be determined in all patients with chronic liver disease, as it predicts clinical outcomes and designates patients with cirrhosis who are usually asymptomatic but are at risk for sudden complications or bleeding varices, encephalopathy, and liver cancer. While biopsy is the gold standard method to stage fibrosis, noninvasive methods have been developed that can assess disease severity. In grading a biopsy for fibrosis, the most common criteria are from the METAVIR system:no fibrosis is F0, and cirrhosis is F4. Hepatic decompensation does not usually occur until the patient has cirrhosis. Liver biopsies are painful and have a mild risk, so non‐invasive ways have been developed to estimate the METAVIR score. The FIB‐4 index uses a combination of four factors to estimate fibrosis: age, platelet count, and levels of AST and ALT, according to this formula:
Applications can be easily found on smartphones and online to perform the calculations.5 The AST‐to‐platelet ratio index (APRI) score with a cutoff value of less than or equal to 0.5 had a negative predictive value of 86% for the absence of significant fibrosis, while a score of more than 1.5 detected the presence of significant fibrosis with a positive predictive value of 88%.6 Vibration‐controlled transient elastography (Fibroscan) can estimate fibrosis level and degree of steatosis. This measurement is used routinely in most hepatology practices and can be done with a portable machine in a few minutes; it also estimates the percentage of fat in the liver.7 For every patient with chronic liver disease, an assessment of whether the patient has cirrhosis must be done.
Acute viral hepatitis
Viral hepatitis, which is caused by hepatitis A, B, C, D, and E, has varying courses of disease and modes of transmission. Hepatitis A and E are transmitted from infected stool by contact with contaminated food or water. The incubation period of hepatitis A averages 28 days. Symptoms occur in 70% of adults and consist initially of abdominal pain, fever, fatigue, and nausea, followed in a few days by jaundice and pruritus. Laboratory values include elevation of transaminases greater than 1000 and alkaline phosphatase to less than 400. Infection does not become chronic, and 99% fully recover by six months, with 85% recovering by 2.3 months. Hepatitis A is much more likely to be symptomatic in the elderly and has a higher mortality rate in the aged. Death due to severe liver failure increased from 0.07% in the age group 15–24 to 4% in those older than 65.8
Vaccination for hepatitis A with two vaccinations six months apart provides 97% protection against the virus in those over 50.9 It is recommended that older people travelling to endemic areas, handling food, with chronic liver disease, or exposed to a case should receive HAV vaccination.
Hepatitis B and C are blood‐borne diseases, and hepatitis B is also transmitted sexually. Acute hepatitis due to these infections is not common, but chronic infections are prevalent in the elderly. Hepatitis E is similar in presentation to Hepatitis A but is far less common.
Chronic hepatitis B and C
Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections account for 1 million deaths worldwide yearly, but this number should dramatically decrease with recent advances in treatment.10 Hepatitis B (an estimated 257 million people worldwide are hepatitis B surface antigen positive) should be tested for in all patients presenting with abnormal transaminases and in asymptomatic patients from high‐risk populations such as people born in high‐risk countries such as sub‐Saharan Africa, China, and Vietnam; former or current intravenous drug users; those on dialysis; and men who have sex with men. The screening tests for hepatitis B are surface antigen and antibody. Those found to have hepatitis B surface antigen should be screened with six‐month ultrasounds to look for hepatocellular carcinoma, which can occur more frequently than in other liver diseases in this condition in the absence of cirrhosis. People who have cirrhosis or persistently elevated transaminases and hepatitis B DNA levels should be given treatment with anti‐virals such as Tenofovir, which are oral and once‐daily and can prevent progression of and reverse fibrosis. Hepatitis C should also be tested for in anyone with abnormal liver tests or with a history of IV drug abuse or those who were born between 1945 and 1965 in the US, who have a 2.6% prevalence.11 The screening test is a hepatitis C antibody test; if the hepatitis C antibody is positive, then the hepatitis C viral load should be determined to confirm infection. Over 15% of patients will be antibody‐positive but not have viral RNA, indicating previously resolved infection. Today, 96% of patients with hepatitis C can be cured with simple once‐daily oral medications taken for 8–12 weeks.12 All patients with chronic hepatitis B and C need to be assessed for fibrosis.
Fatty liver disease
Approximately 30% of the US population has fatty liver disease. Fatty liver disease can be divided into benign steatosis and steatohepatitis. Benign steatosis occurs in 25–30% of the US population, steatohepatitis occurs in about 5–6%,13 and cirrhosis due to fatty liver disease occurs in 1%. Nonalcoholic benign steatosis is liver fat encompassing >5% of a biopsy but with no inflammation or fibrosis. It usually has a benign course. Nonalcoholic steatohepatitis (NASH) is fatty infiltration of the liver >5% with lobular inflammation or fibrosis.14,15
Fatty liver disease is the hepatic manifestation of metabolic syndrome, which is the condition produced when genetically susceptible individuals overconsume carbohydrates and do not exercise sufficiently. A recent study has shown that 80% of patients with nonalcoholic steatohepatitis are overweight or obese, 72% have dyslipidemia, and 44% have received a diagnosis of type 2 diabetes mellitus.16 Patients with fatty liver disease can have normal transaminases, though, when elevated ALT is usually greater than AST; they often have elevated serum ferritin, and fat can usually be detected on ultrasound of the liver, which has a sensitivity of 85–94%.17 Transient elastography can grade the degree of liver fat. Treatment of fatty liver disease consists of weight loss, decreased carbohydrates (particularly the elimination of sweetened beverages), exercise, and control of coexisting risk factors of type 2 diabetes and hyperlipidaemia with appropriate medication. Many medications for this disease are now in development.
Drug‐induced liver injury
Drug‐induced liver injury (DILI) is more common in the elderly due to increased polypharmacy, decreased liver perfusion, and decreased cytochrome p450 function.18 DILI incidence is 15 cases per 100,000 people, with jaundice occurring in 30% of cases. The diagnosis is challenging as other reasons have to be ruled out, and there are no specific markers or tests for DILI. The https://www.ncbi.nlm.nih.gov website sponsored by the National Institute of Health has descriptions of over 1200 agents that may cause liver injury.
DILI can be subdivided into three categories: direct, idiosyncratic, or indirect. Direct agents such as acetaminophen result in liver injury in a predictable dose‐dependent manner, and the onset of injury is one to five days after administration. Idiosyncratic hepatotoxicity is the result of substances that cause injury only in rare cases in susceptible individuals. This liver injury is further characterized as hepatocellular (increases in transaminases: AST/AST), cholestatic (increase in bilirubin and alkaline phosphatase), and mixed. The differences between these types are made by dividing the alanine aminotransferase level by the alkaline phosphatase level at initial presentation, with both levels expressed as multiples of the upper limit of the normal range. The hepatocellular ratio is >5, mixed level 3–5, and cholestatic level <2. Indirect injury is caused by a medication that exacerbates a pre‐existing liver condition.
When a patient presents with abnormal liver tests or jaundice and other diseases have been ruled out via blood tests, history, and imaging, DILI must be suspected. One needs to know all the medications the patient has taken in the last three months. Then those medications should be looked up in the https://www.ncbi.nlm.nih.gov database online, and the usual reaction of the medication should be compared to the clinical situation. For example, amoxicillin‐clavulanate