Chronic Viral Hepatitis

Gastroenterology

Clinicals - History

Fact Explanation
Age Hepatitis B virus (HBV) and Hepatitis C virus (HCV) can cause chronic viral hepatitis.
Fewer than 5 percent of adults acutely infected with HBV progress to chronic infection
Most patients (85 percent or more) with acute HCV infection develop chronic infection

Risk of chronic HBV infection is inversely related to age, with chronic infection developing in about 90 percent of infected infants, 30 percent of children younger than five years, and less than 5 percent in all other persons
Age
Hepatitis B virus (HBV) and Hepatitis C virus (HCV) can cause chronic viral hepatitis.
Fewer than 5 percent of adults acutely infected with HBV progress to chronic infection
Most patients (85 percent or more) with acute HCV infection develop chronic infection

Risk of chronic HBV infection is inversely related to age, with chronic infection developing in about 90 percent of infected infants, 30 percent of children younger than five years, and less than 5 percent in all other persons
Chemotherapy or other immunosuppressant drugs Occult infection may be reactivated by chemotherapy or other immunosuppressants Chemotherapy or other immunosuppressant drugs
Occult infection may be reactivated by chemotherapy or other immunosuppressants
Immunosuppressed conditions (eg:AIDS patients) Occult infection may be reactivated by low immune conditions Immunosuppressed conditions (eg:AIDS patients)
Occult infection may be reactivated by low immune conditions
Intra venous drug abuse Most drug abusers use the same needle to inject the drugs among several people.The risk of transmission is high as HBV and HCV can spread through blood Intra venous drug abuse
Most drug abusers use the same needle to inject the drugs among several people.The risk of transmission is high as HBV and HCV can spread through blood
Multiple blood transfusion The risk of transmission is high as HBV and HCV can spread through blood Multiple blood transfusion
The risk of transmission is high as HBV and HCV can spread through blood
Sex with multiple partners The risk of transmission is high as HBV and HCV can spread through sex Sex with multiple partners
The risk of transmission is high as HBV and HCV can spread through sex
Health care and public safety workers (Specially who are not vaccinated against HBV) Health care and public safety workers are at risk of exposure to blood or blood-contaminated body fluids.Thus, the risk of transmission is high as HBV and HCV can spread through blood Health care and public safety workers (Specially who are not vaccinated against HBV)
Health care and public safety workers are at risk of exposure to blood or blood-contaminated body fluids.Thus, the risk of transmission is high as HBV and HCV can spread through blood
Homosexual people The risk of transmission is high in homosexual people Homosexual people
The risk of transmission is high in homosexual people
Baby born to a mother with Hepatitis B,C HBV , HCV can spread to the child during childbirth if the mother is infected from HBV / HCV Baby born to a mother with Hepatitis B,C
HBV , HCV can spread to the child during childbirth if the mother is infected from HBV / HCV
Symptoms of cirrhosis - yellowish discoloration of eyes, fatigue, loss of appetite, abdominal distension, leg swelling , white nails, hair loss, breast enlargement in males etc. It has been estimated that 12 percent of patients with chronic HBV infection develop cirrhosis annually.The absolute lifetime risk of death from cirrhosis or hepatocellular carcinoma is 15 to 25 percent

Chronic HCV infection leads to cirrhosis in about 10 to 20 percent of patients Mortality caused by liver disease was infrequent (range: 1.6 percent to 6 percent)
Symptoms of cirrhosis - yellowish discoloration of eyes, fatigue, loss of appetite, abdominal distension, leg swelling , white nails, hair loss, breast enlargement in males etc.
It has been estimated that 12 percent of patients with chronic HBV infection develop cirrhosis annually.The absolute lifetime risk of death from cirrhosis or hepatocellular carcinoma is 15 to 25 percent

Chronic HCV infection leads to cirrhosis in about 10 to 20 percent of patients Mortality caused by liver disease was infrequent (range: 1.6 percent to 6 percent)
Symptoms of hepatocellular carcinoma - loss of appetite, loss of weight, yelowish eyes, abdominal distension etc. Smaller percentage of patients with chronic HBV infection develop hepatocellular carcinoma.The absolute lifetime risk of death from cirrhosis or hepatocellular carcinoma is 15 to 25 percent

