Alcoholic Liver Disease:     Therapy    


Immediate and total abstinence from alcohol is critical for patients with alcoholic liver disease. Continued drinking is associated with disease progression, while abstinence benefits patients at any stage of disease. Fibrosis, portal pressures and ascites also often improve with the cessation of drinking.

Patients hospitalized with alcoholic hepatitis are usually very ill with a short-term mortality between 20-50%. Several factors are associated with poor prognosis, especially signs of poor hepatic function (jaundice, encephalopathy, and coagulopathy). In patients who are not infected, leukocytosis and hepatic inflammation also parallel poorer outcomes. Disease severity can be estimated using the Maddrey score or discriminant function. Maddrey and colleagues found that the following equation helped to identify patients that would benefit from aggressive intervention.

Discriminant function = 4.6 [PT (seconds) - control] bilirubin (mg/dL). A value greater than 32 is associated with high mortality.

Standard supportive therapy for patients hospitalized with acute alcoholic hepatitis should include treatment of alcohol withdrawal, nutritional support including vitamins, (thiamine, folate and pyridoxine) minerals (phosphate, magnesium and zinc) and an aggressive search for potential infections. Protein should not be restricted, even in patients with encephalopathy. Specific therapy for severe alcoholic hepatitis should be initiated if the discriminant function is greater than 32 or the patient has hepatic encephalopathy. Currently, the American College of Gastroenterology recommends corticosteroid therapy (prednisolone 40 mg/day or methylprednisolone 32 mg/day for 4 weeks) if there is no evidence of active infection, gastrointestinal bleeding, or pancreatitis and the creatinine level is less than 2.5 mg/dL. Recent studies suggest that pentoxifylline, a tumor necrosis factor inhibitor, may also decrease mortality by preventing deterioration of renal function.

Long-term treatment of alcoholic liver disease is not straightforward. Several studies have evaluated the benefits of treatments including nutrition, propylthiouracil, colchicine, polyunsaturated lecithin, s-adenosylmethionine, pyridoxine and pyrrolidone. To date, the American Gastroenterological Association and the American Association for the Study of Liver Diseases endorse only nutritional supplementation for routine use. Any patient hospitalized for decompensation of alcoholic liver disease should receive aggressive nutritional support, including enteral or parenteral therapy. All patients with decompensated liver disease should be considered for transplantation. Orthotopic liver transplantation improves survival rates when compared to medically managed patients (Figure 13). However, given the fact that donors are scarce and the financial expenditure is sizable, transplantation centers require a demonstrated commitment to a lifetime of sobriety. Six months of documented abstinence and participation in a rehabilitation program are generally required for consideration.  

Figure 11. Liver transplantation.

 For more information about the Johns Hopkins Liver Transplantation Program

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The major complications of alcoholic liver disease are similar to those of nonalcoholic patients with cirrhosis. The best course of management of complications such as portal hypertensive bleeding, ascites, and hepatic encephalopathy is the same in both groups. 


Cirrhosis—a liver disease characterized by extensive fibrosis with nodule formation and disruption of the liver architecture (Figure 14)—is an umbrella term encompassing alcoholic liver disease, chronic hepatitis, primary Biliary cirrhosis, and cirrhosis of unspecified etiology. It has a variety of causes, including alcohol consumption, viral hepatitis, exposure to various drugs and toxic chemical exposure, as well as other viral and infectious diseases.

In 1987, Cirrhosis was the ninth leading cause of death in the United States, with over 26,000 deaths attributed to the disorder and a mortality rate of almost 11% per 100,000 population. Despite the fact that national death rates from cirrhosis are very high (2.6 per 1,000 population), researchers have found that a large proportion of affected individuals are totally asymptomatic. When estimates of numbers of asymptomatic patients are added to prevalence figures, they climb to 3.6 per 1,000 population.

Cirrhosis is typically accompanied by regeneration of the liver substance with marked increase in fibrotic connective tissue and may be preceded by alcoholic fatty liver and/or alcoholic hepatitis (although neither is required for the development of the disorder). The nodular regeneration of liver tissues permanently alters the structure of the liver and is associated with impaired function and scarring.   

