. Routine screening is currently recommended in United States. In 2012, the US Centers for Disease Control and Prevention (CDC) added a recommendation for a single screening test for those born between 1945 and 1966.

Prevention of hepatitis C

As at 2016, no approved vaccine protects against contracting hepatitis C. however, there are a number of vaccine under development and have shown encouraging results. A combination of harm reduction strategies such as the provision of new needles and syringes and treatment of substance use decreases the risk of hepatitis c in intravenous drug users by about 75%.The screening of blood donors  is important at a national level as in adhering universal precautions within health care facilities. In countries where there is an insufficient supply of sterile syringes, medication should be given orally rather than via injection (when possible)

Hepatitis C and alcohol

Alcohol is formed when yeast ferment (breaks down without oxygen) the sugars in different food. For example wine is made from the sugar in grapes, beer from the sugar in malted barley. Alcohol is classed as sedative hypotonic drug when means it adds to depress the central nervous system at high doses. At lower doses. Alcohol can acts as a stimulant, inducing feelings of euphoria and talk activeness, but drinking too much alcohol at one section can lead to respiratory depression. It also has effect on every organ in the body depending on the blood alcohol concentration (BAC) over time (Zakhari, 2006).

Alcohol and hepatitis C are certainly the two primary causes of cirrhosis and liver transplantation in the United States and Europe .many patients with hepatitis C from this region also have a history of problematic alcohol use, and thus have liver injury from both agents. An equivocal first step in the management of patients with HCV who have an “alcohol problem” is ensuring that alcohol causation is put in place (Erieto et al., 2006).

The evidence of alcohol’s dipterous effect on HCV RNA levels, treatment response and disease progression was sufficiently persuasive in USA “2002”. Abstinence is strongly recommended before and during anti viral therapy as even moderate levels of alcohol consumptions may accelerate liver disease progression. Studies have confirmed that excessive alcohol use increases the risk of cirrhosis. A French study of 6600 HCV patients concluded that cirrhosis occurred in 35% of patients who were heavy drinkers.

Conclusion

HCV infection previously known as blood born non-A, non-B-infection is a serious public health problem Worldwide. The diagnosis of HCV is based on the detection of anti-HCV antibodies and viral nucleic acid in serum. Studies over the last few years have developed assays not only for the accurate serodiagnosis of infection, but also identification of HCV serotypes. The pathogenesis of HCV infection is quit complex and regulated by host immunity as well as several metabolic activities influencing liver functions. Moreover, HCV infection is also affected by viral proteins and liver metabolism.

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