Background

The world's population is ageing. Chronic liver disease is increasingly prevalent in developed countries, probably reflecting an increase in alcohol intake, the emerging obesity epidemic and the impact of viral hepatitis. Currently, liver disease is the fifth leading cause of death in the UK.¹

As management of adults with liver disease improves and as the population ages, geriatricians will see increasing numbers of older people with long-standing liver disease as well as older people presenting for the first time.

No liver disease is specific to old age. In general, management is independent of age, but older adults have reduced physiological reserve and are more likely to have accumulated co-morbidity and be on multiple medications. These may impact on investigation and treatment strategies.

We present an overview of the investigation and management of older adults with chronic parenchymal liver disease.

Search strategy

Publications were identified by computerized search of the Ovid Medline database, from 1980 to 2010. Search terms used were: ‘chronic liver disease’, ‘cirrhosis’, ‘alcoholic liver disease’, ‘fatty liver disease’, ‘hepatitis B’, ‘hepatitis C’, ‘autoimmune hepatitis’, ‘primary biliary cirrhosis’, ‘haemochromatosis’, ‘hepatocellular carcinoma’, ‘hepatic encephalopathy’, ‘ascites’, ‘variceal haemorrhage’, ‘transjugular intrahepatic portosytemic shunt’, ‘liver transplant’, ‘aged’ and ‘older’. Studies were considered for inclusion if they were written in the English language and had relevant applications to the older population.

Additional publications were identified through searching the reference lists of retrieved articles. Other sources included reference books and selected references from affiliated bibliographies.

The ageing liver

The liver reaches maximum size in early adult life. Thereafter, there is a steady reduction in liver mass and blood flow by 37 and 40%, respectively.Reference Wynne, Cope and Metch^2, Reference Le Couteur and McLean^3, Reference Wynne and James⁴ Throughout life the liver retains a remarkable ability to regenerate, which is exemplified by the fact that hepatic resection is feasible in older adults. However, this population is heterogeneous. Sub-acute liver failure is a phenomenon peculiar to older people, making it conceivable that age-related physiological changes reduce hepatic function.

Adverse drug reactions

Medication use is common in older people, with 45% of medicines in the UK prescribed to people aged 65 years and over.⁵ Polypharmacy, advancing age and increased drug use are associated with adverse drug reactions (ADRs),Reference Bordet, Gautier, Le Louet, Dupuis and Caron⁶ which cost the National Health Service (NHS) approximately £466 million annually.Reference Cunningham, Dodd, Grant, McMurdo and Richards^7–Reference Piromohamed, Sally and Meakin⁹ Understanding alterations in drug metabolism and drug response in older people is therefore important.

Work-up of suspected chronic liver disease

There are no age-associated changes in conventional laboratory markers of liver disease.Reference James^16–Reference Verslype, George, Buchel, Nevens, van Steenbergen and Fevery¹⁹ Evidence exists that substantial liver damage may be present with even relatively mild liver biochemistry derangement.Reference Green and Flamm²⁰ Therefore, all perturbations should be investigated with equal diligence in the young and old, although there is no clear guidance regarding timing. Some authors suggest only investigating abnormalities that persist after 3 months.Reference Cobbold, Anstee and Thomas²¹ Any person presenting with hepatic decompensation mandates urgent diagnostic evaluation.

A thorough history and clinical examination are essential. An accurate history of alcohol intake and viral risk factors should be elicited. Use of prescription and over-the-counter or herbal remedies in the preceding 6 months should be determined.

First-line tests include ultrasonography (USS) and a hepatic parenchymal screen. Positive results warrant further investigation, as outlined in Table 1. Ultrasonography is non-invasive and readily available. It permits assessment of biliary tree calibre, identifies features suggestive of cirrhosis and portal hypertension, and is useful for detecting focal lesions.

Table 1.

