Medicine-1

Chronic liver disease

(CLD-1)

Dr. Erwa Elmakki, MD,FACP

Assistant prof-Department of Internal Medicine-
Faculty of Medicine -Jazan University

Faculty of Medicine 2022-2023

 Chronic hepatitis:

• Definition:
• Chronic Hepatitis is an ongoing injury to the cells of the liver with inflammation
which lasts for longer than six months.
 Causes

-Viruses: eg (B,C, or B+D)

-Alcohol →Alcoholic hepatitis
-Autoimmune hepatitis
-Non-alcoholic steatohepatitis (NASH)
-Drugs eg: INH, Methyldopa, Amiodarone,
Ketoconazole, Nitrofurantoin
-Inherited metabolic liver diseases (Wilson, hemochromatosis, alpha one antitrypsin
def.).
-Autoimmune cholestatic liver diseases (eg:PBC,PSC)
 Acute Hepatitis B & C
Hepatitis B Hepatitis C

Virus DNA RNA

Spread Blood, sexual, perinatal Blood

Presentation Fever, malaise, anorexia, nausea, arthralgia, Usually asymptomatic early on

jaundice, RUQ pain)

Investigation HBV seromarkers, HBV-DNA(PCR).Biopsy Anti-HCV, HCV- RNA(PCR). Biopsy.

% Chronic 5-10% 85%

Treatment Supportive. Supportive, Antiviral (DAA)

Definition of chronic hepatitis B (CHB)

 HBV is a DNA virus that replicates by reverse transcription.

 CHB infection is the persistence of HBsAg for 6 months or more.
Epidemiology of chronic HBV

 250-350 million worldwide are chronically infected with HBV.

 HBV prevalence varying among geographic regions
 Higher rate of infection is seen in. Australia, India, Subsaharan Africa, Asia
 Occult HBV appears to have an overall prevalence of 4% in Asia.
 Vaccination implemented in highly endemic areas seems to have reduced the
prevalence of HBV infection.
Pathogenesis of CHB
..CHB: Mode of transmission

 Blood & blood products

 Sexual intercourse (body fluids eg: semen, vaginal secretions)
 Perinatal (vertical transmission)
 Horizontal
HBV/HDV co-infection

 Hepatitis D (Delta virus) can occur only with a concomitant HBV.

 HDV uses the HBV surface antigen to form a capsid.
 Co-infection with hepatitis D increases the risk of liver cirrhosis and HCC.
Clinical presentation of CHB

 Most patients are asymptomatic

 Some patients with chronic active hepatitis, may complain of :
-Jaundice, fatigue, anorexia , nausea
-Mild upper quadrant pain or discomfort
 Some patients may present with features of liver cirrhosis or HCC.
 Some patients develop extra-hepatic manifestations
 Extra-hepatic Manifestations of HBV

Extra-hepatic features are present in 1–10% of HBV-infected patients. these include:

 Membranous glomerulonephritis.
 Acute necrotizing vasculitis (polyarteritis nodosa).
 Cryoglobulinemia
 Aplastic anemia
 Screening & diagnosis of CHB

 Groups at High Risk Should Be Screened.

 Screening should be performed using both:
HBsAg and anti-HBs.
 If HBsAg is +ve then HBV-PCR should be requested
 Tests for other HBV sero markers.
 Other tests include LFTs, liver US. and liver biopsy.
 Screening for other viruses ( HDV, HCV, HIV) is
recommended..
HBV Seromarkers

 HBsAg (Surface Ag): Acute infection, chronic infection

 HBcAg (core Ag): found only in liver tissues
 HBeAg (Envelope Ag): High infectivity & replication
 HBsAb: Immunity(previous immunization)
 HBcIgM: Acute infection
 HBcIgG: Chronic infection or previous infection
 HBeAb: Resolving or inactive infection
Interpretation of HBV serology
…CHB diagnosis

 CHB can be subdivided into –Hbe-Ag positive CHB

and Hbe-Ag negative CHB..
 Ten genotypes of HBV have been identified labeled from A to J.
Criteria of chronic inactive HBV infection (carrier state)

 +ve HBsAg
 +ve HBcAb (IgG)
 -ve HBe Ag & +ve HBeAb
 Normal LFTs (normal ALT, AST)
 Low viral load by PCR (Low HBV-DNA by PCR)
Criteria of chronic active HBV infection

 +ve HBsAg
 +ve HBcAb (IgG)
 +ve / –ve HBeAg
 Elevation of transaminases (ALT, AST)
 High viral load by PCR (HBV-DNA)
Complications & Prognosis of hepatitis B

 Most adults with acute HBV spontaneously clear the virus.

 Chronic active infection may progress to liver cirrhosis and HCC or directly can
progress to HCC without cirrhosis.
 An estimated 1 million persons per year globally, including at least 5000 persons
annually in the United States, die from chronic hepatitis B disease.
 The risk of progression depends on the status of infection, viral genotype, and
presence of coinfection
Positive Prognostic factors of hepatitis CHB

 Patients who have lost HBeAg and in whom hepatitis B virus (HBV) DNA is
undetectable have an improved clinical outcome, as characterized by the following:
-A slower rate of disease progression
-Prolonged survival without complications
-Reduced rate of HCC and cirrhosis
-Clinical and biochemical improvement after decompensation
Management of CHB

 The primary goal is to prevent the progression of the disease.

