Liver Pathology PDF - 1/2025

Liver pathology Jin Guo MD 1/2025  Liver pathology - objectives – At the end of this lecture the student will be able to name and discuss the clinicopathologic features of the common lesions: Hepatitis – viral, autoimmue -- Cholestasis – PBC, PSC M...

Liver pathology Jin Guo MD 1/2025  Liver pathology - objectives – At the end of this lecture the student will be able to name and discuss the clinicopathologic features of the common lesions: Hepatitis – viral, autoimmue -- Cholestasis – PBC, PSC Metabolic disorders – fatty liver, hemochromatosis, Alpha-1 antitrypsin deficiency Liver tumors  Zone 3 is next to the central vein and is least supplied by oxygen and at risk for hypotension and congestion. True False  normal congestion congestion “nutmeg” Causes: right heart failure or hepatic vein thrombosis Case A 30-year-old black homosexual man presented to the local clinic complaining of anorexia, nausea, vomiting and malaise. He noted the onset of anorexia and nausea a week prior to presentation but attributed it to the flu. However, intractable symptoms developed and he had lost ten pounds. His past medical history was pertinent for multiple sexual partners. His sexual practices included unprotected anal intercourse and anal-oral sex. There was no history of intravenous drug use or blood transfusion. He admitted to drinking alcohol.  Physical examination revealed a thin man who looked ill. His blood pressure was 110/80 lying down, which decreased to 90/60 upon sitting. His pulse changed from 84 lying down to 108 when sitting. His temperature was 37.5°C, and his respiratory rate was 20. There was mild right upper quadrant abdominal tenderness. The liver percussed to 3 cm below the costal margin with a total span of 13 cm. No spleen was palpated. His eyes were yellow. Laboratory results: -Anti-HAV Total - positive; IgM fraction – negative -HBsAg positive -Anti-HBc Total - positive; IgM fraction – positive -Anti-HCV Negative -Anti-delta virus; Sent to outside lab -Anti-HIV Negative -Urinalysis: pH 7.2; golden brown; protein: trace; glucose: negative; bilirubin - positive(3+)  Diagnosis: Hepatitis B Do we need to have a liver bx?  Acute phase of hepatitis B Ballooning degeneration Inflammatory cell infiltration Councilman body Chronic hepatitis B Ground glass hepatocytes Chronic hepatitis B  Hepatitis B Usually subclinical disease, but may lead to fulminant hepatic failure, chronic liver disease and cirrhosis Causes 40% of hepatitis cases in US Lifetime risk for hepatocellular carcinoma is 40% for men and 15% for women Spread by infected patients or chronic viral carriers through intimate/sexual contact, intravenous drug abuse, contaminated blood or infected instruments, maternal to infant via delivery  Hepatitis B Following acute infection: – clear infection and develop immunity or may – develop chronic hepatitis or chronic carrier state. Chronic infection: – 6 months, normal ALT and AST, no symptoms; occurs in 10%  Viral hepatitis Anti-delta virus antibody titer had returned from the reference laboratory and was negative  Hepatitis C Genome identified in 1989 Major worldwide health problem Leading indication for liver transplantation 4 million in US have anti-HCV, 2.7 million have detectable virus  Hepatitis C High rate of progression to chronicity – 15% exposed will recover spontaneously – 85% develop chronic disease 15-20% of chronic hepatitis C develop cirrhosis End-stage liver disease due to HCV - most common indication for liver transplantation in US Factors promoting disease progression or severity – Alcohol use - also increases risk of HCC – Age at acquisition > 40 years – Male gender – Hepatitis B or HIV coinfection  Acute phase of hepatitis C lobular and portal inflammation Chronic hepatitis C Portal lymphoid infiltration Portal lymphoid infiltration with spillover Fatty change of inflammation into adjacent parenchyma Chronic hepatitis C -Portal lymphocytic infiltration, fatty changes -Bridging fibrosis, may be early stage of cirrhosis Trichrome Grading of chronic hepatitis C Staging of fibrosis Autoimmune Hepatitis Interface hepatitis Autoimmune Hepatitis Plasma cell infiltration  Autoimmune hepatitis 70% women, usually ages 20-45 years A diagnosis of exclusion 60% have other autoimmune disorders – Rheumatoid arthritis – Thyroiditis – Sjogren’s