Answer: <p><strong>Hepatitis</strong>is a disease of the liver characterized by the presence ofinflammatorycellsin thetissueof the organ. Hepatitis may occurwithout symptoms but can lead tojaundice(a yellow discoloration of theskin,mucous membranes, andconjunctivaof the eyes),poor appetite, andfatigue. Depending on the cause, hepatitis can manifest either as an acute or as a chronic disease.Acute hepatitis can beself-limiting(resolving on its own), can progress to chronic hepatitis, or can causeacute liver failurein rare instances. Chronic hepatitis may have no symptoms, or may progress over time tofibrosis(scarring of the liver) andcirrhosis(chronic liver failure).Cirrhosis of the liver increases the risk of developinghepatocellular carcinoma(a form ofliver cancer).</p>
<p>Worldwide,viral hepatitisis the most common cause, followed closely by alcoholic liver disease and non-alcoholic liver disease (NAFLD).Other less common causes of hepatitis includeautoimmune diseases, ingestion of toxic substances, certainmedications(such asparacetamol), some industrial organic solvents, and plants.</p>
<p><strong>PHC Issue</strong></p>
<p>Treatment of hepatitis varies based on the form (acute versus chronic), severity of disease, and cause.</p>
<h3>Hepatitis A</h3>
<p>Hepatitis A generally does not progress to a chronic state and rarely requires hospitalization.Treatment is supportive and includes such measures as providing intravenous (IV) hydration and maintaining adequate nutrition.</p>
<p>Rarely, people with the hepatitis A virus can rapidly develop liver failure, termed<em>fulminant hepatic failure</em>, especially the elderly and those who had a pre-existing liver disease, especially hepatitis C. Mortality risk factors include greater age and chronic hepatitis C.In these cases, more aggressive</p>
<p>supportive therapy and a liver transplant may be necessary.</p>
<h3>Hepatitis B</h3>
<h4>Acute</h4>
<p>In healthy patients, 95&ndash;99% recover with no long-lasting effects, and antiviral treatment is not warranted.Age and comorbid conditions can result in a more prolonged and severe illness. Certain patients warrant hospitalization, especially those who present with clinical signs of ascites, peripheral edema, and hepatic encephalopathy, and laboratory signs ofhypoglycemia, prolongedprothrombin time, low serumalbumin, and very high serumbilirubin.</p>
<p>In these rare, more severe acute cases, patients have been successfully treated with antiviral therapy similar to that used in cases of chronic hepatitis B, with nucleoside analogues such asentecaviror tenofovir. As there is a dearth of clinical trial data and the drugs used to treat are prone to developingresistance, experts recommend reserving treatment for severe acute cases, not mild to moderate.</p>
<h4>Chronic</h4>
<p>Chronic hepatitis B management aims to control viral replication, which is correlated with progression of a disease.There have been 7 drug treatments approved to date in the United States:</p>
<ul>
<li>Injectableinterferon alphawas the first therapy approved for chronic hepatitis B.It has several side effects, most of which are reversible with removal of therapy, but it has been supplanted by newer treatments for this indication.These include long-acting interferon bound topolyethylene glycol(pegylated interferon) and the oral nucleoside analogues.</li>
<li>Pegylated interferon(PEG IFN) is dosed just once a week as a subcutaneous injection and is both more convenient and effective than standard interferon. Although it does not develop resistance as do many of the oral antivirals, it is poorly tolerated and requires close monitoring.PEG IFN is estimated to cost about $18,000 per year in the United States, compared to $2,500-8,700 for the oral medications; however, its treatment duration is 48 weeks as opposed to the oral antivirals, which require indefinite treatment for most patients (minimum 1 year).<a href="https://en.wikipedia.org/wiki/Hepatitis#cite_note-:5-11">^]</a>PEG IFN is not effective in patients with high levels of viral activity and cannot be used in immunosuppressed patients or those with cirrhosis.</li>
<li>Lamivudine was the first approved oral nucleoside analogue.While effective and potent, lamivudine has been replaced by newer, more potent treatments in the Western world and is no longer recommended as first-line treatment.However, it is still used in areas where newer agents either have not been approved or are too costly. Generally, the course of treatment is a minimum of one year with a minimum of six additional months of &ldquo;consolidation therapy.Based on the viral response, longer therapy may be required, and certain patients require indefinite long-term therapy. Due to a less robust response in Asian patients,consolidation therapyis recommended to be extended to at least a year.All patients should be monitored for viral reactivation, which if identified, requires restarting treatment. Lamivudine is generally safe and well-tolerated.Many patients develop resistance, which is correlated with longer treatment duration.If this occurs, an additional antiviral is addedLamivudine as a single treatment is contraindicated in patients coinfected with HIV, as resistance develops rapidly, but it can be used as part of a multidrug regimen.</li>
