Compensated cirrhosis

The most common severity assessment tools in use are the Child-Turcotte-Pugh (CTP) score and the Model for End Stage Liver Disease (MELD) score. The CTP score was originally devised to risk stratify cirrhotic patients in need of portocaval shunt surgery due to oesophageal variceal bleeding and incorporates bilirubin, albumin and prothrombin time as well as encephalopathy and ascites measurements (see Table 24.6).

The MELD score was first developed to predict short-term prognosis in patients undergoing TIPS. The MELD score (http://www.unos.org/resources/meldpeldcalculator.asp) is based on three continuous, objective variables: bilirubin, creatinine and the INR of prothrombin time. Patients are assigned a score based on these three variables, from 6 through 40, corresponding to a 3-month survival of nearly zero and over 80% respectively. The MELD score has been validated as an accurate predictor of survival in acute liver failure, alcoholic hepatitis, a variety of chronic liver diseases and variceal bleeding, amongst others.

A patient with cirrhosis who has not developed jaundice or portal hypertensive complications of hepatic encephalopathy, ascites or variceal bleeding is ‘well compensated’, meaning he or she has adequate hepatic reserve. These patients are often categorised as Child-Turcotte-Pugh class (CTP) A. The median survival age in this group is 9–12 years. Since there are no available medical treatments to reverse cirrhosis, most management strategies are directed towards prevention.

Oesophageal varices

Approximately 50% of cirrhotic patients will have gastro-oesophageal varices with the likelihood being higher in more advanced disease. The risk of haemorrhage is approximately 5–15% per year with a 15–20% risk of mortality per episode. Therefore, all patients with a new diagnosis of cirrhosis should undergo oesophagogastroduodenoscopy to screen for varices. If large varices are noted, oral non-selective beta-blockers and/or variceal band ligation are indicated. Findings of red wale markings—longitudinal dilated venules on the variceal surface—and large varices (greater than 5 mm) signify an increased risk of spontaneous haemorrhage. Advanced liver disease (CTP B or C) also places the patient at a higher risk of variceal bleeding. For large varices and other high-risk features (CTP C or red wale markings) variceal banding is preferred whereas non-selective beta-blockers are preferred for large varices without other high-risk features. Small varices require only primary prophylaxis with non-selective beta blockers. When varices are absent at the initial endoscopy, primary prophylaxis is not recommended, but screening should be repeated in 2–3 years if the patient remains compensated.

Options for non-selective beta-blockade include propranolol, which is typically initiated at 20 mg twice daily, or nadolol which can be started at 20–40 mg once daily. Beta-blockers should be titrated to the maximally tolerated dose. A decrease in heart rate does not correlate with a decrease portal pressures, though it is also a common practice to titrate beta-blocker doses to a heart rate of 55–60 beats per minute.

Nutrition

Cirrhotic patients are often catabolic and suffer from severe muscle wasting and cachexia. Cirrhotic patients are often wrongly counselled to restrict protein intake, thus exacerbating this process. Patients with cirrhosis should eat 1.2–1.5 g/kg of protein daily with a well-balanced diet. Many patients require vitamin supplementation, with assessment specifically for vitamins A, D, E and K and zinc deficiency. Patients with fluid retention (ascites, pleural effusions or peripheral oedema) require a sodium restriction outlined below.

Obesity is seen in epidemic proportions in developed countries. Morbid obesity is a relative contraindication to transplant. Ideally a patient’s BMI should be below 35 before transplantation in many centres, although exceptions are made. Patients with a BMI over 35 have increased risk of wound complications and longer hospital stays.

All cirrhotic patients should abstain from alcohol completely and permanently. Continued alcohol use can result in earlier decompensation, increased risk of hepatocellular carcinoma, synergistic effects with hepatitis C on disease progression, an attenuated effect of interferon therapy, secondary psychiatric conditions and denial of liver transplantation. For patients with alcohol addiction issues, many transplant centres require 6 months of alcohol abstinence before liver transplantation can be considered.

All cirrhotic patients should be counselled on avoidance of raw seafood due to risk of Vibrio vulnificus septicaemia, which carries a particularly high rate of mortality in cirrhotic patients (about 50%). Swimming in contaminated water can also result in wound infections or cellulitis, and should be avoided.

Osteoporosis

Chronic liver disease predisposes patients to the development of hepatic osteodystrophy by multiple pathways that cause decreased bone formation and increased bone resorption. Patients with chronic liver disease plus one of the following: prolonged corticosteroid use (over 3 months), low-trauma fracture, a postmenopausal female or male older than 50 years or hypogonadism should be screened for osteoporosis with a dual energy x-ray absorptiometry. All patients should receive calcium supplementation 1200–1500 mEq/day and vitamin D 1000 IU/day. Counselling on smoking cessation and weight-bearing exercise is appropriate. Bisphosphonates should be considered for patients with known osteoporosis, non-traumatic fractures or inability to withdraw from corticosteroids.

