CIRRHOSIS OF THE LIVER

CIRRHOSIS OF THE LIVER

GOALS

• Know how to diagnose cirrhosis.
• Identify emergency situations and plan their management.
• Argue the therapeutic attitude and plan the patient’s follow-up.
• Describe the principles of long-term care.

1. DIAGNOSING CIRRHOSIS
2. DEFINITION

The normal architecture of the liver is made up of regular trabeculae of hepatocytes, portal spaces and centrilobular veins. Cirrhosis is defined by a diffuse disorganization of the hepatic architecture, with annular fibrosis delimiting nodules of hepatocytes in clusters, called regeneration nodules. The size of the nodules is on average of the order of 3 mm. 

All chronic liver diseases, whatever their causes, can lead to the development of cirrhosis when their evolution is prolonged. Usually, cirrhosis only develops after at least 10 to 20 years of evolution of a chronic disease. 

Depending on the stage of the disease and the cause, the liver may be enlarged, normal or reduced in size (atrophy). The liver contours are irregular. Enlarged areas may coexist with atrophied areas. This results in dysmorphism, which is highlighted by imaging tests. The consistency of the liver becomes firm or hard, with a “sharp” anterior edge.

2. THE DIFFERENT STAGES OF DEVELOPMENT AND COMPLICATIONS OF CIRRHOSIS

At an early stage, lesions corresponding to cirrhosis exist but liver functions are relatively preserved and there are no serious complications. This is compensated cirrhosis. At a more advanced stage, there is a clear alteration of liver functions and serious complications appear. This is then decompensated cirrhosis.

Serious complications of cirrhosis can include:

• digestive hemorrhages related to portal hypertension (rupture of esophageal and/or gastric varices);
• ascites (usually associated with edema);
• bacterial infections (including ascitic fluid infections);
• encephalopathy;
• hepatorenal syndrome.

In cases of advanced liver failure, malnutrition and amyotrophy are frequently associated. Finally, cirrhosis exposes the patient to the risk of developing hepatocellular carcinoma. This risk is of the order of 1 to 5% per year.

3. DIAGNOSIS OF CIRRHOSIS

In practice, cirrhosis is accompanied by characteristic abnormalities that can be demonstrated by clinical examination, simple biological tests and imaging tests. Most often, the diagnosis of cirrhosis can be reasonably established without histological examination of the liver on the association of signs of portal hypertension and hepatic insufficiency.

1. Clinical examination

            The clinical examination may be normal. However, the following are frequently observed:

• signs of hepatocellular insufficiency:

• stellar angiomas predominantly in the upper part of the thorax,
• palmar erythrosis,
• white nails,
• conjunctival or cutaneous jaundice,
• hepatic fetor,
• in men, hypogonadism;
• and signs of portal hypertension:

• ascites,
• dilation of abdominal subcutaneous veins (collateral venous circulation),
• splenomegaly.

When the liver is palpable, it is firm or hard in consistency with an irregular lower edge. In case of encephalopathy, asterixis, confusion or, at a more advanced stage, impaired vigilance may be observed.

CIRRHOSIS OF THE LIVER

2. Biological abnormalities

Liver tests may be normal. However, there is frequently an elevation of transaminases (ASAT, ALAT). There may be an elevation of alkaline phosphatase and gamma glutamyl transferase activity.

Bilirubinemia may be normal or elevated. In most cases, elevated bilirubin predominates over conjugated bilirubin.

Liver failure is characterized by a decrease in coagulation factors (prothrombin time and factor V). The International Normalized Ratio is elevated. In advanced stages, liver failure is also accompanied by a decrease in albuminemia.

Portal hypertension is accompanied by hypersplenism with a fluctuating and moderate decrease in platelets and leukocytes. Moderate anemia is common. In cases of voluminous ascites, hyponatremia is frequently present.