Parenchymal liver screen in older adults

HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e-antigen; Anti-HBe, antibody to hepatitis B e-antigen; DNA, deoxyribonucleic acid; RNA, ribonucleic acid; PCR, polymerase chain reaction; Anti-HCV, antibody to hepatitis C; TIBC, total iron binding capacity; TS, transferrin saturation (iron/TIBC); Ig, immunoglobulin; ANA, anti-neutrophil antibody; ASMA, anti-smooth muscle antibody; AMA, anti-mitochondrial antibody.

If first-line screening tests are positive, referral to a hepatologist is advised. Faced with a negative screen, extra-hepatic diseases such as cardiac failure and inflammatory, infective and mitotic conditions should be considered. If diagnostic doubt persists, a percutaneous ultrasound-guided liver biopsy should be considered. It may clarify diagnosis, thereby directing therapy, and through staging (assessment of fibrosis), prognosticate. It is often overlooked in the older population due to safety concerns. However, complications are rare and mortality is age independent at approximately 0.2%.Reference Gilmore, Burroughs, Murray-Lyon, Williams, Jenkins and Hopkins^22, Reference Bravo, Sheth and Chopra²³

Novel, non-invasive methods of assessing fibrosis, particularly the FibroScan (transient elastography) technique are gaining favour, though validation data are lacking in certain situations and availability is variable.Reference Castera, Forms and Alberti²⁴ This may ultimately reduce the need for biopsy.

Severity assessment of chronic liver disease

There are several evidence-based scoring tools for stratifying severity and prognosticating chronic liver disease, which are also used for prioritizing allocation of liver allografts. The most widely used is the Child-Pugh system for which a score of 1 to 3 is assigned to five variables. The sum translates to a corresponding Child's grade (A, B or C), which predicts survival as outlined in Tables 2 and 3.

Table 2.

Child-Pugh scoring table

Table 3.

Survival in chronic liver disease according to Child's grade

The Model for End-stage Liver Disease (MELD) score (range 6–40) predicts 3-month mortality in patients with cirrhosis.Reference Kamath, Wiesner, Malinchoc, Kremers, Therneau, Kosberg, D'Amico, Dickson and Kim²⁵ It is calculated using a formula based on measurements of serum bilirubin, creatinine and International Normalized Ratio (INR). Unlike the Child-Pugh score, there are no subjective components. Scores of less than 9 and more than 30 are associated with 3-month mortality rates of 1.9 and over 50%, respectively.Reference Wiesner, Edwards, Freeman, Harper, Kim, Kamath, Kremers, Lake, Howard, Merion, Wolfe and Krom²⁶

The United Kingdom End-stage Liver Disease (UKELD) score predicts which patients are at risk of dying while on the transplant waiting list. Its calculation additionally incorporates measurement of serum sodium (which more accurately identifies patients at a greater risk of death).Reference Kim, Biggins, Kremers, Wiesner, Kamath, Benson, Edwards and Therneau²⁷ A score of 49 or greater predicts a 1-year survival of less than 91%, which is equal to the mortality risk (9%) after elective transplantation and is an objective basis minimal listing criterion.Reference Neuberger, Gimson, Davies, Akyol, O'Grady, Burroughs and Hudson²⁸

Alcoholic liver disease

Alcohol consumption is common in older adults who are more susceptible to its deleterious effects.Reference Smith²⁹ Among community-dwellers aged over 60 years, 62% drink alcohol and 6% are classified as ‘heavy’ drinkers.Reference Mirand and Welte³⁰ Moreover, 8% of acute elderly admissions consume alcohol in excess of recommended weekly limits, and of these 24% are admitted with alcohol-related problems.Reference Mangion, Platt and Syam³¹

Alcoholic liver disease (ALD) is perceived as being uncommon in older people; however, it is becoming an increasing problem. In the UK 28% of cases present over the age of 60 years,Reference Potter and James³² while in France 20% are aged over 70 years.Reference Aron, Dupin and Jopard³³

Typically, presentation is non-specific, although decompensated disease is more often seen in the older population, suggestive of more advanced disease.Reference Potter and James^32, Reference Woodhouse and James³⁴ This is supported by histological studies which demonstrate that almost all patients over 70 years are cirrhotic at presentation compared with approximately 50% of those under 60 years of age.Reference Potter and James^32, Reference James³⁵ The long-term outlook is poor, with half of older adults who develop ALD-related cirrhosis being dead within a year of diagnosis.Reference Smith²⁹

No studies of long-term treatment of ALD, specifically in elderly patients, have been conducted. Lifestyle modification and nutritional support are paramount.