 Inactive chronic HBV infection (carriers) need follow-up every 6-12 months by
(LFTs+ HBV-PCR).

 Patients with chronic active infection are indicated for antiviral treatment.
..Management of CHB

 Cirrhotic pts with +ve HbsAg should be treated irrespective of LFTs and viral load
status.
• Vaccinate screened individuals who are negative for anti-HBs.
• Vaccinate for HAV. And avoid alcohol consumption.
.. Management of CHB
 The current effective drugs used for treating chronic
active infection are:
- Tenofovir, Entecavir &
- Pegylated interferon (PEG-IFN alpha 2-a)
 Other non-preferred drugs (high resistance rates)
include:
- Adefovir
- Lamivudine
- Telbivudine
Chronic HCV infection
 Chronic HCV: Epidemiology

⚫ The WHO estimates about 71 million people globally have

chronic hepatitis C.
⚫ Chronic HCV infection can lead to liver cirrhosis &
Hepatocellular carcinoma(HCC).
 HCV pathophysiology

⚫ HCV is a spherical, enveloped, single-stranded RNA virus.

⚫ The natural targets of HCV are hepatocytes and, possibly, B
lymphocytes.
 ..HCV pathophysiology

⚫ In most infected people, viremia persists → hepatic inflammation

and fibrosis.
⚫ HCV has six genotypes (1-6) and many subtypes (!a, !b,…).
⚫ The major HCV genotype worldwide is genotype 1, which accounts
for 40%-80% of all isolates.
 ..HCV pathophysiology

⚫ Genotype 1 is associated with more severe liver disease and a

higher risk of HCC.
⚫ Genotype 1 is more prevalent in US
⚫ Genotype 4 is more prevalent in the Middle East and Africa.
 Symptoms & Signs
of Chronic HCV
⚫ The infection is often asymptomatic
⚫ Most patients with acute and chronic infections are asymptomatic.
⚫ Some patients can have non-specific symptoms such as :
-Fatigue, jaundice, muscle & joint pain
-May present with symptoms & signs of liver cirrhosis.
 Extra-hepatic manifestation
of HCV
⚫ The most commonly occurring extra-hepatic
manifestations are:
⚫ Arthralgias
⚫ Paresthesias
⚫ Myalgias
⚫ Pruritus
⚫ Sicca syndrome
 Diagnosis

⚫ There are a number of diagnostic tests for hepatitis C

including:
⚫ 1-Serological tests: HCV-Antibody by ELISA or RIBA
test
⚫ 2-Molecular tests: HCV-RNA can be detected by PCR
typically 1-2 wks after infection.
 ..Diagnosis

⚫ In immunocompromised pts (eg: HIV) do HCV-PCR as serology is usually

negative.
⚫ 3-HCV genotypes(1-6): predict prognosis and treatment duration.
 Interpretation of
Test Results for HCV Infection
Antibody to HCV RNA Infection Status
HCV

Positive Positive Acute or chronic HCV infection, depending on

clinical context

Positive Negative Resolved HCV infection, or acute HCV infection

during low viremia*
or HCV-related cryoglobulinemia

Negative Positive Early acute HCV infection, or

Chronic HCV infection in immunosuppressed
patient, or
False-positive HCV RNA

Negative Negative No HCV infection

 Treatment of HCV

⚫ Treatment of chronic HCV infection has two goals:

1-To achieve sustained eradication of HCV.
2-To prevent progression to cirrhosis and HCC.
⚫ Pts with chronic HCV are advised to avoid alcohol and
Hepatotoxic drugs.
⚫ They have to be vaccinated for hepatitis A and hepatitis
B.
 Treatment of HCV

⚫ Previously the standard therapy was an interferon-based

regimen(40-55% response rate).
⚫ Interferon-based regimen consisting of pegylated
Interferon plus Ribavirin.
⚫ Since 2014 Direct acting anti-HCV (DAAs) were
introduced for HCV treatment.
⚫ These include a Sofosbuvir-based regimen
⚫ Sofosbuvir+ Velpatasvir is currently used to treat all HCV
genotypes with very high success rates (95-99%).
 AUTOIMMUNE HEPATITIS (AIH)

◼ Chronic hepatitis due to hepatocytes autoantibodies.

