Liver insufficiency

Most sulfonylureas are at least partly metabolized in the liver (SEDA-9, 709) (57), and hence liver insufficiency, liver disease, and liver enzyme inhibition (alcohol) or induction (drugs) can alter the half-life of the drug and its duration of action. 

Eulminant liver failure (ELF) is caused by an extensive lost of the liver parenchyma, which results in a severe deterioration of liver function. This clinical picture, which in most cases ends fatally, is also known as liver cell degeneration coma , endogenous liver coma , acute liver insufficiency or acute liver failure . Its causes are multiple and its pathogenesis is complex, see chapter 20)... 

The hepatorenal syndrome (HRS) is a functional, oliguric, progressive, in principle reversible, circulation-related kidney failure occurring in severe liver disease and portal hypertension and increasing liver insufficiency - assuming there are indeed no other causes of the renal insufficiency. 

Liver transplantation Where the hepatorenal syndrome occurs, consideration should understandably be given to liver transplantation in view of the increasing liver insufficiency, (s. p. 387) With suitable cases, this intervention proved to be efficacious. (12, 13, 22, 30, 35,50) In severe forms of HRS and with inadequate response to conservative therapy, the indication for liver transplantation should be reviewed without further delay. The feasibility of surgical intervention will largely depend on whether the phase of hepatic and renal insufficiency can be bridged - with as favourable clinical findings as possible and perhaps supported by suitable invasive measures - until transplantation can be carried out. The three-year and four-year survival rates were both given as 65.1%. (22)... 

Hypoxaemia (Pa02 < 70 mm Hg) is observed in 45-69% of patients suffering from cirrhosis or liver insufficiency. Only rarely has severe hypoxaemia been demonstrated (Pa02 < 50 mm Hg). (6, 32, 51, 52, 56) Intrapulmonary vasodilations could be ascertained in 13-47% of liver transplant candidates. (27) In about 50% of all cirrhotic patients, a decline in the diffusion capacity for carbon monoxide was detected. (24) About 30% of cirrhotic patients showed no (physiological) reduction in pulmonary vasoconstriction under conditions of hypoxia. The prevalence of HPS in cirrhotic patients varies between 4% and 19%. It occurs more... 

Prognosis Prognosis is poor. The patients die of liver insufficiency or right heart failure as well as from various infectious diseases. The mean survival period after diagnosis was 15 months, with a 6-month mortality of 50%. 

Serious liver disease can affect the 12 main metabolic functions of the liver, with their 60 - 70 even more important partial functions, to widely differing degrees, (s. tab. 3.1) The result is either global insufficiency or partial insufficiency, each with very varied clinical and biochemical symptoms. The failure of certain metabolic functions is responsible to a greater or lesser extent for the development and intensity of liver insufficiency. Impairments in the functions of detoxification and protein metabolism are particularly significant in this respect. 

The compensated stage does not usually display any signs of liver insufficiency (except possibly jaundice), nor are there any typical ailments. Functional parameters that can be quantified in routine laboratory tests (such as cholinesterase, albumin. Quick s value, bile acids) may still be normal or only minimally impaired in the individual instance. In contrast, liver tolerance tests (galactose, indocyanine green, etc.) demonstrate a reduction of liver function which is already quite considerable. 

The decompensated stage, i.e. manifest liver insufficiency, can present as cellular decompensation (e. g. in the case of acute liver failure due to toxic or inflammatory mass necrosis) or be expressed only in the form of portal decompensation (e.g. in cases of postsinusoidal intra-hepatic portal hypertension). As a rule, chronic liver insufficiency is accompanied by a combined decompensation with a loss in function of the liver cells and, at the same time, the sequelae of portal decompensation (collateral varicosis, encephalopathy, ascites, hepatorenal syndrome, variceal bleeding), (see chapters 15 19 and 35)... 

Depending on the time period involved in the course of the disease, acute liver failure without pre-existing liver disease can initially be differentiated by massive liver cell disintegration due to a variety of causes. In contrast, chronic liver insufficiency with pre-existing liver disease is mostly found in advanced liver cirrhosis with a progressive loss of function. A sudden necrotising episode is also able to precipitate the change from chronic and still compensated liver insufficiency into acute liver failure ( acute on chronic ) in the same way that acute liver failure which has been overcome can develop into chronic liver insufficiency. 

Tab. 20.3 Criteria for a poor prognosis in acute liver insufficiency...

Chronic liver insufficiency is due to the progression of an already existing chronic liver disease. This generally tends to be advanced cirrhosis of varied aetiology. Basically, however, any liver disease can be a potential cause of chronic liver insufficiency. Alcohol and infections as well as certain medicaments are also deemed to be common causes. A great number of substances and events can trigger liver insufficiency. 

The clinical picture of chronic liver insufficiency comprises both a compensated and decompensated form. These two stages of manifest chronic liver insufficiency affect the hepatocellular area or the portal system either exclusively or predominantly (= cellular or portal compensation or decompensation) mostly they occur as a combined form of disease. The resulting spectrum of clinical and laboratory findings will reflect either a global or partial insufficiency of the liver, (s. p. 376)... 

General manifestations of the disease The clinical picture of chronic liver insufficiency is characterized by general symptoms such as fatigue, apathy, lack of appetite, lack of concentration, infirmity, sensation of repletion and meteorism. 

Clinical findings Organ-related so-called minor signs of liver insufficiency can be observed over a certain period of time. (s. tab. 20.4)... 

Decompensation in chronic liver insufficiency is characterized by the development of severe, life-threatening complications ... 

Tab. 20.4 So-called minor signs of chronic liver insufficiency...

Ascites and oedema are also found in severe hepatic diseases, pointing to serious disorders in the water and electrolyte metabolism. These complications are signs of decompensation in fiver cirrhosis or chronic liver insufficiency. At the same time, pleural effusion may also be evident. Cirrhosis-related pleural effusion without concomitant ascites has been described as a rarity. (see chapter 16)... 

Except for the treatment of, for example, paracetamol intoxication and Amanita phalloides poisoning, there is no causal therapy for liver insufficiency. All conservative treatment measures are based on four principles ... 

Intensive care Patients with ALE or with decompensated chronic liver insufficiency (such as coma stages II-IV, refractory ascites, hepatorenal syndrome, disseminated intravascular coagulation, gastrointestinal bleeding) require monitoring and treatment in an intensive care unit, preferably in a transplantation centre. (7,13,60, 66, 77)... 

EPL In a pilot study, it was possible to achieve recompensation and lasting stabilization in 9 out of 10 patients suffering from severe liver insufficiency by i.v. administration of a new galenic form of polyenylphos-phatidylcholine. (32) This clinical result might be supported by the finding that a considerable deterioration in liver function was associated with a deficit of essential phospholipids (= EPL). (15) (s. p. 865)... 

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