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), best considered as the hepatic manifestation of the metabolic syndrome, is characterized by hepatic fat accumulation with a clinico-pathological spectrum ranging from bland steatosis to non-alcoholic steatohepatitis (NASH). It has become the commonest reason for deranged liver biochemistry and referral to hepatology clinics in developed countries.Reference Rafiq, Bai, Fang, Srishord, McCullough, Gramlich and Younossi³⁶

As the incidence of metabolic risk factors increases, the prevalence of NAFLD will also increase, particularly in older people.Reference Targher, Bertolini, Padovani, Rodella, Tessari, Zenari, Day and Arcaro^37, Reference Amos, McCarty and Zimmet³⁸ At present 26% of patients with NAFLD are aged over 60 years.Reference Frith, Day, Henderson, Burt and Newton³⁹ Among type II diabetics, the prevalence of NAFLD is 65 and 75% in those aged 40–59 and over 60 years, respectively.Reference Targher, Bertolini, Padovani, Rodella, Tessari, Zenari, Day and Arcaro³⁷

NAFLD is not benign and can cause significant liver diseaseReference Rafiq, Bai, Fang, Srishord, McCullough, Gramlich and Younossi^36, Reference Ekstedt, Franzén, Mathiesen, Thorelius, Holmqvist, Bodemar and Kechagias⁴⁰ with up to 15% progressing to cirrhosis.Reference Angulo⁴¹ A large proportion of cases of so-called cryptogenic cirrhosis are now thought to represent the end-stage liver disease of NASH.Reference Neuschwander-Tetri and Caldwell⁴²

Dietary modification and increased physical activity are the only measures that have been shown to reduce hepatic steatosis and inflammation, and should be addressed as early as possible.Reference Kugelmas, Hill, Vivian, Marsano and McClain^43, Reference Palmer and Schaffner⁴⁴ Associated cardiovascular risk factors, which may represent a greater risk to the patient than the liver disease, should be tackled.

Viral hepatitis

Viral hepatitis is less common in older age. There are, however, several considerations with regard to older adults.

Hepatitis C

It is estimated that hepatitis C virus (HCV) affects up to 400,000 individuals in the UK.Reference Booth, O'Grady and Neuberger⁵⁴ As many as 90% of these develop chronic liver diseaseReference Alter, Margolis and Krawczynski⁵⁵ in whom the incidence of hepatocellular carcinoma (HCC) is high (3–4% per year).Reference Di Bisceglie⁵⁶ HCV-related cirrhosis is the most frequent indication for orthotopic liver transplantation (OLT).Reference Hoofnagle⁵⁷ The average age of patients with hepatitis C is increasing as a consequence of infected middle-aged subjects growing older.Reference Poynard, Yen and Ratzui⁵⁸

In general, the route of infection differs with age. In younger adults infection is typically acquired following intravenous drug use. In contrast, blood transfusion in the pre-screening era (prior to 1991) is often the culprit in the latter. Anti-HCV is present in up to 4.5% of nursing home residents and is attributed to previous transfusion.Reference Chien, Dundoo and Horani⁵⁹

Chronic hepatitis C is generally silent and its diagnosis fortuitous. The median time from infection to cirrhosis is approximately 30 years. Disease progression is not linear and may accelerate with advancing age,Reference Poynard, Bedossa and Opolon^60, Reference Zarski, McHutchison and Bronowicki⁶¹ thus it is unsurprising that cirrhosis and HCC are more prevalent in older subjects.Reference Watson, Brind, Chapman, Bates, Gould, Johnson, Burt, Ferguson, Simmonds and Bassendine^62, Reference Pagliaro, D'Amico and Puleo⁶³

The goal of therapy is to eradicate the virus and prevent the development of cirrhosis and its complications. Combination therapy with pegylated interferon-alpha (PEG IFN-α) and ribavirin represents current standard therapy.

