Hope on horizon for patients with Hepatitis C: Sofosbuvir for 99% less comes to india

Wonder Hepatitis C drug almost here.....at 99% reduced price

Hepatitis C is a viral disease that mainly affects the liver and is transmitted parenterally ( through contaminated blood products, syringes etc), vertically (from mother to child in womb) and sexually.

More than 40% of patients infected with the virus develop chronic infection because the body is unable to eliminate the virus from the system.

Progression of chronic hepatitis is usually slow and culminates within 10-20 years of acquiring infection into cirrhosis and chronic liver failure that may be fatal without transplantation. About 4 out of every 100 patients with cirrhosis due to hepatitis C develop cancerous growths (hepatocellular carcinoma) in the liver that significantly reduces their survival. Alcoholism, obesity, diabetes mellitus, immunosuppressive medication and HIV infection are risk factors for early progression of chronic hepatitis to cirrhosis and liver failure.

In the absence of a reliable vaccine, treatment of chronic hepatitis C has so far yielded less than optimal results (40-55% sustained viral response). Silent undetected progression of disease, multiple genotypes of virus and  poor tolerance of patients to medications ( particularly those with cirrhosis) contribute to the poor response.

Inability of cirrhotic patients to tolerate medications and reduced effectiveness results in most patients having detectable virus in blood at time of transplantation. Reinfection of new liver occurs within hours of transplantation and inflammation of graft starts weeks to months after transplantation depending on various factors like viral load, type of liver graft, immunosuppression, age and other factors. Post transplant recurrence of hepatitis C is more difficult to treat due to the presence of immunosuppression and sustained virological response is between 15-50% in various studies. A significant number of patients may need a second graft between 5-25 years after transplantation for recurrence of hepatitis C and cirrhosis.

Treatment of chronic hepatitis C has hinged on mainly two drugs: the antiviral drug Ribavarin (RBV) and the immunobodulator drug Interferon (IFN). Most regimens for treatment of hepatitis B include RBV and IFN (usually in pegylated form). Genotype 1 infection in particular has significantly poor response to PEG-IFN and RBV. Recently it has been identified that those patients that have infection with CC subtype of IL28 gene has double the response when compared to CT or TT genotypes.

Further research into HCV treatment resulted in a new class of molecules called Protease inhibitors that inhibit viral enzymes 
 Bocepravir and Telaprevir were the first generation of protease inhibitors introduced for management of chronic hepatitis in untreated as well as previously treated patients with chronic HCV and compensated cirrhosis. Addition of a protease inhibitor to combination of IFN & RBV significantly increased the sustained viral response rate ( by 15-30%) for difficult to treat genotype 1 patients over IFN&RBV alone except in treatment experienced patients who were null responders. Monotherapy is not recommended because rapid resistance results.

Simepravir (SPV) is a second generation protease inhibitor effective against HCV introduced about a year ago. It is never used a monotherapy. For genotype 1 a patients , SPV in combination with IFN & RBV for both treatment naive and experienced patients with genotype 1 infection. It can also be effective in combination with RBV and Sofosbuvir for patients who cannot tolerate toxic IFN therapy. SPV based triple therapy is a superior alternative to first generation protease inhibitors and is better tolerated. It can also be used as an alternative to Sofosbuvir in combination with a longer course of IFN & RBV. One of the main disadvantages in the high cost .....about 70000 USD ( approximately Rs 43 lakh) for a 12 week course.

Sofosbuvir (SBV) is also a polymerase inhibitor effective against HCV introduced about a year ago. It is effective for all genotypes of HCV but FDA approved only for 1,2,3 &4. It can be used with RBV with or without PEG-IFN and has shown promise in treatment naive, experienced as well as HIV coinfected patients of chronic hepatitis C and compensated cirrhosis. It has high acceptability due to fewer side-effects and interactions, once daily dosing and pan-genotypic activity. For genotypes 2 & 3 an all oral regimen of SBV and RBV is effective. For 1,3,4 & 5 genotypes addition of PEG-IFN is recommended but for those who cannot tolerate IFN, combination of SBV,SMV with or without RBV is showing promise.

Therefore Sofosbuvir is considered a breakthrough wonder drug for HCV currently and is expected to figure in more and more regimens for HCV. The prohibitive cost of 84000 USD ( 55 lakh INR) has been the main deterrent in greater availability and application of the drug even among insured patients in the western world. The greatest benefit of SBV seems to be in genotype 1 patients which accounts for more than 60% patients in the USA. SBV monotherapy was effective in more than 70% patients in achieving SVR while in combination with IFN & RBV the SVAR rate was more than 90% even among null-responders.

In India the prevalence of HCV is between 3-5 % of the population with 20-25% of patients with chronic liver disease being due to HCV infection. Genotype 3 is the commonest in India (66%) while Genotype 1 is less common (13%). 

Reduction of SBV costs by nearly 99% to USD 900 ( 55000 Rs)  for 12 weeks by the company, is therefore a hugely welcome step to liver physicians caring for patients with HCV infection, particularly null-responders, relapsers or patients with genotype 1 and those who cannot tolerate IFN therapy. Though still out of reach of many patients in India, it will be an option for insured or reimbursed patients who could have more effective treatment to prevent the development of cirrhosis or liver cancer or requirement of liver transplantation in the future.

