Liver CirrhosisK. Dionne Posey, MD, MPHInternal Medicine & Pediatrics December 9, 2004

IntroductionThe two most common causes in the United States are alcoholic liver disease and hepatitis C, which together account for almost one-half of those undergoing transplantation

Introduction 12th leading cause of death in the united states in 2002 On average about 27,000 deaths per year Patients with cirrhosis are susceptible to a variety of complications and their life expectancy is markedly reduced

Exactly How Much Do You Drink?Estimated that the development of cirrhosis requires, on average, the ingestion of 80 grams of ethanol daily for 10 to 20 years This corresponds to approximately one liter of wine, eight standard sized beers, or one half pint of hard liquor each day

Pathophysiology Irreversible chronic injury of the hepatic parenchyma Extensive fibrosis - distortion of the hepatic architecture Formation of regenerative nodules

Clinical Manifestations Spider angiomas Palmar erythema Nail changes Muehrcke's nails Terrys nails Gynecomastia Testicular atrophy

Clinical Manifestations Muehrcke's nails

Terrys nails

Clinical ManifestationsFetor hepaticus JaundiceAsterixis Pigment gallstones Parotid gland enlargement

Cruveilhier-Baumgarten murmur Hepatomegaly SplenomegalyCaput medusa

Laboratory Studiesmost common measured laboratory test classified as LFTs include the enzyme tests (principally the serum aminotransferases, alkaline phosphatase, and gamma glutamyl transpeptidase), the serum bilirubintests of synthetic function (principally the serum albumin concentration and prothrombin time)

Radiologic ModalitiesCan occasionally suggest the presence of cirrhosis, they are not adequately sensitive or specific for use as a primary diagnostic modalityMajor utility of radiography in the evaluation of the cirrhotic patient is in its ability to detect complications of cirrhosis

Diagnosis Liver biopsy Obtained by either a percutaneous, transjugular, laparoscopic, or radiographically-guided fine-needle approach Sensitivity of a liver biopsy for cirrhosis is in the range of 80 to 100 percent depending upon the method used, and the size and number of specimens obtained

Diagnosis not necessary if the clinical, laboratory, and radiologic data strongly suggest the presence of cirrhosis liver biopsy can reveal the underlying cause of cirrhosis

Histopathology

Histopathology

Histopathology

Histopathology

Morphologic ClassificationMicronodular cirrhosisNodules less than 3 mm in diameterBelieved to be caused by alcohol, hemochromatosis, cholestatic causes of cirrhosis, and hepatic venous outflow obstruction

Morphologic ClassificationMacronodular cirrhosis

Nodules larger than 3 mmBelieved to be secondary to chronic viral hepatitis

Morphologic ClassificationRelatively nonspecific with regard to etiologyThe morphologic appearance of the liver may change as the liver disease progresses micronodular cirrhosis usually progresses to macronodular cirrhosis Serological markers available today are more specific than morphological appearance of the liver for determining the etiology of cirrhosisAccurate assessment of liver morphology may only be achieved at surgery, laparoscopy, or autopsy

Evaluation of Cirrhosis

ComplicationsAscitesSpontaneous Bacterial PeritonitisHepatorenal syndromeVariceal hemorrhageHepatopulmonary syndrome

ComplicationsOther Pulmonary syndromesHepatic hydrothoraxPortopulmonary HTNHepatic EncephalopathyHepatocellular carcinoma

AscitesAccumulation of fluid within the peritoneal cavity Most common complication of cirrhosis Two-year survival of patients with ascites is approximately 50 percent

Ascites Assessment of ascitesGrading Grade 1 mild; Detectable only by USGrade 2 moderate; Moderate symmetrical distension of the abdomen Grade 3 large or gross asites with marked abdominal distension Older system -subjective1+ minimal, barely detectable2+ moderate3+ massive, not tense4+massive and tense

AscitesImaging studies for confirmation of ascitesUltrasound is probably the most cost-effective modality

Ascites

Who gets a belly tap?

What do I want to order ?

