Medical Consequences

(Warning, this video is rather graphic) In people who have cirrhosis, high blood pressure in the veins that carry blood from the intestines to the liver can cause many problems. One such serious complication is that of portal hypertension. When blood pressure increases in the portal vein system, veins in the oesophagus, stomach, and rectum enlarge to accommodate blocked blood flow through the liver. The presence of enlarged veins (varices) usually causes no symptoms. (They may be found during an endoscopy exam of the oesophagus.) About 50 to 60 out of 100 people who have cirrhosis develop varices in the oesophagus. Some people may feel that this video sequence is too graphic. For this, I make no apologies. This condition is going to happen to you if your liver becomes too badly damaged. 50% of those people who have cirrhosis of the liver will suffer from a varices condition.

In some people with a liver disorder, ascitic fluid leaks from the surface of the liver and intestine and accumulates within the abdomen. A combination of factors is responsible. They include the following: * Portal hypertension * Fluid retention by the kidneys Alterations in various hormones and chemicals that regulate body fluids. Also, albumin usually leaks from blood vessels into the abdomen. Normally, albumin, the main protein in the blood, helps keep fluid from leaking out of blood vessels. When albumin leaks out of blood vessels, fluid also leaks out. A person with portal hypertension may also develop a build-up of fluid in their abdomen (tummy) and around the intestines. This fluid is known as Ascites. Initially, this can be treated with water tablets (diuretics). If the problem progresses, many litres of fluid can build up, which needs to be drained. This is a procedure known as paracentesis and involves a long, thin tube being placed into the fluid through the skin under local anaesthetic . One of the problems associated with the development of ascites is the risk of infection in the fluid (spontaneous bacterial peritonitis ). This is a potentially very serious complication and is linked to an increased risk of kidney failure and death. The main symptom of ascites is a swollen tummy. Other symptoms include: pain and discomfort in the tummy feeling sick (nausea) reduced appetite indigestion feeling full tiredness breathlessness Ascites can make it difficult for you to get comfortable, sit up and walk.

Hepatic encephalopathy is a brain disorder and refers to the changes in the brain that occur in patients with advanced, acute or chronic liver disease and is one of the major complications of cirrhosis. Hepatic encephalopathy (HE), may occur suddenly in people with acute liver failure however, the condition is more often seen in people with chronic liver disease. An important job of the liver is to change harmful substances that are either made by the body or taken into the body (such as medicines) and make them harmless. However, when the liver is damaged and unable to function fully, these “toxins” may build up in the bloodstream. HE occurs when the liver cannot remove chemicals, such as ammonia. These chemicals then enter the brain and can affect both the mental and physical condition of patients. Often certain factors can be responsible for triggering an episode of HE in liver patients. The following factors may trigger an episode of HE: • Dehydration (loss of water from the body) • Low oxygen levels in the body • Eating too much protein • Constipation • Infections • Intestine, stomach, or oesophagus bleeding • Medications that affect the nervous system, such as tranquilisers or sleep medications • Kidney problems or Surgery Patients with acute liver disease, who have an episode of HE, generally find that once the trigger is removed and their liver condition is treated, the HE disappears. However, some patients with chronic liver disease find they will have recurring episodes of HE. Episodes of HE usually result in hospitalisation, as without treatment, patients remain at high risk for recurrence. Other complications of untreated HE can be brain swelling, permanent nervous system damage, increased risk of heart failure, kidney failure, respiratory failure and sepsis (blood poisoning) and in severe cases coma. HE symptoms can present at a range of stages from mild to overt (severe). Mild Symptoms of HE can be observed in nearly 70% of patients with cirrhosis. Overt HE occurs in about 30-45% of patients with cirrhosis. HE symptoms can vary from person to person; they can develop rapidly or slowly over time. Patients with HE can have both physical symptoms and reduced mental function. (I believe, that it is so important for family members and friends to understand that when a person suffers from a HE episode. It isn’t the individual being mean or nasty. It is a chemical reaction within the brain that is causing this uncommon behaviour. It isn’t the fault of the patient, and although the words are spoken and often confusing, there is no real meaning behind them as they are being chemically driven).