The decision to treat is complex and should be made by a specialist. Treatment is associated with a multitude of adverse effects (Table 4), the incidence of which do not vary with age,Reference Honda, Katano, Urano, Murayama, Hayashi, Ishigami, Nakano, Yoshioka, Toyoda, Kumada and Goto⁶⁴ and cure is not guaranteed. Response to therapy is dependent on host, virological and histological factors. In general, old age, genotype 1, high baseline viral load and a high degree of fibrosis on histology are associated with diminished response.Reference Goa, Hong and Radeva⁶⁵

Table 4.

Side-effects of combination antiviral therapy for chronic hepatitis C

*Mean decrease in haemoglobin of approximately 3 g/dl.Reference Poynard, Marcellin, Lee, Niederau, Minuk, Ideo, Bain, Heathcote, Zeuzem, Trepo and Albrecht⁶⁶

Autoimmune hepatitis

The incidence of autoimmune hepatitis (AIH) exhibits a bi-modal pattern with pubertal and post-menopausal peaks.Reference Al-Chalabi, Boccato, Portmann, McFarlane and Heneghan^17, Reference Schramm, Kanzler, Büschenfelde, Galle and Lohse^18, Reference Parker and Kingham⁶⁷ Disease onset and progression are characteristically insidious and consequently diagnosis is often not secured until features of severe liver disease are present. Subjects aged over 65 years are significantly more likely to have ascites than younger patients (30 vs. 9%, P < 0.001), suggesting more advanced disease at presentation.Reference Schramm, Kanzler, Büschenfelde, Galle and Lohse¹⁸ Fulminant liver failure may occur, but is rare. AIH co-exists with other autoimmune conditions; rheumatoid arthritis, ulcerative colitis and thyroid disease are the most common in the older cohort.Reference Al-Chalabi, Boccato, Portmann, McFarlane and Heneghan¹⁷ Prognosis is not influenced by age.Reference Newton, Burt, Park, Mathew, Bassendine and James⁶⁸

The mainstay of treatment is immunosuppression. Prednisolone alone or combined with azathioprine has been used with similar rates and outcomes in both the old and young.Reference Al-Chalabi, Boccato, Portmann, McFarlane and Heneghan^17, Reference Verslype, George, Buchel, Nevens, van Steenbergen and Fevery¹⁹ As treatment in advanced stages is associated with a higher risk of relapse, early treatment affords most benefit.Reference Kirk, Jain, Pocock, Thomas and Sherlock⁶⁹ It is paramount not to miss diagnosis of this readily treatable condition.

Primary biliary cirrhosis

Half of patients with primary biliary cirrhosis (PBC) present for the first time after the age of 65 years.Reference Parker and Kingham⁶⁷ In northern England, in women over 65 years of age, prevalence is approximately 1 in 1000.Reference Metcalf, Bhopal, Gray, Howel and James⁷⁰ Increasing age has been shown to be an independent prognostic factor for PBC, even when deaths from liver disease alone are considered.Reference Grambasch, Dickson and Kaplan⁷¹ The majority are asymptomatic on presentation, but younger subjects are significantly more likely to report non-specific symptoms.Reference Newton, Jones, Metcalf, Park, Burt, Bassendine and James⁷² Fatigue is a poor prognostic marker, increasingly more so with advancing age.Reference Zein and McCullough⁷³

Transplantation is the only curative option and may be indicated for intractable pruritus and fatigue, as well as for liver failure. There is no satisfactory medical therapy. Ursodeoxycholic acid (UDCA), a synthetic bile acid, is safe, well tolerated and, at a dose of 10–15 mg/kg/day, improves liver biochemistry and histology, but its effect on disease progression and transplant-free survival is debated. Pruritus is usually controlled by cholestyramine (which should not be given at the same time as UDCA), while second-line alternatives include rifampicin, ondansetron, naltrexone and gabapentin.

All patients with cirrhosis are at risk of osteoporosis, with those on steroids at increased risk.Reference Solerio, Isaia and Innarella⁷⁴ Prophylaxis, through the use of calcium and cholecalciferol supplements and bisphosphonate therapy, should be considered.

