Cystic Fibrosis (CF) is an autosomal recessive
disease of mutated cystic fibrosis transmembrane regulator (CFTR) gene
hereditary from both the parents. CF is a progressive disease which affects the
secretory glands, making them unusually thick and sticky, to cause persistent
infections in the respiratory, digestive and reproduction organs. Over period, it causes fluid-filled sacs
(cysts) and scar tissue (fibrosis) in those organs.

With respect to the epidemiology, CF is
generally found in white Caucasian population include Europe, North America and
Australasian in the white population. According to the NHS data collected from
the United States, the prevalence of CF in one case per population is as
follows: Following Whites of north European origin, Hispanics, African
Americans. Asian Americans have also become vulnerable to the disease, which is
increasingly recognized in non-white populations. The possibilities of its spread
to South and East Asia, Africa, and Latin America. Interestingly, the
population with a mixture of the white gene with the Asian or African gene
enhance the CF frequency, comparison to native Asians or Africans.

The phenotype of CFTR mutations alternate on the
ethnicity of the patients, for instance,
in the northern European white population, ?F508 is the most frequent mutation
detected. Interestingly, no data showed any variation found in-patients with
this mutated gene. On the other hand,
some cases found among the young black population who have poor nutritional and
pulmonary dysfunction symptoms when compared to patients in the white population with CF. The reason for this
is still unclear, whether this caused by genetic or socioeconomic factors. In
terms of the gender, females with cystic fibrosis have a greater degeneration
of pulmonary function of time for a younger mean age at death. Some researchers
suggest that puberty may obstruct with the defence for the immune system
mechanisms in female patients by interfering with an increased hormone
secretion, leading to pulmonary involvement in advance; but for this, the
immune system in patients with CF is radically intact.

In general, CF affects males and females
equally. Except this, risk factors leading to CF consist of phenotype,
environmental and lifestyle factors.CF is caused by genetic mutations in the
CFTR gene. The major risk factor is that of the patient inheriting mutated CFTR
gene from both of his/her parents. Regarding the mutated gene class, mutated CF
gene mutations are classified based on the level of damage to the CFTR protein
function. Class 1 to 3 cause classical symptoms which is more severe. Class 4
and 5 are generally milder. Also, other genes called modifier genes can affect
a person’s symptom. Genotype-phenotype is correlated with phenotype severity,
there are more than 1200 mutations have been reported. 32% of patient carry
either of G85E or 5T mutated allele with a severe phenotype and liver
dysfunction symptoms. In, although the standard advice is that CF carriers are
as a generally healthy population, there
is still a higher prevalence to have the CF-like
disease in the single organ.

As for environment and lifestyle factors, people
with CF require consumption of very large amounts of calories to maintain
weight and grow. A healthy lifestyle with daily physical, prevention of smoking or be exposed to second-hand
smoking and non-alcohol activity is
important to help keep the lungs healthy. Also, a huge amount consumption of
calories for the patient is needed to maintaining
the normal weight and growth progress in age line.

Regarding the symptoms of CF, they vary with the
age of the individual, therapies and the types of infection in that person had
previously. CF affects the whole body including the breathing, digestion and
reproduction systems and processes of growth. Concerning the onset of lung
disease, the lungs of patients are essentially normal at birth. There is a
build-up of the sticky and thick mucus and the airways are blocked. Symptoms
include a chronic cough with thick mucus in the infant stage and frequent
respiratory infections, fever, cough, difficulty in breathing, fast respiration
and flaring of the nostrils in childhood. In general, patients have chronic or
a recurrent cough, which can be dry and hacking at the beginning and can
produce mucus in early and purulent sputum in later stages. Other symptoms
include recurring chest colds, wheezing and shortness of breath. In addition,
Individuals with Cystic Fibrosis also tend to have continual lung infections
insensitive to standard treatments. Cystic Fibrosis also causes continual
sinusitis infections. As the disease developing, other important respiratory
complications and patients may develop serious conditions like allergic
bronchopulmonary aspergillosis, pneumothorax, massive haemoptysis, and lung or
lobar collapse. The constant use of antibiotics has led to the destructive
Gram-negative bacilli. Next, the narrow and anaerobic environment in lower
airway flora contains many anaerobes, diverse bacterial and fungal flora. This,
combined with chronic infection, leads to bronchiectasis, pulmonary and death
from respiratory failure, and may require a lung transplant.