For me this is a thorny subject, over the years, I’ve come across several diabetic nurses who for some reason, seem to once again put all type-2 diabetes suffers in the same little box, and labelling everyone with the same condition and cause.“ It’s because your pancreas isn’t producing enough insulin ”. This then blames the poor pancreas, when in truth it’s having to work flat out. I have carried out a lot of my research into the possible cause of my diabetes, and while I tend to avoid a lot of the American websites, I must confess that a huge amount of research has been done into Type 2 Diabetes and liver disease by our esteemed cousins. It makes perfect sense to me, that when the liver becomes damaged through scaring, or alcohol-related liver disease. Strange things will start to happen. This is my understanding as to what is going on: The Liver is one of the most complicated organs in the body, and possibly the least understood. It plays a huge role in handling sugars and starches, making sure our bodies have enough fuel to function. When there’s a lot of sugar in the system, it stores some of the excesses in a storage form of carbohydrate called glycogen. When blood sugar levels get low, as in times of hunger or at night, it converts some of the glycogen to glucose and makes it available for the body to use. Easy to say, but how does the liver know what to do and when to do it? Scientists have found a “molecular switch” called the “CRTC2 gene” (or “Switch Gene” as it’s sometimes called) that controls this process. When the CRTC2 switch is on, the liver pours sugar (glucose) into the system. When there’s enough glucose circulating, CRTC2 should be turned off. The turn-off signal is thought to be insulin. This may be an over simplification , though. In a post-transplant patient – here the medications used to prevent rejection can alter the way hepatocytes in the liver handle sugars and can drive the overproduction and release of glucose into the blood. Also, patients with diabetic risks before transplant are more likely to experience it after transplant. The other wonderful aspect of this CRTC2 switch gene is that during a persons REM sleep pattern, any excess sugars stored in the liver are burnt off and exhaled out through the lungs. So, the CRTC2 gene does indeed act as a switch to produce more sugar in fasting situations and is down-regulated when abundant sugar is present. Levels change in type 2 diabetes and this makes the hyperglycemia worse. What’s most interesting is that the signals that act through this molecule are linked to a protein called calcineurin which is activated and causes the liver to make more sugar. The calcineurin levels increase in insulin-resistant states. CRTC2 is found in many cells including immune cells, heart and placenta and some studies suggest in liver cells too. It is also down-regulated in some cancers. However, calcineurin is also found in immune cells and is linked to growth and functional responses. So, some types of anti-rejection medications used after transplant, target calcineurin to dampen down anti-graft immune responses. Tacrolimus and cyclosporin are calcineurin inhibitors. We can therefore, see how there might be a connection between anti-rejection medication and function of CRTC2.

The human body is composed of billions of cells that are continually ageing, dying and being replaced. Cell death, replacement, growth and development are normally tightly controlled. If this control breaks down, cells begin to grow and divide abnormally, clustering together to form a lump known as a tumour. These tumours are either benign or malignant. Cancer is the name given to a malignant tumour. There are two broad categories of liver cancer: secondary and primary. 1 . Secondary liver cancer is cancer that first develops elsewhere in the body and then spreads (metastasises) to the liver. It is sometimes called metastatic cancer. 2. Primary liver cancers are cancers that start in the liver. The two main types are: Hepatoma, also called hepatocellular carcinoma (HCC) and Biliary tree cancer, which includes cholangiocarcinoma (bile duct cancer) and gallbladder cancer.

The Liver Life Project

Medical Consequences

I’ve been trolling the internet to find a suitable presentation of this procedure, but sadly, there appears to be nothing available from a British perspective. I have therefore used a video taken from the Barcelona Hospital Universitarito to best illustrate this procedure. I suspect, the procedure to be pretty much the same. This procedure does look a little tricky. I think the best way of describing what TIPSS is, is to explain what each of the letters stands for: T. Is for TRANSJUGULAR. This means that the radiologist will put a fine, hollow needle into the jugular vein in your neck while you are asleep. Through this needle, he, or she, will pass a fine, thin wire in a straight line until it reaches the veins from your liver. This is much easier than you would imagine. Over this wire, the radiologist will pass a fine plastic tube called a catheter, about the size of a very long piece of spaghetti. I. Is for INTRAHEPATIC. The catheter that the radiologist has inserted will be passed down one of your liver veins into the liver itself. The radiologist will then take the wire out and insert a long-curved needle. PS. is for PORTO-SYSTEMIC. The long needle will be pushed from your liver vein, (or SYSTEMIC vein) into your PORTAL vein, which lies close to it. It is this portal veinwhich has become partially blocked up by your liver disease. Because of the blockage, there is high blood pressure in this part of your circulation, and this procedure is designed to relieve this. S. is for SHUNT. Once the needle has been passed between your liver vein and the portal vein, a wire will be passed through the needle and the needle is withdrawn. Over the wire, the radiologist will pass a metal spring called a stent. This stent will expand to create a channel between the two veins. Blood will then flow from the high-pressure portal vein into the low-pressure liver (or systemic) vein. The high pressure in the portal vein which is causing your problem will consequently be reduced, back towards normal.