AscitesTreatment aimed at the underlying cause of the hepatic disease and at the ascitic fluid itselfDietary sodium restrictionLimiting sodium intake to 88 meq (2000 mg) per day

AscitesThe most successful therapeutic regimen is the combination of single morning oral doses of Spironolactone and Furosemide, beginning with 100 mg and 40 mg Two major concerns with diuretic therapy for cirrhotic ascites: Overly rapid removal of fluid Progressive electrolyte imbalance

Spontaneous Bacterial PeritonitisInfection of ascitic fluid Almost always seen in the setting of end-stage liver diseaseThe diagnosis is established by A positive ascitic fluid bacterial culture Elevated ascitic fluid absolute polymorphonuclear leukocyte (PMN) count ( >250 cells/mm3)

Spontaneous Bacterial PeritonitisClinical manifestations:FeverAbdominal painAbdominal tendernessAltered mental status

Hepatorenal syndromeacute renal failure coupled with advanced hepatic disease (due to cirrhosis or less often metastatic tumor or severe alcoholic hepatitis)characterized by:Oliguriabenign urine sedimentvery low rate of sodium excretionprogressive rise in the plasma creatinine concentration

Hepatorenal SyndromeReduction in GFR often clinically maskedPrognosis is poor unless hepatic function improvesNephrotoxic agents and overdiuresis can precipitate HRS

Variceal hemorrhageOccurs in 25 to 40 percent of patients with cirrhosisProphylactic measuresScreening EGD recommended for all cirrhotic patients

Hepatopulmonary syndromeHepatopulmonary syndrome Liver disease Increased alveolar-arterial gradient while breathing room air Evidence for intrapulmonary vascular abnormalities, referred to as intrapulmonary vascular dilatations (IPVDs)

Hepatic HydrothoraxPleural effusion in a patient with cirrhosis and no evidence of underlying cardiopulmonary diseaseMovement of ascitic fluid into the pleural space through defects in the diaphragm, and is usually right-sidedDiagnosis -pleural fluid analysis reveals a transudative fluid serum to fluid albumin gradient greater than 1.1

Hepatic hydrothoraxConfirmatory study: Scintigraphic studies demonstrate tracer in the chest cavity after injection into the peritoneal cavityTreatment options:diuretic therapyperiodic thoracentesisTIPS

Portopulmonary HTNRefers to the presence of pulmonary hypertension in the coexistent portal hypertensionPrevalence in cirrhotic patients is approximately 2 percentDiagnosis: Suggested by echocardiography Confirmed by right heart catheterization

Hepatic EncephalopathySpectrum of potentially reversible neuropsychiatric abnormalities seen in patients with liver dysfunctionDiurnal sleep pattern pertubationAsterixisHyperactive deep tendon reflexesTransient decerebrate posturing

Hepatic Encephalopathy

Hepatic EncephalopathyMonitoring for events likely to precipitate HE [i.E.- variceal bleeding, infection (such as SBP), the administration of sedatives, hypokalemia, and hyponatremia]Reduction of ammoniagenic substratesLactulose / lactitolDietary restriction of proteinZinc and melatonin

Hepatocellular CarcinomaPatients with cirrhosis have a markedly increased risk of developing hepatocellular carcinomaIncidence in well compensated cirrhosis is approximately 3 percent per year

Hepatocellular CarcinomaSymptoms are largely due to mass effect from the tumor Pain, early satiety, obstructive jaundice, and a palpable massSerum AFP greater than 500 micrograms/l in a patient with cirrhosis are virtually diagnosticMedian survival following diagnosis is approximately 6 to 20 months

Prognostic ToolsMELD (model for end-stage liver disease)Identify patients whose predicted survival post-procedure would be three months or less

MELD = 3.8[serum bilirubin (mg/dL)] + 11.2[INR] + 9.6[serum creatinine (mg/dL)] + 6.4

Prognostic ToolsChild-Turcotte-Pugh (CTP) scoreinitially designed to stratify the risk of portacaval shunt surgery in cirrhotic patientsbased upon five parameters: serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathygood predictor of outcome in patients with complications of portal hypertension

Prognostic ToolsAPACHE III (acute physiology and chronic health evaluation system)Designed to predict an individual's risk of dying in the hospital

Treatment Options The major goals of treating the cirrhotic patient include:Slowing or reversing the progression of liver diseasePreventing superimposed insults to the liverPreventing and treating the complicationsDetermining the appropriateness and optimal timing for liver transplantation

Liver TransplantationLiver transplantation is the definitive treatment for patients with decompensated cirrhosis Depends upon the severity of disease, quality of life and the absence of contraindications

Liver TransplantationMinimal criteria for listing cirrhotic patients on the liver transplantation list include A child-Pugh score 7Less than 90 percent chance of surviving one year without a transplantAn episode of gastrointestinal hemorrhage related to portal hypertensionAn episode of spontaneous bacterial peritonitis