World Hepatitis Day 2014: Hepatitis is closer than you think....think again

Hepatitis....know it...confront it

Hepatitis is a term used for inflammation of the liver cells due to any cause

Causes of hepatitis

1. Viruses: hepatitis viruses A-H, non-hepatitis viruses: herpes, cytomegalovirus etc
2. Bacteria
3. Parasites
4. Drugs
5. Chemicals & toxins including alcohol

It can manifest in two forms

Acute hepatitis

Recurrent hepatitis

Chronic hepatitis

Common routes of transmission of hepatitis are through contaminated food and drink (feco-oral route), through blood & blood products (parenteral route) and sexual contact.

Transmission through placental circulation from pregnant infected mother to child in the womb is called vertical transmission.

Acute hepatitis is characterised by abdominal discomfort, low-moderate grade fever, nausea, lethargy and loss of appetite. Most viral infections are associated with feeling of uneasiness, weakness, body pain before development of jaundice (prodrome). Jaundice is the hallmark of acute hepatitis and is usually detected by yellow discolouration of eyes and passage of dark yellow urine. Liver function tests show raised bilirubin level (mainly conjugated) accompanied by elevated liver enzymes (AST, ALT and frequently ALP). Urine shows elevated bile salts. Massive elevation of enzymes >1500 IU is rare. High fever usually indicates concurrent inflammation within the biliary system (cholangitis).

Acute hepatitis is a self-limiting disease and in most cases with supportive care, complete uneventful recovery results over a period of a few weeks. Recovery may be prolonged in elderly patients, pregnant women, those receiving medication to reduce immunity or those who have pre-existing liver damage from alcohol, fatty liver or other causes.

Alcoholic hepatitis is a unique form of hepatitis that occurs after years of large consumption of alcohol. It usually follows a binge of alcohol but can occasionally seen in early phases of abstinence. 

It is a severe form of hepatitis that causes a systemic inflammatory state often associated with infection, kidney dysfunction and progression to liver failure. The underlying liver is usually pre-cirrhotic or frankly cirrhotic in patients with alcoholic hepatitis. Many patients with alcoholic hepatitis have muscle wasting and nutritional defects making them prone to infections and multi organ failure leading to significant mortality despite supportive care.

In less than 5% cases, the liver damage caused by inflammation overwhelms the body immunity and the capacity of the liver to repair and regenerate. In such situations patients may progressively and rapidly develop cardinal features of liver failure : Deep jaundice  Mental changes (Encephalopathy & Clotting dysfunction. This syndrome is called Acute liver failure if patient had normal liver to start with and Acute on chronic liver failure if patient has a recognised or unrecognised chronic liver disease to start with.

Both are very severe conditions and if condition does not respond to medical measures, can be fatal.

Chronic hepatitis is usually the result of persistent or recurrent damage or the failure of immunity to clear the acute infection or insult. Chronic hepatitis is seen in 20-30% most of which is due to hepatitis B or C virus infections. Common hepatitis virus A is never chronic while less common hepatitis can rarely cause chronic infection.

Chronic hepatitis can follow an indolent course being asymptomatic for years before detection. Until liver damage has exceeded the reserve of the liver, liver function tests may be normal apart from subtle alterations.

The chronic inflammation in the liver can lead to development of primary liver cancer ( hepatocellular carcinoma) in unto 4% patients with chronic hepatitis every year.

Chronic inflammation can also lead to progressive scarring and changes in the micro architecture  of the liver leading to fibrosis and eventually cirrhosis. Once cirrhosis develops, the average survival is less than 10 years in most cases. Progressive damage can lead to features of chronic liver failure like jaundice, accumulation of fluid in abdomen (ascites), clotting deficiency and mental changes (hepatic encephalopathy). Reduction in liver function reduces immunity leading to increased propensity for infections and strain on other organ systems. In such a state average survival is less than one year.

Once cirrhosis develops the risk for developing hepatocellular carcinoma doubles to 8% per year.

As in most diseases, prevention is better than cure

Prevention of hepatitis

1. Consumption of safe food and drink
2. Vaccination: hepatitis B, hepatitis A
3. Avoid alcohol & IV drug abuse
4. Avoid unprotected high-risk sexual activity
5. Avoid contaminated syringes, needles, blood and blood products
6. Manage body weight & keep diabetes in check

Early detection of hepatitis

1. Periodic health checks
2. Screening of high risk patients
• children of parents with liver cancer or hepatitis
• siblings & spouses of patients with liver cancer or hepatitis
• patients receiving blood products (haemophiliacs, thalassemics) or dialysis
• iv drug abuse history
• high risk unprotected sexual activity & commercial sex workers
• healthcare workers
• patients with suppressed immunity or those on immunity reducing drugs

Treatment of hepatitis

1. Most cases of acute hepatitis need only supportive care
2. No specific treatment available for most viral hepatitis except hepatitis B and C
3. Inciting cause should be detected, avoided and treated accordingly
4. If acute or acute on chronic liver failure results patients should receive ICU management including ventilator support: some patients who don't respond can be salvaged by urgent liver transplantation
5. Measures to prevent developing chronic hepatitis & cirrhosis should be taken
6. Patients with chronic hepatitis should be aggressively followed for detection of cirrhosis or development of cancer
7. Early cases of liver cancer can be cured by liver surgery if there is no cirrhosis. If thesre is cirrhosis, liver transplant is the best option
8. Patients with complications of liver cirrhosis can be salvaged with liver transplant
9. Measures to prevent recurrence of hepatitis should be instituted even after transplant