Using heat to destroy Cancer/Tumour cells (Ablation) Ablation uses heat to destroy cancer cells. There are three types of ablation that produce heat in different ways. These are: • Microwave • Radiofrequency • Laser ablation. Each type destroys cancer cells by heating them to a high temperature. They may be used if you have previously had surgery or if you’re not fit enough to have surgery. You will be given a sedative drug to make you feel drowsy and a local anaesthetic to numb the skin of your abdomen. Sometimes ablation is performed using a general anaesthetic. The doctor puts a fine needle through the skin over your liver and into the centre of each tumour. An ultrasound or CT scan is used to guide them. The microwave, radio-frequency or laser then produces heat which passes through the needle and into the tumour. This treatment takes about 30–60 minutes and can be used to treat tumours up to 5cm (2in) in size. You can usually go home a few hours after you’ve had your treatment. The side effects of ablation are usually mild and may last up to a week. They include pain in the liver area, which you can control by taking regular painkillers. Other side effects are a fever (high temperature) and feeling tired and generally unwell. These side effects are due to the body getting rid of the cells that have been destroyed. Try to drink plenty of fluids and get enough rest. Your doctor or nurse may ask you to contact the hospital if your temperature doesn’t settle within a few days or if it goes higher than 38˚C (100.4°F). This is to make sure you don’t have an infection. Your specialist can give you more information about the possible benefits and risks of these procedures. There is a useful guide from Southampton University Hospital that may be of interest at the following web address: https://www.uhs.nhs.uk/Media/UHS-website- 2019/Patientinformation/Cancercare/Having-a-microwave-ablation-of-the-liver-2103-PIL.pdf

Normally the blood from your gut returns in veins via the liver to the heart. The largest of these veins is called the Portal Vein. Due to the disease in your liver there is increased pressure in your blood vessels. This means the blood struggles to flow through them and is forced to find alternative routes to reach your heart. One of these routes uses the veins in the bottom of your gullet. These veins start to carry more blood and become enlarged, leaky and can bleed easily. These distended veins are called varices. If the varices start to bleed, this can lead to a very dangerous loss of blood. The distended and bleeding vein can be prevented from bursting by placing an elastic type of band over it. If this operation does not control the bleeding your doctor may have to consider other alternatives to reduce the pressure, such as a TIPSS procedure.

TIPSS (Transjugular Intrahepatic PortoSystemic Shunt)

I felt that the subject of “Alcohol Induced Cancer” was too big a subject to be included here. I have therefore addressed this it’s on separate page.

Alcohol very easily finds its way into the brain, and when there, has a profound effect on many of the brain’s structures and functions. Alcohol is a neurotoxin, meaning it is poisonous to neurons, the main type of brain cell. It causes both short-term and long-term effects and harm to the brain, although the risks and harms change throughout our life course. This film looks at how alcohol gets into the brain, which parts of the brain it affects, the acute and chronic harms it can cause, how it can harm the brain of foetuses, adolescents, adults, and older people, and what can be done to reduce this harm.

