Inflammatory Bowel Disease (ibd)

1. ALCOHOLIC LIVER DISEASE

Diksha Bhatla 01 Jan 1970

ALCOHOLIC LIVER DISEASE 

Alcoholic Liver Disease is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of alcohol. The pathogenesis is not completely understood. 

Though alcoholic liver disease is most likely to occur in people who drink heavily over many years, the relationship between drinking and alcoholic liver disease is complex. Not all heavy drinkers develop alcoholic liver disease, and the disease can occur in people who drink only moderately. 

Patients who are severely affected present with subacute onset of fever, hepatomegaly, leukocytosis, marked impairment of liver function (e.g., jaundice, coagulopathy), and manifestations of portal hypertension (e.g., ascites, hepatic encephalopathy, variceal hemorrhage). However, milder forms of alcoholic liver disease often do not cause any symptoms. 

Alcoholic liver disease usually persists and progresses to cirrhosis if heavy alcohol use continues. If alcohol use ceases, alcoholic liver disease resolves slowly over weeks to months, sometimes without permanent sequelae but often with residual cirrhosis. Of all chronic heavy drinkers, only 15–20% develops hepatitis or cirrhosis, which can occur concomitantly or in succession. 

Causes 

Alcoholic liver disease occurs when the liver is damaged by the excessive consumption of alcohol. How alcohol damages the liver and why it does so only in a minority of heavy drinkers is not clear. It is known that the process of breaking down ethanol; the alcohol in beer, wine and liquor produces highly toxic chemicals, such as acetaldehyde. These chemicals trigger inflammation that destroys liver cells. Over time, web-like scars and small knots of tissue replace healthy liver tissue, interfering with the liver’s ability to function. This irreversible scarring, called cirrhosis, is the final stage of alcoholic liver disease. 

Malnutrition: Many people who drink heavily are malnourished, either because they eat poorly or because alcohol and its toxic by-products prevent the body from properly absorbing and breaking down nutrients, especially protein, certain vitamins and fats. In both cases, the lack of nutrients contributes to liver cell damage. 

Sex: Women have a higher risk of developing alcoholic liver disease than men do. This disparity may result from differences in the way alcohol is processed by women. 

Genetic factors: A number of genetic mutations have been identified that affect the way alcohol is broken down in the body. Having one or more of these mutations may increase the risk of alcoholic liver disease. 

Pathophysiology 

Some signs and pathological changes in liver histology include: 

Alcoholic liver disease is characterized by the inflammation of hepatocytes. Between 10% and 35% of heavy drinkers develop alcoholic liver disease. While development of hepatitis is not directly related to the dose of alcohol, some people seem more prone to this reaction than others. This is called alcoholic steato necrosis and the inflammation appears to predispose to liver fibrosis. Inflammatory cytokines (TNF-alpha, IL6 and IL8) are thought to be essential in the initiation and perpetuation of liver injury by inducing apoptosis and necrosis. 

Symptoms 

It may not have symptoms in the early stages. Symptoms tend to be worse after a period of heavy drinking. Digestive symptoms include: 

• Pain and swelling in the abdomen and tenderness,

• Decreased appetite and weight loss,

• Nausea and vomiting,

• Fatigue,

• Dry mouth and increased thirst,

• Bleeding from enlarged veins in the walls of the lower part of the oesophagus. 

Skin problems such as: 

• Yellow colour in the skin, mucus membranes, or eyes (jaundice). 

• Small, red spider-like veins on the skin.

• Very dark or pale skin.

• Redness on the feet or hands.

• Itching.

Treatment 

In most patients with alcoholic liver disease, the illness is mild. Their short-term prognosis is good, and no specific treatment is required. Hospitalization is not always necessary. Alcohol use must be stopped, and care should be taken to ensure good nutrition; providing supplemental vitamins and minerals, including folate and thiamine, is reasonable. Patients who are coagulopathic should receive vitamin K parenterally. Anticipate symptoms of alcohol withdrawal, and manage them appropriately. 

Cessation of Alcohol Intake: Cessation of alcohol use is the mainstay of treatment of alcoholic liver disease. 

