Hepatitis C

Introduction

Hepatitis C is usually spread through contact with blood or contaminated needles, including tattoo needles. Although hepatitis C may cause only mild symptoms or none at all, about 20% to 30% of those infected develop cirrhosis within 20 years to 30 years. The disease can be passed on through blood transfusions, but screening has greatly reduced the number of such cases. Hepatitis C is generally not spread through sex.

Organ

Hepatitis C is an infectious disease affecting primarily the liver, caused by the hepatitis C virus (HCV). The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure, liver cancer or life-threatening esophageal and gastric varices.

Spread

HCV is spread primarily by blood-to-blood contact associated with intravenous drug use, poorly sterilized medical equipment and transfusions. It can be contracted from eating roadside iced food such as ais tapai cendol, which is a favourite ice-based food in Kelantan during hot days or the hot and dry season.

Infection

An estimated 150–200 million people worldwide are infected with hepatitis C. The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proven in 1989. Hepatitis C infects only humans and chimpanzees.

Treatment

The virus persists in the liver in about 85% of those infected. This persistent infection can be treated with medication: the standard therapy is a combination of peginterferon and ribavirin, with either boceprevir or telaprevir added in some cases. Prescribed therapeutic drugs can take longer to cure, up to a month to cure hepatitis, compared to traditional cures.

A traditional cure is to take the boiled infusion of a common weed, pokok dukung anak, with raw goat's milk (should be clean bread goats and the milk should be TB-free) until malaise resolves and the patient gains sufficient energy to move and clean himself properly, i.e., able to take care of his personal hygiene. Cure is expected within 2 weeks of diagnosis of suspected hepatitis (with jaundice), and confirmed hepatitis C.

Cure

Overall, 50–80% of people treated are cured on prescribed drugs.

Traditional cures have a better outcome, and continue to be used by the Malay community in Kelantan.

Liver transplant

Those who develop cirrhosis or liver cancer may require a liver transplant. Hepatitis C is the leading reason for liver transplantation, though the virus usually recurs after transplantation.

Vaccine

No vaccine against hepatitis C is available yet.

Vaccine research will require knowledge of how the virus attaches to the human cell types. Vaccines can then be created against component(s) involved with viral attachment and viral replication.

Acute infection

Hepatitis C infection causes acute symptoms in 15% of cases.

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.

Most cases of acute infection are not associated with jaundice.

The infection resolves spontaneously in 10-50% of cases, which occurs more frequently in individuals who are young and female.

Women can experience sudden weakness, lack of energy and jaundice. These clear up within 2 weeks with consumption of herbal infusion of pokok dukung anak and raw goat's milk.

Chronic infection

About 80% of those exposed to the virus develop a chronic infection. This is defined as the presence of detectable viral replication for at least six months. Most experience minimal or no symptoms during the initial few decades of the infection, although chronic hepatitis C can be associated with fatigue. Chronic infection after several years may cause cirrhosis or liver cancer. The liver enzymes are normal in 7-53%.

As for liver enzymes, ALP levels may remain high long after a hepatitis infection has occurred, but eventually resolves with avoidance of fatty foods and consumption of a mixture of apple cider vinegar (ACV), ginger, lemon and honey in cold water. Mix 1 teaspoon ACV + 1 slice ginger + 1 slice lemon and 2 tablespoons of honey in a cup of cold water. Consume twice daily - once in the morning before breakfast, and once before bedtime at night.

Liver changes

Fatty changes to the liver occur in about half of those infected and are usually present before cirrhosis develops. Usually (80% of the time) this change affects less than a third of the liver.

Worldwide hepatitis C is the cause of 27% of cirrhosis cases and 25% of hepatocellular carcinoma. About 10–30% of those infected develop cirrhosis over 30 years.

In those with hepatitis C, excess alcohol increases the risk of developing cirrhosis 100-fold. Those who develop cirrhosis have a 20-fold greater risk of hepatocellular carcinoma. This transformation occurs at a rate of 1–3% per year.

Liver cirrhosis may lead to portal hypertension, ascites (accumulation of fluid in the abdomen), easy bruising or bleeding, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy. Ascites occurs at some stage in more than half of those who have a chronic infection. Late relapses after apparent cure have been reported, but these can be difficult to distinguish from reinfection.