Wernicke-Korsakeoff Syndrome (sometimes referred to as “Wet Brain”)

While “Korsakeoff Syndrome” isn’t a liver-related condition. I felt this important alcohol-induced condition should be featured, and spoken of somewhere here. Alcohol-related brain damage (also known as alcohol-related brain impairment) is caused by drinking alcohol excessively over a prolonged period of time. It can be caused by a combination of reasons including vitamin B1 deficiency (thiamine), the toxic effects of alcohol on nerve cells, head injury and blood vessel damage. There are three main types of alcohol related brain damage; Wernicke’s encephalopathy, Korsakoff’s syndrome and alcoholic dementia. Both Wernicke’s and Korsakoff’s can occur singularly or in combination when it is called Wernicke-Korsakoff Syndrome (WKS). Wernicke’s encephalopathy often has a sudden onset and is characterised by movement and balance problems, loss of coordination, confusion, disorientation and abnormal eye movements. Korsakoff’s syndrome occurs more gradually and the symptoms are usually attention and concentration problems, gaps in memory which are usually filled inaccurately (confabulation) and a difficulty learning new information. Alcoholic dementia is characterised by a deteriorating ability in planning, decision making and assessment of risk. There tends to be a change in personality, reduced impulse and emotional control which may lead to conflict and socially inappropriate behaviour. In addition there are problems with attention, concentration and memory. Alcohol related brain damage tends to be more common in people in their 40s and 50s and comprises about 10% of the cases of young onset dementia diagnosed. Middle aged women are more at risk of the negative effects of alcohol due to differences in hormones, body fat composition and height weight ratios. Stick within low risk drinking guidelines of no more than 14 units per week (equates to 6 pints lager or 1.5 bottles of wine per week) Spread alcohol intake over three or more days Have alcohol free days Increase physical and mental activity Have a healthy balanced diet Avoid smoking Manage stress, depression and anxiety symptoms by finding alternative methods of coping than alcohol use Keeping weight, cholesterol and blood pressure in check

Interventions and support for people with alcohol-related brain damage.

If the excessive consumption of alcohol is stopped and vitamin B1 levels increase, about 25% of cases recover completely, 50% of the cases show a partial recovery with some degree of damage (but this tends to remain static) and 25% of the cases diagnosed progress with damage to the brain and nervous system and may need long term care eventually. People who are drinking excessively should have a gradual withdrawal of alcohol as suddenly stopping or rapidly reducing the intake may lead to: tremors, delirium, sweating, hallucinations, depression, anxiety and insomnia. The person who is drinking alcohol to excess should see their GP for an assessment of the issue and for referral for treatments and services available to treat the alcohol misuse. The GP may refer the person for managed withdrawal of alcohol, counselling and prescribe medication to stop the withdrawal symptoms and reduce the urge to drink alcohol. They may also advise that the person attend a local self-help group. In addition, if the GP suspects that there may be cognitive damage they may refer the person for an assessment of the cognitive damage and for ongoing support if needed. If alcohol related brain damage is diagnosed, the person and the family should be assisted to: devise an individualised plan focusing on strengths and interests follow guidance to remain alcohol free attend a self-help group eat a healthy balanced diet high in thiamine (leafy green vegetables, oily fish and whole grains) and take a vitamin supplement if required. There is a danger of GPs misdiagnosing Wernicke-Korsakoff Syndrome, as the symptoms may mimic that of hepatic encephalopathy. If it is known that the patient has a history of alcohol abuse, then they could be prescribed Lactulose rather than the much-needed thiamine (Vitamin B1). This video maybe of some help.

Alcohol interferes with communication pathways in the brain. This causes the loss of control that happens when you are drunk. In the longer term, drinking too much alcohol can damage, shrink or kill brain cells. This can change the way the brain works. Alcohol can affect the brain in different ways to cause problems. Some of these problems include: 1. lowering the level of serotonin in the brain, which can lead to depression 2. stopping new brain cells from developing 3. damaging nerve cells and blood vessels in the brain

Drinking heavily over a long period can cause long-lasting or permanent changes to the brain. The symptoms of alcohol-related brain injury include: 1. Poor memory 2. Difficulties with new learning 3. Balance and coordination problems 4. Changes in temperament or personality 5. Attention and concentration difficulties 6. Mental health problems, like anxiety and depression

The following video from the, “Institute of Alcohol Studies” explains this well. Prof Annie Britton talks about the impact this has upon our society.

