First: Cirrhosis
Definition
Cirrhosis; Compromised hypertension is the most common cause of ascites and hepatocellular cancer.
Etiology
Hepatitis C and alcoholic liver disease are the most common causes of cirrhosis.
Important causes of cirrhosis;
Viral hepatitis: Hepatitis B, C, D
Alcohol
NASH (non-alcoholic fatty hepatitis)
Metabolic: Primary hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, galactosemia, cystic fibrosis
Autoimmune: Autoimmune hepatitis, primary biliary cholangitis
Cardiac: Constrictive pericarditis, right heart failure
Biliary tract diseases: Sclerosing cholangitis, biliary atresia in children
Cryptogenic cirrhosis (Cause unclear, may be associated with NASH)
Important causes of cirrhosis;
Viral hepatitis: Hepatitis B, C, D
Alcohol
NASH (non-alcoholic fatty hepatitis)
Metabolic: Primary hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, galactosemia, cystic fibrosis
Autoimmune: Autoimmune hepatitis, primary biliary cholangitis
Cardiac: Constrictive pericarditis, right heart failure
Biliary tract diseases: Sclerosing cholangitis, biliary atresia in children
Cryptogenic cirrhosis (Cause unclear, may be associated with NASH)
Clinic
Hepatic encephalopathy is due to both hepatocellular insufficiency and portal hypertension.
• In practice, compensated-decompensated periods are often mentioned according to the signs of deterioration in liver functions and severe insufficiency.
Compensated cirrhosis: It is the period in which the liver can maintain the basic functions of the body and there is no obvious insufficiency. Patients may be asymptomatic or may present with nonspecific symptoms and signs.
Decompensated cirrhosis: It is the period when there are clinically evident hepatocellular insufficiency and signs of partial hypertension, together with severe deterioration in liver functions.
Decompensated cirrhosis is considered to develop in the presence of varicose bleeding, jaundice, ascites, and hepatic encephalopathy.
Diagnosis
• The diagnosis of cirrhosis can often be made with clinical findings and imaging methods.
• An increase in the ALT/AST ratio in favor of AST and a decrease in the platelet count may be important clues to the progression to cirrhosis.
• Heterogeneity in the parenchymal structure of the liver, nodules, irregularity in the margins and shrinkage in the liver in the future are important findings in ultrasonography and other imaging methods.
• Non-invasive fibrosis tests and elastography, which have been used in recent years, are also very helpful in diagnosis.
• Definitive diagnosis is made pathologically by liver biopsy. However, in most cases this is not necessary.
Treatment
• All patients with cirrhosis are included in the screening program for esophageal varices and hepatocellular cancer.
• Drugs used in the treatment of hepatitis B and C can reverse compensated cirrhosis.
• Chronic liver failure in the decompensated period can be treated with orthotopic liver transplantation.
• Liver transplantation is most commonly performed in viral hepatitis (hepatitis C), alcoholic liver disease, and cirrhosis due to NASH.
Prognosis
• The modified Child-Pugh classification is most commonly used in clinical follow-up to determine prognosis and survival. While stage A patients are compensated and a long survival is expected, stage C is generally decompensated and the expected survival is quite short.
In order to determine the child class, it is checked how many points the patient gets from each parameter according to the values specified in the table, and the scores of the 5 parameters are added and the stage specified below is found.
Stage A = 5 - 6
Stage B = 7 - 9
Stage C = 10 - 15
MELD (model for end stage liver disease) is a scoring system used to determine the risk of mortality in liver cirrhosis and especially to determine the priority for liver transplantation.
For scoring, serum bilirubin, creatinine, and INR are checked. Additional points are added to patients on dialysis.
According to the above parameters, patients are scored between 5-40. The higher the score, the greater the urgency for transplantation.
The addition of sodium to the MELD scoring system is defined as Na-MELD and may increase its prognostic value.
Cirrhosis Complications
Portal Hypertension (PoHT)
Definition and etiology:
• It is a clinical condition that leads to congestion in the organs draining into the portal system due to increased portal pressure, and opening of normally closed anastomoses and drainage of portal blood into the caval system.
• Splenomegaly, esophageal varices, ascites and portosystemic collaterals occur in PoHT.
• The most important reason for the increase in portal pressure is the increase in resistance to portal blood flow. The most common cause is cirrhosis (90%).
Classification:
• Portal hypertension is classified in 3 ways according to the anatomical region where resistance to vascular flow develops.
Diagnosis
• Imaging methods: Doppler USG, spiral tomography and MR angiography help the diagnosis by visualizing the portal flow. MR angiography is more sensitive.
• Pressure measurements: Portal vein pressure is best measured indirectly by hepatic vein catheterization.
