User:Danati265/sandbox

My additions to the Hepatitis article:

Mechanism
The specific mechanism varies and depends on the underlying cause of the hepatitis. Generally, there is an initial insult that causes liver injury and activation of an inflammatory response which if chronic leads to progressive fibrosis and cirrhosis.

Viral hepatitis

 * The pathway by which hepatic viruses cause viral hepatitis is best understood in the case of Hepatitis B and C. The viruses do not directly cause cell death or apoptosis. Rather, infection of liver cells activates the innate and adaptive arms of the immune system leading to an inflammatory response which causes cellular damage and death.   Depending on the strength of the immune response, the types of immune cells involved and the ability of the virus to evade the body's defense, infection can either lead to clearance (acute disease) or persistence ( chronic disease) of the virus.  The chronic presence of the virus within liver cells results in multiple waves of inflammation, injury and wound healing that overtime results in scarring or fibrosis and culminates in hepatocellular carcinoma.  Individuals with an impaired immune response are at greater risk of developing chronic infection. Natural killer cells are the primary drivers of the initial innate response and create a cytokine environment that results in the recruitment of CD4 T-helper and CD8 cytotoxic T-cells.   In chronic Hepatitis B and C, natural killer cell function is impaired .  Type I interferons are the cytokines that drive the antiviral response.

Non-alcoholic steatohepatitis

 * Obesity, insulin resistance, and lipid dysregulation are thought to initiate a cascade of events eventually lead up to non-alcoholic steatohepatitis.  Free fatty acids (FFA) and their breakdown products accumulate in the liver cells in a process called steatosis or fatty liver.   This initially reversible process overwhelms the hepatocytes ability to maintain lipid homeostasis leading to a toxic effect  as fat molecules accumulate and are oxidized in the setting of an oxidative stress response.    Overtime, this abnormal lipid deposition triggers the immune system via toll-like receptor 4 ( TLR4) resulting in cytokines that promote an inflammatory response that causes hepatocyte injury and death.    These events mark the transition to steatohepatitis and in the setting of chronic injury, fibrosis eventually develops as hepatocytes undergo repeated waves of injury and healing setting up events that lead to progression to cirrhosis and hepatocellular carcinoma. Microscopically, changes that can be seen include steatosis with large and swollen hepatocytes ( ballooning), evidence of cellular injury and cell ( apoptosis, necrosis), evidence of inflammation in particular in zone 3 of the liver,  and variable degree of fibrosis.

Viral Hepatitis
Viral hepatitis is a leading cause of both acute and chronic liver disease, liver cirrhosis and liver transplantation.

Hepatitis A
Hepatitis A is found throughout the world and manifest as large outbreaks and epidemics associated with fecal contamination of water and food sources. Hepatitis A viral infection is predominant in children ages 5-14 with rare infection of infants. Infected children have little to no apparent clinical illness in contrast to adults where greater than 80% are symptomatic if infected. Infection rates are highest in low resource countries with inadequate public sanitation and large concentrated populations. In such regions, as much as 90% of children younger than 10 years old have been infected and are immune corresponding both to lower rates of clinically symptomatic disease and outbreaks. The availability of a childhood vaccine has significantly reduced infections in the United states, with incidence declining by more than 95% as of 2013. Paradoxically, the highest rates of new infection now occur in young adults and adults who present with worse clinical illness. Specific populations at greatest risk include: Travelers to endemic regions, men who have sex with men, occupational exposure to non-human primates, individuals with clotting disorders who have received clotting factors, Individuals with a history of chronic liver disease where co-infection with Hepatitis A can lead to fulminant hepatitis, intravenous drug users ( rare).

Hepatitis E
Similarly to Hepatitis A, manifest as large outbreaks and epidemics associated with fecal contamination of water sources. It accounts for greater than 55,000 deaths annually with approximately 20 million people worldwide though to be infected with the virus. It affects predominantly young adults causing acute hepatitis. In infected pregnant women, Hepatitis E infection can lead to fulminant hepatitis with third trimester mortality rates as high as 30%. Individuals with weakened immune systems such organ transplant recipients are also susceptible. Infection is rare in the United states but high rates in the developing world ( Africa, Asia, Central America, Middle east). Many genotypes exist with differential distribution around the world. There is some evidence of of HEV infection of animals, serving as reservoir for human infection.