Vaccinations

Hepatitis A and BPneumococcal vaccine Influenza vaccination

Surveillance Screening recommendations: serum AFP determinations and ultrasonography every six months

Avoidance of Superimposed Insults Avoidance of:AlcoholAcetaminophenHerbal medications

References Up to Date Harrisons New England Journalhttp://www.openclinical.org/aisp_apache.html Nail abnormalities: clues to systemic disease, American Family Physician, March 15, 2004 Robert Fawcett

Muehrcke's nails are paired horizontal white bands separated by normal color. The exact pathogenesis is unknown but it is believed to be caused by hypoalbuminemia They are not specific for cirrhosis since they may also be seen in other conditions associated with a low serum albumin, such as the nephrotic syndrome.

Terry's nails. first reported this nail finding in 1954 in association with patients who had hepatic cirrhosis. His initial description detailed the nail bed as white in appearance with a ground-glass opacity.In addition, the nail bed contained a pink distal band that measured 1 to 2 mm in width.In 1984, Holzberg and colleagues revised the original inclusion criteria for classifying a patient as having Terry's nails to what is used today. The affected nails have a nail bed that is white or light pink with a distal transverse band measuring 0.5 to 3.0 mm in width that is pink to brown in color. The lunula of the nail may or may not be present. The degree of pallor of the nail bed and the darkness of the distal band can vary based on how long the underlying systemic disease has affected the patient.Terry's nails are associated with several diseases and advancing age. Type 2 diabetes mellitus, congestive heart failure, chronic renal failure, and cirrhosis are all systemic diseases that are associated with Terry's nails. The pathogenesis of these nail changes is unclear, but it is believed to involve changes in the microvascular system. aging is a common cause of Terry's nails

The gold standard for diagnosis of cirrhosis is examination of an explanted liver at autopsy or following liver transplantation during which the architecture of the entire liver can be appreciated.

However, liver biopsy is not necessary if the clinical, laboratory, and radiologic data strongly suggest the presence of cirrhosis. Alcoholic Cirrhosis Alcohol coming from the gut first makes contact with the hepatocytes nearest the portal triad. These liver cells, therefore, will be affected first by the toxicity of alcohol. The fibrosis (in blue in this trichrome stain) is coming "from the outside in" with respect to the lobule. At this stage, the lobules themselves are spared. Hepatitis HemochromatosisNonalcoholic steatohepatitisEvaluation of the patient with cirrhosisa specific etiology can usually be determined by the history combined with serologic and histologic evaluation. The two most common causes in the United States are alcoholic liver disease and hepatitis C Once a patient develops complications of cirrhosis, they are considered to have decompensated disease. The high morbidity and mortality of cirrhosis is secondary to these devastating complications. The quality of life and survival of cirrhotic patients can be improved by the prevention and treatment of these complications Nearly 60 percent of all patients with compensated cirrhosis will develop ascites in 10 years The two-year survival of patients with ascites is approximately 50 percent 85 percent of all cases of ascites in the US are due to liver cirrhosis ascites is the most common complication of cirrhosis

Grading A grading system for ascites has been proposed by the International Ascites Club : Grade 1 mild ascites detectable only by ultrasound examination Grade 2 moderate ascites manifested by moderate symmetrical distension of the abdomen Grade 3 large or gross asites with marked abdominal distension.

An older system that grades ascites from 1+ to 4+ is also used. In this system 1+ is minimal and barely detectable, 2+ is moderate, 3+ is massive but not tense, and 4+ is massive and tense

Patients with ascites should be "imaged" to confirm or refute the presence of ascites, cirrhosis, or malignancy. Ultrasound is probably the most cost-effective modality. Another advantage of ultrasound is that it involves no radiation or intravenous access, and no risk of contrast allergy or nephropathy. These features contrast dramatically with computerized tomographic scanning, although ascites can be seen easily on CT Serum-to-ascites albumin gradient The serum-to-ascites albumin gradient (SAAG) accurately identifies the presence of portal hypertension and is more useful than the protein-based exudate/transudate concept. The SAAG is easily calculated by subtracting the ascitic fluid albumin value from the serum albumin value, which is obtained on the same day. The presence of a gradient 1.1 g/dL (11 g/L) indicates that the patient has portal hypertension with 97 percent accuracy. A gradient