Persons with HCV infection and cirrhosis have a 20-fold increased risk of hepatocellular carcinoma compared with persons without HCV infection Mortality caused by liver disease was infrequent (range: 1.6 percent to 6 percent)
Symptoms of hepatocellular carcinoma - loss of appetite, loss of weight, yelowish eyes, abdominal distension etc.
Smaller percentage of patients with chronic HBV infection develop hepatocellular carcinoma.The absolute lifetime risk of death from cirrhosis or hepatocellular carcinoma is 15 to 25 percent

Persons with HCV infection and cirrhosis have a 20-fold increased risk of hepatocellular carcinoma compared with persons without HCV infection Mortality caused by liver disease was infrequent (range: 1.6 percent to 6 percent)
Blistering of the skin in areas that receive higher levels of exposure to sunlight Porphyria cutanea tarda is an identified extra-hepatic manifestation of chronic HCV Blistering of the skin in areas that receive higher levels of exposure to sunlight
Porphyria cutanea tarda is an identified extra-hepatic manifestation of chronic HCV
Decrease in the amount of urine in the presence of hypertension Membranoproliferative glomerulonephritis is an identified extra-hepatic manifestation of chronic HCV and HBV Decrease in the amount of urine in the presence of hypertension
Membranoproliferative glomerulonephritis is an identified extra-hepatic manifestation of chronic HCV and HBV
Excessive alcohol consumption Alcohol consumption and HCV / HBV act synergistically to promote the progression of liver damage Excessive alcohol consumption
Alcohol consumption and HCV / HBV act synergistically to promote the progression of liver damage
Past history of HBV / HCV infections Hepatitis B virus (HBV) and Hepatitis C virus (HCV) can cause chronic viral hepatitis.
Fewer than 5 percent of adults acutely infected with HBV progress to chronic infection
Most patients (85 percent or more) with acute HCV infection develop persistent infection.Most symptoms of chronic hepatitis C don’t appear until cirrhosis develops and the liver begins to fail.
Past history of HBV / HCV infections
Hepatitis B virus (HBV) and Hepatitis C virus (HCV) can cause chronic viral hepatitis.
Fewer than 5 percent of adults acutely infected with HBV progress to chronic infection
Most patients (85 percent or more) with acute HCV infection develop persistent infection.Most symptoms of chronic hepatitis C don’t appear until cirrhosis develops and the liver begins to fail.

Clinicals - Examination

Fact Explanation
Tattoo marks / intra venous drug injection sites Most drug abusers use the same needle to inject the drugs among several people.The risk of transmission is high as HBV and HCV can spread through blood Tattoo marks / intra venous drug injection sites
Most drug abusers use the same needle to inject the drugs among several people.The risk of transmission is high as HBV and HCV can spread through blood
Symptoms of cirrhosis - ascites, jaundice, gynecomastia, loss of body hair, ankle odema etc. It has been estimated that 12 percent of patients with chronic HBV infection develop cirrhosis annually

Chronic HCV infection leads to cirrhosis in about 10 to 20 percent of patients
Symptoms of cirrhosis - ascites, jaundice, gynecomastia, loss of body hair, ankle odema etc.
It has been estimated that 12 percent of patients with chronic HBV infection develop cirrhosis annually

Chronic HCV infection leads to cirrhosis in about 10 to 20 percent of patients
Symptoms of hepatocellular carcinoma - mass in right hypochondriac area, cachectic appearance, jaundice, ascites, ankle odema etc. Smaller percentage of patients with chronic HBV infection develop hepatocellular carcinoma
more than 50% of patients with HCC are HBV carriers

Persons with HCV infection and cirrhosis have a 20-fold increased risk of hepatocellular carcinoma compared with persons without HCV infection
Symptoms of hepatocellular carcinoma - mass in right hypochondriac area, cachectic appearance, jaundice, ascites, ankle odema etc.
Smaller percentage of patients with chronic HBV infection develop hepatocellular carcinoma
more than 50% of patients with HCC are HBV carriers

Persons with HCV infection and cirrhosis have a 20-fold increased risk of hepatocellular carcinoma compared with persons without HCV infection
Skin rash - Porphyria cutanea tarda Porphyria cutanea tarda is an identified extra-hepatic manifestation of chronic HCV Skin rash - Porphyria cutanea tarda
Porphyria cutanea tarda is an identified extra-hepatic manifestation of chronic HCV