Postsinusoidal Portal Hypertensions
Budd-Chiari Syndrome
• It develops due to thrombosis of hepatic veins.
• Etiology
Myeloproliferative diseases (most common cause) (especially polycythemia vera)
All hematological disorders characterized by hypercoagulability
Behcet 's disease
Pregnancy and postpartum period
Oral contraceptive use
Paroxysmal nocturnal hemoglobinuria
• Patients usually present with acute right upper quadrant pain and/or ascites due to hepatomegaly.
• Doppler USG is the primary choice in diagnosis. Since caudate lobe drainage is directly to the caval vein, it compensatory hypertrophy.
• Definitive diagnosis is made by hepatic venography.
• Thrombolytic therapy and anticoagulation are performed in acute cases. However, in cases of decompensated cirrhosis, the treatment is liver transplantation.
Venoocclusive Disease (sinusoidal obstruction syndrome)
• It is a non-thrombotic occlusion of intrahepatic small and medium hepatic venules.
• It usually develops after heavy chemotherapy such as bone marrow transplantation.
Peliosis hepatis
• It is a vascular malformation characterized by multiple, blood-filled vesicles in the liver.
• Often associated with anabolic steroids.
Cardiac Cirrhosis
• It develops as a result of liver congestion secondary to chronic cardiac pathologies (right heart failure, valve diseases, constrictive pericarditis, etc.).
Esophageal Varicose and Varicose Bleeding
Definition and General Information
• Varicose veins occur as a result of enlargement of the venous plexus in the lower esophagus. Variceal bleeding mortality is high in cirrhosis.
Clinic:
• Varices are usually asymptomatic unless they bleed.
Diagnosis:
The patient often presents with hematemesis and hematochezia. It can cause severe upper GI bleeding.
Hepatic encephalopathy may develop in these patients as the nitrogen load transferred to the intestine increases during varicose bleeding.
• The definitive diagnosis of varicose veins and varicose bleeding is made by endoscopy.
Treatment
In the treatment of esophageal varices; (1) Prevention of initial bleeding (primary prophylaxis) and re-bleeding (secondary prophylaxis) due to varicose veins, (2) Treatment of acute bleeding.
• Prophylaxis: It is applied to reduce the risk of bleeding in patients with varicose veins.
In primary prophylaxis (patients without varicose bleeding yet), the primary choice is non-selective B-blocker (propronalol or nadolol) or endoscopic ligation.
Secondary prophylaxis (patient with previous variceal bleeding) is performed in combination with non-selective B-blocker and endoscopic ligation to prevent re-bleeding.
• Treatment of acute varicose bleeding:
The steps of approach in the patient who is thought to have esophageal variceal bleeding are as follows.
- Emergency resuscitation of the patient:
Vital signs monitoring, IV fluid replacement, IV PPI and transfusion if necessary should be performed.
- Pharmacological treatment:
Vasoconstrictor agents are started in all patients whether or not endoscopic treatment is performed.
The most commonly used drugs are octreotide (somatostatin analogue) and
is terlipressin.
- Endoscopic treatment:
After general resuscitation, all patients are immediately taken to endoscopy. The most effective treatment of esophageal varices bleeding is still endoscopic treatment methods.
sclerotherapy
band ligation
Endoscopic varicose occlusion
- Balloon tamponade: It is used for bleeding that does not stop or recurs despite endoscopy. It is made with a Sengstaken-Blakemore tube.
- Transjugular intrahepatic portosystemic shunt (TIPSS):
In cases where medical treatment is unsuccessful, an alternative to surgery is the placement of a metal stent between the hepatic vein and the portal vein.
- Surgical treatment
Considerations for patients with varicose bleeding
Beta-blockers are not used.
Antibiotics are given for encephalopathy prophylaxis.
Blood transfusion should be done carefully (Target hemoglobin 8 g/dl).
Acid and its Differential Diagnosis
Definition:
Ascites is the accumulation of fluid in the peritoneal cavity.
• The most common cause is cirrhosis.
• The most important complications of ascites are that it can cause spontaneous bacterial peritonitis and hepatorenal syndrome, especially in patients with cirrhosis.
Etiology:
• Portal hypertension: The most common cause is liver cirrhosis.
• Acute liver failure
• Tumors: Ovarian, pancreatic and colorectal cancers
• Infections: Tuberculosis, HIV
• Pancreatitis: It is seen in acute and chronic pancreatitis.