Medication counselling

Paracetamol (acetaminophen) can be hepatotoxic above a dose of 4 g/day. Certainly, patients with concurrent alcohol use or malnutrition can experience additional liver injury at lower doses of paracetamol. In this subset of patients, it is probably safest to avoid chronic dosing of paracetamol, but a low dose (2 g/day) one time or infrequent dosing appears safe. In other cirrhotic patients, paracetamol at doses under 4 g/day for short periods of time appear safe, but less than 2.6 g/day is now the standard of care. The chronic use of paracetamol has not been studied in cirrhotic patients, thus most hepatologists will recommend dose reduction (2 g/day in divided doses) for longer term dosing. Many over-the-counter herbal medications can be hepatotoxic and can cause acute liver failure and thus should be avoided.

Surgery counselling

Patients with cirrhosis are at an increased risk of complications and mortality from surgery. Reasons for this are multiple, but include altered drug metabolism and preexisting hyperdynamic circulation that responds atypically to the stress of surgery and pharmacologic support. The MELD and CTP scores are reasonably accurate in predicting operative risks. In a retrospective study, the risk of 30-day mortality in patients undergoing intraabdominal non-transplant surgery was 5% at a MELD under 10 and 14% for a MELD over 15. In the interpretation of this study, it was suggested that for each increase in MELD score from 6–20 there is a 1% increase in 30-day mortality, and MELD scores over 20 give an additional 2% risk per point. For example, a patient with a MELD score of 7 has an approximately 7% risk of death whereas a MELD score of 25 would correlate to an approximate 30-day mortality of 50% It has been suggested that patients with CTP class A or MELD score less than 10 are acceptable candidates for elective surgery. Elective surgery for patients with CTP class B or MELD over 10 but under 15 should be approached with caution and, if surgery is necessary, work-up for transplant should be completed; performing the operation in a transplant centre is optimal. Elective surgery should not be performed on cirrhotic patients with CTP class C cirrhosis or a MELD score over 15.

Hepatocellular carcinoma

Approximately 80–90% of hepatocellular carcinomas (HCCs) occur in patients that have cirrhosis. Patients with cirrhosis, regardless of aetiology should have HCC surveillance every 6 months with an ultrasound of the liver. The alpha-fetoprotein test has recently fallen out of favour for use in HCC surveillance programs. Non-cirrhotic patients with hepatitis B are also at risk of developing HCC and should also undergo screening if they are in one of the following categories: Asian females over 50 years old, Asian males over 40 years old, Africans over 20 years old, or with a family history of HCC.

The alpha-fetoprotein measurement for screening of HCC is an imperfect test. An alpha-fetoprotein level over 20 ng/mL alone has a sensitivity of 60%. However, in the setting of a liver lesion over 2 cm in diameter, this carries a very high positive predictive value for the diagnosis of HCC.

Ultrasonographic findings in HCC are variable, ranging from an echogenic lesion in small HCCs (due to tumoural fat) to hypoechoic in larger lesions. These findings can be difficult to distinguish from those seen in macronodular cirrhosis and a CT scan is recommended for further evaluation. CT findings of arterial enhancement and venous wash-out are highly specific for HCC.

An algorithmic approach to diagnosing HCC has been recommended by the American Association for the Study of Liver Diseases. For lesions smaller than 1 cm in diameter identified by ultrasound, surveillance ultrasound should be performed every 3 months and, if stable over 1–2 years, reversion to standard 6–12-month surveillance interval is recommended. If a lesion over of 1 cm diameter is identified by ultrasound, it is recommended that a CT or MRI be obtained. If an atypical vascular pattern is noted on one imaging test (CT or MRI), the other imaging modality should be used for further clarification. If a typical vascular pattern (arterial phase enhancement with venous phase washout) is seen on both CT and MRI, the lesion should be treated as HCC, and biopsy is not needed. If imaging does not provide diagnostic features, a biopsy should be pursued. If biopsy results are non-diagnostic, ultrasound on 3-month intervals is recommended. Biopsy confirmation is rarely needed if imaging is characteristic and may cause needle-tract seeding, spreading the cancer. If a liver biopsy is considered under any of the aforementioned circumstances, the authors recommend that this be discussed with a hepatologist before proceeding.

Several treatment options are available for HCC including resection, locoregional therapy such as transarterial chemoembolisation (TACE), radiofrequency ablation (RFA) and liver transplantation. Radiofrequency ablation technique utilises a probe inserted percutaneously into the tumour with ultrasound or CT guidance and induces coagulative necrosis from heat generated by electromagnetic radiation. TACE delivers small embolic particles and a chemotherapeutic agent (cisplatin or doxorubicin commonly) to deprive the tumour of its vascular supply and concomitantly deliver cytotoxic therapy, resulting in tumour hypoxaemia and necrosis.

The optimal use of conventional strategies and novel therapies is evolving. A careful multidisciplinary approach involving a transplant surgeon, transplant hepatologist, interventional radiologist, and oncologist results in the best outcome.