Investigations - Diagnosis

Fact Explanation
Chronic hepatitis B (HBV) - HBsAg HBsAg positive for longer than six months Chronic hepatitis B (HBV) - HBsAg
HBsAg positive for longer than six months
Chronic hepatitis B (HBV) - Serum HBV DNA Serum HBV DNA >100,000 copies per mL Chronic hepatitis B (HBV) - Serum HBV DNA
Serum HBV DNA >100,000 copies per mL
Chronic hepatitis B (HBV) - Alanine transaminase and aspartate transaminase levels Persistent or intermittent elevation of alanine transaminase and aspartate transaminase levels Chronic hepatitis B (HBV) - Alanine transaminase and aspartate transaminase levels
Persistent or intermittent elevation of alanine transaminase and aspartate transaminase levels
Liver biopsy Liver biopsy showing chronic hepatitis (necroinflammatory score ≥4)
In chronic hepatitis B, there is a varying degree of predominantly lymphocytic portal inflammation with interface hepatitis. and spotty lobular inflammation.Bridging necrosis is identified as inflammation “connecting” portal tracts to one another
or to central veins
In patients with hepatitis C, liver biopsy provides information about fibrosis and histology.Fibrosis usually begins in the portal area in HCV
Liver biopsy
Liver biopsy showing chronic hepatitis (necroinflammatory score ≥4)
In chronic hepatitis B, there is a varying degree of predominantly lymphocytic portal inflammation with interface hepatitis. and spotty lobular inflammation.Bridging necrosis is identified as inflammation “connecting” portal tracts to one another
or to central veins
In patients with hepatitis C, liver biopsy provides information about fibrosis and histology.Fibrosis usually begins in the portal area in HCV
Chronic hepatitis C (HCV) - HCV antibody detection by enzyme immunoassay, recombinant immunoblot assay, and quantitative HCV RNA polymerase chain reaction (PCR) The most widely used initial assay for detecting HCV antibodies is the enzyme immunoassay. A positive enzyme immunoassay should be followed by a confirmatory test. When used in low-risk groups, an enzyme immunoassay may yield false-positive results.Recombinant immunoblot assay, a confirmatory test for a positive enzyme immunoassay, detects antibodies to individual HCV antigens and has a greater specificity Chronic hepatitis C (HCV) - HCV antibody detection by enzyme immunoassay, recombinant immunoblot assay, and quantitative HCV RNA polymerase chain reaction (PCR)
The most widely used initial assay for detecting HCV antibodies is the enzyme immunoassay. A positive enzyme immunoassay should be followed by a confirmatory test. When used in low-risk groups, an enzyme immunoassay may yield false-positive results.Recombinant immunoblot assay, a confirmatory test for a positive enzyme immunoassay, detects antibodies to individual HCV antigens and has a greater specificity
Chronic hepatitis C (HCV) - viral load testing- polymerase chain reaction (PCR) assays for HCV RNA Recombinant immunoblot assay used in conjunction with viral load tests to distinguish between a resolved infection and a false-positive enzyme immunoassay Chronic hepatitis C (HCV) - viral load testing- polymerase chain reaction (PCR) assays for HCV RNA
Recombinant immunoblot assay used in conjunction with viral load tests to distinguish between a resolved infection and a false-positive enzyme immunoassay
Chronic hepatitis C (HCV) - Alanine transaminase One of the hallmarks of chronic hepatitis C is a fluctuating ALT pattern, and some patients may have prolonged periods (12 months or more) of normal ALT activity Chronic hepatitis C (HCV) - Alanine transaminase
One of the hallmarks of chronic hepatitis C is a fluctuating ALT pattern, and some patients may have prolonged periods (12 months or more) of normal ALT activity

Investigations - Management

Fact Explanation
α-fetoprotein levels α-fetoprotein levels will be increased in hepatocellular carcinoma ( HCC ). HCC surveillance in patients with chronic HBV infection is often performed every six to 12 months using α-fetoprotein levels and abdominal ultrasonography.A systematic review found that the sensitivity was 60 percent (95% CI 44-76%) and specificity was 97 percent (95% CI 95-98%)
The relative risk of HCC in HBsAg-positive persons compared to HBsAg-negative controls was 18.8 for men and 33.2 for women.

