​Kembara Xtra - Medicine - Liver Cirrhosis

​Kembara Xtra - Medicine - Liver Cirrhosis 
Introduction
a long-term condition that can cause vascular remodeling, necrosis, fibrosis, hepatocellular dysfunction, and liver failure as well as cancer

Incidence and prevalence in Epidemiology 
The age range at diagnosis was primarily between 40 and 60.
More women suffer from cirrhosis due to alcohol misuse than males do.
Cirrhosis and liver disease are the 12th and 9th main causes of death overall in the United States, respectively, among adult males.
NASH, which is predicted to overtake alcohol as the primary cause of cirrhosis in the coming ten years, is a condition that is becoming more and more widespread.
Cirrhosis is estimated to affect 30,000 people annually, albeit this number is likely an underestimate given the high rate of patients who are not aware of their condition.
Prevalence
Cirrhosis affects 630,000 Americans, or 0.3% of the population, and chronic liver disease affects 2%.
Non-Hispanic blacks, Mexican Americans, and those in poverty have the highest rate of cirrhosis

Pathophysiology and Etiology 
Hepatitis C virus (HCV) chronic (26%)
NASH/obesity (10%), and alcohol misuse (21%),
Hepatitis D infection (15%) and hepatitis B virus (HBV) infection
Other: drug-induced liver disease (e.g., methotrexate, -methyldopa, amiodarone); venous outflow obstruction (e.g., Budd-Chiari syndrome, venoocclusive disease); chronic right-sided heart failure; tricuspid regurgitation
Hepatocellular damage causes angiogenesis, fibrous alterations, and cellular hyperplasia (regenerating nodules). Portal hypertension is the outcome of blood flow irregularities.
Cirrhosis is genetically linked to hemochromatosis, Wilson disease, and adult-onset 1-antitrypsin deficiency.

Risk Elements 
Abuse of intravenous drugs, fat, and alcohol

Prevention 
Reduce risk factors, such as alcohol consumption and hepatitis C testing; chronic liver disease is largely preventable (>80%).
Limit alcohol consumption and encourage individuals who are overweight or obese to lose weight.

Accompanying Conditions 
Diabetes, depression, alcohol and drug abuse, and obesity

Introducing History 
Review the risk factors, which may include alcoholism, viral hepatitis, a history of primary liver cancer in the family, other liver conditions, or autoimmune diseases.
Symptoms: Anorexia, weight loss (or weight gain if there is ascites or edema), right upper abdominal pain, tea-colored urine, clay-colored stools, bruising, bleeding, hematemesis, hematochezia, melena, chronic anovulation, diminished libido, erectile dysfunction, and night blindness.

clinical assessment 
Up to the final stages of an illness, a physical examination may be normal; many of these relate to symptoms of portal hypertension and/or hyperestrinism.
Spider angiomas, palmar erythema, jaundice, scleral icterus, ecchymoses, caput medusa, hyperpigmentation, lessening of body hair, and facial telangiectasias are a few examples of the skin alterations.
Splenomegaly (if portal hypertension) and hepatomegaly
Wave-like abdominal fluid, varying dullness (ascites)
Gynecomastia and contractures of Dupuytren
Clubbing and presacral pitting edema in the pretibia, especially in cases of hepatopulmonary disease.
Asterixis and altered mental state (hepatic encephalopathy)
Muscle atrophy and weakness
(In cases of extensive portosystemic shunting) Fetor hepaticus

Multiple Diagnoses 
Acute alcoholic hepatitis, steatohepatitis, other portal hypertension-causing conditions (such as portal vein thrombosis and lymphoma), metastatic or multifocal liver cancer, and vascular obstruction

Diagnostic tests and laboratory results 
Age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count (1) are the three factors that make up the Fibrosis-4 (FIB-4) index.
AST/ALT: moderately increased, usually AST > ALT; as cirrhosis advances, enzymes may return to normal.
Increased levels of total/direct bilirubin, -glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP)
Anemia brought on by hemolysis, a lack of folate, and/or splenomegaly
Cirrhosis is 95% specific for thrombocytopenia (110); FIB- 4 1.45 or AST to platelet ratio index (APRI) 0.7;
Hypoalbuminemia, low cholesterol, a prolonged prothrombin time (PT), an increased international normalized ratio (INR), and a prolonged partial thromboplastin time (PTT) are signs of impaired synthetic liver function; coagulopathy of vitamin K-dependent clotting factors (II, VII, IX, and X) is another.
Hyperammonemia, high BUN, hyperkalemia, and hyponatremia are signs of progressive cirrhosis.
Hepatorenal syndrome: urine volume 500 mL/day, urine sodium 10 mEq/L, creatinine clearance 40 mL/min (or serum creatinine >1.5)
Hepatocellular carcinoma (HCC) is screened for using abdominal ultrasound every 6–12 months.
Elastography or Doppler ultrasound to evaluate the liver parenchyma and Doppler for the hepatic/portal vein