Figure 12. A, Cirrhosis of the liver; B, histological image.


Portal Hypertensive Bleeding
Varices are varicose veins, visible on endoscopy or an upper GI series, which occur in the esophagus or in the stomach as a result of portal hypertension (Figure 15). Cirrhosis, causes severe scarring of the liver and impedes the normal circulation of blood. Varices develop when portal blood is rerouted to the systemic circulation, through collateral vessels, because of increased resistance to blood flow to or through the liver. Obstructions may occur in the hepatic veins, sinusoids, or the portal veins. The pressure within these irregular vessels is great, increasing the potential for ruptures.   

Figure 13., A-C. Esophageal and gastric varices with corresponding endoscopic images.

Instances of acute bleeding from varices or non-variceal sites in patients with portal hypertension require prompt and appropriate measures. Therapy is aimed at prevention of bleeding episodes, control of acute bleeding, and prevention of recurrent episodes of variceal bleeding through the lowering of portal pressure and the elimination of varices.

Medical therapy
Medical management of bleeding esophageal or gastric varices can be instituted once the cause of the hemorrhage has been documented as variceal in origin. Drug treatment is aimed at reducing portal inflow or collateral or intrahepatic resistance (hepatic venous pressure gradients below 12 mm Hg reduce the danger of variceal bleeding). Use of beta-blockers has been shown to decrease portal pressures, but side effects of the drugs are sometimes prohibitive. Propranolol is a non-selective beta-blocker that has been studied extensively, and is effective in decreasing portal pressures. It decreases the risk of variceal bleeding both as primary prophylaxis, and after an initial episode of bleeding. The dose needs to be titrated to decrease resting heart rate by 25%. There are no other medical therapies that can be recommended to prevent variceal bleeding.

Use of vasopressin in acutely bleeding patients is effective, and works by decreasing splanchnic blood flow. It should be administered in an intensive care unit through a central venous access line. Side effects include vasoconstriction in other vascular beds, including cardiac vessels. Vasopressin should be administered with sublingual nitroglycerin. Octreotide or somatostatin is now the preferred drug for acute variceal bleeding. It also acts as a vasoconstrictor, but works only on the splanchnic bed, and consequently has fewer side effects. It is given as an IV bolus at 50 micrograms, followed by a constant infusion of 50 micrograms per hour.

Endoscopic therapy
Endoscopy plays a critical role in the diagnosis and treatment of gastrointestinal hemorrhage. Endoscopic examination allows the physician to visualize and/or biopsy the patient’s upper gastrointestinal tract. Endoscopy also permits visualization of the esophagus, stomach, and duodenum. During the procedure the patient is given a numbing agent to help to prevent gagging. Pain medication and a sedative may also be administered prior to the procedure. The patient is placed in the left lateral position (Figure 16).

Figure 14. Room set up and patient positioning for endoscopy

For the acutely bleeding patient, there are several options. The use of sclerotherapy, or injection of a sclerosing agent directly into and around the varices, has been studied extensively. It is generally safe, and effective (Figure 17). The technique consists of injecting 1 to 10 mL of sclerosing agent (sodium morrhuate, sodium tetradecyl sulfate, ethanolamine oleate or absolute alcohol) into the varix beginning at the gastroesophageal junction and circumferentially into all columns. There is considerable variation in the type and volume of the agent used as well as the site of injection. Comparison studies of various techniques and solutions have not shown significant advantages of any one method. After performance of the initial sclerotherapy, subsequent sessions are scheduled with the intention of completely obliterating the varices. Weekly sessions appear to offer the best advantage. Common side effects include tachycardia, chest pain, fever, and ulceration at the injection site.

Figure 15. Sclerotherapy for esophageal varices.

Another modality is ligation of varices through banding (Figure 18).

Banding employs the use of small elastic rings that are endoscopically placed over a suctioned varix—and has been shown to be safe and effective. Banding has fewer side effects and complications than sclerotherapy and has been found to be just as effective. Both methods can be used to electively obliterate varices in the non-bleeding patient.     

Figure 16. Technique of endoscopic esophageal banding; A. endoscope with band ligators on the tip; B, banded esophageal varices; C, corresponding endoscopic images.