Complications

Extrahepatic 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.

Hepatitis C is also associated with Sjögren's syndrome (an autoimmune disorder); thrombocytopenia; lichen planus; porphyria cutanea tarda; necrolytic acral erythema; insulin resistance; diabetes mellitus; diabetic nephropathy; autoimmune thyroiditis and B-cell lymphoproliferative disorders.

Thrombocytopenia is estimated to occur in 0.16% to 45.4% of people with chronic hepatitis C. 20-30% of people infected have rheumatoid factor - a type of antibody.

Possible associations include Hyde's prurigo nodularis and membranoproliferative glomerulonephritis. Cardiomyopathy with associated arrhythmias has also been reported. A variety of central nervous system disorders have been reported. Chronic infection seems to be associated with an increased risk of pancreatic cancer.

Occult infection

Persons who have been infected with hepatitis C may appear to clear the virus but remain infected. The virus is not detectable with conventional testing but can be found with ultra-sensitive tests.

The original method of detection was by demonstrating the viral genome within 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 particles by ultracentrifugation.

A form of infection with persistently moderately elevated serum liver enzymes but without antibodies to hepatitis C has also been reported. This form is known as cryptogenic occult infection. Several clinical pictures have been associated with this type of infection. It may be found in people with anti-hepatitis-C antibodies but with normal serum levels of liver enzymes; in antibody-negative people with ongoing elevated liver enzymes of unknown cause; in healthy populations without evidence of liver disease; and in groups at risk for HCV infection including those on haemodialysis or family members of people with occult HCV. The clinical relevance of this form of infection is under investigation.

The consequences of occult infection appear to be less severe than with chronic infection but can vary from minimal to hepatocellular carcinoma.

The rate of occult infection in those apparently cured is controversial but appears to be low. 40% of those with hepatitis but with both negative hepatitis C serology and the absence of detectable viral genome in the serum have hepatitis C virus in the liver on biopsy.

Virology

The hepatitis C virus (HCV) is a small, enveloped, single-stranded, positive-sense RNA virus. It is a member of the Hepacivirus genus in the family Flaviviridae. There are seven major genotypes of HCV, which are known as genotypes one to seven. The genotypes are divided into several subtypes with the number of subtypes depending on the genotype.

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 genotype distribution in Malaysia is unknown.

The half life of the virus particles in the serum is around 3 hours and may be as short as 45 minutes. In an infected person, about 1012 virus particles are produced each day. In addition to replicating in the liver the virus can multiply in lymphocytes. The virus can be detected in the blood plasma, lymphocytes, and liver cells (hepatocytes).

Transmission

The routes of transmission are intravenous drug use (IDU), blood transfusions and unsafe medical procedures. The cause of transmission remains unknown in 20% of cases; however, many of these are believed to be accounted for by IDU.

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

Limitations in the implementation and enforcement of stringent standard precautions in public and private medical and dental facilities are known to be the primary cause of the spread of HCV in Egypt, which has the highest rate of infection in the world.

Diagnosis

Serologic profile of Hepatitis C infection

There are a number of diagnostic tests for hepatitis C, including HCV antibody enzyme immunoassay or ELISA, recombinant immunoblot assay, and quantitative HCV RNA polymerase chain reaction (PCR). HCV RNA can be detected by PCR typically one to two weeks after infection, while antibodies can take substantially longer to form and thus be detected.

Chronic hepatitis C infection

Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months based on the presence of its RNA. Chronic infections are typically asymptomatic during the first few decades, and thus are most commonly discovered following the investigation of elevated liver enzyme levels or during a routine screening of high-risk individuals. Testing is not able to distinguish between acute and chronic infections.

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 the parenchyma, lymphoid follicles in portal triad, and changes to the bile ducts. There are a number of blood tests available that try to determine the degree of hepatic fibrosis and alleviate the need for biopsy.

Treatment

HCV induces chronic infection in 50–80% of infected persons. Approximately 40–80% of these clear with treatment. In rare cases, infection can clear without treatment.