<li>Adefovir dipivoxil, a nucleotide analogue, has been used to supplement lamivudine in patients who develop resistance but is no longer recommended as first-line therapy.</li>
<li>Entecavir is safe, well tolerated, less prone to developing resistance, and the most potent of the existing hepatitis B antivirals; it is thus a first-line treatment choice. It is not recommended for lamivudine-resistant patients or as monotherapy in patients who are HIV positive.</li>
<li>Telbivudine is effective but not recommended as first-line treatment; as compared to entecavir, it is both less potent and more resistance-prone.</li>
<li>Tenofovir is a nucleotide analogue and an antiretroviral drug that is also used to treat HIV infection.It is preferred to adefovir both in lamivudine-resistant patients and as initial treatment since it is both more potent and less likely to develop resistance.</li>
</ul>
<p>First-line treatments currently used include PEG IFN, entecavir, and tenofovir, subject to patient and physician preference.Treatment initiation is guided by recommendations issued by The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) and is based on detectable viral levels, HBeAg positive or negative status, ALT levels, and in certain cases, family history of HCC and liver biopsy.In patients with compensated cirrhosis, treatment is recommended regardless of HBeAg status or ALT level, but recommendations differ regarding HBV DNA levels; AASLD recommends treating at DNA levels detectable above 2x10³IU/mL; EASL and WHO recommend treating when HBV DNA levels are detectable at any level.In patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if HBV DNA is detectable.Currently, multidrug treatment is not recommended for treatment of chronic HBV as it is no more effective in the long-term than individual treatment with entecavir or tenofovir.</p>
<h3>Hepatitis C</h3>
<p>In contrast to hepatitis A and B, progression to chronic hepatitis C is much more common.The ultimate goal of hepatitis C treatment is a prevention of hepatocellular carcinoma (HCC).The best way to reduce the long-term risk of HCC is to achieve sustained virological response (SVR).SVR is defined as an undetectable viral load at 12 weeks after treatment completion and indicates a cure. Currently available treatments include indirect and direct acting antiviral drugs.The indirect acting antivirals include pegylated interferon (PEG IFN) and ribavirin (RBV), which in combination have historically been the basis of therapy for HCV.Duration of and response to these treatments varies based on genotype. These agents are poorly tolerated but are still used in some resource-poor areas.In high-resource countries, they have been supplanted by direct acting antiviral agents, which first appeared in 2011; these agents target proteins responsible for viral replication and include the following three classes:</p>
<ul>
<li>NS3/4A protease inhibitors, including telaprevir, boceprevir, simeprevir, and others</li>
<li>NS5A inhibitors, including ledipasvir, daclatasvir, and others</li>
<li>NS5B polymerase inhibitors, including sofosbuvir, dasabuvir, and others</li>
</ul>
<p>These drugs are used in various combinations, sometimes combined with ribavirin, based on the patient's genotype (delineated as genotypes 1-6)Genotype 1 (GT1), which is the most prevalent genotype in the United States and around the world, can now be cured with a direct-acting antiviral regimen.First-line therapy for GT1 is a combination of sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks for most patients, including those with advanced fibrosis or cirrhosis. Certain patients with the early disease need only 8 weeks of treatment while those with advanced fibrosis or cirrhosis who have not responded to prior treatment require 24 weeks. Cost remains a major factor limiting access to these drugs, particularly in low-resource nations; the cost of the 12-week GT1 regimen (SOF/LDV) has been estimated at US$94,500.</p>
<p>The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) recommend antiviral treatment for all patients with chronic hepatitis C infection except for those with additional chronic medical conditions that limit their life expectancy.</p>