Hepatitis B
Hepatitis B is the most common cause of viral hepatitis in the world with more than 240 million chronic carriers of the virus, a million of whom are in the United states. . It is transmitted predominantly via  sexual contact and exposure or contact with blood products and other bodily fluids. In approximately two-thirds of patients who develop acute hepatitis B infection, no identifiable exposure is evident. Of those acutely infected, 25% become lifetime carriers of the virus. Risk of infection is highest among intravenous drug users, individuals with high risk sexual behaviors, health care workers,  individuals with a history of multiple transfusions, organ transplant patients, hemodialysis patients and  newborns infected during the birthing process. Close to 780,000 deaths in the world are attributed to Hepatitis B. The most endemic regions are in sub-Saharan Africa and East Asia where as much as 10% of adults are chronic carriers. Carrier rates in developed nations are significantly lower, encompassing less than 1% of the population. In endemic regions, transmission is thought associated with exposure during birth and close contact between young infants

Hepatitis D
Hepatitis D virus causes chronic and fulminant hepatitis in the context of co-infection with Hepatitis B virus. it is primarily transmitted via non-sexual contact and percutaneously  Susceptibility to hepatitis D differs depending on the region affected. In the United states and Northern Europe, populations at risk are intravenous drug users and individuals who receive multiple transfusions. In the mediterranean, Hepatitis D is predominant among HBV co-infected individuals.

Hepatitis C
Chronic Hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma. It is a common medical reason for liver transplantation due to its severe complications. It is estimated that 130-180 million people in the world are affected by this disease representing a little more than 3% of the world population. . In the developing regions of Africa, Asia and South America, prevalence can be as high as 10% of the population. In Egypt, rates of hepatitis C infection as high as 20 % have been documented and are associated with iatrogenic contamination related to  shistosomiasis treatment in the 1950s-1980s. In the United states, approximately 3.5 million adults are estimated to be currently infected. Hepatitis C is particularly prevalent among people born between 1945-1965, a group of about 800,000 people, with prevalence as high 3.2% versus 1.6% in the general US population. Most chronic carriers of hepatitis C are ignorant of their infection status. The most common mode of transmission of Hepatitis C virus is exposure to blood products via blood transfusions (prior to 1992) and intravenous drug injection. A history of intravenous drug injection is the most important risk factor for chronic hepatitis C. Other susceptible populations include individuals with high risk sexual behavior, in utero transmission from mother to infant, health care workers.

Alcoholic Hepatitis
Alcoholic hepatitis (AH) is a distinct clinical entity within the continuum of alcoholic liver diseases (ALD). In its severe form, one month mortality can be as high as 50%. The number one risk factor for AH is long-term sustained excessive alcohol consumption. Most people who develop AH are men but women are at higher risk of developing AH and its complications likely secondary to high body fat, differences in alcohol metabolism. Other contributing factors include younger age <60, binge pattern drinking, poor nutritional status, obesity and hepatitis C co-infection. It is estimated that as much as 20% of AH patients are co-infected with HCV. In this population, the presence of Hepatitis C virus leads to more severe disease with faster progression to cirrhosis and Hepatocellular carcinoma and increased mortality. Obesity increases the likelihood of progression to cirrhosis in individuals with alcoholic Hepatitis. . It is estimated that a high proportion of individuals (70%) who have AH will progress to Cirrhosis.

Non-Alcoholic steatohepatitis
Non-alcoholic steatophepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) characterized by inflammation and variable fibrosis of the liver due to the accumulation of fat molecules. It is projected become the top reason for liver transplantation by the year 2020, supplanting hepatitis C chronic liver disease. The estimated prevalence of NASH in the world is 3-5%. Of NASH patients who develop cirrhosis, about two percent a year will likely progress to hepatocellular carcinoma. Worldwide, the estimated prevalence of hepatocellular carcinoma related to NAFLD is 15-30%. In the United states, NASH is thought to be the primary cause in approximately 25% of patients who develop cirrhosis representing 1-5-2% of the general population.

Special populations
Persons infected with HIV have a particularly high burden of HCV co-infection. In a recent study by the WHO, the likelihood of being infected with hepatitis C virus was six times greater in individuals who also had HIV. The prevalence of HCV co-infection among HIV infected individuals worldwide was estimated to be 6.2 percent representing more than 2.2 million people. Intravenous drug use is an independent risk factor for HCV infection. In the WHO study the prevalence of HIV-HCV co-infection was markedly higher at 82.4% in those who injected drugs compared to the general population ( 2.4%). In a study of HCV co-infection among HIV+ men who have sex with men ( MSM), the prevalence of anti-HCV antibodies in this cohort was estimated at 8.1% and increased to 40% among HIV+ MSM who also injected drugs