Abdominal Distension (Ascites)

Cirrhosis is the most common cause of ascites (85%) and ascites is the most common complication of cirrhosis. Up to 60% of patients with compensated cirrhosis develop ascites within 10 years [3]. Clinically, patients present with gradually progressive abdominal distension with or without pedal edema, history of weight gain, increase in waist size of clothing, sometimes with a decrease in urine output, or the development of abdominal hernias as a result of increased intra-abdominal pressure. The ascites in cirrhosis resulting from portal hypertension is usually responsive to diuretic therapy, hence such a history must be sought in any patient presenting with ascites. History of cardiac failure, renal disease, malignancy, and tuberculosis must be ruled out. A history of ascitic tap is a strong clue to the presence of ascites, hence the nature of fluid tapped may add further valuable information to the diagnosis.

Jaundice

Jaundice as a clinical manifestation may be seen in cirrhosis depending on the degree of decompensation. Jaundice (icterus) is a clinical manifestation of hyperbilirubinemia and presents as yellow discoloration of the skin and mucous membranes. It is the most obvious sign of liver disease and is best seen in the conjunctivae. It is usually detectable when the serum level of bilirubin exceeds 2 mg/dL (34 mmol/L). Elevation of both unconjugated and conjugated bilirubin occurs in patients with hepatocellular disease resulting from impaired canalicular excretion or biliary obstruction. Unconjugated hyperbilirubinemia in cirrhosis is caused by either associated hemolysis or decreased conjugating enzyme in the endoplasmic reticulum of hepatocytes, namely bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT) or associated Gilbert’s syndrome. Serum bilirubin levels are usually below 5 mg/dL; however, values above this may also be seen in certain patients who are in a decompensated state. A serum bilirubin level >5 mg/dL is one of the clinical defining criteria for acute on chronic liver failure [4]. The clinical significance of jaundice in cirrhosis lies in assessing the decompensated state of cirrhosis as jaundice is not specific to cirrhosis alone as it is seen in many other liver disorders and even in nonhepatic disorders.

Upper Gastrointestinal Bleeding

Gastroesophageal varices are present in approximately 50% of patients with cirrhosis. Up to 40% of patients with Child A cirrhosis have varices which increases to 85% in Child C cirrhosis [5]. Variceal bleeding occurs at a rate of 5–15% per year [6]. Variceal bleeding presenting as hematemesis with or without melena is one of the most common complications of cirrhosis with portal hypertension. The presentation is usually a painless, effortless bleed and may be precipitated by drugs like nonsteroidal anti-inflammatory drugs (NSAIDs). There may be associated melena which is passage of black tarry stools, which are offensive, semi-solid, and difficult to flush down the toilet. Patients may have postural hypotensive symptoms such as light-headedness and fainting episodes in cases of a significant bleed. Once a patient has a variceal bleed, the portal pressure (i.e., hepatic venous pressure gradient; HVPG) is usually >12 mmHg [7], because the development of varices occurs with HVPG >10 mmHg. However, variceal bleed alone is not a feature of cirrhosis; it may well be seen in noncirrhotic portal hypertensive conditions such as extrahepatic portal vein obstruction (EHPVO) or noncirrhotic portal fibrosis (NCPF).

Hepatic Encephalopathy

Hepatic encephalopathy is a neuropsychiatric syndrome with multiple variable manifestations. It may be covert (which includes minimal hepatic encephalopathy; MHE) and stage I encephalopathy) or an overt (stage II–IV) encephalopathy. Patients with MHE may present only with cognitive dysfunction in cirrhosis. The prevalence of MHE is 30–84% [8] and that of overt hepatic encephalopathy is 30–50% in cirrhotic patients [9,10]. The presentation of hepatic encephalopathy has marked variability among patients. Drowsiness, disorientation with reference to time, place, or person, delirium, and confusion can occur. Disturbance in sleep develops early with hypersomnia and altered sleep rhythm. There is further development of apathy, somnolence, tremors, apathy, and slowness of response. As further worsening occurs, the patient may become aroused on noxious stimuli or may become deeply unresponsive and comatose. Seizures may occur, especially in deeper grades of encephalopathy. Personality disturbance is another mode of presentation in the form of irritability, euphoria, and features of social disinhibition. Patients often present with loss of bladder and bowel control. Intellectual deterioration, memory impairment, and cognitive dysfunction also frequently occur. Constructional apraxia, micrographia, slow slurred monotonous speech, dysphasia, and perseveration can all occur.