Risk Factors for Developing HCC with Chronic HBV Infection-
Alcohol abuse
Asian or African race
Cirrhosis
Coinfection with hepatitis C and D virus
Exposure to aflatoxin
Family history of HCC
HBV DNA viral load >10,000 IU per mL
HBV genotype C
Longer duration of infection
Male sex
Older age
Presence of hepatitis B e antigen
Smoking

The average annual risk of HCC in patients with cirrhosis from HCV is 3.2%
α-fetoprotein levels
α-fetoprotein levels will be increased in hepatocellular carcinoma ( HCC ). HCC surveillance in patients with chronic HBV infection is often performed every six to 12 months using α-fetoprotein levels and abdominal ultrasonography.A systematic review found that the sensitivity was 60 percent (95% CI 44-76%) and specificity was 97 percent (95% CI 95-98%)
The relative risk of HCC in HBsAg-positive persons compared to HBsAg-negative controls was 18.8 for men and 33.2 for women.

Risk Factors for Developing HCC with Chronic HBV Infection-
Alcohol abuse
Asian or African race
Cirrhosis
Coinfection with hepatitis C and D virus
Exposure to aflatoxin
Family history of HCC
HBV DNA viral load >10,000 IU per mL
HBV genotype C
Longer duration of infection
Male sex
Older age
Presence of hepatitis B e antigen
Smoking

The average annual risk of HCC in patients with cirrhosis from HCV is 3.2%
Ultrasound (US) abdomen To detect HCC - On US, HCC often appears as a small hypo-echoic lesion with poorly defined margins and coarse irregular internal echoes. When the tumor grows, it can sometimes appear heterogeneous with fibrosis, fatty change, and calcifications.ultrasonography was less effective for detecting early hepatocellular carcinoma, with a sensitivity of only 63 percent

To detect cirrhosis -
surface nodularity,
overall coarse and heterogeneous echotexture,
fatty change (variable)
segmental hypertrophy / atrophy,
signs of portal hypertension-
doppler flow changes
enlarged portal vein
Ultrasound (US) abdomen
To detect HCC - On US, HCC often appears as a small hypo-echoic lesion with poorly defined margins and coarse irregular internal echoes. When the tumor grows, it can sometimes appear heterogeneous with fibrosis, fatty change, and calcifications.ultrasonography was less effective for detecting early hepatocellular carcinoma, with a sensitivity of only 63 percent