• Chylose acid
• Bile acid
• Collagen tissue diseases
• Endocrine diseases: Hypothyroidism
• Cardiac causes: Right heart failure and constrictive pericarditis
• Kidney diseases: Nephrotic syndrome, chronic kidney disease
Pathogenesis:
Acid is formed by the following mechanisms;
• Increased hydrostatic pressure in the partal system (fibrosis due to cirrhosis)
• Secondary hyperaldosteronism (renin-angiotensin system activation due to hypovolemia)
• Decreased plasma oncotic pressure (due to low albumin)
• Decreased resorption ability of the peritoneal membrane (peritoneal infiltration)
• Increased peritoneal permeability (infections)
Clinic and Diagnosis:
• Physical examination: In the abdominal examination, the matte opening is upward facing.
• Ultrasonography: It is the most reliable and first step radiological examination in the diagnosis of ascites.
• Diagnostic paracentesis:
" It is the best method for detecting the cause of ascites.
Albumin, total protein and cell count/formula are routinely checked in the paracentesis fluid.
" Today, serum acid albumin gradient (SAAG) is used in the differential diagnosis of ascitic fluid.
• Serum albumin-Acid albumin difference >1.1 (SAAG > 1.1)
It is seen in conditions with portal hypertension (such as cirrhosis, heart failure, constrictive pericarditis, portal vein thrombosis and Budd-Chiari syndrome).
These are conditions characterized by fluid accumulation, usually transudate.
• Serum albumin-Acid albumin difference < 1.1 (SAAG < 1.1)
Occurs in conditions other than portal hypertension (such as primary or secondary tumors of the peritoneum (most common), tuberculosis, pancreatitis, vasculitis, nephrotic syndrome, biliary acid, and intestinal infarcts).
These are conditions characterized by fluid accumulation, usually exudate, apart from nephrotic syndrome.
Other ascites findings helpful in differential diagnosis:
• Neutrophil dominance: Indicates bacterial infection.
• Lymphocyte dominance: It is in favor of tuberculosis.
• Erythrocyte dominance: Hepatoma (HCC) favors tuberculosis. It can also be seen in traumatic paracentesis.
• Amylase increase: It is in favor of pancreatic acid.
• Adenosine deaminase increase: It suggests tuberculosis and malignancies.
• Triglyceride increase: It shows chylous acid.
Treatment
The following treatments are applied sequentially:
• General precautions: The first step is salt restriction (< 2 g/day), water restriction is done if serum sodium is below 130 mEq/L.
• Spironolactone: Spironolactone is preferred first in diuretic therapy. It is given to prevent secondary hyperaldosteronism. It is started with 100-200 mg/day.
• Furosemide: It is given in combination with spironolactone, especially in the presence of peripheral edema. It is started with 40-80 mg/day.
• Therapeutic paracentesis:
It is performed in the presence of refractory acid (salt restriction + 160 mg furosemide + continued acid despite the use of 400 mg spironolactone). It is usually done in conjunction with a volume expander such as albumin.
• Invasive treatment: Peritonovenous shunt and TIPS are other alternatives in resistant cases.
Patients with cirrhosis should be evaluated for transplantation.
• Diuretics are contraindicated in patients with ascites:
hepatic encephalopathy
deep hyponatremia
kidney dysfunction
Spontaneous Bacterial Peritonitis (SBP)
Definition and Pathogenesis:
Infection that develops in ascitic fluid without any intervention or intra-abdominal source to cause infection is defined as primary peritonitis or spontaneous bacterial peritonitis (SBP).
• Intestinal bacteria pass from the edematous intestinal wall to the peritoneum by translocation.
• The low protein content of the ascitic fluid significantly increases the risk of SBP. Therefore, SBP is more common in ascites due to cirrhosis.
• Advanced liver failure and variceal bleeding are the most important conditions that increase the risk of SBP.
etiology
The most common causative agent in adults is E. coli.
Clinic
If a patient with ascites has fever, abdominal pain and/or general condition deterioration, the first thing to come to mind should be spontaneous bacterial peritonitis.
Diagnosis
• At least 250/mm3 neutrophils (PMNL) should be present in the ascitic fluid for diagnosis.
• Culture should be requested for the isolation of agents in ascitic fluid.
Treatment
• Empirical antibiotic therapy should be started immediately (without waiting for culture results) in patients with suspected SBP.
• Generally, 3rd generation cephalosporins (especially cefotaxime) are the primary choice, quinolones and other broad-spectrum antibiotics are alternatives.
• The duration of treatment is 7-10 days. A relapse of SBP can be seen within a year in 70% of recovered cases.
Prophylaxis
• Long-term antibiotic prophylaxis is applied for life or until transplantation in order to prevent new peritonitis attack in patients with SBP.
• Norfloxacin is preferred for prophylaxis. Trimethoprim-sulfomethoxazole is an alternative.