Advice

Those with chronic hepatitis C are advised to avoid alcohol and medications toxic to the liver, and to be vaccinated for hepatitis A and hepatitis B.

Ultrasound

Ultrasound surveillance for hepatocellular carcinoma is recommended in those with accompanying cirrhosis.

Medications

In general, treatment is recommended for those with proven HCV infection liver abnormalities. All are combination drugs (combo drugs).

Treatment during the first six months is more effective than once hepatitis C has become chronic.

(i) Pegylated interferon alpha and ribavirin

Since 2010, treatments consist of a combination of pegylated interferon alpha and the antiviral drug ribavirin for a period of 24 or 48 weeks, depending on HCV genotype. This results cure rates of between 70–80% for genotype 2 and 3, and 45 to 70% for other genotypes.

When combined with ribavirin, pegylated interferon-alpha-2a may be superior to pegylated interferon-alpha-2b, though the evidence is not strong.

If someone develops a new infection and it has not cleared after eight to twelve weeks, 24 weeks of pegylated interferon is recommended.

In people with thalassemia, ribavirin appears to be useful but increases the need for transfusions.

(ii) Sofosbuvir and ribavirin

Another agent, sofosbuvir, when combined with ribavirin, shows improved response rates in the 95% range for genotype 2. This benefit is somewhat offset by a greater rate of adverse effects.

(iii) Boceprevir or teleprevir with ribavirin and peginterferon alfa

Combining either boceprevir or telaprevir with ribavirin and peginterferon alfa improves antiviral response for hepatitis C genotype 1.

Adverse effects

Adverse effects with treatment are common, with half of people getting flu like symptoms and a third experiencing emotional problems.

Surgery

Cirrhosis due to hepatitis C is a common reason for liver transplantion though the virus usually (80–90% of cases) recurs afterwards. Infection of the graft leads to 10–30% of people developing cirrhosis within five years. Treatment with pegylated interferon and ribavirin post transplant decreases the risk of recurrence to 70%.

Alternative medicine

Several alternative therapies are claimed by their proponents to be helpful for hepatitis C including milk thistle, ginseng, and colloidal silver. However, no alternative therapy has been shown to improve outcomes in hepatitis C, and no evidence exists that alternative therapies have any effect on the virus at all.

Also refer to previous posts on fatty liver and alternative medicine (Ayurvedic herbs).

Prognosis

The responses to treatment is measured by sustained viral response and vary by HCV C genotype. A 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 genotypes 2 and 3 with 24 weeks of treatment. A sustained response occurs about 65% in those with genotype 4 after 48 weeks of treatment. The evidence for treatment in genotype 6 disease is sparse and what evidence there is supports 48 weeks of treatment at the same doses used for genotype 1 disease. Successful treatment decreases the future risk of hepatocellular carcinoma by 75%.

Among those chronically infected, the risk of cirrhosis after 20 years varies between studies but has been estimated at ~10%-15% for men and ~1-5% for women. The reason for this difference is not known. Once cirrhosis is established, the rate of developing hepatocellular carcinoma is ~1%-4% per year. Rates of new infections have decreased in the Western world since the 1990s due to improved screening of blood before transfusion.

Research

Since 2011, there are about 100 medications in development for hepatitis C. These include vaccines to treat hepatitis, immunomodulators, and cyclophilin inhibitors. These potential new treatments have come about due to a better understanding of the hepatitis C virus.

External links
http://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/natural-history/core-concept/all
http://www.herbalprovider.com/liver-enzymes.html
http://www.webmd.com/hepatitis/hepatitis-prevent-10/hepatitis-basics?page=2
http://en.wikipedia.org/wiki/Hepatitis_C
http://www.khatorepharma.com/wellness-1/kamalahar-wellness-1.html
http://en.wikipedia.org/wiki/Peginterferon_alfa-2b
http://www.drugs.com/cdi/peginterferon-alfa-2b.html
http://www.pegintron.com/peg/pegintron/consumer/index.jsp
http://en.wikipedia.org/wiki/Ribavirin
http://en.wikipedia.org/wiki/Sofosbuvir
http://en.wikipedia.org/wiki/Boceprevir
http://www.sahealth.sa.gov.au/