Follow-Up Tests & Particular Considerations Take into account:
Serologies for hepatitis
If alcohol addiction is suspected, serum ethanol and GGT
Antimitochondrial antibody for the detection of primary cirrhosis of the bile duct
Antibodies against smooth muscle and nuclear proteins to detect chronic active (autoimmune) hepatitis
Check for hemochromatosis using transferrin saturation (> 50%) and ferritin (markedly raised); if abnormal, consult a hemochromatosis (HFE) genetics/mutation analysis.
Screen for the phenotype of 1-antitrypsin
Wilson disease can be detected using ceruloplasmin; if it is low, examine copper excretion (serum copper plus 24-hour urine copper).
-Fetoprotein level for HCC screening

Other/Diagnostic Procedures
Liver biopsy: necessary for a conclusive diagnosis; transjugular if INR 1.5 and no ascites; percutaneous if not; biopsy advised if noninvasive markers are inconsistent with imaging
Ultrasound-based elastography: a growing noninvasive liver biopsy substitute that assesses fibrosis.
Endoscopy (EGD) if port hypertensive gastropathy or esophageal varices are a problem
The best imaging for obese or non-alcoholic fatty liver disease (NAFLD) patients is magnetic resonance elastography. Test interpretation Fibrous bands and regenerating nodules are typical biopsy characteristics of cirrhosis. 
Additional histological patterns
Alcohol-related liver disease includes steatosis, a polymorphonuclear (PMN) leukocyte infiltration, hepatocytes that are deteriorating rapidly, Mallory bodies, and enormous mitochondria.
HBV/HCV: inflamed periportal lymphocytes
NASH is the same as alcoholic liver disease; in severe disease, steatosis may "burn-out".
Biliary cirrhosis: bile duct wall PMN infiltrate, increased inflammation in portal spaces, and progressive bile duct loss in portal spaces
Hemochromatosis is characterized by an increase in intrahepatic iron reserves measured by iron stain or weighted biopsy tissue.
Positive periodic acid-Schiff bodies in hepatocytes indicate a lack of antitrypsin.

Management 
Except for serious gastrointestinal bleeding, altered mental status, sepsis/infection, rapid hepatic decompensation, or renal failure, outpatient care is provided.

Measures 
Refrain from using narcotics, alcohol, and hepatotoxic medicines and herbs.
Hepatitis A/B, influenza, and pneumococcal-23 vaccines
Exercise, lipid/glucose regulation, and weight reduction
The distinction between compensated and uncompensated diseases, such as ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, coagulopathy, and variceal hemorrhage, is a crucial first step.

Medication 
Initial Line
To stop the condition from progressing, address the underlying cause first (notice the need for precautions in decompensated cirrhosis).
HCV: The objective is to eliminate viral RNA in serum. If there is no cirrhosis (e.g., FIB-4 3.25, FibroScan 12.5 kPa, normal biopsy, or platelet count >150,000), direct acting antivirals (DAAs) such as glecaprevir-pibrentasvir for 8 weeks in genotypes 1 to 6 or sofosbuvir-velpatasvir for 12 weeks in genotypes 1, 2, 4, 5, and 6 are recommended. If
With 48 weeks of therapy, compensated cirrhosis with viremia can be treated with the intention of lowering the risk of HCC and decompensation. Indefinite therapy is advised if decompensated. First-line medications include telbivudine 600 mg PO daily, entecavir 0.5 to 1.0 mg PO daily, and tenofovir 300 mg PO daily.

Weight loss of 7–10% is recommended for NAFLD to enhance histopathologic characteristics. Metabolic and hepatic indicators are improved by increased physical fitness and/or >150 minutes per week of exercise.
Alcoholic hepatitis: Treat alcohol withdrawal; Maddrey Discriminant Function score for risk stratification; >32 indicates poor prognosis; patients may benefit from prednisolone 40 mg/day for 28 days with a taper of 2 to 4 weeks; taper to reduce short-term mortality; pentoxifylline for patients who are unable to tolerate steroids
Phlebotomy every 1 to 2 weeks as tolerated to reach a goal serum ferritin of 50 to 100 g/L (often to 40 g/L), and then 2 to 6 times per year as necessary; deferoxamine 40 mg/kg/day over 8 to 12 hours for 5 to 7 days in dyserythropoietic syndrome and chronic hemolytic anemia to quickly reduce iron overload.
Ursodeoxycholic acid (ursodiol) 13 to 15 mg/kg PO divided BID-QID with food is the recommended dosage for treating primary biliary cirrhosis. Bile acid sequestrants, such as cholestyramine 4 to 8 g PO BID and antihistamines, are also recommended in the event that ursodiol is ineffective for treating pruritus. Malabsorption, deficits in fat-soluble vitamins, metabolic bone disease, hypercholesterolemia, hypothyroidism, and anemia should all be assessed for and treated.

Wilson disease: start with trientine 750–1,500 mg/day PO BID–TID or penicillamine 1,000–1,500 mg/day PO BID–QID on an empty stomach. Better tolerated is trientine 750–1,500 mg/day PO BID–TID. Zinc acetate 150 mg/day PO BID-TID for maintenance after a year; zinc for pregnant women, children, and presymptomatic individuals.
Treatment for autoimmune hepatitis includes prednisone 30 mg/day for 1 week, 20 mg/day for 1 week, 10 mg/day for 2 weeks, maintenance at 5 mg/day with azathioprine 50 mg/day throughout, and treatment to normalize transaminases after induction. If AST and ALT are normal after at least 24 months of therapy, stop maintenance.