Hereditary haemochromotosis

Despite estimates of C282Y homozygosity (the commonest genetic mutation underlying hereditary haemochromatosis (HHC)) ranging from 1-in-100 to 1-in-300, HHC is considered a rare disease.Reference Jeffrey, Adams, McDonald, Burroughs and Feagan⁷⁵ This is a consequence of variable phenotypic penetrance amongst homozygotes and a ‘clinical iceberg’ of undiagnosed subjects. Estimates suggest that 70,000 people in the UK have symptomatic HHC, although only about 3000 cases are recognized.Reference Rosenberg, Howell, Roderick, Eccles and Day⁷⁶

HHC is classically diagnosed in middle age,Reference Niederau, Fischer, Pürschel, Stremmel, Häussinger and Strohmeyer⁷⁷ but can present in old age,Reference Willis, Wimperis, Smith, Fellows and Jennings⁷⁸ by which time significant iron overload may have developed. It is ten times more common in males than females who are spared by therapeutic menstruation.Reference Sheldon⁷⁹

Due to the lack and non-specific nature of symptoms, diagnosis is not straightforward, particularly in a population who may have accumulated multiple co-morbidities. It should be considered in older subjects presenting with fatigue (the commonest complaint), arthralgia and diabetes mellitus. Those presenting with movement disorders may be misdiagnosed with Parkinson's disease or cerebellar syndromes.Reference Demarquay, Setiey, Morel, Trepo, Chazot and Broussolle⁸⁰

HHC is an important diagnosis to consider in older adults, not only for family screening, but because the complications are preventable with early de-ironing. Venesection is the mainstay of treatment, with an aim to achieve a target ferritin less than 50 μg/l (although there is no evidence base for this endpoint) while maintaining a haemoglobin concentration above 10 g/dl.⁸¹ Therapeutic phlebotomy is well toleratedReference Adams⁸² but may induce orthostatic hypotension in older adults. Adequate hydration and avoidance of vigorous physical activity for 24 hours is recommended.⁸¹ Chelation therapy is a second-line treatment alternative. Venesection prevents the progression of, and may even reverse, fibrosis in pre-cirrhotic patients.Reference Milman, Pederson and Steig^83–Reference Powell and Kerr⁸⁵ It improves fatigue and skin pigmentation.Reference Niederau, Fischer, Pürschel, Stremmel, Häussinger and Strohmeyer⁷⁷ Glycaemic control may improve, although insulin dependence is not reversed.Reference Niederau, Fischer, Pürschel, Stremmel, Häussinger and Strohmeyer⁷⁷ Arthropathy is typically unaffected.Reference Milman, Pederson and Steig⁸³

Once iron depletion has been achieved some patients may not show re-accumulation of iron at the expected rate. Proton pump inhibitors are associated with reduced iron absorption,Reference Hutchison, Geissler and Powell⁸⁶ while non-steroidal anti-inflammatory drugs (NSAIDS) may cause occult blood loss. In older patients it is necessary to be alert to co-morbid conditions that may lead to iron loss which warrant appropriate investigation.

Patients with cirrhosis have an increased risk of death, while non-cirrhotic treated patients have a survival rate similar to age- and sex-matched controls.Reference Niederau, Fischer, Pürschel, Stremmel, Häussinger and Strohmeyer^77, Reference Adams, Speechley and Kertesz⁸⁷

Wilson's disease

Wilson's disease is a disease of children and young adults and will not be discussed further.

Drug-induced liver injury

Drug-induced liver injury (DILI) may be divided into direct-toxic and idiosyncratic reactions. While the former are predictable, dose dependent and typically manifest within 48 hours of exposure, the latter are dose independent and arise unpredictably, following a latent period ranging from days to months, in a small percentage of susceptible individuals.