Liver Transplantation: Orthotopic liver transplantation is widely used in patients with end-stage liver disease. Most patients with active alcoholic liver disease are excluded from transplantation because of ongoing alcohol abuse. In most liver transplantation programs, patients must abstain from alcohol for at least 6 months before they can be considered for transplantation, and a thorough psychosocial evaluation must demonstrate that patients have a low likelihood of reverting to alcohol abuse. 

Surgical Considerations: 

Patients with acute alcoholic liver disease are at high risk of developing hepatic failure following general anesthesia and major surgery. Because postoperative mortality rates are high, surgery should be avoided in the setting of acute alcoholic liver disease unless it is absolutely necessary. 

Herbal Agents: 

Milk thistle: Herbal agents have also been tried in alcoholic liver disease. Silymarin is the active ingredient in milk thistle, is a member of the flavonoids. The precise mechanism of its hepatoprotective mediation is not known, but it is probably related to its antioxidant properties. 

2. Hepatitis

Diksha Bhatla 01 Jan 1970

HEPATITIS 

Hepatitis means injury to the liver with inflammation of the liver cells. Toxins, certain drugs, some diseases, heavy alcohol use, bacterial and viral infections can all cause hepatitis. 

Hepatitis is also the name of a family of viral infections that affect the liver; the most common types in the India and Asian countries are hepatitis A, hepatitis B and hepatitis C. 

Types of Viral Hepatitis: 

A group of viruses known as the hepatitis viruses cause most cases of liver damage worldwide. Common viruses cause hepatitis include A, B, C, D, E and G (95% cause of viral hepatitis). Other viruses include, Herpes simplex virus, Cytomegalovirus, Epstein-Barr virus, Yellow fever virus and Adenoviruses also cause hepatitis. 

HCV infection in India has a population prevalence of around 1%, and occurs predominantly through blood transfusion and the use of unsterile glass syringes. 

Etiology 

• Transfusion of infected blood and blood products,  
• Unprotected sexual contact with an infected partner. 

Most common cause of all viral hepatitis includes — • 

• Use of infected needle and syringes,
• Intravenous drug users,

Hepatitis A virus: Infection causes due to eating raw shellfish from water polluted with sewage and contaminated food and water. Travel or work in regions with high rates of hepatitis A. 

Carrier of Hepatitis B virus: Some people with Hepatitis B never fully recover from the infection (chronic infection), they still carry the virus and can infect others for the rest of their lives. HBV can be transmitted between family members within households by contact of non-intact skin or mucous membrane with secretions or saliva containing HBV. 

Causes of Hepatitis C virus: Occurs as the result of percutaneous transmission of the hepatitis C virus through infectious blood. It can be passed from an infected mother to her baby. HCV can also be transmitted through household contact (sharing of personal items such as razors, toothbrushes, scissors and manicuring equipment within the same household). 

Causes of Hepatitis D virus: HDV is transmitted parenterally, it can replicate independently within the hepatocyte, but it requires HBs Ag for propagation. Sexual transmission is less efficient than with HBV. Perinatal transmission is rare. 

Causes of Hepatitis E virus: Infection spread by fecally contaminated water within endemic areas. On the other hand, in non-endemic areas, the major mode of the spread of HEV is food borne, especially undercooked pork. 

Causes of Hepatitis G virus: It has been identified in all ethnicities, and 1% - 4% of worldwide blood donors are carriers of the virus at the time of blood donation. 

Pathophysiology of Hepatitis 

[I] Hepatitis A 

Hepatitis A is a highly contagious liver infection caused by the hepatitis A virus. The hepatitis A virus is one of several types of hepatitis viruses that cause inflammation that affects liver’s ability to perform normal function. Nearly everyone who develops Hepatitis A makes a full recovery; it does not lead to chronic disease. Mild cases of hepatitis A do not require treatment, and most people who are infected recover completely with no permanent liver damage. 

Pathophysiology 

After oral inoculation the virus is transported across the intestinal epithelium. After travelling through the mesenteric veins to the liver, the virus enters hepatocytes, where replication of hepatitis A virus (HAV) occurs exclusively within the cytoplasm via RNA-dependent polymerase. 