Trials are currently underway to assess the utility of primary prevention of bleeding using banding and/or sclerotherapy in combination. The suggested technique would be to perform variceal ligation first and then sclerotherapy in the hope that the sclerosing agent would be trapped by the banded varix, thereby preventing systemic complications associated with sclerotherapy. Complications related to this combined approach appear to be less severe than sclerotherapy alone, but greater than band ligation on its own.

For the secondary prevention of bleeding, these modalities should be used to reduce variceal size.

Balloon tamponade
Balloon tamponade is useful in controlling variceal bleeding by use of compression (Figure 19)—and is most often employed when medical management has been proven ineffective and endoscopic management is unavailable or has failed. Typically, physicians use one of three commercially available balloons to tamponade bleeding esophageal or gastric varices. Although quite effective as a temporary measure, tamponading carries with it a high risk of complications, especially aspiration . Only those physicians who have extensive experience with this procedure should perform the tube placement, and the patient should be carefully and continuously monitored.     

Figure 17. Technique of balloon tamponade for control of variceal bleeding.

Shunting Procedures

Transjugular Intrahepatic Portal-Systemic Shunt (TIPSS)

Transjugular intrahepatic portal-systemic shunting (TIPSS) is a radiological procedure that has become very popular as an alternative method to control acute bleeding, especially if gastric varices are present (Figure 20). It is also used in patients that have had recurrent bleeding in spite of medical or endoscopic management.

The procedure requires a high level of expertise, and is performed under fluoroscopic guidance using moderate sedation. Access to the hepatic veins is obtained through the right internal jugular vein. A needle is passed through liver parenchyma into the portal vein, followed by dilation of the tract, and subsequent placement of a metal stent—which is dilated to achieve a portal to hepatic vein gradient of less than 10 mm Hg. 

Figure 18. Transjugular intrahepatic portal systemic shunt(TIPSS);A,B, shunt placement and balloon inflation;A'B',corresponding radiographs;C,expendable metal stent;C,corresponding radiograph. (Click on the blue letters to view the consecutive images)

Success rates exceed 90% in experienced hands, although the long-term utility of the stent is limited by a high occlusion rate from thrombosis or stenosis. The main side effect is worsening hepatic encephalopathy, which can be severe in a minority of patients, requiring occlusion of the stent. The patency of the stent can be checked by Doppler ultrasound. Stenosed stents can generally be revised.

The aim of surgical shunting in portal hypertension is threefold: 1) to reduce portal venous pressure, 2) to maintain hepatic and portal blood flow, and 3) to reduce or (or at least not complicate) hepatic encephalopathy (Figure 21). Currently, there is no procedure that reliably and consistently fulfills all of these criteria.

The operative mortality in shunting procedures is about 5% in patients who are good surgical risks and about 50% in those who are poor surgical risks. 

Table 1. Surgical Shunts
Figure 19. Portal system,presurgical shunting;B,end-to-side portocaval shunt;C,side-to-side portocaval shunt;D,mesocaval
Figure 20. Partial portal systemic shunt: Interpositional “H” shunt.

Figure 21. A. Distal splenorenal shunt;B,coronary caval shunt.(Click on the blue letter to view the next image)


The development of free peritoneal fluid or ascites is another complication of alcoholic liver disease. Ascites is lymphatic fluid that leaks across hepatic sinusoidal endothelium due to high hepatic sinusoidal pressure (Figure 24). 

Figure 22. Mechanism of ascites in portal hypertension; s=stomach; c=colon; I=intestine.

Flow across hepatic sinusoidal endothelium is normally controlled by an oncotic pressure gradient. However, in this instance an increase in lymphatic flow results in a loss of this oncotic gradient and the formation of ascites fluid. In addition, splanchnic lymph formation also contributes to ascites (although the relative contribution of splanchnic lymph is not known). Intra-abdominal fluid is normally absorbed by the peritoneum. The exact mechanism of this fluid resorption is not known, but high intraperitoneal pressure results in net increase in absorption. Abdominal paracentesis is the technique by which ascites is removed from the abdominal cavity (Figure 25). Paracentesis is performed at the bedside. After sterilization of the abdomen, local anesthetic is administered, a sterile needle is inserted into the abdomen and the ascitic fluid is aspirated. After large volume abdominal paracentesis, intraperitoneal pressures drop and there is rapid re-accumulation of ascites.   