To detect cirrhosis -
surface nodularity,
overall coarse and heterogeneous echotexture,
fatty change (variable)
segmental hypertrophy / atrophy,
signs of portal hypertension-
doppler flow changes
enlarged portal vein
Computed tomography (CT) To detection of hepatocellular carcinoma-
On CT, HCC can have three distinct patterns of growth:
A single large tumor
Multiple tumors
Poorly defined tumor with an infiltrative growth pattern
Computed tomography (CT)
To detection of hepatocellular carcinoma-
On CT, HCC can have three distinct patterns of growth:
A single large tumor
Multiple tumors
Poorly defined tumor with an infiltrative growth pattern
Liver function tests - Alanine transaminase , aspartate aminotransferase, Gamma-glutamyl transpeptidase, albumin, prothrombin time Alanine transaminase , aspartate aminotransferase, Gamma-glutamyl transpeptidase will be elevated in liver diseases due to liver cell destruction.Albumin will be decreased in liver diseases due to reduced production.Prothrombin time will be increased due to reduced platelet production from the liver in liver diseases Liver function tests - Alanine transaminase , aspartate aminotransferase, Gamma-glutamyl transpeptidase, albumin, prothrombin time
Alanine transaminase , aspartate aminotransferase, Gamma-glutamyl transpeptidase will be elevated in liver diseases due to liver cell destruction.Albumin will be decreased in liver diseases due to reduced production.Prothrombin time will be increased due to reduced platelet production from the liver in liver diseases
Serum cretinine levels Important to assess as, anti viral drugs which are given for the treatment can cause nephrotoxicity Serum cretinine levels
Important to assess as, anti viral drugs which are given for the treatment can cause nephrotoxicity
HBV viral load (PCR) high HBV viral load has an adverse effect on overall survival, and it is associated with the rapid progression of HCC after initial treatment HBV viral load (PCR)
high HBV viral load has an adverse effect on overall survival, and it is associated with the rapid progression of HCC after initial treatment
Full blood count Patients with liver failure has reduced platelet levels due to decreased platelet production from the liver in liver diseases
Variceal bleeding which is a complication of portal hypertension can give rise to low hemoglobin levels
Full blood count
Patients with liver failure has reduced platelet levels due to decreased platelet production from the liver in liver diseases
Variceal bleeding which is a complication of portal hypertension can give rise to low hemoglobin levels
Serum creatinine Important to assess as, anti viral drugs which are given for the treatment can cause nephrotoxicity Serum creatinine
Important to assess as, anti viral drugs which are given for the treatment can cause nephrotoxicity
α-fetoprotein levels α-fetoprotein levels will be increased in hepatocellular carcinoma ( HCC ).HCC surveillance in patients with chronic HBV infection is often performed every six to 12 months using α-fetoprotein levels and abdominal ultrasonography.A systematic review found that the sensitivity was 60 percent (95% CI 44-76%) and specificity was 97 percent (95% CI 95-98%)
Cirrhosis proved to be the primary risk factor for HCC. At the time of presentation, liver cirrhosis (LC) was present in 10% associated viral B hepatitis (HBV) and 6% viral C hepatitis (HCV), with no signs of LC . Thus a similar percentage may have HCC
α-fetoprotein levels
α-fetoprotein levels will be increased in hepatocellular carcinoma ( HCC ).HCC surveillance in patients with chronic HBV infection is often performed every six to 12 months using α-fetoprotein levels and abdominal ultrasonography.A systematic review found that the sensitivity was 60 percent (95% CI 44-76%) and specificity was 97 percent (95% CI 95-98%)
Cirrhosis proved to be the primary risk factor for HCC. At the time of presentation, liver cirrhosis (LC) was present in 10% associated viral B hepatitis (HBV) and 6% viral C hepatitis (HCV), with no signs of LC . Thus a similar percentage may have HCC
Chronic hepatitis B (HBV) - HBsAg HBsAg positive for longer than six months in chronic HBV infected patients Chronic hepatitis B (HBV) - HBsAg
HBsAg positive for longer than six months in chronic HBV infected patients
Chronic hepatitis C (HCV) - HCV antibody detection by enzyme immunoassay, recombinant immunoblot assay, and quantitative HCV RNA polymerase chain reaction (PCR) The most widely used initial assay for detecting HCV antibodies is the enzyme immunoassay. A positive enzyme immunoassay should be followed by a confirmatory test. When used in low-risk groups, an enzyme immunoassay may yield false-positive results.Recombinant immunoblot assay, a confirmatory test for a positive enzyme immunoassay, detects antibodies to individual HCV antigens and has a greater specificity Chronic hepatitis C (HCV) - HCV antibody detection by enzyme immunoassay, recombinant immunoblot assay, and quantitative HCV RNA polymerase chain reaction (PCR)
The most widely used initial assay for detecting HCV antibodies is the enzyme immunoassay. A positive enzyme immunoassay should be followed by a confirmatory test. When used in low-risk groups, an enzyme immunoassay may yield false-positive results.Recombinant immunoblot assay, a confirmatory test for a positive enzyme immunoassay, detects antibodies to individual HCV antigens and has a greater specificity