The exact prevalence of DILI is difficult to define, although it is thought to be more common with advancing age.Reference Woodhouse, Mortimer, Wilholm and Kitani⁸⁸ In older adults DILIs are responsible for up to 40% of presentations with acute hepatitic biochemistry.Reference Benhamous and Fillastre⁸⁹ Polypharmacy and co-morbidity may potentiate the adverse effects of some medications on the liver; however, age-related decline in drug clearance is probably irrelevant as most reactions are idiosyncratic. The clinical and biochemical pattern of liver injury can mimic any acute or chronic liver disease, as outlined in Table 5.

Table 5.

Simple classification of hepatic drug reactions and common culprit agents (an individual drug may cause more than one type of reaction)

Manifestations of drug-related hepatotoxicity are variable, ranging from asymptomatic liver enzyme derangement to fulminant hepatic failure. Knowledge of the commonly implicated agents and a high index of suspicion are essential in diagnosis. Early detection and drug withdrawal can lessen the severity. In the UK all suspected cases should be referred to the Medicines and Healthcare products Regulatory Agency (MHRA) via the ‘Yellow Card’ scheme.

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide.^90, Reference Bosch, Ribes, Díaz and Cléries⁹¹ Up to 90% of cases arise in the setting of cirrhosisReference Kumagi, Hiasa and Hirschfield⁹² with ALD, HBV and HCV the most common underlying aetiologies.Reference Michielson, Sven and Van Dongen⁹³

Incidence increases with ageReference Ikeda, Saitoh, Suzuki, Kobayashi, Tsubota, Koida, Arase, Fukuda, Chayama, Murashima and Kumada⁹⁴ with 15–31% of cases occurring in the over-70s.Reference Collier, Curless, Bassendine and James^95–Reference Schöniger-Hekele, Müller, Kutilek, Oesterreicher, Ferenci and Gangl⁹⁷ Moreover, the number of elderly subjects diagnosed with HCC is expected to increase in developed countries because of the rising incidence of NASH-related cirrhosisReference Bugianesi⁹⁸ and the ‘delaying’ effect of anti-viral therapy in cases of viral hepatitis.Reference Cammà, Giunta, Andreone and Craxì⁹⁹

Owing to surveillance programmes, HCCs in older adults tend to be detected at a less advanced stage and, consequently, symptomatic disease is significantly less prevalent than in younger counterparts.Reference Mirici-Cappa, Gramenzi, Santi, Zambruni, Di Micoli, Frigerio, Maraldi, Di Nolfo, Del Poggio, Benvegnù, Rapaccini, Farinati, Zoli, Borzio, Giannini, Caturelli, Bernardi and Trevisani^100, Reference Trevisani, Cantarini, Wands and Bernardi¹⁰¹ In all subjects with chronic liver disease HCC must be excluded in the setting of acute decompensation.

There are three potentially curative treatment modalities, namely percutaneous ablation, most commonly radiofrequency ablation (RFA), surgical resection and liver transplantation. For those deemed unsuitable for radical intervention, transcatheter arterial chemo-embolization (TACE) is a palliative option shown to prolong survival from a median of 16 to 20 months.Reference Llovet and Bruix¹⁰² Three-year survival is best in transplanted patients (70%), followed by resection (30.9%), ablation (9.8%) and TACE (6.1%).Reference El-Serag, Siegal and Davila¹⁰³

Treatment strategy is dependent on the severity of underlying chronic liver disease, stage at diagnosis and performance status. Although treatment outcomes are not age dependent, in practice older adults more frequently undergo ablation therapy and less often resection or TACE.Reference Mirici-Cappa, Gramenzi, Santi, Zambruni, Di Micoli, Frigerio, Maraldi, Di Nolfo, Del Poggio, Benvegnù, Rapaccini, Farinati, Zoli, Borzio, Giannini, Caturelli, Bernardi and Trevisani¹⁰⁰

Cirrhotic patients who are potential candidates for intervention warrant surveillance with sonography and serum alpha-fetoprotein (AFP) measurement at 6-monthly intervals.Reference Ryder^104, Reference Bruix and Sherman¹⁰⁵

Managing decompensated chronic liver disease

When chronic liver disease decompensates it may manifest with hepatic encephalopathy (HE), ascites and/or variceal haemorrhage. Management strategies are independent of the underlying aetiology and do not differ with age.