In cases of cirrhosis secondary to excessive alcohol consumption, macrocytosis and a β-γ block are observed on protein electrophoresis. A significant increase in ferritin levels may be observed, which does not indicate the presence of associated genetic hemochromatosis. Transferrin saturation is less than 60%.

3. Imaging and endoscopy examinations

Ultrasound is the first-line imaging examination. It must be systematic. Ultrasound abnormalities associated with cirrhosis are an irregularity of the liver contours, dysmorphism with atrophy of certain sectors (often the right lobe) and hypertrophy of other sectors (often the left lobe), ascites, an increase in the size of the spleen, the presence of collateral venous bypass pathways ( fig. 19.1 ).

In case of associated steatosis, the hepatic parenchyma has a hyperechoic appearance. This appearance may be inhomogeneous.

Regeneration macronodules may be visible within the liver parenchyma.

In severe portal hypertension, blood flow may be reversed in the portal vein (hepatofugal flow).

Computed tomography and magnetic resonance imaging are second-line examinations. They are of no major interest for the simple diagnosis of cirrhosis.

Apart from imaging tests, the demonstration of signs of portal hypertension by gastroscopy (esophageal varices) is a strong argument in favour of cirrhosis if there is chronic liver disease.

Fig. 19.1. Appearance of cirrhosis on computed tomography scan with dysmorphism, bumpy liver contours, and ascites

4. Histological examination

Histological examination confirms the existence of cirrhosis ( fig. 19.2 ). It can be obtained from a percutaneous biopsy if the prothrombin rate is greater than 50%, if the platelets are greater than 50 × 109/L and if there is no large ascites. In other cases, the biopsy should preferably be performed by the transjugular route in order to limit the risk of hemorrhage.

CIRRHOSIS OF THE LIVER

5. Non-invasive alternatives to biopsy

The degree of liver fibrosis can be estimated by a combination of blood biological tests ( Fibrotest® ) or elastometry ( Fibroscan® ). Fibrotest® gives a semi-quantitative estimate of the degree of fibrosis. Elastometry is based on the analysis of an ultrasound wave propagated to the liver by a probe comparable to an ultrasound probe. These two tests have not been validated for all causes of cirrhosis.

1. DIAGNOSIS OF THE CAUSE OF CIRRHOSIS

The most common causes of cirrhosis are listed in Table 19.I.

Table 19.I. Causes of cirrhosis in adults

1. Diagnosis and assessment of severity

Digestive hemorrhage due to rupture of esophageal varices is manifested by hematemesis and/or melaena, associated with acute anemia (decrease in the hemoglobin level). The examination shows pale skin and mucous membranes. There is also tachycardia. The absence of tachycardia suggests taking beta-blockers. In the event of massive hemorrhage, there may be hypotension or even shock with marbling. In the absence of externalization of the bleeding, melaena should be sought by digital rectal examination.

The severity of the hemorrhage is estimated by the drop in blood pressure, tachycardia, increased respiratory rate and impaired consciousness. Hematocrit measured very early (e.g. during home care) may underestimate the severity of the hemorrhage.

2. Management of digestive hemorrhage linked to portal hypertension
3. General measures

Cirrhotic patients with upper gastrointestinal bleeding should be transferred to an intensive care or resuscitation unit.

Place one or two peripheral venous lines of good caliber and then perform vascular filling with the aim of obtaining a mean arterial pressure of around 80 mmHg. Either crystalloids (saline serum for example) or colloids can be used. 

Transfusion is warranted if anemia is poorly tolerated or if the hematocrit is less than 25% and/or the hemoglobin level is less than 7 g/dL. The goal of transfusion is to achieve a hematocrit between 25 and 30% and a hemoglobin level greater than 7 g/dL.

It is recommended to insert a nasogastric tube. Its purpose is to check for the presence of blood in the stomach.

Correction of hemostasis disorders by transfusions of fresh frozen plasma or other blood-derived products is not recommended.