Management - Supportive

Fact Explanation
Pregnancy Every pregnant woman should be tested for HBsAg at her first prenatal visit. The risk of an infant acquiring HBV from an HBsAg- or HBeAg-positive mother is 80 to 90 percent if the infant is not given an intramuscular injection of 0.5 mg of hepatitis B immune globulin within 12 hours of birth, followed by three timed doses of hepatitis B vaccine Pregnancy
Every pregnant woman should be tested for HBsAg at her first prenatal visit. The risk of an infant acquiring HBV from an HBsAg- or HBeAg-positive mother is 80 to 90 percent if the infant is not given an intramuscular injection of 0.5 mg of hepatitis B immune globulin within 12 hours of birth, followed by three timed doses of hepatitis B vaccine
Hepatitis B vaccination Health care professionals should receive hepatitis B vaccination.
Following the primary course of 3 vaccinations ( Time of first injection and then at one to two, and four to six months) , a blood test may be taken after an interval of 1–4 months to establish if there has been an adequate response, which is defined as an anti-hepatitis B surface antigen (anti-Hbs) antibody level above 100 mIU/ml. Such a full response occurs in about 85–90% of individuals
Hepatitis B vaccination
Health care professionals should receive hepatitis B vaccination.
Following the primary course of 3 vaccinations ( Time of first injection and then at one to two, and four to six months) , a blood test may be taken after an interval of 1–4 months to establish if there has been an adequate response, which is defined as an anti-hepatitis B surface antigen (anti-Hbs) antibody level above 100 mIU/ml. Such a full response occurs in about 85–90% of individuals
Hepatitis A vaccine Persons with chronic HBV / HCV infection who are not immune to hepatitis A should receive two doses of hepatitis A vaccine at least six months apart Hepatitis A vaccine
Persons with chronic HBV / HCV infection who are not immune to hepatitis A should receive two doses of hepatitis A vaccine at least six months apart
Regular monitoring Patients in the inactive or immune tolerant phases of chronic HBV infection should be monitored on a regular basis assessing the serum viral load, (every six to 12 months) for reactivation of their infection Regular monitoring
Patients in the inactive or immune tolerant phases of chronic HBV infection should be monitored on a regular basis assessing the serum viral load, (every six to 12 months) for reactivation of their infection
Abstain from alcohol Persons with chronic HCV infection should abstain from alcohol consumption as alcohol together with the infection causes more liver damage Abstain from alcohol
Persons with chronic HCV infection should abstain from alcohol consumption as alcohol together with the infection causes more liver damage
Avoidance of hepatotoxic drugs Hepatotoxic drugs should be avoided in persons with chronic HCV / HBV infection and cirrhosis as it causes more liver damage Avoidance of hepatotoxic drugs
Hepatotoxic drugs should be avoided in persons with chronic HCV / HBV infection and cirrhosis as it causes more liver damage

Management - Specific

Fact Explanation
Chronic HBV treatment - Pegylated interferon alfa-2a Administered subcutaneously in well-compensated patients once weekly for six to 12 months. More than 50 percent of patients with HBeAg-positive genotype A infections will achieve seroconversion.Serum HBV DNA level, HBeAg, and HBeAb should be measured at the end of treatment, and at three and six months after treatment Chronic HBV treatment - Pegylated interferon alfa-2a
Administered subcutaneously in well-compensated patients once weekly for six to 12 months. More than 50 percent of patients with HBeAg-positive genotype A infections will achieve seroconversion.Serum HBV DNA level, HBeAg, and HBeAb should be measured at the end of treatment, and at three and six months after treatment
Chronic HBV treatment - Oral antiviral drugs ( Adefovir , Entecavir , Lamivudine , Telbivudine , Tenofovir ) Five oral nucleotide reverse transcriptase inhibitors are approved for the treatment of HBV infection. If HBV DNA levels do not become undetectable within six to 12 months, a second antiviral agent should be used. The incidence of seroconversion increases in a stepwise fashion with ongoing treatment and with the duration of undetectable HBV DNA levels. Chronic HBV treatment - Oral antiviral drugs ( Adefovir , Entecavir , Lamivudine , Telbivudine , Tenofovir )
Five oral nucleotide reverse transcriptase inhibitors are approved for the treatment of HBV infection. If HBV DNA levels do not become undetectable within six to 12 months, a second antiviral agent should be used. The incidence of seroconversion increases in a stepwise fashion with ongoing treatment and with the duration of undetectable HBV DNA levels.
Chronic HCV treatment - Pegylated interferon alfa-2a Peginterferon alfa-2a is a long acting interferon. Interferons are proteins released in the body in response to viral infections. Interferons are important for fighting viruses in the body, for regulating reproduction of cells, and for regulating the immune system Chronic HCV treatment - Pegylated interferon alfa-2a
Peginterferon alfa-2a is a long acting interferon. Interferons are proteins released in the body in response to viral infections. Interferons are important for fighting viruses in the body, for regulating reproduction of cells, and for regulating the immune system
Chronic HCV treatment - Ribavarin Analog used to stop viral RNA synthesis and viral mRNA capping, thus, it is a nucleoside inhibitor Chronic HCV treatment - Ribavarin
Analog used to stop viral RNA synthesis and viral mRNA capping, thus, it is a nucleoside inhibitor

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