Figure 23. Technique of abdominal pericentesis for ascites.

Ascitic fluid is sent for laboratory analysis that includes protein content, cytological analysis, and cultures for bacterial infections. Ascitic fluid was previously classified based on protein content. Low protein ascites was termed transudative and implied hepatic congestion, typically due to chronic liver disease. Fluid transfer occurs across hepatic sinusoids into interstitial tissues and the liver capsule into the peritoneal space. Exudative ascites on the other hand, had higher protein content and implied a different pathogenesis. Namely, production was felt to be from the peritoneum. 

Table 2. Ascites

A more important distinction to make when assessing ascitic fluid is whether the fluid is portal hypertensive in origin. An albumin gradient greater than 1.1 grams/dl between the serum and ascitic fluid is highly suggestive of fluid that is portal hypertensive in origin.

The most important sequela of ascites is the risk for development of spontaneous bacterial peritonitis (SBP). Due to the low protein content and oncotic pressure of portal hypertensive ascitic fluid, the risk of infection is very high. SBP can be difficult to diagnose due to an inconsistent clinical presentation. Pain is often absent and the only reliable diagnosis is through paracentesis. Most cases involve a single bacterial organism, with over 70% of cases being secondary to gram-negative bacilli. Streptococcal species and Staphylococcus make up the majority of other cases.

Diagnosis of spontaneous bacterial peritonitis (SBP) is based on an ascitic fluid (PNM) cell count—with PMN counts over 250/ml suggestive of SBP. The preferred method is to inoculate two blood culture bottles with 10 to 20 mL of ascitic fluid. The treatment of choice for documented SBP is cefotaxime, 1 gram every 8 hours for a minimum of 5 days. Repeat paracentesis is recommended to check therapy response. Ciprofloxacin, norfloxacin, or trimethoprim-sulfamethoxazole is recommended for patients with recurrent SBP.


Hepatic Encephalopathy
Hepatic encephalopathy is characterized by neuropsychiatric symptoms such as changes in consciousness, behavior, and/or personality that may complicate acute or chronic liver disease. It is caused by direct or indirect exposure of the central nervous system to substances that have not been cleared by the liver (primarily ammonia and other toxins) causing a deficit in neurotransmission. Manifestations are widely variable, ranging from mild subclinical disturbances (e.g., slow reaction times) to deep coma.

Hepatic encephalopathy may also be caused by potentially reversible metabolic abnormalities. These abnormalities (such as cirrhosis or hepatitis) may reduce liver function or cause blood circulation to be diverted from the liver. As a result, the liver does not metabolize and detoxify potentially harmful substances and the accumulation of these substances leads to damage to the central nervous system.

There are two forms of hepatic encephalopathy. Portal systemic encephalopathy accompanies portal systemic shunting, arising as a result of portal hypertension or following TIPS or surgery targeted at relieving portal hypertension. This form of hepatic encephalopathy may develop slowly beginning with altered sleep patterns and progressing to include personality changes, lack of coordination, and coma. It is often the result of a gastrointestinal bleed, or use of a sedative. In contrast, hepatic encephalopathy in the face of fulminant hepatic failure carries high mortality. In this case, encephalopathy progresses within days or hours to coma. Muscle irritability, seizures, coma, and increased intracranial pressure are common.

The mainstay of conventional treatment for hepatic encephalopathy is reduction in the production and absorption of circulating nitrogenous compounds, particularly blood ammonia concentrations. Dietary alterations that reduce the absorption of neurotoxic substances from the gastrointestinal tract are recommended. Nonabsorbable disaccharides, such as lactulose, Lactinol, or oral lactose help remove these substrates from the intestinal lumen. Neomycin and metronidazole, antibiotics that act against urease-producing bacteria, are also useful. Additionally, the restriction of dietary protein may be useful in patients refractory to lactulose. Liver transplantation is the definitive treatment for patients with intractable encephalopathy and improves long-term survival.

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