2. Vasoactive treatment

Vasoactive treatment to reduce portal pressure should be instituted urgently. 

This treatment should be administered between 2 and 5 days after admission. Beyond this early phase, a relay should be taken with long-term beta-blockers.

CIRRHOSIS OF THE LIVER

3. Antibiotic prophylaxis

Systematic antibiotic prophylaxis significantly reduces mortality. 

4. Endoscopy

An upper digestive endoscopy is essential to establish the cause of the bleeding. 

Endoscopy can be diagnostic (visualization of esophageal varices, active bleeding or a platelet plug adhering to a varice as evidence of recent bleeding) or therapeutic, allowing the stopping of active bleeding.

CIRRHOSIS OF THE LIVER

2. Management of encephalopathy

Encephalopathy results partly from hepatic insufficiency and partly from portosystemic venous shunts. Severe encephalopathy may occur in a cirrhotic patient even if there is no significant hepatic insufficiency.

 The most common triggers are:

• bacterial infections;
• digestive hemorrhages;
• taking sedative medications;
• kidney failure;
• profound hyponatremia.

The first step in management is to look for one of these triggers and correct it.

Encephalopathy may be accompanied by impaired vigilance leading to deep coma. In case of doubt, a brain CT scan may be justified in order to rule out an organic cause (hemorrhage or ischemia).

In case of impaired consciousness, management consists essentially of preventing inhalation of gastric contents by inserting a nasogastric tube and placing the patient in a semi-sitting position. If, despite these measures, congestion and severe hypoxemia appear (which is rare), intubation and assisted ventilation may be necessary.

CIRRHOSIS OF THE LIVER

3. Management of ascitic fluid infection

Ascitic fluid infection occurs in 10 to 30% of patients hospitalized with cirrhotic ascites. It may manifest as:

• a fever;
• abdominal pain;
• diarrhea;
• hyperleukocytosis;
• encephalopathy.

In the initial stage, the infection may be asymptomatic, hence the need to perform a systematic exploratory puncture at each outbreak of ascites.

Diagnosis is based on exploratory puncture of ascites, which shows a neutrophil count greater than 250/mm3. Direct examination is rarely positive. Culture is not always positive. However, the most common causative organisms are enterobacteria. Bacterascites is defined by a positive culture with a neutrophil count less than 250/mm3 in the ascites. Treatment is based on the administration of antibiotics and albumin infusion. The following regimens are recommended:

• cefotaxime, 1 g × 4/day IV;
• amoxicillin-clavulanic acid, 1 g – 0.125 g × 3/day with possible oral relay after 24 hours;
• ofloxacin, 200 mg/day orally or intravenously.

The duration of treatment is 5 to 7 days. Albumin should be administered at a dose of 1.5 g/kg on the first day and then 1 g/kg on the third day.

4. Management of hepatorenal syndrome

Hepatorenal syndrome corresponds to functional renal failure, appearing at an advanced stage of cirrhosis and which is not corrected by vascular filling. Hepatorenal syndrome is most often observed in patients who have severe liver failure (prothrombin rate < 50%) and refractory ascites. It manifests itself by oliguria, a rapid increase in serum creatinine and urea as well as collapsed natriuresis. The prognosis of hepatorenal syndrome is poor with a life expectancy of a few weeks.

By definition, hepatorenal syndrome is not corrected by volume expansion. Effective vascular filling is an essential prerequisite before making the diagnosis of hepatorenal syndrome.

2. Argue the therapeutic attitude and plan the patient’s follow-up
   1. TREATMENT OF THE CAUSE
3. Alcoholic cirrhosis and alcoholic hepatitis

The elements of severity in a patient with alcoholic cirrhosis result more often from the existence of alcoholic hepatitis added to the cirrhosis than from the cirrhosis itself. In addition to recent consumption of excessive quantities of alcohol, the arguments that suggest the existence of alcoholic hepatitis are jaundice, moderate elevation of transaminases predominating over ASAT and hyperleukocytosis. There may be a fever.