Alcohol Intake: How much is Significant

Fatty liver develops in up to 90% of patients who drink more alcohol than 60 g/day [13]. Fibrosis progression and development of cirrhosis may occur in up to 5–15% of patients despite abstinence. Continued alcohol use increases the risk of progression to cirrhosis in 30% of patients [14]. The risk of developing cirrhosis increases with the ingestion of >60–80 g/day of alcohol for 10 years or longer in men, and >20 g/day in women. Yet, even drinking at these levels, only 6–41% develop cirrhosis [15–17]. Hence, there are several other risk factors involved in the development of alcoholic liver disease: sex (female), drinking patterns (early age of drinking, daily heavy drinking, episodic binge drinking), obesity, dietary factors, non-sex-linked genetic factors, cigarette smoking, other chronic liver disorders (hepatitis B or C, hemochromatosis, nonalcoholic fatty liver disease; NAFLD).

In a population-based cohort study of almost 7000 subjects in two northern Italian communities, even among patients with very high daily alcohol intake (>120 g/day), only 13.5% developed alcoholic liver disease (ALD). Homemade brew has variable amounts of alcohol and associated trace metals which may cause the development of liver disease with fewer years of consumption.

The history of alcohol consumption should be obtained both from the patient and family members, enquiring about alcohol-associated illnesses like pancreatitis and peripheral neuropathy, driving under the influence of alcohol, and history of any withdrawal symptoms. The amount of alcohol for reference purposes is 30 mL whisky, 360 mL beer, 120 mL wine – all equivalent to 10–11 g alcohol, and each of them is considered as one unit. The CAGE questionnaire is frequently used to assess the degree of alcohol-related problems and alcohol dependence [18].

History of Other Risk Factors

A history including blood transfusion, surgery, needlestick injuries, sexual contact, tattooing, skin piercing, dialysis, sharing of razors or toothbrushes must be taken to assess the risk of exposure to hepatitis B and C viruses. Metabolic risk factors include diabetes mellitus, hypertension, obesity, and dyslipidemia which must be asked about in view of nonalcoholic steatohepatitis-related cirrhosis. A family history of chronic liver disease may be relevant in certain situations like Wilson’s disease, autoimmune disorders, and even hepatitis B and C-related cirrhosis. A history of abnormal involuntary movements like choreoathetosis should arouse the suspicion of Wilson’s disease. Autoimmune disorders like vitiligo, diabetes mellitus, thyroid disorder, pernicious anemia, and inflammatory bowel disease are associated with autoimmune hepatitis. A past history of biliary obstruction and biliary surgery could give a clue to the diagnosis of secondary biliary cirrhosis as pruritus and fatigue may be seen in primary biliary cirrhosis. A personal history of sexual dysfunction like loss of libido, loss of secondary sexual characteristics, breast enlargement in males and amenorrhea or infertility in females are clues to hypogonadism, often seen in cirrhosis. A history of smoking is also important as it has been shown to have a role in progression of chronic liver disease: hepatitis C and alcoholic cirrhosis [19].

General Examination

A patient with cirrhosis appears malnourished, with shrunken eyes, temporal hollowing, parched lips, muddy complexion of the face, dried skin (xerosis), and hyperpigmentation, with features of various nutritional deficiencies. Patients have a hyperkinetic circulation. They may also have petechiae, purpura, or ecchymotic patches suggestive of underlying coagulopathy and thrombocytopenia. Fetor hepaticus is a sign of hepatocellular failure characterized by a sweetish, slightly faecal smell of the breath similar to freshly opened corpses of mice.