In terms of pancreatic insufficiency, 85% of the
patients suffer from malabsorption of nutrients due to the distal intestinal
obstruction syndrome (DIOS), caused by the accumulation of thick tenacious
secretions and mal-absorbed fat in the terminal ileum, as distinguished from
constipation. Another less common issue is biliary cirrhosis leading to portal
hypertension. Pancreatic insufficiency results in malabsorption mainly of fats
and proteins, leading to fat-soluble vitamin deficiency. Malabsorption results
in steatorrhea, characterized by persistent, poorly formed, massive, stinking,
oily stools that float in water. The newborn period might have persistent diarrhoea, bulky, foul-smelling, greasy and
pale stools. When the infants grow up, they present recurrent abdominal pain,
poor appetite, malnutrition, poor growth and failure to thrive. On the other
hand, patients having hepatobiliary involvement may present jaundice or
gastrointestinal tract bleeding.

CF can also derive other consequent symptoms,
such as enlargement of the right heart, except the indicated factors including
dysfunction of the rectum through the anus, liver, pancreatic and gallbladder.
In addition, CF patients are more likely to experience delayed puberty and
reproductive abnormalities, especially male sterility which accounts for 90%.

As for treatment option, a gain of nutrition and
healthy weight are major goals. For instance, fat-soluble vitamins (A, D, E, K1), a supplement
of calories and replacement of pancreatic enzyme such as Pancrelipase used to
improve nutrient absorption. In addition,
pulmonary treatment like chest physiotherapy loosens the mucus by literally
banging on the chest as inhalers. Also, medications such as

Bronchodilators (Albuterol ) results in smooth
muscle relaxation of the bronchi, uterus, and skeletal muscle; CFTR
Potentiators like lumacaftor/ivacaftor control
inner cell protein channel signalling.Mucolytic
Agents like dornase alfa which reduce viscoelasticity and surface tension of
purulent sputum. Further, due to the
chronic infections and loss of pulmonary function over time, a lung transplant
is sometimes needed. Recently, personalized therapy has been developed to
target specific CFTR mutation types. In addition, there are new genetic
technologies on the horizon aimed at correcting specific gene mutations. Also,
pulmonary function tests are regularly used to monitor the disease with the
used of treatment.

There has been an improvement in patient care and disease management and improved
neonatal screening, cascade screening, and prenatal diagnosis of CFTR.
According to research, the Brittany region in France showed the expectation of reducing the incidence
of CF in the past 10 years.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hepatocellular carcinoma (HCC) is a major
primary liver malignancy cancer accounting for 85% of all primary liver
cancers. There are 250,000 new cases per year within a male and 4 times of it
for female respectively. Women developed HCC with fibrosis and cirrhosis in
high prevalence, with a general mean age of presentation of 70 years, with a
rare occurrence before 40 years. Its prevalence is greater in men than in
females. HCC is familiar in Asia, Africa, Pacific Islanders or Pasifikas The
age-adjusted incidence of liver cancer has risen from 1.6 to 4.6 per 100,000.
Furthermore, particular ethnic groups have significantly increased the risk of
HCC.

cirrhosis and chronic liver disease still the
major cause of developing HCC in
worldwide. Chronic hepatitis B and C are the most common causes of chronic
hepatitis. Within hepatitis C, genotypes A and D are more familiar in Europe and the Middle East, whereas
genotypes B and C are more familiar in
Asia and genotype C has been associated with a higher risk of HCC than other.
There are 5% of the global population is infected with hepatitis B through the
transmission including contaminated blood transfusions, intravenous injections,
drug users sharing needles, sexual contact and from mother to foetus. and the
carriers have an approximately 20% of the risk of developing HCC in average during
their lifetime particularly for those patients with genotype C in active
infection with HBV, it carries more than 2.5 times risk of developing
HCC in the following 10 years. The negative for Hepatitis B virus surface
antigen (HBsAg) and positive state of hepatitis B core antibody (Anti-HBc total
(Anti-Hepatitis B core total antibodies) are the detector for HCC.