The first step in treatment is to stop drinking alcohol. In cases of severe alcoholic hepatitis, after screening for infectious contraindications, corticosteroid therapy (prednisolone, 40 mg/day for 4 weeks) is recommended (after ruling out the possibility of an evolving infection) because it improves the prognosis. It is preferable to perform a liver biopsy to confirm the diagnosis of alcoholic hepatitis.

However, biopsy is not essential to initiate treatment. Improvement of symptoms after stopping alcohol and/or corticosteroid therapy is slow. It may take 3 to 6 months.

2. Cirrhosis secondary to chronic hepatitis B

Viral replication should be quantified by testing for B virus DNA in serum. Antiviral treatment should be initiated in patients with high viral replication. In decompensated cirrhosis, stopping B virus replication by antiviral treatment may be accompanied by regression of complications and return to compensated cirrhosis. As with alcoholic hepatitis, improvement is slow.

3. Cirrhosis secondary to chronic hepatitis C

The standard antiviral treatment is based on the combination of pegylated interferon and ribavirin. However, in cases of cirrhosis, the benefit of antiviral treatment is limited for the following reasons:

• the efficacy of this association to interrupt the replication of the C virus is lower in cirrhotic patients than in non-cirrhotic patients;
• treatment tolerance is less good;
• Due to frequent side effects, it is often not possible to administer optimal doses of pegylated interferon and ribavirin, which contributes to limiting the effectiveness of treatment.
• CIRRHOSIS OF THE LIVER

In cases of decompensated cirrhosis, the administration of antiviral treatment is not recommended due to a high risk of worsening liver failure. Overall, antiviral treatment is unlikely to result in an improvement in the symptoms. Complete cessation of alcohol consumption is essential. Alcohol contributes to the worsening of the lesions.

4. Other causes of cirrhosis

In case of non-alcoholic steatohepatitis, measures aimed at achieving control of excess weight, diabetes and dyslipidemia are recommended. 

There is no specific treatment for primary biliary cirrhosis and primary sclerosing cholangitis. In cases of primary biliary cirrhosis, the administration of bile acids (ursodeoxycholic acid) is recommended. However, the effect of bile acids is limited.

In case of autoimmune hepatitis, the combination of corticosteroids and azathioprine is recommended when the disease is active.

The diagnosis of hemochromatosis implies the initiation of iron depletion by phlebotomy. The diagnosis of Budd-Chiari syndrome (obstruction of the hepatic veins) justifies the initiation of anticoagulant treatment. Finally, the diagnosis of Wilson’s disease (exceptional) requires the administration of copper chelators (D-penicillamine) which, in this specific case, may be accompanied by an improvement

notable.

2. Treatment of ascites and edema
3. Management of tense ascites

Tense ascites is treated by evacuation puncture. In addition to the tense nature of the ascites, evacuation puncture is motivated by functional discomfort. Evacuation puncture must be accompanied by a cytobacteriological examination. There is no obstacle to complete evacuation of ascites in a single session, even if the volume is greater than 5 liters. On the other hand, complex mechanisms mean that evacuation of ascites is followed by activation of the antinatriuretic systems and circulatory dysfunction, contributing to the deterioration of renal function. This dysfunction must be prevented by volume expansion. Beyond 2 liters of evacuated ascites, the infusion of 500 mL of colloids per 2 liters of evacuated ascites is recommended. Administration of human albumin (14 g per 2 liters of evacuated ascites) is an alternative.

However, it is more expensive. Apart from infection of ascitic fluid, its superiority over synthetic colloids has not been demonstrated.

2. Treatment of ascites flare-ups

Treatment is based on a low-sodium diet and diuretics. A low-sodium diet with little restriction (2 to 3 g of salt per day) should be preferred to a more restrictive diet which may be poorly followed and lead to dietary restriction.