Hepatic encephalopathy

HE is a potentially reversible neuropsychiatric state that may complicate cirrhosis. It ranges from life-threatening coma to sub-clinical forms and should be staged according to the West-Haven criteria, as outlined in Table 6. It may interfere with quality of life and can be chronically debilitating. It should be considered in any patient with liver disease and confusion or altered consciousness. Diagnosis is clinical, but may be more challenging in the older population where delirium and dementia are both common. Treatment aims are to reduce ammonia production and absorption and manage any precipitating factors, as listed in Table 7.

Table 6.

West Haven criteria for grading mental state in hepatic encephalopathy

Table 7.

Common precipitants of hepatic encephalopathy in chronic liver disease

Lactulose reduces ammoniagenic substrate absorption from the gut and, although it has no survival benefit,Reference Morgan, Blei, Grüngreiff, Jalan, Kircheis, Marchesini, Riggio and Weissenborn¹⁰⁶ has been shown to improve cognition and quality of life.Reference Prasad, Dhiman, Duseja, Chawla, Sharma and Agarwal¹⁰⁷ When prescribing laxatives in older people, special consideration should be given to the effects on faecal continence, hydration and electrolyte homeostasis.Reference Romero, Evans, Fleming and Phillips¹⁰⁸ Non-absorbable antimicrobials reduce the colonic load of ammoniagenic bacteria and may be used as secondary prophylaxis. Rifaximin is well tolerated and has been reported to significantly reduce the risk of an episode and hospitalization over a 6-month period.Reference Bass, Mullen, Sanyal, Poordad, Neff, Leevy, Sigal, Sheikh, Beavers, Frederick, Teperman, Hillebrand, Huang, Merchant, Shaw, Bortey and Forbes¹⁰⁹

Orthotopic liver transplantation

OLT is principally aimed at restoring health and improving quality of life and survival. However, limited donor availability restricts the number of beneficiaries. In the UK approximately 600 transplants are undertaken annually with the average recipient over the age of 50 years.¹⁴⁶

The average age of patients undergoing OLT is consistently increasing.Reference Montalti, Rompianesi, Di Benedetto, Ballarin, Gerring, Busani, De Pietri, De Ruvo, Iemmolo, Guerrini, Smerieri and Gerunda¹⁴⁷ According to the European Liver Transplant Registry (ETLR) the proportion of adult liver recipients older than 60 years increased from 9% in 1990 to more than 16% in 1999, and approximately 20% in 2008.¹⁴⁸ The lead indications for OLT among those aged 60 years or older in Europe between 1988 and 2008 were cirrhosis (63%), cancer (25%), and acute liver failure (4%).¹⁴⁸

Advanced age was previously considered a contraindication to OLT. However, recent studies comparing younger and older adults have reported similar lengths of hospitalization, incidence of complications and survival rates.Reference Montalti, Rompianesi, Di Benedetto, Ballarin, Gerring, Busani, De Pietri, De Ruvo, Iemmolo, Guerrini, Smerieri and Gerunda^147, Reference Collins, Pirsch, Becker, Hanaway, Van Der Werf, D'Alessandro, Knechtle, Odorico, Leverson, Musat, Armbrust, Becker, Sollinger and Kalayoglu^149, Reference Audet, Piardi, Panaro, Cag, Ghislotti, Habibeh, Giulini, Jaeck and Wolf¹⁵⁰ A recent Italian study, comparing older (over 65 years) adults and younger (41–64 years) matched controls, demonstrated 1-, 3- and 5-year survival rates of 83.9, 80.6 and 80.6%, respectively, for the older group, and 80.6, 73.8 and 73.8%, respectively, for the younger group.Reference Montalti, Rompianesi, Di Benedetto, Ballarin, Gerring, Busani, De Pietri, De Ruvo, Iemmolo, Guerrini, Smerieri and Gerunda¹⁴⁷ A similar French study showed that older subjects are more likely to have coronary heart disease (50 vs. 12%), and subsequently cardiac complications are more frequent in this cohort (8.8 vs. 1.4%).Reference Audet, Piardi, Panaro, Cag, Ghislotti, Habibeh, Giulini, Jaeck and Wolf¹⁵⁰ These studies suggest that chronological age alone should not deter OLT when an adequate cardiac assessment has been performed.