When liver cells are damaged and replaced with
scar tissue, it causes cirrhosis. The
causes include hepatitis B or C infection, alcohol drinking, abuse of drugs,
and overload iron disease. In addition, excess alcohol intake over time
exacerbate the prevalence of HCC which five times higher than that of hepatitis
C from the NHS report from the USA, it also accounts for 40%–50% of all HCC
cause in Europe population, with the average citizen ingesting more than 7
drinks and 14 drinks per week in women and men respectively. In the USA,
persons drinking higher than 60 g/d of alcohol are 4 times at risk of having
HCC. in addition, the consumption of more than 3 drinks and 6 drinks per day
raised the risk to 16% and 22% respectively. Moreover, both Obesity and
diabetes raise the risk of liver cancer. obesity due to high insulin levels in
diabetes patients or liver damage can lead to non-alcoholic fatty liver
disease, it enhances the risk of hepatocellular carcinoma. Diabetes precisely
affects the liver since the liver is
essential in the mechanism of glucose
metabolism, so dysfunction of liver induce chronic hepatitis, fatty liver, and
cirrhosis. Also, it enhances the hazard
for carcinogenesis since insulin play role in adjusting of the
anti-inflammatory cascade and cellular proliferation. In spite of regulating of
cellular proliferation, insulin-like growth factor and insulin receptor
substrate-1 also promote apoptosis inhibition. On the other side, the iron
storage disease causes excessive iron to be stored in the liver that may
increase the risk for hepatocellular carcinoma.

In general, the patient
might not have any sensation of abnormal
with symptoms at an early stage. As cancer grows, more of the symptoms may be
noticed, painful and a lump or feeling of heaviness in the upper stomach,
bloating in the stomach, loss of appetite and feelings of fullness, weight loss
,weakness or deep fatigue, nausea and vomiting, yellow skin and eyes, pale,
chalky bowel movements, dark urine and fever.

Diagnostic methods include Imaging techniques
such as Ultrasound, Computed Tomography and Magnetic resonance imaging (MRI).
Ultrasound is the investigation which should identify the largest number of
hepatocellular carcinomas and ideally used for monitoring of cirrhosis during
half a year observation period, to detect
whether a new development of nodules or
any conformation change of nodules has been detected.  Computed tomography is used to detect a
staging assessment and investigate signs of portal hypertension. Magnetic
resonance imaging (MRI) is still the best investigation to detect and characterize
the different nodules, which develop into cirrhosis.

Surgery is one of the common options for
early-stage non-cirrhotic patients, who still have a normal liver function. The
respectability of a tumour depends on the size and location of a tumour and
liver function, and the possibility allows for the resection of the remaining
liver volume and also evidence of vascular invasion, which enhance the
possibilities for prevention of morbidity and mortality. From previous studies,
5-year survival rates after resection of around 40% to 75% of patients who have
a solitary tumour without evidence of vascular invasion and normal liver
function. To the contrary, in patients who had significant portal hypertension,
the 5-year survival rate range under 50%. both elevated pressure within the
portal system and bilirubin levels are
presented. Also, the 5-year survival rate ranging from 30% to 50% of patients
with cirrhosis. Although the survival rate in patients with hepatic resection,
the disease-free survival has not changed and the recurrence rates may be as
high as 70% after 5 years which occurs within 1–2 years, by proliferation or
metastasis from a primary tumour. Recently, laparoscopic liver resection has
been found is a safer and effective surgical method in the treatment of HCC or
as a bridge to liver transplantation.

For liver transplantation, the criteria
considered include tumour size, number and volume under the recent United
Network of Organ Sharing policy, patients
with newly diagnosed hepatocellular carcinoma (HCC) and liver transplantation
may suitable for their cases, it  should
meet the Model For End-Stage Liver Disease (MELD) score which requires more
than 2 years of waiting time. Also, vascular invasion is the most important
prognostic. It may be solved by living donor liver transplantation with
Ablative therapies, which reduce tumour size to allow enrolling for
transplantation for larger and more numerous tumours in the absence of
microvascular invasion. However, the mortality of the donor is less than 1 %
and life-threatening complications are
2%.

In general, the surgical resection or liver
transplantation is the first line treatment option for early-stage HCC, whereas
asymptomatic patients with intermediate stage disease benefit from
chemoembolization. Patients with end-stage HCC or extensive extrahepatic
disease often have a less than the 3-month rate of survival, therefore pain and
symptom are controlled and improving quality of life should be the major focus.

The HBV vaccination has shown the significant
prevalence of HCC. The vaccination
program for an infant in East Asia lead
to an 85% reduction in the incidence of
hepatitis B, but others still remain at risk of postnatal hepatitis B
infection. The therapeutic treatment using nucleoside analogues in treating HBV
mothers in their 3rd pregnancy has shown the success of vaccination in preventing neonatal transmission.