Cirrhosis progression

Chinese Liver Fluke. The adult worm of the Chinese Hver fluke Clonorchis sinensis) can grow to be 2 cm long. Worms infect the bihary tree where they cause local inflammation, diarrhea, and hepatomegaly in the acute infection. Progressive biUary obstmction and cirrhosis can occur in the more advanced disease state. The presence of 20—200 worms is common, but they may number over 20,000. Infection is the consequence of eating raw fish that contain viable parasites. Untreated worms can Hve for up to 30 years. Treatment is with pra2iquantil (1). 

Similar to HBV, infections with hepatitis C virus (HCV) have a high rate of progression from an acute to a chronic state that frequently leads to cirrhosis or hepatocellular carcinoma [2]. Monotherapy for HCV infection with IFN-a or combined therapy with ribavirin and IFN-a is associated with initial rates of response as high as 40%. The rates of sustained responses are, however, lower and also depend on the viral genotype. In patients infected with HCV genotype 2 or 3, the response was maximal after 24 weeks of treatment, whereas patients infected with genotype 1 -the most frequent in the USA and Europe - required a minimum treatment course of 48 weeks for an optimal outcome. 

Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YE (2007) Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol 46 45-52... 

For a variety of reasons, lipid—mainly as triacylglycerol—can accumulate in the hver (Figure 25—6). Extensive accumulation is regarded as a pathologic condition. When accumulation of lipid in the Ever becomes chronic, fibrotic changes occur in the cells that progress to cirrhosis and impaired liver function. 

Hepatobiliary disease occurs due to bile duct obstruction from abnormal bile composition and flow. Hepatomegaly, splenomegaly, and cholecystitis may be present. Hepatic steatosis may also be present due to effects of malnutrition. The progression from cholestasis (impaired bile flow) to portal fibrosis and to focal and multilobar cirrhosis, esophageal varices, and portal hypertension takes several years. Many patients are compensated and asymptomatic but maybe susceptible to acute decompensation in the event of extrinsic hepatic insult from viruses, medications, or other factors.7... 

Cirrhosis is irreversible treatments are directed at limiting disease progression and minimizing complications. 

Cirrhosis is the progressive replacement of normal hepatic cells by fibrous scar tissue. This scarring is accompanied by the loss of viable hepatocytes, which are the functional cells of the liver. Progressive cirrhosis is irreversible and leads to portal hypertension that is in turn responsible for many of the complications of advanced liver disease. These consequences include (but are not limited to) spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, and variceal bleeding.1... 

Once cirrhosis is diagnosed, disease progression is relentless, regardless of the initial insult to the liver. Determining the specific cause of cirrhosis requires examination of both physical presentation and past medical history. An accurate social history is particularly important because few factors in the physical and laboratory examination aid in determining disease etiology. Understanding the cause of a patient s cirrhosis is imperative because it can affect therapeutic options and treatment decisions. 

Sinusoidal damage from cirrhosis is the most common cause of portal hypertension. The sinusoids are porous vessels within the liver that surround radiating rows of hepatocytes, the basic functional cells of the liver (Fig. 19-2). Progressive destruction of hepatocytes and an increase in fibroblasts and connective tissue surrounding the hepatocytes culminate in cirrhosis. Fibrosis and regenerative nodules of scar tissue... 

Progression of alcoholic liver disease moves through several distinct phases from development of fatty liver to the development of alcoholic hepatitis and cirrhosis. Fatty liver and alcoholic hepatitis may be reversible with cessation of alcohol intake, but cirrhosis itself is irreversible. Although the scarring of cirrhosis is permanent, maintaining abstinence from alcohol can still decrease complications and slow development to end-stage liver disease.22 Continuing to imbibe speeds the advancement of liver dysfunction and its complications. 

Genetics and metabolic risk factors mediate other less common causes of cirrhosis. These diseases vary widely in prevalence, disease progression, and treatment options. 

Primary biliary cirrhosis is characterized by progressive inflammatory destruction of the bile ducts. Immune-mediated inflammation of intrahepatic bile ducts results in remodeling and scarring, causing retention of bile within the liver and subsequent hepatocellular damage and cirrhosis. The number of patients affected with primary biliary cirrhosis is difficult to estimate because many people are asymptomatic and incidental diagnosis during routine health care visits is common. 

Non-alcoholic fatty liver disease begins with asymptomatic fatty liver but may progress to cirrhosis. This is a disease of exclusion elimination of any possible viral, genetic, or environmental causes must be made prior to making this diagnosis. Non-alcoholic fatty liver disease is related to numerous metabolic abnormalities. Risk factors include diabetes mellitus, dyslipidemia, obesity, and other conditions associated with increased hepatic fat.26... 

O Prevention and treatment of viral hepatitis may prevent progression to chronic hepatitis, cirrhosis, and end-stage liver disease. 

Only 10% to 15% of patients have acute hepatitis C that resolves without any further sequelae.10 In more than 85% of cases, hepatitis C develops into a chronic disease. Approximately 70% of chronic HCV cases progress to mild, moderate, or severe hepatitis. While the natural history of the progression to cirrhosis is not clear, it is estimated that 10% to 20% of cases may take up to 20 to 40 years from the time of exposure to advance from fibrosis to cirrhosis.10 Fifteen to twenty percent of patients infected with HCV develop complications associated with cirrhosis. Once cirrhosis is confirmed, the rate of developing hepatocellular carcinoma increases to 1% to 4% per year.10 The estimated death rate from HCV infection is 1.8 deaths per 100,000 persons per year.12,15... 

The incidence of liver complications associated with PN ranges from approximately 7% to 84%, and end-stage liver disease develops in as many as 15% to 40% of adult patients on long-term PN.35 Patients often develop a mild increase in liver enzymes within 1 to 2 weeks of initiating PN, but this generally resolves when PN is discontinued. Severe liver complications include hepatic steatosis (fat deposition in liver), steatohepatitis (a severe form of liver disease characterized by hepatic inflammation that may progress rapidly to liver fibrosis and cirrhosis), cholestasis, and cholelithiasis.35... 

Cirrhosis Widespread disruption of normal liver structure by fibrosis and the formation of regenerative nodules that is caused by any of various chronic progressive conditions affecting the liver. 

Steatohepatitis A severe form of liver disease caused by fat deposition in the liver, characterized by hepatic inflammation that may rapidly progress to liver fibrosis and cirrhosis. 

The key goals of therapy are to increase the likelihood of immunoclearance of the virus, prevent disease progression to cirrhosis or hepatocellular carcinoma, and to minimize further liver injury. Successful therapy is associated with loss of HBcAg status and seroconversion to anti-HBcAg. 

The most common symptom of chronic HCV infection is persistent fatigue. An estimated 20% of patients with chronic HCV infection will develop cirrhosis and half of those patients will progress to decompensated cirrhosis or hepatocellular carcinoma. 

In the course of studies on other pathological amino acidurias, the accompanying peptiduria has also been observed by many authors. Rapp de Eston et al. (R2) observed a marked increase in the excretion of both free amino acids and peptides in patients with diffuse hepatic necrosis. Using a simplified chromatographic method adapted to clinical purposes and suitable for analysis of amino acids excreted with urine, Skarzynski et al. (S5) demonstrated a raised level of a certain peptide which is always present in normal urine in smaller quantities, as well as the appearance of some new peptides in cases of jaundice and liver cirrhosis. Some abnormal peptide spots were also detected on the chromatograms in cases of progressive muscular dystrophy (K4) and in patients irradiated with X-rays (S2). 

---