While younger patients are most likely to die from infection, the commonest cause of death in those aged over 60 years is malignancy.Reference Collins, Pirsch, Becker, Hanaway, Van Der Werf, D'Alessandro, Knechtle, Odorico, Leverson, Musat, Armbrust, Becker, Sollinger and Kalayoglu¹⁴⁹ Mortality related to cardiovascular events is similar in both age groups, perhaps because the older age group undergo more comprehensive pre-transplant screening for co-morbidities.Reference Collins, Pirsch, Becker, Hanaway, Van Der Werf, D'Alessandro, Knechtle, Odorico, Leverson, Musat, Armbrust, Becker, Sollinger and Kalayoglu¹⁴⁹

Transplantation is not an option for frail older adults or those with significant co-morbidity, for whom a palliative strategy should be adopted.

As the 20-year survival rate following transplantation exceeds 50%, geriatricians will increasingly encounter OLT recipients.Reference Dawwas, Gimson, Lewsey, Copley and Van Der Meulen^151, Reference Pomfret, Fryer, Sima, Lake and Merion¹⁵² It is paramount to consider the potential for drug interactions with maintenance immunosuppression. Medications that impact on the cytochrome P-450 system affect the serum levels of calcineurin inhibitors (CNI), namely cyclosporin and tacrolimus. Enzyme inducers produce sub-therapeutic levels, thereby risking allograft rejection, while enzyme inhibitors may cause toxicity. In particular, macrolide antimicrobials and phenytoin should be avoided.

Medical morbidity is substantial in the long-term following transplantation. Hypertension develops in 60% of recipients, diabetes in 35% and chronic kidney disease (CKD) in up to 20%.Reference Sheiner, Magliocca, Bodian, Kim-Schluger, Altaca, Guarrera, Emre, Fishbein, Guy, Schwartz and Miller^153, Reference Ojo, Held, Port, Wolfe, Leichtman, Young, Arndorfer, Christensen and Merion¹⁵⁴ Furthermore, more than 20% of non-obese recipients become obese 2 years after grafting.Reference Everhart, Lombardero, Lake, Wiesner, Zetterman and Hoofnagle¹⁵⁵ Such metabolic disturbances broadly relate to the aetiology of the original disease, post-transplant weight gain and the side-effects of immunosuppression. Transplantation is also associated with an increased risk of malignancy, in particular cutaneous and gastrointestinal carcinomas and lymphoproliferative disorders.Reference Fung, Jain, Kwak, Kusne, Dvorchik and Eghtesad¹⁵⁶

Prognosis in chronic liver disease

Increased age is the most important independent adverse risk factor influencing survival in cirrhosis.Reference Johnson, Hayllar and Metivier¹⁵⁷ While older, fatigued patients with PBCReference Zein and McCullough⁷³ and those with ALDReference Woodhouse and James³⁴ and NAFLDReference Adams, Lymp, St Sauver, Sanderson, Lindor, Feldstein and Angulo¹⁵⁸ all demonstrate age-associated increased risk of death,Reference Woodhouse and James^34, Reference Zein and McCullough^73, Reference Adams, Lymp, St Sauver, Sanderson, Lindor, Feldstein and Angulo¹⁵⁸ the majority of deaths in older people with PBC,Reference Newton, Jones, Metcalf, Park, Burt, Bassendine and James⁷² AIHReference Newton, Burt, Park, Mathew, Bassendine and James⁶⁸ and HCVReference Watson, Brind, Chapman, Bates, Gould, Johnson, Burt, Ferguson, Simmonds and Bassendine^62, Reference Monica, Lirussi, Pregun, Vasile, Fabris and Okolicsanyi¹⁵⁹ are unrelated to the liver.

Conflicts of interest

The authors declared no conflicts of interest.