syndrome – Ulcerative colitis Laboratory – viral markers negative – elevated IgG Antinuclear antibody Anti-smooth muscle actin antibody Anti-liver-kidney-microsomal antibody – high ALT and AST (300-500 mg/dl) Fulminant hepatitis The liver volume is smaller than normal due to extensive liver necrosis Fulminant hepatitis Extensive necrosis with scattered residual bile ducts  Fulminant hepatitis - massive hepatic necrosis Uncommon complication of acute viral hepatitis Progresses from onset of symptoms to hepatic encephalopathy in 2-3 weeks in previously healthy patient Causes: drugs (acetaminophen, carbon tetrachloride, halothane, isoniazid, rifampin), viruses (Hepatitis B, A), acute fatty liver of pregnancy, hepatic vein obstruction, hyperthermia, ischemia, tumor, Wilson’s disease Treatment - liver transplant Mortality without liver transplant is 25-90% Summary - hepatitis histologic features Acute phase of hepatitis: – inflammatory infiltrates and Councilman bodies Chronic phase of hepatitis: – Hepatitis B: ground glass hepatocytes – Hepatitis C: portal tract lymphoid aggregates – Autoimmune hepatitis: interface hepatitis, plasma cell infiltrates, autoantibodies – Fulminant hepatitis: massive hepatic necrosis  Metabolic disorders – Fatty liver – Hemochromotosis – Alpha-1 antitrypsin deficiency  Steatosis Macrovesicular fatty change  Alcoholic hepatitis Inflammation, Hepatocyte injury and Mallory bodies  Alcoholic hepatitis Alcoholic hepatitis is an acute form of alcohol- induced liver injury that occurs with the consumption of a large quantity of alcohol over a prolonged period of time. It encompasses a spectrum of severity ranging from asymptomatic derangement of biochemistries to fulminant liver failure and death. The diagnosis of alcoholic hepatitis is based on a thorough history, physical examination and review of laboratory tests. Characteristically, the ratio of AST/ALT is approximately 2:1. Cirrhosis Trichrome stain Bridging fibrosis, scar tissue and regenerative nodules  Clinical presentations of cirrhosis? -progressive liver failure -complications related to portal hypertension -development of hepatocellular carcinoma caput medusae splenomegaly esophageal varices hepatocellular ca Hemochromatosis Iron stain  Hemochromatosis Abnormal accumulation of iron in parenchymal organs, leading to organ toxicity. Most common inherited liver disease in white persons and autosomal recessive genetic disorder. Two mutations in the HFE gene have been described. C282Y and H63D Secondary hemochromatosis is caused by disorders of erythropoiesis and treatment of the diseases with blood transfusions. Alpha-1 antitrypsin deficiency PAS  Alpha-1 antitrypsin deficiency Most common genetic liver disorder identified in infants and children. It is caused by reduced synthesis of normal alpha-1 antitrypsin which is a protease inhibitor. In mutant variants the synthesized protein lacks the ability to migrate from endoplasmic reticulum to Golgi zone and thus accumulates inside ER as hyaline globules. Case A 57-year-old white man presented to the ER with a h/o increasing abdominal girth, increasing somnolence and vomiting blood. Family members related that he had consumed alcohol for many years, drinking up to 1 liter of liquor per day. Two months prior to admission, increasing abdominal girth was noted with the need to purchase new pants. The patient had been increasingly somnolent over the previous few days, although still drinking large amount of alcohol.  On the day of admission, he vomited some blood, followed by increased confusion. His past medical history was notable for unknown prior abdominal surgical procedures, for which he received blood products. The physical examination showed that the patient was a cachectic man who appeared older than his stated age. His blood pressure was 90/60, pulse 120, and temperature 36.8°C. He could not sit up for check of his blood pressure or pulse. His respiratory rate was 24. He was jaundiced. Ascites with severe muscle wasting or cachexia He had a protuberant abdomen Skin of neck, spider telangiectasia  Laboratory results: Hematocrit 25% WBC 12,000/µL Prothrombin time 15.8 seconds (11 to 13.5) AST 190 U/L ALT 65 U/L ALP 170 U/L Total bilirubin 7.4 mg/dL  Laboratory results: Total protein 7.8 g/dL (6.0 to 8.3) Albumin 2.8 g/dL (3.5 - 5.2) Alcohol 110 mg/Dl (