The Liver Life Project

Medical Consequences

(Warning, this video is rather graphic) In people who have cirrhosis, high blood pressure in the veins that carry blood from the intestines to the liver can cause many problems. One such serious complication is that of portal hypertension. When blood pressure increases in the portal vein system, veins in the oesophagus, stomach, and rectum enlarge to accommodate blocked blood flow through the liver. The presence of enlarged veins (varices) usually causes no symptoms. (They may be found during an endoscopy exam of the oesophagus.) About 50 to 60 out of 100 people who have cirrhosis develop varices in the oesophagus. Some people may feel that this video sequence is too graphic. For this, I make no apologies. This condition is going to happen to you if your liver becomes too badly damaged. 50% of those people who have liver cirrhosis of the will suffer from a variceal bleed condition. And believe me, it’s not very pleasant.

The following video from the, “Institute of Alcohol Studies” explains this well. Prof Annie Britton talks about the impact this has upon our society.

Wernicke-Korsakeoff Syndrome (sometimes referred to as “Wet Brain”)

While “Korsakeoff Syndrome” isn’t a liver-related condition. I felt this important alcohol-induced condition should be featured, and spoken of somewhere here. Alcohol-related brain damage (also known as alcohol-related brain impairment) is caused by drinking alcohol excessively over a prolonged period of time. It can be caused by a combination of reasons including vitamin B1 deficiency (thiamine), the toxic effects of alcohol on nerve cells, head injury and blood vessel damage. Thereare three main types of alcohol related brain damage; Wernicke’s encephalopathy, Korsakoff’s syndrome and alcoholic dementia. Both Wernicke’s and Korsakoff’s can occur singularly or in combination when it is called Wernicke-Korsakoff Syndrome (WKS). Wernicke’s encephalopathy often has a sudden onset and is characterised by movement and balance problems, loss of coordination, confusion, disorientationand abnormal eye movements. Korsakoff’s syndrome occurs more gradually and the symptoms are usually attention and concentration problems, gaps in memory which are usually filled inaccurately (confabulation) and a difficulty learning new information. Alcoholic dementia is characterised by a deteriorating ability in planning, decision making and assessment of risk. There tends to be a change in personality, reduced impulse and emotional control which may lead to conflict and socially inappropriate behaviour. In addition there are problems with attention, concentration and memory. Alcohol related brain damage tends to be more common in people in their 40s and 50s and comprises about 10% of the cases of young onset dementia diagnosed. Middle aged women are more at risk of the negative effects of alcohol due to differences in hormones, body fat composition and height weight ratios. Stick within low risk drinking guidelines of no more than 14 units per week (equates to 6 pints lager or 1.5 bottles of wine per week) Spread alcohol intake over three or more days Have alcohol free days Increase physical and mental activity Have a healthy balanced diet Avoid smoking Manage stress, depression and anxiety symptoms by finding alternative methods of coping than alcohol use Keeping weight, cholesterol and blood pressure in check

Interventions and support for people with alcohol-related brain damage.

If the excessive consumption of alcohol is stopped and vitamin B1 levels increase, about 25% of cases recover completely, 50% of the cases show a partial recovery withsome degree of damage (but this tends to remain static) and 25% of the cases diagnosed progress with damage to the brain and nervous system and may need long term care eventually. People who are drinking excessively should have a gradual withdrawal of alcohol as suddenly stopping or rapidly reducing the intake may lead to: tremors, delirium, sweating, hallucinations, depression, anxiety and insomnia. The person who is drinking alcohol to excess should see their GP for an assessment of the issue and for referral for treatments and services available to treat the alcohol misuse. The GP may refer the person for managed withdrawal of alcohol, counselling and prescribe medication to stop the withdrawal symptoms and reduce the urge to drink alcohol. They may also advise that the person attend a local self-help group. In addition, if the GP suspects that there may be cognitive damage they may refer the person for an assessment of the cognitive damage and for ongoing support if needed. If alcohol related brain damage is diagnosed, the person and the family should be assisted to: devise an individualised plan focusing on strengths and interests follow guidance to remain alcohol free attend a self-help group eat a healthy balanced diet high in thiamine (leafy green vegetables, oily fish and whole grains) and take a vitamin supplement if required. There is a danger of GPs misdiagnosing Wernicke-Korsakoff Syndrome, as the symptoms may mimic that of hepatic encephalopathy. If it is known that the patient has a history of alcohol abuse, then they could be prescribed Lactulose rather than the much-needed thiamine (Vitamin B1). This video maybe of some help.

I felt that the subject of “Alcohol Induced Cancer” was too big a subject to be included here. I have therefore addressed this it’s on separate page.