Propranolol >40 mg, carvedilol 6.25 mg, or nadolol 40 mg PO daily are recommended for treating esophageal varices in order to reduce portal pressure by 20 mm Hg, systolic pressure from 90 to 100 mm Hg, and pulse rate by 25%. PPI is also recommended for treating portal hypertensive gastropathy.
Ascites/edema: low-sodium diet (2 g/day) and spironolactone 100–400 mg/day with or without furosemide 40–160 mg/day PO; torsemide may be used in place of furosemide. Water restriction of 1.0 to 1.5 L/day is necessary if serum sodium is less than 120 mmol/L. To rule out SBP, if new onset. Consider SBP prophylaxis (TMPSMX DS daily, norfloxacin 400 mg PO daily) if there is a history of SBP.
Lactulose 15 to 45 mL BID; titrate to induce 2 to 3 loose bowel motions each day if you have encephalopathy. Rifaximin combination therapy (550 mg PO BID) is advised as part of a treatment plan to avoid recurring hepatic encephalopathy.
Ursodiol, cholestyramine, or antihistamines (such as hydroxyzine) for pruritus
NSAID, diuretic, and nephrotoxic medication cessation; normalization of electrolytes; hospitalization for plasma expansion or dialysis.
Second line HBV: adefovir 10 mg PO daily second line; PEG-IFN 2a 180 g SC weekly for 48 weeks in compensated cirrhosis, if not contraindicated; lamivudine not advised as first-line drug due to resistance

Motive for Additional Consultations 
When problems like ascites, variceal hemorrhage, encephalopathy, jaundice, or liver lesions suggestive of HCC first appear, as well as when signs of hepatic dysfunction like Child-Turcotte-Pugh (CTP) >7 and the Model for End-Stage Liver Disease (MELD) >10 emerge, liver transplantation should be considered.

Surgical Techniques 
Varices: transjugular intrahepatic shunt (TIPS), second-line or salvage therapy for acute bleed, 4–6 treatments of endoscopic ligation (if acute hemorrhage, employ pre-esophagogastroduodenoscopy [EGD] octreotide as vasoconstrictor).
Therapeutic paracentesis every two weeks PRN if ascites are tight; use caution if there is no pedal edema.
Transplantation of the liver for fulminant hepatic failure
HCC can be treated if it is tiny with radiofrequency ablation, excision, or transplant.

Treatment Options 
Zinc sulfate 220 mg BID, an adjuvant for hepatic encephalopathy, may improve dysgeusia and appetite.
Milk thistle may reduce transaminases and ameliorate signs and symptoms.

Admission
renal failure, severe gastrointestinal bleeding, altered mental status, sepsis or infection, quickly developing hepatic decompensation,

Constant Care 
Monitor sodium, creatinine, platelets, and PT every six to twelve months; compute the MELD score.
Patients with cirrhosis should have periodic liver ultrasonography screening and serial -fetoprotein testing. Patients over the age of 55 who have chronic HBV or HCV, an increased INR, or insufficient platelets are most at risk for developing HCC.

If liver mass is detected on ultrasound and/or fetoprotein is increased, MRI with contrast is the best follow-up test for HCC.
EGD to screen for varices at the time of cirrhosis diagnosis, every 3 years (compensated), and every 1 year (decompensated).

Take Action 
Regular physical exercise may lessen weariness.
patient observation
At each appointment, keep an eye out for general symptoms including weakness, weariness, decreased appetite, and itchy skin.
Jaundice, changes in mental status, or abdominal pain are serious issues.
Protein (1.2 to 1.5 g/kg body weight per day), high fiber, multivitamins (without iron), sodium restriction (2 g/day), in combination with fluid restriction, are all necessary if ascites or edema are present.
Inform people on when to seek emergency care (such as in cases of hematemesis or altered mental status).
Cannabis-free drug, alcohol, and smoking cessation
Updating necessary vaccinations; HCV transmission safety measures

Prognosis 
Asymptomatic disease for 5 to 20 years after the first diagnosis.
MELD and CTP scores have previously been used to predict outcomes. These results don't take into account nutritional evaluation, even though sarcopenia (muscle wasting) has been identified as a significant predictor of mortality in cirrhosis patients.
Death without transplant usually occurs within 5 years of the onset of complications. HCC develops at a rate of 5% per year. Ascites develops in 50% of cirrhotics over a 10-year period. The most common fatal complication is acute variceal bleeding, which results in a 30% mortality rate.
- After transplant, annual mortality is 5%; after transplant, 85% survive for a year.
Due to a lack of organ donors, 25% of eligible patients obtain transplants.

Complications 
Ascites, edema, infections, hepatic encephalopathy, GI hemorrhage, esophageal varices, gastropathy, colopathy, hepatopulmonary syndrome, HCC, and post-transplant problems (such as surgery, rejection, and infections)

---