Diuretics can be associated with the sodium-free diet from the outset. The first-line diuretic is spironolactone with an initial dose of 75 mg/day. The dose can be increased to 300 mg/day depending on the response, measured by weight loss and natriuresis. In the absence of a sufficient response with spironolactone, furosemide can be associated, starting at a dosage of 40 mg/day. The dose of furosemide can be increased. It is recommended not to exceed 120 mg/day.

The effectiveness of ascites treatment is judged by the reduction in abdominal circumference, the reduction in functional discomfort and weight loss. When ascites is undetectable by clinical examination, ultrasound may be useful to confirm its disappearance. The institution of treatment with diuretics requires regular monitoring of the blood ionogram in order to look for severe hyponatremia, an increase in serum creatinine, hyperkalemia or hypokalemia. A blood ionogram should be performed at least every 2 weeks after initiation of treatment. When the treatment is balanced, monitoring can be spaced out.

The treatment of edema is the same as that of ascites. The evolution of edema is parallel to that of ascites.

3. Treatment of refractory ascites

Refractory ascites is defined as ascites that persists or recurs despite optimal medical treatment. 

The different therapeutic options are iterative evacuation punctures, transjugular intrahepatic portocaval shunt (TIPS), surgical peritoneojugular diversions and liver transplantation.

4. Umbilical hernia

Umbilical hernia is one of the common complications of refractory ascites. The main risks are hernial strangulation and rupture.

3. Chronic encephalopathy

Chronic encephalopathy is a rare complication of cirrhosis . It occurs preferentially in patients who have developed large spontaneous portosystemic shunts, who have received TIPS, or who have concomitant chronic renal failure. 

CIRRHOSIS OF THE LIVER

4. Management of comorbidities

Comorbidities are common in cirrhotic patients. They may be related to the consequences of excessive alcohol consumption, smoking, excess weight or even active or past drug addiction.

In patients with alcoholic cirrhosis and/or who have smoked, it is recommended to carry out a detailed ENT and esophageal assessment in order to look for pre-neoplastic or neoplastic lesions. A cardiovascular assessment should also be carried out.

performed in smoking patients. If necessary, the management of diabetes must be optimized.

5. Referral to transplantation

Liver transplantation remains the only radical and lasting treatment in cases of decompensated cirrhosis and without the possibility of improving liver function through specific treatment. 

The main complications that should lead to consideration of a transplant are:

• severe hepatic impairment with a decrease in prothrombin time below 50% (or an increase in INR above 1.7);
• jaundice;
• refractory ascites;
• an infection of the ascitic fluid;
• repeated episodes of encephalopathy;
• chronic encephalopathy;
• repeated episodes of digestive hemorrhage despite appropriate treatment.

In patients with alcoholic cirrhosis, transplantation is in principle only considered after 6 months of complete cessation of alcohol (in order to ensure that liver failure does not improve spontaneously).

In case of viral B cirrhosis with significant viral replication, antiviral treatment is an essential prerequisite.

Apart from the complications of cirrhosis listed above, the development of small hepatocellular carcinoma is also a possible indication for liver transplantation.

The main contraindications to transplantation are advanced age (over 65-70 years), a serious, untreatable extrahepatic condition that constitutes a significant operative risk, a recent history of cancer other than hepatic, and psychological or psychiatric disorders that would compromise follow-up.

Dental crowns are used to restore the shape and function of a damaged tooth.
Bruxism, or teeth grinding, can cause premature wear and often requires wearing a retainer at night.
Dental abscesses are painful infections that require prompt treatment to avoid complications. Gum grafting is a surgical procedure that can treat gum recession. Dentists use composite materials for fillings because they match the natural color of the teeth.
A diet high in sugar increases the risk of developing tooth decay.
Pediatric dental care is essential to establish good hygiene habits from an early age.
 

CIRRHOSIS OF THE LIVER