Hepatorenal Syndrome (HRS)
Definition and Pathogenesis:
It is functional renal failure due to advanced liver failure.
• Kidneys are anatomically and histopathologically normal.
• It is often associated with dilutional hyponatremia and refractory acid.
• It occurs as a result of progression of pathophysiological mechanisms that cause ascites and severe vasoconstriction in renal arteries.
• It is the most mortal complication of cirrhosis.
• HRS displays clinical and laboratory findings of prerenal acute kidney injury. However, the patient did not have a condition that would cause hypovolemia.
Clinic
There are 2 clinical types of HRS.
• Type It progresses with rapid deterioration in kidney functions within two weeks. It is a picture with a very high mortality (80%).
• Ti It is kidney failure progressing with slow deterioration in kidney functions and refractory acid. Its prognosis is better than Type 1 HRS.
Diagnosis
HRS should be considered when oliguria and elevated creatinine are detected in a patient with severe hepatic impairment and ascites. Other renal pathologies should be excluded for the diagnosis. Commonly used diagnostic criteria for HRS are;
Decreased glomerular filtration; serum creatinine > 1.5 mg/dl
Absence of shock, bacterial infection, dehydration, or nephrotoxic drug intake
• No permanent improvement in renal functions despite administration of isotonic fluid and albumin after discontinuation of diuretic therapy
• Proteinuria (>500 mg/day), obstructive uropathy and renal parenchyma on USG! absence of signs of illness
Treatment
• The aim of pharmacological treatment is to increase renal blood flow.
• The most commonly used for this purpose is terlipressin and albumin infusion, which has been shown to prolong survival in patients.
• Noradrenaline, midodrine and octreotide can be used in selected cases.
• Definitive treatment is liver transplantation.
Hepatic Encephalopathy
Diagnosis
It is the name given to reversible neuropsychiatric findings due to liver failure and portosystemic shunt.
pathogenesis
• It is the direct addition of intestinal toxic substances to the systemic circulation due to the insufficiency of hepatic clearance of intestinal toxic substances due to hepatic insufficiency and portocaval shunts.
Clinic
• The first symptoms may be impaired cognitive functions and difficulty in drawing shapes.
• Neuromuscular irritability is another important finding of hepatic coma, and the most reliable indicator is rough, asymmetrical and non-rhythmic tremors in the hands, defined as 'flapping tremor' (asterixis).
Factors precipitating hepatic encephalopathy
Gastrointestinal bleeding:
Varicose bleeding, portal gastropathy, gastric/duodenal ulcer, Mallory-Weis tear
Medications:
Diuretics, hypnosedatives, morphine, hepatotoxic agents
Infections:
Spontaneous bacterial peritonitis, urinary infections, pulmonary infections
Electrolyte and acid-base imbalance:
Metabolic alkalosis / acidosis, hypomagnesemia, hypokalemia (increases renal ammonia synthesis), vomiting, diarrhea, hyponatremia
Diet:
Excessive protein intake
Azotemia:
Prerenal or renal acute kidney injury
Constipation:
Drugs that reduce intestinal motility or systemic diseases
Diagnosis:
Hepatic encephalopathy should be suspected in any mental or mental status change observed in a patient with known chronic liver disease.
Treatment:
• The first step in treatment is to find and correct the causes that precipitate or increase encephalopathy.
• Liver transplantation is the last resort in acute or chronic liver injuries whose encephalopathy does not improve despite appropriate treatment and whose liver functions are severely impaired.
• General precautions in treatment:
It is not recommended to limit protein intake in the diet, it is recommended to meet protein needs with plant foods.
• Lactulose
It converts into lactic acid in the intestines, reducing the pH of the small intestine and causing suppression of ammonia-producing bacteria.
It also accelerates intestinal transit with osmotic diarrhea and reduces the absorption of toxic substances.
• Antibiotic treatment: It targets suppression of intestinal flora.
Rifaxamine, neomycin, and metronidazole are the most commonly used
are antibiotics.
• Other treatments: Drugs such as flumazenil that alter the neurotransmitter balance, acarbose and branched chain amino acid replacement (LOLA: L-ornithine L-aspartate) can be given in selected cases.
Hepatopulmonary Syndrome
• In the presence of advanced liver disease; It is a picture consisting of increased alveolar arterial gradient (when inhaled in room air) and intrapulmonary vascular dilatation (shunt development in the lung).
• Pleural effusion and decrease in lung volume may accompany this picture.
• The main pulmonary symptom is dyspnea.
• Cyanosis, hypoxia (PaO2 < 60 mmHg), platypnea (difficulty breathing in upright position) may be seen.
Treatment:
• The only successful treatment is liver transplantation.