The liver damage is due to direct killing of hepatocytes and by the host’s immune system response to infected hepatocytes indicates inflammation of liver. Microscopically there is spotty parenchymal cell degeneration, with necrosis of hepatocytes, with disruption of liver cell cords. 

[II] Hepatitis B 

Hepatitis B is a serious liver infection caused by the hepatitis B virus (HBV), which infects the liver and causes an inflammation called hepatitis, originally known as “serum hepatitis”. It ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead to liver cancer or cirrhosis (a condition that causes permanent scarring of the liver). 

Pathophysiology 

HBV infection in itself does not lead to the death of infected hepatocytes. The host’s immune response to viral antigens is thought to be the cause of the liver injury in HBV infection. 

Liver damage arises from cytolytic effects of the immune system's cytotoxic T lymphocytes (CTL) which attempt to clear infection by killing infected cells. The cellular immune response, rather than the humoral immune response, seems to be primarily involved in disease pathogenesis. Induction of antigen-specific T-lymphocyte response is thought to occur when host T lymphocytes are presented with viral epitopes by antigen-presenting cells in lymphoid organs. These antigen-specific T cells mature, expand and then migrate to the liver. In acute HBV infection, most HBV DNA is cleared from hepatocytes through non-cytocidal effects of inflammatory byproducts of CD8+ T lymphocytes, stimulated by CD4+ T lymphocytes, notably interferon-gamma and tumour necrosis factor-alfa. 

These cause down-regulation of viral replication, and trigger direct lysis of infected hepatocytes by HBV-specific CD8+ cytotoxic T cells. In contrast, people with chronic HBV infection display weak, infrequent, and narrowly focused HBV- specific T-cell responses, and the majority of mononuclear cells in livers of chronic HBV- infected people are non-antigen-specific. 

[III] Hepatitis C 

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The virus can cause both acute and chronic hepatitis infection, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness. Hepatitis C is usually spread through direct contact with the blood of infected person. 

Pathophysiology 

The natural targets of HCV are hepatocytes and possibly, B lymphocytes. Viral clearance is associated with the development and persistence of strong virus-specific responses by cytotoxic T lymphocytes and helper T cells. In most infected people, viremia persists and is accompanied by variable degrees of hepatic inflammation and fibrosis. 

[V] Hepatitis E 

It is a serious liver disease caused by the hepatitis E virus (HEV), usually results in an acute infection. It does not lead to a chronic infection. 

Hepatitis E is an enterically transmitted infection typically self-limited. Hepatitis E has many similarities with hepatitis A. Hepatitis E has been associated with chronic hepatitis in solid organ transplant recipients, patients infected by HIV, and an individual on rituximab treatment for non-Hodgkin lymphoma. 

Etiology and Pathophysiology 

The hepatitis E virus (HEV) genome contains 3 open reading frames (ORFs). The largest, ORF-1, codes for the non-structural proteins responsible for viral replication. ORF-2 contains genes encoding the capsid. The function of ORF-3 is unknown, but the antibodies directed against ORF-3 epitopes have been identified. 

HEV is an RNA virus of the genus Hepevirus. The virus is icosahedral and non- enveloped. It has a diameter of approximately 34 nanometres, and it contains a single strand of RNA approximately 7.5 kilobases in length. Four HEV genotypes have been identified. Genotypes 1 and 2 are considered human viruses; genotypes 3 and 4 are zoonotic and have been isolated from humans and animals. 

[VI] Hepatitis G 

A new virus recently identified in humans. 

GB virus C (GBV-C), formerly known as hepatitis G virus (HGV) and also known as HPgV is a virus in the flaviviridae family and a member of the Pegivirus genus, is 

known to infect humans, but is not known to cause human disease. 

Hepatitis G virus and GB virus C (GBV-C) are RNA viruses that were independently identified in 1995, and were subsequently found to be two isolates of the same virus. 

Symptoms 

Common symptoms of all viral hepatitis includes — 

• Nausea and vomiting

• Loss of appetite

• Weakness and fatigue

• Fever

• Dark urine

• Pale stool

• Jaundice

• Stomach pain and side pain.

• Abdominal pain