◼ Can progress to cirrhosis
◼ May be associated with other autoimmune diseases.
◼ Female to male ratio 3:1
 …AIH

◼ AIH characteristics findings include:

– Evidence of hepatitis
– Presence of autoimmune antibody
– Elevation of serum globulins (IgG)
 PATHOGENESIS

◼ Environmental Triggers: presumed to be certain viruses, toxins, drugs

◼ Drugs:
– Methyldopa
– Nitrofurantoin
– NSAIDs (eg: Diclofenac)
– Minocycline
– Lipid lowering drugs (eg: Statins)
 CLINICAL PRESENTATION

◼ Non-specific symptoms: malaise, Fever, fatigue, lethargy, nausea, abdominal pain,

anorexia.
◼ Jaundice
◼ Hepatomegaly
◼ Splenomegaly
◼ Stigmata (signs) of CLD
 CLASSIFICATION

◼ TYPE 1(Adult type): Antinuclear antibodies (ANA) or Anti-Smooth Muscle

antibody(ASMA) positive.
◼ TYPE 2(Children type): Presence of anti-Liver/Kidney Microsome
Antibodies(ALKM) or anti-Liver Cytosol antibody (ALC-1).
◼ Type 3:Antibody to Soluble Liver antigens (SLA)
 DIAGNOSIS

◼ Elevated AST and ALT

◼ Elevated IgG
◼ Rule out other causes of CLD (viral infection)
◼ Presence of autoimmune antibodies
◼ Liver biopsy
 TREATMENT of AIH

◼ Corticosteroids +/-
◼ Other Immunosupressants eg: Azathioprine
◼ Liver transplantation: for those with end-stage liver cirrhosis
Alcoholic Hepatitis
 ..Alcoholic hepatitis: Definition

• Is a syndrome of progressive inflammatory liver injury

associated with long-term heavy intake of ethanol.
 Alcoholic hepatitis: Prognosis

➢ Quantity and duration of alcohol iare the most important risk

factors
➢ Type of alcohol and pattern of drinking are less important
➢ Gender differences: Women are more susceptible than men
(shorter period and smaller amount)/
 …Alcoholic hepatitis: Prognosis

• If an alcoholic continue drinking after the diagnosis of

alcoholic liver disease the 5 yr survival rate is 30% in women
and & 70% in men.
 Pathogenicity of alcoholic hepatitis

➢ Alcoholic fatty liver disease (AFLD)

➢ Alcoholic hepatitis
➢ Alcoholic cirrhosis – end result of chronic heavy drinking
➢ Hepatocellular carcinoma
 Alcoholic hepatitis: Clinical Features

➢ Alcoholic fatty liver (AFLD)

- Seen in >90% of chronic drinkers
-Benign and reversible
-Most often asymptomatic except for hepatomegaly
-10%-20% of AFLD develop alcoholic hepatitis
 Alcoholic hepatitis: Clinical Features

• Alcoholic hepatitis
-In mild form: The patient is usually asymptomatic.
(mild elevation of liver enzymes)
-In severe form: patients present with:
fever, jaundice, hepatomegaly, marked impairment of liver
function and manifestations of portal hypertension.
 …Alcoholic hepatitis: How to diagnose?

• The diagnosis of alcoholic hepatitis is straightforward

• However, Lab studies can reveal characteristic features.
 ..Alcoholic hepatitis: Laboratory Findings

➢ Elevation of AST and ALT (<400 IU/L)

AST level is higher than ALT with AST/ALT ratio of > 2
➢ Elevatation of gamma glutamyl transpeptidase (GGT)
➢ High IgA level
➢ Reduction of serum albumin and prolongation of
prothrombin time if the patient develop cirrhosis.
 Management of alcoholic hepatitis

• Stop alcohol Intake

• Good nutrition: supplemental folic acid and Thiamine
• Mild alcoholic hepatitis: no specific treatment is required.
• Acute severe hepatitis: To decrease inflammation and
mortality consider either
-Steroids (Prednisolone) or
-Pentoxifylline (Trental) especially if prednisolone cannot be
used.
NAFLD/ NASH
 NAFLD/NASH: Definition & Risk
Factors
• NAFLD (Non-alcoholic fatty liver disease)=Abnormal
accumulation of lipids in the liver.
• NASH(Non-alcoholic steatohepatitis)
• NASH is one of the leading causes of liver cirrhosis
currently.
• Major risk factors for NAFLD/NASH are:
Type 2 DM, Obesity, DM, HTN, and metabolic syndrome
• NASH can lead to fibrosis and cirrhosis (30%).

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 NAFLD/NASH: Definition & Risk
Factors

• NAFLD is subdivided into:

1-Nonalcoholic fatty liver (NAFL) and
2-Non-alcoholic steatohepatitis (NASH).
• In NAFL, hepatic steatosis is present without
• in NASH, hepatic steatosis is associated with
hepatic inflammation

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 Metabolic Syndrome
“Syndrome of Insulin Resistance”

Visceral Steatosis
Obesity NASH

NIDDM TG HDL Hypertension

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NAFLD Vs NASH
 Diagnosis of NAFLD
& NASH

 US abdomen: is diagnostic for NAFLD, typically show bright liver.

 CT scan or MRI: also detect fatty infiltration
 NASH is a histological diagnosis (confirmed by liver biopsy).
 Fibro scan: can detect liver fibrosis
 LFTs: may show a mild elevation in transaminases (ALT, AST)
Normal liver Vs Fatty liver on US
 Treatment of NAFLD/NASH

 Lifestyle modification
 Treat & control the underlying risk factors
 Vitamin E (Tocopherol) is indicated only in biopsy-proven NASH in non-diabetic
patients.
 Pioglitazone is used for treating diabetic and non-diabetic patients with NASH.